Question:

How much water will it take for me to pass a drug test in five days? I weigh 197 pounds and am 6 foot?

Answer:

It would depend on what kind of drug you were using and how long you were using it. I would advice not using it anymore! AnswerParty!

More Info:

In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or procedure, this is called a medical error and not a complication. Adverse effects are sometimes referred to as "iatrogenic" because they are generated by a physician/treatment. Some adverse effects only occur only when starting, increasing or discontinuing a treatment. Using a drug or other medical intervention which is contraindicated may increase the risk of adverse effects. Adverse effects may cause complications of a disease or procedure and negatively affect its prognosis. They may also lead to non-compliance with a treatment regimen. The harmful outcome is usually indicated by some result such as morbidity, mortality, alteration in body weight, levels of enzymes, loss of function, or as a pathological change detected at the microscopic, macroscopic or physiological level. It may also be indicated by symptoms reported by a patient. Adverse effects may cause a reversible or irreversible change, including an increase or decrease in the susceptibility of the individual to other chemicals, foods, or procedures, such as drug interactions. In clinical trials, a distinction is made between adverse events (AEs) and serious adverse events (SAEs). Generally, any event which causes death, permanent damage, birth defects, or requires hospitalization is considered an SAE. The results of these trials are often included in the labeling of the medication to provide information both for patients and the prescribing physicians. In many countries, adverse effects are required by law to be reported, researched in clinical trials and included into the patient information accompanying medical devices and drugs for sale to the public. The Yellow Card Scheme is a United Kingdom initiative run by the Medicines and Healthcare products Regulatory Agency (MHRA) and the Commission on Human Medicines (CHM) to gather information on adverse effects to medicines. This includes all licensed medicines, from medicines issued on prescription to medicines bought over the counter from a supermarket. The scheme also includes all herbal supplements and unlicensed medicines found in cosmetic treatments. Adverse drug reactions (ADRs) can be reported by a number of health care professionals including physicians, pharmacists and nurses, as well as patients. In the United States several reporting systems have been built, such as the Vaccine Adverse Event Reporting System (VAERS), the Manufacturer and User Facility Device Experience Database (MAUDE) and the Special Nutritionals Adverse Event Monitoring System. MedWatch is the main reporting center, operated by the Food and Drug Administration. In Australia, adverse effect reporting is administered by the Adverse Drug Reactions Advisory Committee (ADRAC), a subcommittee of the Australian Drug Evaluation Committee (ADEC). Reporting is voluntary, and ADRAC requests healthcare professionals to report all adverse reactions to its current drugs of interest, and serious adverse reactions to any drug. ADRAC publishes the Australian Adverse Drug Reactions Bulletin every two months.The Government's Quality Use of Medicines program is tasked with acting on this reporting to reduce and minimize the number of preventable adverse effects each year. Adverse reaction reporting is an important component of New Zealand's pharmacovigilance activities. The Centre for Adverse Reactions Monitoring (CARM) in Dunedin is New Zealand's national monitoring centre for adverse reactions. It collects and evaluates spontaneous reports of adverse reactions to medicines, vaccines, herbal products and dietary supplements from health professionals in New Zealand. Currently the CARM database holds over 80,000 reports and provides New Zealand-specific information on adverse reactions to these products, and serves to support clinical decision making when unusual symptoms are thought to be therapy related In Canada, adverse reaction reporting is an important component of the surveillance of marketed health products conducted by the Health Products and Food Branch (HPFB) of Health Canada. Within HPFB, the Marketed Health Products Directorate leads the coordination and implementation of consistent monitoring practices with regards to assessment of signals and safety trends, and risk communications concerning regulated marketed health products. MHPD also works closely with international organizations to facilitate the sharing of information. Adverse reaction reporting is mandatory for the industry and voluntary for consumers and health professionals. Surgery may have a number of undesirable or harmful effects, such as infection, hemorrhage, inflammation, scarring, loss of function, or changes in local blood flow. They can be reversible or irreversible, and a compromise must be found by the physician and the patient between the beneficial or life-saving consequences of surgery versus its adverse effects. For example, a limb may be lost to amputation in case of untreatable gangrene, but the patient's life is saved. Presently, one of the greatest advantages of minimally invasive surgery, such as laparoscopic surgery, is the reduction of adverse effects. Other nonsurgical physical procedures, such as high-intensity radiation therapy, may cause burns and alterations in the skin. In general, these therapies try to avoid damage to healthy tissues while maximizing the therapeutic effect. Vaccination may have adverse effects due to the nature of its biological preparation, sometimes using attenuated pathogens and toxins. Common adverse effects may be fever, malaise and local reactions in the vaccination site. Very rarely, there is a serious adverse effect, such as eczema vaccinatum, a severe, sometimes fatal complication which may result in persons who have eczema or atopic dermatitis. Diagnostic procedures may also have adverse effects, depending much on whether they are invasive, minimally invasive or noninvasive. For example, allergic reactions to radiocontrast materials often occur, and a colonoscopy may cause the perforation of the intestinal wall. Adverse effects can occur as a collateral or side effect of many interventions, but they are particularly important in pharmacology, due to its wider, and sometimes uncontrollable, use by way of self-medication. Thus, responsible drug use becomes an important issue here. Adverse effects, like therapeutic effects of drugs, are a function of dosage or drug levels at the target organs, so they may be avoided or decreased by means of careful and precise pharmacokinetics, the change of drug levels in the organism in function of time after administration. Adverse effects may also be caused by drug interaction. This often occurs when patients fail to inform their physician and pharmacist of all the medications they are taking, including herbal and dietary supplements. The new medication may interact agonistically or antagonistically (potentiate or decrease the intended therapeutic effect), causing significant morbidity and mortality around the world. Drug-drug and food-drug interactions may occur, and so-called "natural drugs" used in alternative medicine can have dangerous adverse effects. For example, extracts of St John's wort (Hypericum perforatum), a phytotherapic used for treating mild depression are known to cause an increase in the cytochrome P450 enzymes responsible for the metabolism and elimination of many drugs, so patients taking it are likely to experience a reduction in blood levels of drugs they are taking for other purposes, such as cancer chemotherapeutic drugs, protease inhibitors for HIV and hormonal contraceptives. The scientific field of activity associated with drug safety is increasingly government-regulated, and is of major concern for the public, as well as to drug manufacturers. The distinction between adverse and nonadverse effects is a major undertaking when a new drug is developed and tested before marketing it. This is done in toxicity studies to determine the nonadverse effect level (NOAEL). These studies are used to define the dosage to be used in human testing (phase I), as well as to calculate the maximum admissible daily intake. Imperfections in clinical trials, such as insufficient number of patients or short duration, sometimes lead to public health disasters, such as those of fenfluramine (the so-called fen-phen episode), thalidomide and, more recently, of cerivastatin (Baycol, Lipobay) and rofecoxib (Vioxx), where drastic adverse effects were observed, such as teratogenesis, pulmonary hypertension, stroke, heart disease, neuropathy, and a significant number of deaths, causing the forced or voluntary withdrawal of the drug from the market. Most drugs have a large list of nonsevere or mild adverse effects which do not rule out continued usage. These effects, which have a widely variable incidence according to individual sensitivity, include nausea, dizziness, diarrhea, malaise, vomiting, headache, dermatitis, dry mouth, etc. These can be considered a form of pseudo-allergic reaction, as not all users experience these effects; many users experience none at all. Drugs contain side effects which is the reason why commercials or advertisements put many disclaimers about the unwanted symptoms after taking the drug(s). Sometimes, putative medical adverse effects are regarded as controversial and generate heated discussions in society and lawsuits against drug manufacturers. One example is the recent controversy as to whether autism was linked to the MMR vaccine (or by thiomersal, a mercury-based preservative used in some vaccines). No link has been found in several large studies, and despite removal of thimerosal from vaccines a decade ago the rate of autism has not decreased as would be expected if it had been the causative agent. Another instance is the potential adverse effects of silicone breast implants, which led to hundreds of thousands of litigations against manufacturers of gel-based implants, due to allegations of damage to the immune system which have not yet been conclusively proven. Due to the exceedingly high impact on public health of widely used medications, such as hormonal contraception and hormone replacement therapy, which may affect millions of users, even marginal probabilities of adverse effects of a severe nature, such as breast cancer, have led to public outcry and changes in medical therapy, although its benefits largely surpassed the statistical risks. In principle, medical professionals are required to report all adverse effects related to a specific form of therapy. In practice, it is at the discretion of the professional to determine whether a medical event is at all related to the therapy. For example, a leg fracture in a skiing accident in a patient who years before took antibiotics for pneumonia is not likely to get reported.][ As a result, routine adverse effects reporting often may not include long-term and subtle effects that may ultimately be attributed to a therapy.][ Part of the difficulty is identifying the source of a complaint. A headache in a patient taking medication for influenza may be caused by the underlying disease or may be an adverse effect of the treatment. In patients with end-stage cancer, death is a very likely outcome and whether the drug is the cause or a bystander is often difficult to discern.][
Substance dependence, commonly called drug addiction, is a compulsive need to use drugs in order to function normally. When such substances are unobtainable, the user suffers from withdrawal. The section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders (more specifically, the 2000 "text revision", the DSM-IV-TR) does not use the word addiction at all. It explains: When an individual persists in use of alcohol or other drugs despite problems related to use of the substance, substance dependence may be diagnosed. Compulsive and repetitive use may result in tolerance to the effect of the drug and withdrawal symptoms when use is reduced or stopped. This, along with Substance abuse are considered Substance Use Disorders.... This is far from the only way of defining the relevant terms, however (see "Defining terms" section below). Doug Sellman at the National Addiction Center offers what he calls "The 10 most important things to know about addiction". He offers the following points, before explaining them in more detail (although even his full paper does not presume to be able to discuss all the important facts about addiction). First, Sellman says that the most important thing to know about addiction may be that addiction is "fundamentally about compulsive behavior". Second of all, such habits originate outside of consciousness (i.e. from the unconscious mind). The compulsive sequence of behaviors are so practiced that they can be extremely difficult to avoid initiating, and even harder to interrupt. Sellman maintains, thirdly, that addiction is 50% heritable. In other words, family background and genetics play a large role (see also Nature versus Nurture). The fourth most important thing is that people with addictions often have other psychiatric problems (e.g. psychiatric disorders), which can complicate matters. Next, fifth, Sellman explains that addiction is characterized by frequent relapse, and that one should not expect to overcome addiction on the first try. The sixth point he makes is that the different forms of psychotherapy all produce similar results that may be based on what is common between them (i.e. a strong bond with a trusted friend). Sellman's seventh most important thing about addiction is that ‘come back when you're motivated’ is an inappropriate approach to addiction. Individuals have very specific problems, and so it is important to find ways to engage the addicted individual (Sellman describes how empathy is crucial, for example). His next, eighth point expands on this idea: Sellman says that doctors should apply as broad an approach to the individual as possible. This means combining various rejuvenating approaches, including prescription drugs, family therapy, social and legal support, providing accommodations, and more. The ninth important thing about addiction is that epiphanies are rare - even though they are the most popular kind of story to spread. The tenth, and final important thing that Sellman explains is that change takes time (months or years of failing and trying again). He advocates for the importance of patience and persistence in practicing new behaviors over long periods of time. He concludes by appealing to all professionals involved in combating addiction; he asks that they all work together - because the combined knowledge of all fields is what is required. According to the current Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), substance dependence is defined as: When an individual persists in use of alcohol or other drugs despite problems related to use of the substance, substance dependence may be diagnosed. Compulsive and repetitive use may result in tolerance to the effect of the drug and withdrawal symptoms when use is reduced or stopped. This, along with Substance Abuse are considered Substance Use Disorders.... Substance dependence can be diagnosed with physiological dependence, evidence of tolerance or withdrawal, or without physiological dependence. By the American Society of Addiction Medicine definition, drug addiction differs from drug dependence and drug tolerance. It is, both among scientists and other writers, quite usual to allow the concept of drug addiction to include persons who are not drug abusers according to the definition of the American Society of Addiction Medicine. The term drug addiction is then used as a category which may include the same persons who, under the DSM-IV, can be given the diagnosis of substance dependence or substance abuse. (See also DSM-IV Codes) The terms abuse and addiction have been defined and re-defined over the years. The 1957 World Health Organization (WHO) Expert Committee on Addiction-Producing Drugs defined addiction and habituation as components of drug abuse: Drug addiction is a state of periodic or chronic intoxication produced by the repeated consumption of a drug (natural or synthetic). Its characteristics include: (i) an overpowering desire or need (compulsion) to continue taking the drug and to obtain it by any means; (ii) a tendency to increase the dose; (iii) a psychic (psychological) and generally a physical dependence on the effects of the drug; and (iv) detrimental effects on the individual and on society. Drug habituation (habit) is a condition resulting from the repeated consumption of a drug. Its characteristics include (i) a desire (but not a compulsion) to continue taking the drug for the sense of improved well-being which it engenders; (ii) little or no tendency to increase the dose; (iii) some degree of psychic dependence on the effect of the drug, but absence of physical dependence and hence of an abstinence syndrome [withdrawal], and (iv) detrimental effects, if any, primarily on the individual. In 1964, a new WHO committee found these definitions to be inadequate, and suggested using the blanket term "drug dependence": The definition of addiction gained some acceptance, but confusion in the use of the terms addiction and habituation and misuse of the former continued. Further, the list of drugs abused increased in number and diversity. These difficulties have become increasingly apparent and various attempts have been made to find a term that could be applied to drug abuse generally. The component in common appears to be dependence, whether psychic or physical or both. Hence, use of the term "drug dependence", with a modifying phase linking it to a particular drug type in order to differentiate one class of drugs from another, had been given most careful consideration. The Expert Committee recommends substitution of the term "drug dependence" for the terms "drug addiction" and "drug habituation". The committee did not clearly define dependence, but did go on to clarify that there was a distinction between physical and psychological ("psychic") dependence. It said that drug abuse was "a state of psychic dependence or physical dependence, or both, on a drug, arising in a person following administration of that drug on a periodic or continued basis." Psychic dependence was defined as a state in which "there is a feeling of satisfaction and psychic drive that requires periodic or continuous administration of the drug to produce pleasure or to avoid discomfort" and all drugs were said to be capable of producing this state: There is scarcely any agent which can be taken into the body to which some individuals will not get a reaction satisfactory or pleasurable to them, persuading them to continue its use even to the point of abuse – that is, to excessive or persistent use beyond medical need. The 1957 and 1964 definitions of addiction, dependence and abuse persist to the present day in medical literature. It should be noted that at this time (2006) the Diagnostic Statistical Manual (DSM-IV-TR) now spells out specific criteria for defining abuse and dependence. (DSM-IV-TR) uses the term substance dependence instead of addiction; a maladaptive pattern of substance abuse, leading to clinically significant impairment or distress, as manifested by three (or more) specified criteria, occurring at any time in the same 12-month period. This definition is also applicable on drugs with smaller or nonexistent physical signs of withdrawal, e.g., cannabis. In 2001, the American Academy of Pain Medicine, the American Pain Society, and the American Society of Addiction Medicine jointly issued "Definitions Related to the Use of Opioids for the Treatment of Pain", which defined the following terms: Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Physical dependence is a state of being that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist. Tolerance is the body's physical adaptation to a drug: greater amounts of the drug are required over time to achieve the initial effect as the body "gets used to" and adapts to the intake. Pseudo addiction is a term which has been used to describe patient behaviors that may occur when pain is undertreated. Patients with unrelieved pain may become focused on obtaining medications, may "clock watch," and may otherwise seem inappropriately "drug seeking." Even such behaviors as illicit drug use and deception can occur in the patient's efforts to obtain relief. Pseudoaddiction can be distinguished from true addiction in that the behaviors resolve when pain is effectively treated. A definition of addiction proposed by professor Nils Bejerot: An emotional fixation (sentiment) acquired through learning, which intermittently or continually expresses itself in purposeful, stereotyped behavior with the character and force of a natural drive, aiming at a specific pleasure or the avoidance of a specific discomfort. Drugs known to cause addiction include both legal and illegal drugs as well as prescription or over-the-counter drugs, according to the definition of the American Society of Addiction Medicine.][ Addictive drugs also include a large number of substrates that are currently considered to have no medical value and are not available over the counter or by prescription. Several theories of drug addiction exist, some of the main ones being genetic predisposition, the self-medication theory, and factors involved with social/economic development. There are strong associations between poverty and addiction. It has long been established that genetic factors along with social and psychological factors are contributors to addiction. A common theory along these lines is the self-medication hypotheses. Epidemiological studies estimate that genetic factors account for 40–60% of the risk factors for alcoholism. Similar rates of heritability for other types of drug addiction have been indicated by other studies. Knestler hypothesized in 1964 that a gene or group of genes might contribute to predisposition to addiction in several ways. For example, altered levels of a normal protein due to environmental factors could then change the structure or functioning of specific brain circuits during development. These altered brain circuits could change the susceptibility of an individual to an initial drug use experience. In support of this hypothesis, animal studies have shown that environmental factors such as stress can affect an animal's genotype. The addictive potential of a drug varies from substance to substance, and from individual to individual. Dose, frequency, pharmacokinetics of a particular substance, route of administration, and time are critical factors for developing a drug addiction. An article in The Lancet compared the harm and addiction of 20 drugs, using a scale from 0 to 3 for physical addiction, psychological addiction, and pleasure to create a mean score for addiction. A caffeine control was not included in the study. Selected results can be seen in the chart below. Espoused by both psychoanalysts and biological researchers, self-medication hypotheses predict that certain individuals abuse drugs in an attempt to self-medicate their unique and seemingly intolerable states of mind. The self-medication theory has a long history. Freud in 1884, first raised this concept in noting the anti-depressing properties of cocaine. Stress has long been recognized as a major contributor for drug cravings and relapse and is therefore supportive of the self-medication theory. In line with this theory, a person's use of a particular drug of choice is not an accident, but rather it is chosen for its pharmacological effect in relieving stressful symptoms or unwanted feelings. Research has shown that people who survive disasters are prone to stress-related disorders such as posttraumatic stress disorder (PTSD) and depression. People who experience major trauma in their life may self-medicate with alcohol or other drugs to relieve the symptoms of PTSD and depression. Social development and adjustment factors also play a role in drug abuse and addiction. An assumption of the developmental perspective, as mentioned by Thornberry 1987, is that the course of one's life is a process in which life circumstances change, milestones are met or missed and new social roles are created while old ones are abandoned. There are well known and widely accepted norms about when certain developmental events should happen in a person's life. Studies of the social factors involved in drug use have mostly focused either on adolescence or young adulthood, but surprisingly a significant amount of cocaine users may not initiate use until middle adulthood. The majority of people enter into adult social roles on schedule. However, some people enter these roles earlier or later than their same-age peers. The developmental perspective predicts that this will lead to less than satisfactory adjustment and possibly negative consequences including drug and alcohol dependence. Researchers have conducted numerous investigations using animal models and functional brain imaging on humans in order to define the mechanisms underlying drug addiction in the brain. Changes to several areas of the brain are thought to be involved. Acute (or recreational) use of most psychoactive drugs causes the release and prolonged action of dopamine and serotonin within the reward circuit. Different types of drugs produce these effects by different methods. Dopamine (DA) appears to harbor the largest effect and its action is characterized. DA binds to the D1 receptor, triggering a signaling cascade within the cell. cAMP-dependent protein kinase (PKA) phosphorylates cAMP response element binding protein (CREB), a transcription factor, which induces the transcription of certain genes including C-Fos. When examining the biological basis of drug addiction, one must first understand the pathways in which drugs act and how drugs can alter those pathways. The reward circuit, also referred to as the mesolimbic system, is characterized by the interaction of several areas of the brain. Dopamine is the primary neurotransmitter of the reward circuit in the brain. It regulates movement, emotion, cognition, motivation, and feelings of pleasure. Natural rewards, like eating, as well as recreational drug use cause a release of dopamine, and are associated with the reinforcing nature of these stimuli. Nearly all addictive drugs, directly or indirectly, act upon the brain’s reward system by flooding the circuit with dopamine. When addictive drugs are abused, dopamine release can be two to ten-fold over what is released under "normal" conditions. Since addictive drugs are perceived by the brain as being very rewarding, this can lead to repetitive behavior. Individuals vulnerable to addiction (due to genetics, developmental or environmental factors) tend to use long-term. Long-term abuse of drugs results in repeated release of high amounts of dopamine, which in turn affects the reward circuit in multiple ways. Abnormally high levels of dopamine can block subsequent dopamine from binding and leave excess amounts of dopamine in the synapse. In turn, the bombardment of the receptors by dopamine results in a down regulation of the receptors. This is confirmed in PET imaging studies, which have found that drug addicts have reduced levels of dopamine receptors. The down regulation of receptors results in a decrease in the sensitivity to natural reinforcers. This is why individuals who are substance dependent lose interest in normal activities; these activities are no longer perceived as pleasurable. Long-term drug use also results in the individual feeling normal rather than high. In turn, drug abusers have to continuously increase the amount of drug they are using if they want to continue to feel normal or rewarded; this is referred to as tolerance. Another affect of long-term use is the loss of control, and their ability to make sound decisions. Dopamine is also involved in the prediction of reward and may play a role in triggering cravings even to non-drug-related environmental stimuli. Overall, continued use leads to dopamine tolerance, which alters the circuitry of the brain and the reward system leading to altered behavior. This can potentially lead to severely compromised long-term health and functioning of the person's brain. Inherent differences in the dopamine system between individuals may also increase the vulnerability of some to become and addict. Using PET imaging, it has been determined that individuals who already possess a reduced number of dopamine receptors are more likely to describe drug use as pleasurable than those who have more receptors. So a high number of dopamine receptors may result in a natural aversion to drug use. In addition to the reward circuit, it is hypothesized that stress mechanisms also play a role in addiction. Koob and Kreek have hypothesized that during drug use, the corticotropin-releasing factor (CRF) activates the hypothalamic-pituitary-adrenal axis (HPA) and other stress systems in the extended amygdala. This activation influences the dysregulated emotional state associated with drug addiction. They have found that as drug use escalates, so does the presence of CRF in human cerebrospinal fluid (CSF). In rat models, the separate use of CRF antagonists and CRF receptor antagonists both decreased self-administration of the drug of study. Other studies in this review showed a dysregulation in other hormones associated with the HPA axis, including enkephalin which is an endogenous opioid peptide that regulates pain. It also appears that the µ-opioid receptor system, which enkephalin acts on, is influential in the reward system and can regulate the expression of stress hormones. Understanding how learning and behavior work in the reward circuit can help understand the action of addictive drugs. Drug addiction is characterized by strong, drug seeking behaviors in which the addict persistently craves and seeks out drugs, despite the knowledge of harmful consequences. Addictive drugs produce a reward, which is the euphoric feeling resulting from sustained dopamine concentrations in the synaptic cleft of neurons in the brain. Operant conditioning is exhibited in drug addicts as well as laboratory mice, rats, and primates; they are able to associate an action or behavior, in this case seeking out the drug, with a reward, which is the effect of the drug. Evidence shows that this behavior is most likely a result of the synaptic changes which have occurred due to repeated drug exposure. The drug seeking behavior is induced by glutamatergic projections from the prefrontal cortex to the NAc. This idea is supported with data from experiments showing the drug seeking behavior can be prevented following the inhibition of AMPA glutamate receptors and glutamate release in the NAc. Allostasis is the process of achieving stability through changes in behavior as well as physiological features. As a person progresses into drug addiction, he or she appears to enter a new allostatic state, defined as divergence from normal levels of change which persist in a chronic state. Addiction to drugs can cause damage to a brain and body as an organism enters the pathological state; the cost stemming from damage is known as allostatic load. The dysregulation of allostasis gradually occurs as the reward from the drug decreases and the ability to overcome the depressed state following drug use begins to decrease as well. The resulting allostatic load creates a constant state of depression relative to normal allostatic changes. What pushes this decrease is the propensity of drug users to take the drug before the brain and body have returned to original allostatic levels, producing a constant state of stress. Therefore, the presence of environmental stressors may induce stronger drug seeking behaviors. Neuroplasticity is the putative mechanism behind learning and memory. It involves physical changes in the synapses between two communicating neurons, characterized by increased gene expression, altered cell signaling, and the formation of new synapses between the communicating neurons. When addictive drugs are present in the system, they appear to hijack this mechanism in the reward system so that motivation is geared towards procuring the drug rather than natural rewards. Depending on the history of drug use, excitatory synapses in the nucleus accumbens(NAcc) experience two types of neuroplasticity: long-term potentiation (LTP) and long-term depression (LTD). Using mice as a model, Kourrich et al. showed that chronic exposure to cocaine increases the strength of synapses in NAc after a 10–14 day withdrawal period, while strengthened synapses did not appear within a 24 hour withdrawal period after repeated cocaine exposure. A single dose of cocaine did not elicit any attributes of a strengthened synapse. When drug-experienced mice were challenged with one dose of cocaine, synaptic depression occurred. Therefore, it seems the history of cocaine exposure along with withdrawal times affects the direction of glutamatergic plasticity in the NAc. Once a person has transitioned from drug use to addiction, behavior becomes completely geared towards seeking the drug, even though addicts report the euphoria is not as intense as it once was. Despite the differing actions of drugs during acute use, the final pathway of addiction is the same. Another aspect of drug addiction is a decreased response to normal biological stimuli, such as food, sex, and social interaction. Through functional brain imaging of patients addicted to cocaine, scientists have been able to visualize increased metabolic activity in the anterior cingulate and orbitofrontal cortex (areas of the prefrontal cortex) in the brain of these subjects. The hyperactivity of these areas of the brain in addicted subjects is involved in the more intense motivation to find the drug rather than seeking natural rewards, as well as an addict's decreased ability to overcome this urge. Brain imaging has also shown cocaine-addicted subjects to have decreased activity, as compared to non-addicts, in their prefrontal cortex when presented with stimuli associated with natural rewards. The transition from recreational drug use to addiction occurs in gradual stages and is produced by the effect of the drug of choice on the neuroplasticity of the neurons found in the reward circuit. During events preceding addiction, cravings are produced by the release of dopamine (DA) in the prefrontal cortex. As a person transitions from drug use to addiction, the release of DA in the NAcc becomes unnecessary to produce cravings; rather, DA transmission decreases while increased metabolic activity in the orbitofrontal cortex contributes to cravings. At this time a person may experience the signs of depression if cocaine is not used. Before a person becomes addicted and exhibits drug-seeking behavior, there is a time period in which the neuroplasticity is reversible. Addiction occurs when drug-seeking behavior is exhibited and the vulnerability to relapse persists, despite prolonged withdrawal; these behavioral attributes are the result of neuroplastic changes which are brought about by repeated exposure to drugs and are relatively permanent. The exact mechanism behind a drug molecule's effect on synaptic plasticity is still unclear. However, neuroplasticity in glutamatergic projections seems to be a major result of repeated drug exposure. This type of synaptic plasticity results in LTP, which strengthens connections between two neurons; onset of this occurs quickly and the result is constant. In addition to glutamatergic neurons, dopaminergic neurons present in the VTA respond to glutamate and may be recruited earliest during neural adaptations caused by repeated drug exposure. As shown by Kourrich, et al., history of drug exposure and the time of withdrawal from last exposure appear to play an important role in the direction of plasticity in the neurons of the reward system. An aspect of neuron development that may also play a part in drug-induced neuroplasticity is the presence of axon guidance molecules such as semaphorins and ephrins. After repeated cocaine treatment, altered expression (increase or decrease dependent on the type of molecule) of mRNA coding for axon guidance molecules occurred in rats. This may contribute to the alterations in the reward circuit characteristic of drug addiction. Drug addiction also raises the issue of potential harmful effects on the development of new neurons in adults. Eisch and Harburg raise three new concepts they have extrapolated from the numerous recent studies on drug addiction. First, neurogenesis decreases as a result of repeated exposure to addictive drugs. A list of studies show that chronic use of opiates, psychostimulants, nicotine, and alcohol decrease neurogenesis in mice and rats. Second, this apparent decrease in neurogenesis seems to be independent of HPA axis activation. Environmental factors other than drug exposure such as age, stress and exercise, can also have an effect on neurogenesis by regulating the hypothalamic-pituitary-adrenal (HPA) axis. Mounting evidence suggests this for three reasons: small doses of opiates and psychostimulants increase corticosterone concentration in serum but with no effect of neurogenesis; although decreased neurogenesis is similar between self-administered and forced drug intake, activation of HPA axis is greater in self-administration subjects; and even after the inhibition of opiate induced increase of corticosterone, a decrease in neurogenesis occurred. These, of course, need to be investigated further. Last, addictive drugs appear to only affect proliferation in the subgranular zone (SGZ), rather than other areas associated with neurogenesis. The studies of drug use and neurogenesis may have implications on stem cell biology. The reward system is partly responsible for the psychological part of drug tolerance. The CREB protein, a transcription factor activated by cyclic adenosine monophosphate (cAMP) immediately after a high, triggers genes that produce proteins such as dynorphin, which cuts off dopamine release and temporarily inhibits the reward circuit. In chronic drug users, a sustained activation of CREB thus forces a larger dose to be taken to reach the same effect. In addition it leaves the user feeling generally depressed and dissatisfied, and unable to find pleasure in previously enjoyable activities, often leading to a return to the drug for an additional "fix". A similar mechanism, interfering also with the dopamine system, but relying on a different transcription factor, CEBPB, has also been proposed. In this case dopamine release onto the nucleus accumbens neurons would trigger the increased synthesis of substance P which, in turn, would increase the dopamine synthesis in the VTA. The effect of this positive feedback is suggested to be dampened by repeated substance abuse. Sensitization is the increase in sensitivity to a drug after prolonged use. The proteins delta FosB and regulator of G-protein Signaling 9-2 (RGS9-2) are thought to be involved: A transcription factor, known as delta FosB, is thought to activate genes that, counter to the effects of CREB, actually increase the user's sensitivity to the effects of the substance. Delta FosB slowly builds up with each exposure to the drug and remains activated for weeks after the last exposure—long after the effects of CREB have faded. The hypersensitivity that it causes is thought to be responsible for the intense cravings associated with drug addiction, and is often extended to even the peripheral cues of drug use, such as related behaviors or the sight of drug paraphernalia. There is some evidence that delta FosB even causes structural changes within the nucleus accumbens, which presumably helps to perpetuate the cravings, and may be responsible for the high incidence of relapses that occur in treated drug addicts. Regulator of G-protein Signaling 9-2 (RGS9-2) has recently been the subject of several animal knockout studies. Animals lacking RGS9-2 appear to have increased sensitivity to dopamine receptor agonists such as cocaine and amphetamines; over-expression of RGS9-2 causes a lack of responsiveness to these same agonists. RGS9-2 is believed to catalyze inactivation of the G-protein coupled D2 receptor by enhancing the rate of GTP hydrolysis of the G alpha subunit which transmits signals into the interior of the cell. The basic mechanisms by which different substances activate the reward system are as described above, but vary slightly among drug classes. Depressants such as alcohol, barbiturates, and benzodiazepines work by increasing the affinity of the GABA receptor for its ligand; GABA. Narcotics such as morphine and heroin work by mimicking endorphins—chemicals produced naturally by the body which have effects similar to dopamine—or by disabling the neurons that normally inhibit the release of dopamine in the reward system. These substances (sometimes called "downers") typically facilitate relaxation and pain relief. Stimulants such as amphetamines, nicotine, and cocaine increase dopamine signaling in the reward system either by directly stimulating its release, or by blocking its absorption (see "Reuptake"). These substances (sometimes called "uppers") typically cause heightened alertness and energy. They cause a pleasant feeling in the body and euphoria, known as a high. Once this high wears off, the user may feel depressed. This makes them want another dose of the drug, and can worsen the addiction. Addiction is a complex but treatable disease. It is characterized by compulsive drug craving, seeking, and use that persists even if the user is aware of severe adverse consequences. For some people, addiction becomes chronic, having periodic relapses even after long periods of abstinence. As a chronic, relapsing disease, addiction may require continued treatments to increase the intervals between relapses and diminish their intensity. While some with substance issues recover and lead fulfilling lives, others require ongoing additional support. The ultimate goal of addiction treatment is to enable an individual to manage their substance misuse; for some this may mean abstinence. Immediate goals are often to reduce substance abuse, improve the patient's ability to function, and minimize the medical and social complications of substance abuse and their addiction this is called Harm Reduction. Treatments for addiction vary widely according to the types of drugs involved, amount of drugs used, duration of the drug addiction, medical complications and the social needs of the individual. Determining the best type of recovery program for an addicted person depends on a number of factors, including: personality, drug(s) of choice, concept of spirituality or religion, mental or physical illness, and local availability and affordability of programs. Many different ideas circulate regarding what is considered a "successful" outcome in the recovery from addiction. Programs that emphasize controlled drinking exist for alcohol addiction. Opiate replacement therapy has been a medical standard of treatment for opioid addiction for many years. Treatments and attitudes toward addiction vary widely among different countries. In the USA and developing countries, the goal of commissioners of treatment for drug dependence is generally total abstinence from all drugs. Other countries, particularly in Europe, argue the aims of treatment for drug dependence are more complex, with treatment aims including reduction in use to the point that drug use no longer interferes with normal activities such as work and family commitments; shifting the addict away from more dangerous routes of drug administration such as injecting to safer routes such as oral administration; reduction in crime committed by drug addicts; and treatment of other comorbid conditions such as AIDS, hepatitis and mental health disorders. These kinds of outcomes can be achieved without eliminating drug use completely. Drug treatment programs in Europe often report more favourable outcomes than those in the USA because the criteria for measuring success are functional rather than abstinence-based. The supporters of programs with total abstinence from drugs as a goal believe that enabling further drug use just means prolonged drug use and risks an increase in addiction and complications from addiction. It is occasionally sometimes difficult to convince people with substance dependencies to engage in any form of treatment. Family Interventions have been highly successful in helping these people accept help they need.][ Residential drug treatment can be broadly divided into two camps: 12 step programs or Therapeutic Communities. 12 step programs have the advantage of coming with an instant social support network, though some find the spiritual context not to their taste. In the UK drug treatment is generally moving towards a more integrated approach with rehabs offering a variety of approaches. These other programs may use a Cognitive-Behavioral Therapy approach, such as SMART Recovery, that looks at the relationship between thoughts, feelings and behaviors, recognizing that a change in any of these areas can affect the whole. CBT sees addiction as a behavior rather than a disease and subsequently curable, or rather, unlearnable. CBT programs recognize that for some individuals controlled use is a more realistic possibility. One of many recovery methods is the 12 step recovery program, with prominent examples including Alcoholics Anonymous, Narcotics Anonymous, Drug Addicts Anonymous and Pills Anonymous. They are commonly known and used for a variety of addictions for the individual addicted and the family of the individual. Substance-abuse rehabilitation (or "rehab") centers offer a residential treatment program for some of more seriously addicted in order to isolate the patient from drugs and interactions with other users and dealers. Outpatient clinics usually offer a combination of individual counseling and group counseling. Frequently a physician or psychiatrist will assist, with prescriptions, the side effects of the addiction. Medications can help immensely with anxiety and insomnia, can treat underlying mental disorders (cf. Self-medication hypothesis, Khantzian 1997) such as (manic-)depression, and can help reduce or eliminate withdrawal symptomology when withdrawing from physiologically addictive drugs. Some examples are using benzodiazepines for alcohol detoxification, which prevents delirium tremens and complications; using a slow taper of benzodiazepines or a taper of phenobarbital, sometimes including another antiepileptic agent such as gabapentin, pregabalin, or valproate, for withdrawal from barbiturates or benzodiazepines; using drugs such as baclofen to reduce cravings and propensity for relapse amongst addicts to any drug, especially effective in stimulant users, and alcoholics (in which it is nearly as effective as benzodiazepines in preventing complications); using clonidine, a benzodiazepine, and loperamide for opioid detoxification, for first-time users or those who wish to attempt an abstinence-based recovery (90% of opioid users relapse to active addiction within 8 months and/or are "multiple relapse patients"); or replacing an opioid that is interfering with or destructive to a user's life, such as illicitly-obtained heroin, Dilaudid, or oxycodone, with an opioid that can be administered legally, reduces or eliminates drug cravings, and does not produce a high, such as methadone or buprenorphine - opioid replacement therapy - which is the gold standard for treatment of opioid dependence in developed countries, reducing the risk and cost to both user and society more effectively than any other treatment modality (for opioid dependence), and shows the best short-term and long-term gains for the user, with the greatest longevity, least risk of fatality, greatest quality of life, and lowest risk of relapse and/or legal issues including arrest and incarceration. In a survey of treatment providers from three separate institutions (the National Association of Alcoholism and Drug Abuse Counselors, Rational Recovery Systems and the Society of Psychologists in Addictive Behaviors) measuring the treatment provider's responses on the Spiritual Belief Scale (a scale measuring belief in the four spiritual characteristics AA identified by Ernest Kurtz); the scores were found to explain 41% of the variance in the treatment provider's responses on the Addiction Belief Scale (a scale measuring adherence to the disease model or the free-will model addiction). Other forms of treatment include replacement drugs such as suboxone/subutex (both containing the active ingredient buprenorphine),and methadone, and all are used as substitutes for illicit opiate drugs. Although these drugs perpetuate physical dependence, the goal of opiate maintenance is to provide a clinically supervised, stable dose of a particular opioid in order to provide a measure of control to both pain and cravings. This provides a chance for the addict to function normally and to reduce the negative consequences associated with obtaining sufficient quantities of controlled substances illicitly, by both reducing opioid cravings and withdrawal symptomology. Once a prescribed dosage is stabilized, treatment enters maintenance or tapering phases. In the United States, opiate replacement therapy is tightly regulated in methadone clinics and under the DATA 2000 legislation. In some countries, other opioid derivatives such as levomethadyl acetate, dihydrocodeine, dihydroetorphine and even heroin are used as substitute drugs for illegal street opiates, with different drugs being used depending on the needs of the individual patient. Baclofen has been shown successful in attenuating cravings for most drugs of abuse - stimulants, ethanol, and opioids - and also attenuates the actual withdrawal syndrome of ethanol. Many patients have stated they "became indifferent to alcohol" or "indifferent to cocaine" overnight after starting baclofen therapy. It is possible that one of the best, albeit relatively unexplored, treatment modalities for opioid addiction - notoriously the most difficult addiction to treat (and to recover from), having relapse rates of around 60% at four weeks and 97% at twelve months if not on maintenance therapy with a mu-opioid agonist - would be to combine an opioid maintenance agent, such as methadone or buprenorphine, to block withdrawal symptomology, with baclofen, to attenuate cravings and the desire to use, in people who find that they are still using or still craving drugs while on methadone or buprenorphine maintenance. Substitute drugs for other forms of drug dependence have historically been less successful than opioid substitute treatment, but some limited success has been seen with drugs such as dextroamphetamine to treat stimulant addiction, and clomethiazole to treat alcohol addiction. Bromocriptine and desipramine have been reported to be effective for treatment of cocaine but not amphetamine addiction. Other pharmacological treatments for alcohol addiction include drugs like naltrexone, disulfiram, acamprosate and topiramate, but rather than substituting for alcohol, these drugs are intended to reduce the desire to drink, either by directly reducing cravings as with acamprosate and topiramate, or by producing unpleasant effects when alcohol is consumed, as with disulfiram. These drugs can be effective if treatment is maintained, but compliance can be an issue as alcoholic patients often forget to take their medication, or discontinue use because of excessive side effects. Additional drugs acting on glutamate neurotransmission such as modafinil, lamotrigine, gabapentin and memantine have also been proposed for use in treating addiction to alcohol and other drugs. Opioid antagonists such as naltrexone and nalmefene have also been used successfully in the treatment of alcohol addiction, which is often particularly challenging to treat. Some have also attempted to use these drugs for maintenance treatment of former opiate addicts with little success. They cannot be started until the patient has been abstinent for an extended period - unlikely with opioid addicts who are not on maintenance with a full or partial mu-opioid agonist - or they will trigger acute opioid withdrawal symptoms. No study has found them to be efficacious treatments in preventing relapse. They do nothing to block craving, and block endorphin and enkephalin, two natural neurotransmitters that regulate one's sense of well-being. An addict must discontinue the drug for just eighteen hours in order to use again. Treatment of stimulant addiction can often be difficult, with substitute drugs often being ineffective, although newer drugs such as nocaine, vanoxerine and modafinil may have more promise in this area, as well as the GABAB agonist baclofen. Another strategy that has recently been successfully trialled used a combination of the benzodiazepine antagonist flumazenil with hydroxyzine and gabapentin for the treatment of methamphetamine addiction. Another area in which drug treatment has been widely used is in the treatment of nicotine addiction. Various drugs have been used for this purpose such as bupropion, mecamylamine and the more recently developed varenicline. The cannaboinoid antagonist rimonabant has also been trialled for treatment of nicotine addiction but has not been widely adopted for this purpose. Ibogaine is a hallucinogen (psychotomimetic) that some claim interrupts addiction and reduces or eliminates withdrawal syndromes, specifically in regards to opioids. Its mechanism of action is unknown, but likely linked to nAchR α3ß4 antagonism. In one animal trial, it was shown to slightly reduce self-administration of cocaine. Another uncontrolled trial showed it reduced tremor by a mild to moderate degree during morphine withdrawal in rats. These finding can not be extrapolated to human beings with any certainty. Research is complicated by the fact that ibogaine is illegal in many developed countries, and a Schedule I substance in the US, and as a result no controlled human trials have ever been performed. A semi-synthetic analogue of ibogaine, 18-methoxycoronaridine was developed, in an attempt to reduce the toxic (ibogaine is significantly cardiotoxic, and several deaths have been reported from its use; because of its illegal, underground nature, it is impossible to know how toxic the drug is) and psychotomimetic effects of the drug. Behavioral programming is considered critical to helping those with addictions achieve abstinence. From the applied behavior analysis literature and the behavioral psychology literature several evidenced based intervention programs have emerged (1) behavioral marital therapy; (2) community reinforcement approach; (3) cue exposure therapy; and (4) contingency management strategies. In addition, the same author suggest that Social skills training adjunctive to inpatient treatment of alcohol dependence is probably efficacious. Community reinforcement has both efficacy and effectiveness data. In addition, behavioral treatment such as community reinforcement and family training (CRAFT) have helped family members to get their loved ones into treatment. Alternative therapies, such as acupuncture, are used by some practitioners to alleviate the symptoms of drug addiction. In 1997, the American Medical Association (AMA) adopted as policy the following statement after a report on a number of alternative therapies including acupuncture: There is little evidence to confirm the safety or efficacy of most alternative therapies. Much of the information currently known about these therapies makes it clear that many have not been shown to be efficacious. Well-designed, stringently controlled research should be done to evaluate the efficacy of alternative therapies. Acupuncture has been shown to be no more effective than control treatments in the treatment of opiate dependence. Acupuncture, acupressure, laser therapy and electrostimulation][ have no demonstrated efficacy for smoking cessation. Important phases in treating substance dependence include establishing coping mechanisms to deal with the hardships of withdrawal symptoms. Additionally, precautions should be established with the patient to avoid relapse by designing a treatment plan around the patients lifestyle. With the correct approaches, the patient can live a healthier life. Online websites have been a resource to aid in helping people to overcome addictions. These websites act as ways for struggling addicts, family members of addicts, and people who are in the recovery stage to confide in each other (anonymously if they so choose). They provide an alternative way for these people to seek help, support and information. Sites typically include chat rooms, forums, and blogs for members to interact.][ The most common drug addictions are to legal substances such as: The phenomenon of drug addiction has occurred to some degree throughout recorded history (see "Opium"). Modern agricultural practices, improvements in access to drugs, advancements in biochemistry, and dramatic increases in the recommendation of drug usage by clinical practitioners have exacerbated the problem significantly in the 20th century. Improved means of active biological agent manufacture and the introduction of synthetic compounds, such as methamphetamine are also factors contributing to drug addiction. Different abused substances have different origins and history, as illustrated here. Depending on the jurisdiction, addictive drugs may be legal, legal only as part of a government sponsored study, illegal to use for any purpose, illegal to sell, or even illegal to merely possess. Most countries have legislation which brings various drugs and drug-like substances under the control of licensing systems. Typically this legislation covers any or all of the opiates, amphetamines, cannabinoids, cocaine, barbiturates, benzodiazepines, anesthetics, hallucinogenics, derivatives and a variety of more modern synthetic drugs. Unlicensed production, supply or possession is a criminal offence. Usually, however, drug classification under such legislation is not related simply to addictiveness. The substances covered often have very different addictive properties. Some are highly prone to cause physical dependency, while others rarely cause any form of compulsive need whatsoever. Also, under legislation specifically about drugs, alcohol, caffeine and nicotine are not usually included. Although the legislation may be justifiable on moral or public health grounds, it can make addiction or dependency a much more serious issue for the individual: reliable supplies of a drug become difficult to secure, and the individual becomes vulnerable to both criminal abuse and legal punishment. It is unclear whether laws against illegal drug use do anything to stem usage and dependency. In jurisdictions where addictive drugs are illegal, they are generally supplied by drug dealers, who are often involved with organized crime. Even though the cost of producing most illegal addictive substances is very low, their illegality combined with the addict's need permits the seller to command a premium price, often hundreds of times the production cost. As a result, addicts sometimes turn to crime to support their habit. M: PSO/PSI mepr dsrd (o, p, m, p, a, d, s), sysi/epon, spvo proc (eval/thrp), drug (N5A/5B/5C/6A/6B/6D)
A drug test is a technical analysis of a biological specimen – for example urine, hair, blood, breath air, sweat, or oral fluid / saliva – to determine the presence or absence of specified parent drugs or their metabolites. Major uses of drug testing are to detect the presence of performance enhancing steroids in sport or for drugs prohibited by laws, such as cannabis, cocaine and heroin. A "10-panel urine screen" consists of 10 of the following: The following chart from LabCorp gives approximate detection periods for each substance by test type. The detection windows depend upon multiple factors—drug class, amount and frequency of use, metabolic rate, body mass, age, overall health, and urine pH. For ease of use, the detection times of metabolites have been incorporated into each parent drug. For example, heroin and cocaine can only be detected for a few hours after use, but their metabolites can be detected for several days in urine. In this type of situation, we will report the (longer) detection times of the metabolites. Oral fluid or saliva testing results for the most part mimic that of blood. The only exceptions are THC (tetrahyrocannabinol) and benzodiazepines. Oral fluid will likely detect THC from ingestion up to a maximum period of 6–12 hours. This continues to cause difficulty in oral fluid detection of THC and benzodiazepines. Breath Air also results for the most part mimic that of blood. Due to the very low levels of substances in the breath air Liquid Chromatography - Mass Spectrometry has to be used to analyze the sample. According to recent publication 12 analytes was investigated. Rapid oral fluid products are not approved for use in workplace drug testing programs and are not FDA cleared. Using rapid oral fluid drug tests in the workplace is prohibited in only: K2, also known as synthetic cannabinoids, is detectable for up to 3 days after single use or up to 30 days for chronic users. It wasn't tested until a year ago, but now is frequently tested for. Drug Screens are reported as PASS, or FAIL with urine reported invalid or adulterated. When an employer requests a drug test from an employee, or a physician requests a drug test from a patient, the employee or patient is typically instructed to go to a collection site or their home. The urine sample goes through a specified 'chain of custody' to ensure that it is not tampered with or invalidated through lab or employee error. The patient or employee’s urine is collected at a remote location in a specially designed secure cup, sealed with tamper-resistant tape, and sent to a testing laboratory to be screened for drugs (typically the SAMHSA 5 panel). The first step at the testing site is to split the urine into two aliquots. One aliquot is first screened for drugs using an analyzer that performs immunoassay as the initial screen. If the urine screen is positive then another aliquot of the sample is used to confirm the findings by gas chromatography – mass spectrometry (GC-MS) methodology. If requested by the physician or employer, certain drugs are screened for individually; these are generally drugs part of a chemical class that are, for one of many reasons, considered more abuse-prone or of concern. For instance, oxycodone and diamorphine may be tested, both sedative analgesics. If such a test is not requested specifically, the more general test (in the preceding case, the test for opiates) will detect the drugs, but the employer or patient will not have the benefit of the identity of the drug. Employment-related test results are relayed to an MRO (Medical Review Office) where a medical physician reviews the results. If the result of the screen is negative, the MRO informs the employer that the employee has no detectable drug in the urine. However, if the test result of the immunoassay and GC-MS are non-negative and show a concentration level of parent drug or metabolite above the established limit, the MRO contacts the employee to determine if there is any legitimate reason—such as a medical treatment or prescription. On-site instant drug testing is a more cost-efficient method of effectively detecting drug abuse amongst employees, as well as in rehabilitation programs to monitor patient progress.][ These instant tests can be used for both urine and saliva testing. Although the accuracy of such tests varies with the manufacturer, some kits boast extremely high rates of accuracy, correlating closely with laboratory test results.][ Hair analysis to detect drugs of abuse has been used by court systems in the United States, United Kingdom, Canada, and other countries worldwide. In the United States, hair testing has been accepted in court cases as forensic evidence following the Frye Rule, the Federal Rules of Evidence, and the Daubert Rule. As such, hair testing results are legally and scientifically recognized as admissible evidence.][ Although some lower courts may have accepted hair test evidence, there is no controlling judicial ruling in either the federal or any state system declaring any type of hair test as reliable. Hair testing for alcohol markers is now recognised in both the UK and US judicial systems. There are guidelines for hair testing that have been published by the Society of Hair Testing (a private company in France) that specify the markers to be tested for and the cutoff concentrations that need to be tested. Drugs of abuse that can be detected include Cannabis, Cocaine, Amphetamines and drugs new to the UK such as Mephedrone. In contrast to other drugs consumed, alcohol is not deposited directly in the hair. For this reason the investigation procedure looks for direct products of ethanol metabolism. The main part of alcohol is oxidized in the human body. This means it is released as water and carbon dioxide. One part of the alcohol reacts with fatty acids to produce esters. The sum of the concentrations of four of these fatty acid ethyl esters (FAEEs: ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate) are used as indicators of the alcohol consumption. The amounts found in hair are measured in nanograms (one nanogram equals only one billionth of a gram), however with the benefit of modern technology, it is possible to detect such small amounts. In the detection of ethyl glucuronide, or EtG, testing can detect amounts in picograms (one picogram equals 0.001 nanograms). However there is one major difference between most drugs and alcohol metabolites in the way in which they enter into the hair: on the one hand like other drugs FAEEs enter into the hair via the keratinocytes, the cells responsible for hair growth. These cells form the hair in the root and then grow through the skin surface taking any substances with them. On the other hand the sebaceous glands produce FAEEs in the scalp and these migrate together with the sebum along the hair shaft (Auwärter et al., 2001, Pragst et al., 2004). So these glands lubricate not only the part of the hair that is just growing at 0.3 mm per day on the skin surface, but also the more mature hair growth, providing it with a protective layer of fat. FAEEs (nanogram = one billionth of a gram) appear in hair in almost one order of magnitude lower than (the relevant order of magnitude of) EtG (picogram = one trillionth of a gram). It has been technically possible to measure FAEEs since 1993, and the first study reporting the detection of EtG in hair was done by Sachs in 1993. In practice, most hair which is sent for analysis has been cosmetically treated in some way (bleached, permed etc.). It has been proven that FAEEs are not significantly affected by such treatments (Hartwig et al., 2003a). FAEE concentrations in hair from other body sites can be interpreted in a similar fashion as scalp hair (Hartwig et al., 2003b). Saliva / oral fluid-based drug tests can generally detect use during the previous few days to roughly 2 weeks. THC may only be detectable for less than 12.0 hours in some cases. On site drug tests are allowed per the Department of Labor. Detection in saliva tests begins almost immediately upon use of the following substances, and lasts for approximately the following times: Sweat patches are attached to the skin to collect sweat over a long period of time (up to 14 days). These are used by child protective services, parole departments, and other government institutions concerned with drug use over long periods, when urine testing is not practical. There are also surface drug tests that test for the metabolite of parent drug groups in the residue of drugs left in sweat. Drug-testing a blood sample measures whether or not a drug or a metabolite is in the body at a particular time. These types of tests are considered to be the most accurate way of telling if a person is intoxicated. Blood drug tests are not used very often because they need specialized equipment and medically trained administrators. Depending on how much marijuana was consumed, it can usually be detected in blood tests within six hours of consumption. After six hours has passed, the concentration of marijuana in the blood decreases significantly. It generally disappears completely within 30 days. Anabolic steroids are used to enhance performance in sport and as they are prohibited in most high-level competitions drug testing is used extensively in order to enforce this prohibition. This is particularly so in individual (rather than team) sports such as athletics and cycling. Can occur at anytime, usually when the investigator has reason to believe that a substance is possibly being abused by the subject by behavior or immediately after an employee-related accident occurs during work hours. In the case of life-threatening symptoms, unconsciousness, or bizarre behavior in an emergency situation, screening for common drugs and toxins may help find the cause, called a toxicology test or tox screen to denote the broader area of possible substances than self-administered drugs. The test is usually done within 96 h (4 days) after the estimated time of intoxication. Both a urine sample and a blood sample may be tested. A blood sample is routinely used to detect ethanol/methanol and ASA/paracetamol intoxication. Various panels are used for screening urine samples for common substances, e.g. triage 8 that detects amphetamines, benzodiazepines, cocaine, methadone, opiates, cannabis, barbiturates and tricyclic antidepressants. Results are given in 10–15 min. Similar screenings may be used to evaluate the possible use of date rape drugs. This is usually done on a urine sample. Before testing samples, the tamper-evident seal is checked for integrity. If it appears to have been tampered with or damaged, the laboratory rejects the sample and does not test it. Next, the sample must be made testable. Urine and oral fluid can be used "as is" for some tests, but other tests require the drugs to be extracted from urine. Strands of hair, patches, and blood must be prepared before testing. Hair is washed in order to eliminate second-hand sources of drugs on the surface of the hair, then the keratin is broken down using enzymes. Blood plasma may need to be separated by centrifuge from blood cells prior to testing. Sweat patches are opened and the sweat collection component is removed and soaked in a solvent to dissolve any drugs present. Laboratory-based drug testing is done in two steps. The first step is the screening test, which is an immunoassay based test applied to all samples. The second step, known as the confirmation test, is usually undertaken by a laboratory using highly specific chromatographic techniques and only applied to samples that test positive during the screening test. Screening tests are usually done by immunoassay (EMIT, ELISA, and RIA are the most common). A "dipstick" drug testing method which could provide screening test capabilities to field investigators has been developed at the University of Illinois. After a suspected positive sample is detected during screening, the sample is tested using a confirmation test. Samples that are negative on the screening test are discarded and reported as negative. The confirmation test in most laboratories (and all SAMHSA certified labs) is performed using mass spectrometry, and is precise but expensive. False positive samples from the screening test will almost always be negative on the confirmation test. Samples testing positive during both screening and confirmation tests are reported as positive to the entity that ordered the test. Most laboratories save positive samples for some period of months or years in the event of a disputed result or lawsuit. For workplace drug testing, a positive result is generally not confirmed without a review by a Medical Review Officer who will normally interview the subject of the drug test. Urine drug test kits are available as on-site tests, or laboratory analysis. Urinalysis is the most common test type and used by federally mandated drug testing programs and is considered the Gold Standard of drug testing. Urine based tests have been upheld in most courts for more than 30 years. However, urinalysis conducted by the Department of Defense has been challenged for reliability of testing the metabolite of cocaine. There are two associated metabolites of cocaine, benzoylecgonine (BZ) and ecgonine methyl ester (EME), the first (BZ) is created by the presence of cocaine in an aqeous solution with a pH greater than 7.0, while the second (EME) results from the actual human metabolic process. The presence of EME confirms actual ingestion of cocaine by a human being, while the presence of BZ is indicative only. BZ without EME is evidence of sample contamination, however, the US Department of Defense has chosen not to test for EME in its urinalysis program. A disadvantage of saliva based drug testing is that it is not approved by FDA or SAMHSA for use with DOT / Federal Mandated Drug Testing. Oral fluid is not considered a bio-hazard unless there is visible blood; however, it should be treated with care. Spray (sweat) drug test kits are non-invasive. It is a simple process to collect the required specimen, no bathroom is needed, no laboratory is required for analysis, and the tests themselves are difficult to manipulate and relatively tamper-resistant. The detection window is long and can detect recent drug use within several hours. There are also some disadvantages to spray or sweat testing. There is not much variety in these drug tests, only a limited number of drugs can be detected, prices tend to be higher, and inconclusive results can be produced by variations in sweat production rates in donors. They also have a relatively long specimen collection period and are more vulnerable to contamination than other common forms of testing. Hair drug testing is a method that can detect drug use over a much longer period of time, and is often used for highly safety-critical positions where there is zero tolerance of illegal drug use. Standard hair follicle screen covers a period of 30 to 90 days. The growth of hair is usually at the rate of 0.5 inches per month. The hair sample is cut close to the scalp and 80 to 120 strands of hair are needed for the test. In the absence of hair on the head, body hair can be used as an acceptable substitute. Even if the person being tested has a shaved head, hair can also be taken from almost any other area of the body. This includes facial hair, the underarms, arms, and legs or even pubic hair. Because body hair grows at a different rate than head hair, the timeframe changes, with scientists estimating that drug use can be detected in body hair for up to 12 months. Currently, most entities that use hair testing have prescribed consequences for individuals removing hair to avoid a hair drug test. The claim that a hair test cannot be tampered with has been shown to be debatable. One study has shown that THC does not readily deposit inside epithelial cells so it is possible for cosmetic and other forms of adulteration to reduce the amount of testable cannabinoids within a hair sample. The results of federally mandating drug testing were similar to the effects of simply extending to the trucking industry the right to perform drug tests, and it has been argued that the latter approach would have been as effective at lower cost. A study in 2004 by the Independent Inquiry into Drug Testing at Work found that attempts by employers to force employees to take drug tests could potentially be challenged as a violation of privacy under the Human Rights Act 1998 and Article 8 of the European Convention of Human Rights. However, this does not apply to industries where drug testing is a matter of personal and public safety or security rather than productivity. In consultation with Dr. Carlton Turner, President Ronald Reagan issued Executive Order 12564. In doing so, he instituted mandatory drug-testing for all safety-sensitive executive-level and civil-service Federal employees. This was challenged in the courts by the National Treasury Employees Union. In 1988, this challenge was considered by the US Supreme Court. A similar challenge resulted in the Court extending the drug-free workplace concept to the private sector. These decisions were then incorporated into the White House Drug Control Strategy directive issued by President George H.W. Bush in 1989. All defendants serving on federal probation or federal supervised release are required to submit to at least three drug tests. Failing a drug test can be construed as possession of a controlled substance, resulting in mandatory revocation and imprisonment. There have been inconsistent evaluation results as to whether continued pretrial drug testing has beneficial effects. Testing positive can lead to bail not being granted, or if bail has already been granted, to bail revocation or other sanctions. Arizona also adopted a law in 1987 authorizing mandatory drug testing of felony arrestees for the purpose of informing the pretrial release decision, and the District of Columbia has had a similar law since the 1970s. It has been argued that one of the problems with such testing is that there is often not enough time between the arrest and the bail decision to confirm positive results using GC/MS technology. It has also been argued that such testing potentially implicates the Fifth Amendment privilege against self-incrimination, the right to due process (including the prohibition against gathering evidence in a manner that shocks the conscience or constitutes outrageous government conduct), and the prohibition against unreasonable searches and seizures contained in the Fourth Amendment. According to Henriksson, the anti-drug appeals of the Reagan administration "created an environment in which many employers felt compelled to implement drug testing programs because failure to do so might be perceived as condoning drug use. This fear was easily exploited by aggressive marketing and sales forces, who often overstated the value of testing and painted a bleak picture of the consequences of failing to use the drug testing product or service being offered." On March 10, 1986, the Commission on Organized Crime asked all U.S. companies to test employees for drug use. By 1987, nearly 25% of the Fortune 500 companies used drug tests. According to co-study done by DATIA and Society for Human Resource Management in 2012 (sample of 6,000 randomly selected human resource professionals), human resource professionals reported the following results after implementing a drug testing program: 19% of companies experienced an increase in employee productivity, 15% reported decrease in absenteeism, 56% reported improvement of workers' compensation incidence rates and 16% employee turnover decreased. According to US Chamber of Commerce 70% of all illicit drug users are employed. Some industries have high rates of employee drug use such as construction (12.8%), repair (11.1%), and hospitality (7.9-16.3%). According to the Canadian Human Rights Act, random and pre-employment alcohol and drug tests are not allowed in Canada. The one exception to the ban on random drug tests in Canada is alcohol testing including breathalysers in situations where the safety of employees could be at risk if alcohol is consumed at work. In 2009, a Belgian bodybuilding championship was canceled after doping officials showed up and the competitors fled. Likewise, in 2010, Iranian super heavyweight class weightlifters refused to submit to a drug test authorized by the Iran Weightlifting League. In 2000, an Australian Mining Company South Blackwater Coal Ltd with 400 employees, imposed drug-testing procedures, and the trade unions advised their members to refuse to take the tests, partly because a positive result does not necessarily indicate present impairment; the workers were stood-down by the company without pay for a week. In 2006, Levy County, Florida volunteer librarians resigned en masse rather than take drug tests. In 2003, sixteen members of the Chicago White Sox considered refusing to take a drug test, in hopes of making steroid testing mandatory. In the United States federal criminal system, refusing to take a drug test triggers an automatic revocation of probation or supervised release.
The Food and Drug Administration (FDA or USFDA) is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments. The FDA is responsible for protecting and promoting public health through the regulation and supervision of food safety, tobacco products, dietary supplements, prescription and over-the-counter pharmaceutical drugs (medications), vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), and veterinary products. The FDA also enforces other laws, notably Section 361 of the Public Health Service Act and associated regulations, many of which are not directly related to food or drugs. These include sanitation requirements on interstate travel and control of disease on products ranging from certain household pets to sperm donation for assisted reproduction. The FDA is led by the Commissioner of Food and Drugs, appointed by the President with the advice and consent of the Senate. The Commissioner reports to the Secretary of Health and Human Services. The 21st and current Commissioner is Dr. Margaret A. Hamburg. She has served as Commissioner since May 2009. The FDA has its headquarters in unincorporated White Oak, Maryland. The agency also has 223 field offices and 13 laboratories located throughout the 50 states, the United States Virgin Islands, and Puerto Rico. In 2008, the FDA started opening offices in foreign countries, including China, India, Costa Rica, Chile, Belgium, and the United Kingdom. In June 1906, President Theodore Roosevelt signed into law the Food and Drug Act, also known as the "Wiley Act" after its chief advocate Dr. Harvey Washington Wiley who riveted the country's and eventually congress's attention with public hygiene demonstrations. This act was the basis for the modern USFDA, being originally given the name of the Food, Drug, and Insecticide organization. The name eventually was shortened to the Food and Drug Administration (FDA) a few years later. The FDA comprises several offices and centers: In recent years, the agency began undertaking a large-scale effort to consolidate its operations in the Washington Metropolitan Area from its main headquarters in Rockville and several fragmented office buildings in the vicinity to the former site of the Naval Ordnance Laboratory in the White Oak area of Silver Spring, Maryland. When the FDA arrived, the site was renamed from the White Oak Naval Surface Warfare Center to the Federal Research Center at White Oak. The first building, the Life Sciences Laboratory, was dedicated and opened with 104 employees on the campus in December 2003. The project is slated to be completed by 2014. While most of the Centers are located around the Washington, D.C., area as part of the Headquarters divisions, two offices – the Office of Regulatory Affairs (ORA) and the Office of Criminal Investigations (OCI) – are primarily field offices with a workforce spread across the country. The Office of Regulatory Affairs is considered the "eyes and ears" of the agency, conducting the vast majority of the FDA's work in the field. Consumer Safety Officers, more commonly called Investigators, are the individuals who inspect production and warehousing facilities, investigate complaints, illnesses, or outbreaks, and review documentation in the case of medical devices, drugs, biological products, and other items where it may be difficult to conduct a physical examination or take a physical sample of the product. The Office of Regulatory Affairs is divided into five regions, which are further divided into 13 districts. Districts are based roughly on the geographic divisions of the federal court system. Each district comprises a main district office, and a number of Resident Posts, which are FDA offices located away from the district office to serve a particular geographic area. ORA also includes the Agency's network of laboratories, which analyze any physical samples taken. Though samples are usually food-related, some laboratories are equipped to analyze drugs, cosmetics, and radiation-emitting devices. The Office of Criminal Investigations was established in 1991 to investigate criminal cases. Unlike ORA Investigators, OCI Special Agents are armed, and are not focused on the technical aspects of the regulated industries. OCI agents pursue and develop cases where criminal actions have occurred, such as fraudulent claims, or knowingly and willfully shipping known adulterated goods in interstate commerce. In many cases, OCI will pursue cases where Title 18 violations have occurred (e.g. conspiracy, false statements, wire fraud, mail fraud), in addition to prohibited acts as defined in Chapter III of the FD&C Act. OCI Special Agents often come from other criminal investigations backgrounds, and work closely with the Federal Bureau of Investigation, Assistant Attorney General, and even Interpol. OCI will receive cases from a variety of sources, including ORA, local agencies, and the FBI, and will work with ORA investigators to help develop the technical and science-based aspects of a case. OCI is a smaller branch, comprising about 200 agents nationwide. The FDA frequently works in conjunction with other federal agencies including the Department of Agriculture, Drug Enforcement Administration, Customs and Border Protection, and Consumer Product Safety Commission. Often local and state government agencies also work in cooperation with the FDA to provide regulatory inspections and enforcement action. The FDA regulates more than $1 trillion worth of consumer goods, about 25% of consumer expenditures in the United States. This includes $466 billion in food sales, $275 billion in drugs, $60 billion in cosmetics and $18 billion in vitamin supplements. Much of the expenditures is for goods imported into the United States; the FDA is responsible for monitoring a third of all imports. The FDA's federal budget request for fiscal year (FY) 2012 totaled $4.36 billion. About $2 billion of this budget is generated by user fees. Pharmaceutical firms pay the majority of these fees, which are used to expedite drug reviews. The FDA's federal budget request for fiscal year (FY) 2008 (October 2007 through September 2008) totaled $2.1 billion, a $105.8 million increase from what it received for fiscal year 2007. In February 2008, the FDA announced that the Bush Administration's FY 2009 budget request for the agency was just under $2.4 billion: $1.77 billion in budget authority (federal funding) and $628 million in user fees. The requested budget authority was an increase of $50.7 million more than the FY 2008 funding – about a three percent increase. In June 2008, Congress gave the agency an emergency appropriation of $150 million for FY 2008 and another $150 million. Most federal laws concerning the FDA are part of the Food, Drug and Cosmetic Act, (first passed in 1938 and extensively amended since) and are codified in Title 21, Chapter 9 of the United States Code. Other significant laws enforced by the FDA include the Public Health Service Act, parts of the Controlled Substances Act, the Federal Anti-Tampering Act, as well as many others. In many cases these responsibilities are shared with other federal agencies. The programs for safety regulation vary widely by the type of product, its potential risks, and the regulatory powers granted to the agency. For example, the FDA regulates almost every facet of prescription drugs, including testing, manufacturing, labeling, advertising, marketing, efficacy and safety, yet FDA regulation of cosmetics is focused primarily on labeling and safety. The FDA regulates most products with a set of published standards enforced by a modest number of facility inspections. Inspection observations are documented on Form 483. On February 4, 2011, Canadian Prime Minister Harper and United States President Obama issued a "Declaration on a Shared Vision for Perimeter Security and Economic Competitiveness" and announced the creation of the Canada-United States Regulatory Cooperation Council (RCC) "to increase regulatory transparency and coordination between the two countries." Health Canada and the United States Food and Drug Administration (FDA) under the RCC mandate, undertook the "first of its kind" initiative by selecting "as its first area of alignment common cold indications for certain over-the-counter antihistamine ingredients (GC 2013-01-10)." The Center for Food Safety and Applied Nutrition is the branch of the FDA that is responsible for ensuring the safety and accurate labeling of nearly all food products in the United States. One exception is meat products derived from traditional domesticated animals, such as cattle and chickens, which fall under the jurisdiction of the United States Department of Agriculture Food Safety and Inspection Service. Products that contain minimal amounts of meat are regulated by FDA, and the exact boundaries are listed in a memorandum of understanding between the two agencies. However, medicines and other products given to all domesticated animals are regulated by the FDA through a different branch, the Center for Veterinary Medicine. Other consumables that are not regulated by the FDA include beverages containing more than 7% alcohol (regulated by the Bureau of Alcohol, Tobacco, Firearms and Explosives in the Department of Justice), and non-bottled drinking water (regulated by the United States Environmental Protection Agency (EPA)). CFSAN's activities include establishing and maintaining food standards, such as standards of identity (for example, what the requirements are for a product to be labeled, "yogurt") and standards of maximum acceptable contamination. CFSAN also sets the requirements for nutrition labeling of most foods. Both food standards and nutrition labeling requirements are part of the Code of Federal Regulations. The Dietary Supplement Health and Education Act of 1994 mandated that the FDA regulate dietary supplements as foods, rather than as drugs. Therefore, dietary supplements are not subject to safety and efficacy testing and there are no approval requirements. The FDA can take action against dietary supplements only after they are proven to be unsafe. Manufacturers of dietary supplements are permitted to make specific claims of health benefits, referred to as "structure or function claims" on the labels of these products. They may not claim to treat, diagnose, cure, or prevent disease and must include a disclaimer on the label. Bottled water is regulated in America by the FDA. State governments also regulate bottled water. Tap water is regulated by state and local regulations, as well as the United States EPA. FDA regulations of bottled water generally follow the guidelines established by the EPA, and new EPA rules automatically apply to bottled water if the FDA does not release an explicit new rule. Federal bottled water regulations have been criticized as weaker than the tap water regulations facing city water supplies. The Center for Drug Evaluation and Research has different requirements for the three main types of drug products: new drugs, generic drugs and over-the-counter drugs. A drug is considered "new" if it is made by a different manufacturer, uses different excipients or inactive ingredients, is used for a different purpose, or undergoes any substantial change. The most rigorous requirements apply to "new molecular entities": drugs that are not based on existing medications. New drugs receive extensive scrutiny before FDA approval in a process called a New Drug Application (NDA). New drugs are available only by prescription by default. A change to over-the-counter (OTC) status is a separate process, and the drug must be approved through an NDA first. A drug that is approved is said to be "safe and effective when used as directed." The FDA's Office of Prescription Drug Promotion reviews and regulates prescription drug advertising and promotion through surveillance activities and issuance of enforcement letters to pharmaceutical manufacturers. Advertising and promotion for over-the-counter drugs is regulated by the Federal Trade Commission. The drug advertising regulation contains two broad requirements: (1) a company may advertise or promote a drug only for the specific indication or medical use for which it was approved by FDA. Also, an advertisement must contain a "fair balance" between the benefits and the risks (side effects) of a drug. The term off-label refers to drug usage for indications other than those approved by the FDA. After approval of an NDA, the sponsor must review and report to the FDA every patient adverse drug experience of which it learns. Unexpected serious and fatal adverse drug events must be reported within 15 days, and other events on a quarterly basis. The FDA also receives directly adverse drug event reports through its MedWatch program. These reports are called "spontaneous reports" because reporting by consumers and health professionals is voluntary. While this remains the primary tool of postmarket safety surveillance, FDA requirements for postmarketing risk management are increasing. As a condition of approval, a sponsor may be required to conduct additional clinical trials, called Phase IV trials. In some cases, the FDA requires risk management plans for some drugs that may provide for other kinds of studies, restrictions, or safety surveillance activities. Generic drugs are chemical equivalents of name-brand drugs whose patents have expired. In general, they are less expensive than their name brand counterparts, are manufactured and marketed by other companies and, in the 1990s, accounted for about a third of all prescriptions written in the United States. For approval of a generic drug, the U.S. Food and Drug Administration (FDA) requires scientific evidence that the generic drug is interchangeable with or therapeutically equivalent to the originally approved drug. This is called an "ANDA" (Abbreviated New Drug Application). In 1989, a major scandal erupted involving the procedures used by the FDA to approve generic drugs for sale to the public. Charges of corruption in generic drug approval first emerged in 1988, in the course of an extensive congressional investigation into the FDA. The oversight subcommitee of the United States House Energy and Commerce Committee resulted from a complaint brought against the FDA by Mylan Laboratories Inc. of Pittsburgh. When its application to manufacture generics were subjected to repeated delays by the FDA, Mylan, convinced that it was being discriminated against, soon began its own private investigation of the agency in 1987. Mylan eventually filed suit against two former FDA employees and four drug-manufacturing companies, charging that corruption within the federal agency resulted in racketeering and in violations of antitrust law. "The order in which new generic drugs were approved was set by the FDA employees even before drug manufacturers submitted applications" and, according to Mylan, this illegal procedure was followed to give preferential treatment to certain companies. During the summer of 1989, three FDA officials (Charles Y. Chang, David J. Brancato, Walter Kletch) pleaded guilty to criminal charges of accepting bribes from generic drugs makers, and two companies (Par Pharmaceutical and its subsidiary Quad Pharmaceuticals) pleaded guilty to giving bribes. Furthermore, it was discovered that several manufacturers had falsified data submitted in seeking FDA authorization to market certain generic drugs. Vitarine Pharmaceuticals of New York, which sought approval of a generic version of the drug Dyazide, a medication for high blood pressure, submitted Dyazide, rather than its generic version, for the FDA tests. In April 1989, the FDA investigated 11 manufacturers for irregularities; and later brought that number up to 13. Dozens of drugs were eventually suspended or recalled by manufacturers. In the early 1990s, the U.S. Securities and Exchange Commission filed "securities fraud charges against the Bolar Pharmaceutical Company, a major generic manufacturer based in Long Island, New York. Over-the-counter (OTC) drugs are drugs and combinations that do not require a doctor's prescription. The FDA has a list of approximately 800 approved ingredients that are combined in various ways to create more than 100,000 OTC drug products. Many OTC drug ingredients had been previously approved prescription drugs now deemed safe enough for use without a medical practitioner's supervision. The Center for Biologics Evaluation and Research is the branch of the FDA responsible for ensuring the safety and efficacy of biological therapeutic agents. These include blood and blood products, vaccines, allergenics, cell and tissue-based products, and gene therapy products. New biologics are required to go through a premarket approval process called a Biologics License Application (BLA), similar to that for drugs. The original authority for government regulation of biological products was established by the 1902 Biologics Control Act, with additional authority established by the 1944 Public Health Service Act. Along with these Acts, the Federal Food, Drug, and Cosmetic Act applies to all biologic products, as well. Originally, the entity responsible for regulation of biological products resided under the National Institutes of Health; this authority was transferred to the FDA in 1972. The Center for Devices and Radiological Health (CDRH) is the branch of the FDA responsible for the premarket approval of all medical devices, as well as overseeing the manufacturing, performance and safety of these devices. The definition of a medical device is given in the FD&C Act, and it includes products from the simple toothbrush to complex devices such as implantable brain pacemakers. CDRH also oversees the safety performance of non-medical devices that emit certain types of electromagnetic radiation. Examples of CDRH-regulated devices include cellular phones, airport baggage screening equipment, television receivers, microwave ovens, tanning booths, and laser products. CDRH regulatory powers include the authority to require certain technical reports from the manufacturers or importers of regulated products, to require that radiation-emitting products meet mandatory safety performance standards, to declare regulated products defective, and to order the recall of defective or noncompliant products. CDRH also conducts limited amounts of direct product testing. Clearance requests are for medical devices that prove they are "substantially equivalent" to the predicate devices already on the market. Approved requests are for items that are new or substantially different and need to demonstrate "safety and efficacy", for example it may be inspected for safety in case of new toxic hazards. Both aspects need to be proved or provided by the submitter to ensure proper procedures are followed. Cosmetics are regulated by the Center for Food Safety and Applied Nutrition, the same branch of the FDA that regulates food. Cosmetic products are not in general subject to premarket approval by the FDA unless they make "structure or function claims", which make them into drugs (see Cosmeceutical). However, all color additives must be specifically approved by the FDA before they can be included in cosmetic products sold in the U.S. The labeling of cosmetics is regulated by the FDA, and cosmetics that have not been subjected to thorough safety testing must bear a warning to that effect. Though the cosmetic industry is predominantly responsible in ensuring the safety of its products, the FDA also has the power to intervene when necessary to protect the public but in general does not require pre-market approval or testing. Companies are required to place a warning note on their products if they have not been tested. Experts in cosmetic ingredient reviews also play a role in monitoring safety through influence on the use of ingredients, but also lack legal authority. Overall the organization has reviewed about 1,200 ingredients and has suggested that several hundred be restricted, but there is no standard or systemic method for reviewing chemicals for safety and a clear definition of what is meant by 'safety' so that all chemicals are tested on the same basis. The Center for Veterinary Medicine (CVM) is the branch of the FDA that regulates food, food additives, and drugs that are given to animals, including food animals and pets. CVM does not regulate vaccines for animals; these are handled by the United States Department of Agriculture.][ CVM's primary focus is on medications that are used in food animals and ensuring that they do not affect the human food supply. The FDA's requirements to prevent the spread of bovine spongiform encephalopathy are also administered by CVM through inspections of feed manufacturers.][ Since the Family Smoking Prevention and Tobacco Control Act became law in 2009, the FDA also has had the authority to regulate tobacco products. In 2009, Congress passed a law requiring color warnings on cigarette packages and on printed advertising, in addition to text warnings from the U.S. Surgeon General. The nine new graphic warning labels were announced by the FDA in June 2011 and were scheduled to be required to appear on packaging by September 2012. The implementation date is uncertain, due to ongoing proceedings in the case of R.J. Reynolds Tobacco Co. v. U.S. Food and Drug Administration. R.J. Reynolds, Lorillard, Commonwealth Brands Inc., Liggett Group LLC and Santa Fe Natural Tobacco Company Inc. have filed suit in Washington, D.C. federal court claiming that the graphic labels are an unconstitutional way of forcing tobacco companies to engage in anti-smoking advocacy on the government's behalf. A First Amendment lawyer, Floyd Abrams, is representing the tobacco companies in the case, contending requiring graphic warning labels on a lawful product cannot withstand constitutional scrutiny. The Association of National Advertisers and the American Advertising Federation have also filed a brief in the suit, arguing that the labels infringe on commercial free speech and could lead to further government intrusion if left unchallenged. In November 2011, Federal judge Richard Leon of the U.S. District Court for the District of Columbia temporarily halted the new labels, likely delaying the requirement that tobacco companies display the labels. The U.S. Supreme Court ultimately could decide the matter. With acceptance of premarket notification 510(k) k033391 in January 2004, the FDA granted Dr. Ronald Sherman permission to produce and market medical maggots for use in humans or other animals as a prescription medical device. Medical maggots represent the first living organism allowed by the Food and Drug Administration for production and marketing as a prescription medical device. In June 2004, the FDA cleared Hirudo medicinalis (medicinal leeches) as the second living organism to be used as a medical devices. In addition to its regulatory functions, the FDA carries out research and development activities to develop technology and standards that support its regulatory role, with the objective of resolving scientific and technical challenges before they become impediments. The FDA's research efforts include the areas of biologics, medical devices, drugs, women's health, toxicology, food safety and applied nutrition, and veterinary medicine. Up until the 20th century, there were few federal laws regulating the contents and sale of domestically produced food and pharmaceuticals, with one exception being the short-lived Vaccine Act of 1813. The history of the FDA can be traced to the latter part of the 19th century and the U.S. Department of Agriculture's Division of Chemistry (later Bureau of Chemistry). Under Harvey Washington Wiley, appointed chief chemist in 1883, the Division began conducting research into the adulteration and misbranding of food and drugs on the American market. Wiley's advocacy came at a time when the public had become aroused to hazards in the marketplace by muckraking journalists like Upton Sinclair, and became part of a general trend for increased federal regulations in matters pertinent to public safety during the Progressive Era. The 1902 Biologics Control Act was put in place after diphtheria antitoxin was collected from a horse named Jim who contracted tetanus, resulting in several deaths. In June 1906, President Theodore Roosevelt signed into law the Food and Drug Act, also known as the "Wiley Act" after its chief advocate. The Act prohibited, under penalty of seizure of goods, the interstate transport of food that had been "adulterated". The act applied similar penalties to the interstate marketing of "adulterated" drugs, in which the "standard of strength, quality, or purity" of the active ingredient was not either stated clearly on the label or listed in the United States Pharmacopoeia or the National Formulary. The responsibility for examining food and drugs for such "adulteration" or "misbranding" was given to Wiley's USDA Bureau of Chemistry. Wiley used these new regulatory powers to pursue an aggressive campaign against the manufacturers of foods with chemical additives, but the Chemistry Bureau's authority was soon checked by judicial decisions, which narrowly defined the bureau's powers and set high standards for proof of fraudulent intent. In 1927, the Bureau of Chemistry's regulatory powers were reorganized under a new USDA body, the Food, Drug, and Insecticide organization. This name was shortened to the Food and Drug Administration (FDA) three years later. By the 1930s, muckraking journalists, consumer protection organizations, and federal regulators began mounting a campaign for stronger regulatory authority by publicizing a list of injurious products that had been ruled permissible under the 1906 law, including radioactive beverages, the mascara Lash lure, which caused blindness, and worthless "cures" for diabetes and tuberculosis. The resulting proposed law was unable to get through the Congress of the United States for five years, but was rapidly enacted into law following the public outcry over the 1937 Elixir Sulfanilamide tragedy, in which over 100 people died after using a drug formulated with a toxic, untested solvent. President Franklin Delano Roosevelt signed the new Food, Drug, and Cosmetic Act (FD&C Act) into law on June 24, 1938. The new law significantly increased federal regulatory authority over drugs by mandating a pre-market review of the safety of all new drugs, as well as banning false therapeutic claims in drug labeling without requiring that the FDA prove fraudulent intent. Soon after passage of the 1938 Act, the FDA began to designate certain drugs as safe for use only under the supervision of a medical professional, and the category of "prescription-only" drugs was securely codified into law by the 1951 Durham-Humphrey Amendment. These developments confirmed extensive powers for the FDA to enforce post-marketing recalls of ineffective drugs. In 1959, the thalidomide tragedy, in which thousands of European babies were born deformed after their mothers took that drug – marketed for treatment of nausea – during their pregnancies, led to the 1962 Kefauver-Harris Amendment to the FD&C Act, which represented a "revolution" in FDA regulatory authority. The most important change was the requirement that all new drug applications demonstrate "substantial evidence" of the drug's efficacy for a marketed indication, in addition to the existing requirement for pre-marketing demonstration of safety. This marked the start of the FDA approval process in its modern form. These reforms had the effect of increasing the time required to bring a drug to market. One of the most important statutes in establishing the modern American pharmaceutical market was the 1984 Drug Price Competition and Patent Term Restoration Act, more commonly known as the "Hatch-Waxman Act" after its chief sponsors. The act extended the patent exclusivity terms of new drugs, and tied those extensions, in part, to the length of the FDA approval process for each individual drug. For generic manufacturers, the Act created a new approval mechanism, the Abbreviated New Drug Application (ANDA), in which the generic drug manufacturer need only demonstrate that their generic formulation has the same active ingredient, route of administration, dosage form, strength, and pharmacokinetic properties ("bioequivalence") as the corresponding brand-name drug. This act has been credited with in essence creating the modern generic drug industry. Concerns about the length of the drug approval process were brought to the fore early in the AIDS epidemic. In the mid- and late 1980s, ACT-UP and other HIV activist organizations accused the FDA of unnecessarily delaying the approval of medications to fight HIV and opportunistic infections. Partly in response to these criticisms, the FDA issued new rules to expedite approval of drugs for life threatening diseases, and expanded pre-approval access to drugs for patients with limited treatment options. All of the initial drugs approved for the treatment of HIV/AIDS were approved through these accelerated approval mechanisms. In two instances, state governments have sought to legalize drugs that have not been approved by the FDA. Because federal law passed pursuant to Constitutional authority overrules conflicting state laws][, federal authorities still claim the authority to seize, arrest, and prosecute for possession and sales of these substances, even in states where they are legal under state law. The first wave was the legalization by 27 states of laetrile in the late 1970s. This drug was used as a treatment for cancer, but scientific studies both before and after this legislative trend found it to be ineffective. The second wave concerned medical marijuana in the 1990s and 2000s (decade). Though Virginia passed a law with limited effect in 1979, a more widespread trend began in California in 1996. The Critical Path Initiative is FDA's effort to stimulate and facilitate a national effort to modernize the sciences through which FDA-regulated products are developed, evaluated, and manufactured. The Initiative was launched in March 2004, with the release of a report entitled Innovation/Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products. A 2006 court case, Abigail Alliance v. von Eschenbach, would have forced radical changes in FDA regulation of unapproved drugs. The Abigail Alliance argued that the FDA must license drugs for use by terminally ill patients with "desperate diagnoses," after they have completed Phase I testing. The case won an initial appeal in May 2006, but that decision was reversed by a March 2007 rehearing. The US Supreme Court declined to hear the case, and the final decision denied the existence of a right to unapproved medications. Critics of the FDA's regulatory power argue that the FDA takes too long to approve drugs that might ease pain and human suffering faster if brought to market sooner. The AIDS crisis created some political efforts to streamline the approval process. However, these limited reforms were targeted for AIDS drugs, not for the broader market. This has led to the call for more robust and enduring reforms that would allow patients, under the care of their doctors, access to drugs that have passed the first round of clinical trials. The widely publicized recall of Vioxx, a non-steroidal anti-inflammatory drug now estimated to have contributed to fatal heart attacks in thousands of Americans, played a strong role in driving a new wave of safety reforms at both the FDA rulemaking and statutory levels. Vioxx was approved by the FDA in 1999, and was initially hoped to be safer than previous NSAIDs, due to its reduced risk of intestinal tract bleeding. However, a number of pre- and post-marketing studies suggested that Vioxx might increase the risk of myocardial infarction, and this was conclusively demonstrated by results from the APPROVe trial in 2004. Faced with numerous lawsuits, the manufacturer voluntarily withdrew it from the market. The example of Vioxx has been prominent in an ongoing debate over whether new drugs should be evaluated on the basis of their absolute safety, or their safety relative to existing treatments for a given condition. In the wake of the Vioxx recall, there were widespread calls by major newspapers, medical journals, consumer advocacy organizations, lawmakers, and FDA officials for reforms in the FDA's procedures for pre- and post- market drug safety regulation. In 2006, a congressionally requested committee was appointed by the Institute of Medicine to review pharmaceutical safety regulation in the U.S. and to issue recommendations for improvements. The committee was composed of 16 experts, including leaders in clinical medicinemedical research, economics, biostatistics, law, public policy, public health, and the allied health professions, as well as current and former executives from the pharmaceutical, hospital, and health insurance industries. The authors found major deficiencies in the current FDA system for ensuring the safety of drugs on the American market. Overall, the authors called for an increase in the regulatory powers, funding, and independence of the FDA. Some of the committee's recommendations have been incorporated into drafts of the PDUFA IV bill, which was signed into law in 2007. As of 2011, Risk Minimization Action Plans (RiskMAPS) have been created to ensure risks of a drug never outwiegh the benefits of that drug within the postmarketing period. This program requires that manufacturers design and implement periodic assessments of their programs' effectiveness. The Risk Minimization Action Plans are set in place depending on the overall level of risk a prescription drug is likely to pose to the public. . Prior to the 1990s, only 20% of all drugs prescribed for children in the United States were tested for safety or efficacy in a pediatric population. This became a major concern of pediatricians as evidence accumulated that the physiological response of children to many drugs differed significantly from those drugs' effects on adults. There were several reasons that not many medical trials were done with children. For many drugs, children represented such a small proportion of the potential market, that drug manufacturers did not see such testing as cost-effective. Also, because children were thought to be ethically restricted in their ability to give informed consent, there were increased governmental and institutional hurdles to approval of these clinical trials, as well as greater concerns about legal liability. Thus, for decades, most medicines prescribed to children in the U.S. were done so in a non-FDA-approved, "off-label" manner, with dosages "extrapolated" from adult data through body weight and body-surface-area calculations. An initial attempt by the FDA to address this issue was the 1994 FDA Final Rule on Pediatric Labeling and Extrapolation, which allowed manufacturers to add pediatric labeling information, but required drugs that had not been tested for pediatric safety and efficacy to bear a disclaimer to that effect. However, this rule failed to motivate many drug companies to conduct additional pediatric drug trials. In 1997, the FDA proposed a rule to require pediatric drug trials from the sponsors of New Drug Applications. However, this new rule was successfully preempted in federal court as exceeding the FDA's statutory authority. While this debate was unfolding, Congress used the 1997 Food and Drug Administration Modernization Act to pass incentives that gave pharmaceutical manufacturers a six-month patent term extension on new drugs submitted with pediatric trial data. The act reauthorizing these provisions, the 2002 Best Pharmaceuticals for Children Act, allowed the FDA to request NIH-sponsored testing for pediatric drug testing, although these requests are subject to NIH funding constraints. Most recently, in the Pediatric Research Equity Act of 2003, Congress codified the FDA's authority to mandate manufacturer-sponsored pediatric drug trials for certain drugs as a "last resort" if incentives and publicly funded mechanisms proved inadequate. Since the 1990s, many successful new drugs for the treatment of cancer, autoimmune diseases, and other conditions have been protein-based biotechnology drugs, regulated by the Center for Biologics Evaluation and Research. Many of these drugs are extremely expensive; for example, the anti-cancer drug Avastin costs $55,000 for a year of treatment, while the enzyme replacement therapy drug Cerezyme costs $200,000 per year, and must be taken by Gaucher's Disease patients for life. Biotechnology drugs do not have the simple, readily verifiable chemical structures of conventional drugs, and are produced through complex, often proprietary techniques, such as transgenic mammalian cell cultures. Because of these complexities, the 1984 Hatch-Waxman Act did not include biologics in the Abbreviated New Drug Application (ANDA) process, in essence precluding the possibility of generic drug competition for biotechnology drugs. In February 2007, identical bills were introduced into the House to create an ANDA process for the approval of generic biologics, but were not passed. The FDA currently has regulatory oversight over a large array of products that affect the health and life of American citizens. As a result, the FDA's powers and decisions are carefully monitored by several governmental and non-governmental organizations. A $1.8 million 2006 Institute of Medicine report on pharmaceutical regulation in the U.S. found major deficiencies in the current FDA system for ensuring the safety of drugs on the American market. Overall, the authors called for an increase in the regulatory powers, funding, and independence of the FDA. Nine FDA scientists appealed to then president-elect Barack Obama over pressures from management, experienced during the George W. Bush presidency, to manipulate data, including in relation to the review process for medical devices. Characterized as "corrupted and distorted by current FDA managers, thereby placing the American people at risk," these concerns were also highlighted in the 2006 report on the agency as well. The FDA has also been criticized from the opposite viewpoint, as being too tough on industry. According to an analysis published on the website of the libertarian Mercatus Center as well as published statements by economists, medical practitioners, and concerned consumers, many feel the FDA oversteps its regulatory powers and undermines small business and small farms in favor of large corporations. Three of the FDA restrictions under analysis are the permitting of new drugs and devices, the control of manufacturer speech, and the imposition of prescription requirements. The authors argue that in the increasingly complex and diverse food marketplace, the FDA is not equipped to adequately regulate or inspect food.][ However, in an indicator that the FDA may be too lax in their approval process, in particular for medical devices, a 2011 study by Dr. Diana Zuckerman and Paul Brown of the National Research Center for Women and Families, and Dr. Steven Nissen of the Cleveland Clinic, published in the Archives of Internal Medicine, showed that most medical devices recalled in the last five years for "serious health problems or death" had been previously approved by the FDA using the less stringent, and cheaper, 510(k) process. In a few cases the devices had been deemed so low-risk that they did not need FDA regulation. Of the 113 devices recalled, 35 were for cardiovascular health purposes.
The Drug Enforcement Administration (DEA) is a United States federal law enforcement agency under the U.S. Department of Justice, tasked with combating drug smuggling and use within the United States. Not only is the DEA the lead agency for domestic enforcement of the Controlled Substances Act, sharing concurrent jurisdiction with the Federal Bureau of Investigation (FBI) and Immigration and Customs Enforcement (ICE), it also has sole responsibility for coordinating and pursuing U.S. drug investigations abroad. The Drug Enforcement Administration was established on July 1, 1973, by Reorganization Plan No. 2 of 1973, signed by President Richard Nixon on July 28. It proposed the creation of a single federal agency to enforce the federal drug laws as well as consolidate and coordinate the government's drug control activities. Congress accepted the proposal, as they were concerned with the growing availability of drugs. As a result, the Bureau of Narcotics and Dangerous Drugs (BNDD), the Office of Drug Abuse Law Enforcement (ODALE), and other federal offices merged to create the DEA. From the early 1970s, DEA headquarters was located at 1405 I ("Eye") Street NW in downtown Washington, D.C. With the overall growth of the agency in the 1980s (owing to the increased emphasis on federal drug law enforcement efforts) and a concurrent growth in the headquarters staff, DEA began to search for a new headquarters location; locations in Arkansas, Mississippi, and various abandoned military bases around the U.S. were considered. However, then–Attorney General Edwin Meese determined that the headquarters had to be located in close proximity to the Attorney General's office. Thus, in 1989, the headquarters relocated to 600-700 Army-Navy Drive in the Pentagon City area of Arlington, Virginia, near the Metro station with the same name. On April 19, 1995, Timothy McVeigh attacked the Alfred P. Murrah Federal Building in Oklahoma City because it housed regional offices for the FBI, Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF), and DEA, all of which had carried out raids that he viewed as unjustified intrusions on the rights of the people; this attack caused the deaths of two DEA employees, one task force member, and two contractors in the Oklahoma City bombing. Subsequently, the DEA headquarters complex was classified as a Level IV installation under United States federal building security standards, meaning it was to be considered a high-risk law enforcement target for terrorists. Security measures include hydraulic steel roadplates to enforce standoff distance from the building, metal detectors, and guard stations. In February 2003, the DEA established a Digital Evidence Laboratory within its Office of Forensic Sciences. The DEA is headed by an Administrator of Drug Enforcement appointed by the President of the United States and confirmed by the U.S. Senate. The Administrator reports to the Attorney General through the Deputy Attorney General. The Administrator is assisted by a Deputy Administrator, the Chief of Operations, the Chief Inspector, and three Assistant Administrators (for the Operations Support, Intelligence, and Human Resources Divisions). Other senior staff include the Chief Financial Officer and the Chief Counsel. The Administrator and Deputy Administrator are the only presidentially-appointed personnel in the DEA; all other DEA officials are career government employees. DEA's headquarters is located in Arlington, Virginia across from the Pentagon. It maintains its own DEA Academy located on the United States Marine Corps base at Quantico, Virginia along with the FBI Academy. It maintains 21 domestic field divisions with 227 field offices and 86 foreign offices in 62 countries. With a budget exceeding 2.415 billion dollars, DEA employs over 10,800 people, including over 5,500 Special Agents. Becoming a Special Agent with the DEA is a competitive process. After receiving a conditional offer of employment, recruits must then make it through a 19 week rigorous training which consist of firearms proficiency including basic marksmanship, weapons safety, tactical shooting, and deadly force decision training. In order to graduate, students must maintain an academic average of 80 percent on academic examinations, pass the firearms qualification test, successfully demonstrate leadership and sound decision-making in practical scenarios, and pass rigorous physical task tests. Upon graduation, recruits earn themselves the title of DEA Special Agent. Job applicants who have a history of any drug use are excluded from consideration. Investigation usually includes a polygraph test for special agent, diversion investigator, and intelligence research specialist positions. Applicants who are found, through investigation or personal admission, to have experimented with or used narcotics or dangerous drugs, except those medically prescribed, will not be considered for employment with the Drug Enforcement Administration (DEA). Exceptions to this policy may be made for applicants who admit to limited youthful and experimental use of marijuana. Such applicants may be considered for employment if there is no evidence of regular, confirmed usage and the full-field background investigation and results of the other steps in the process are otherwise favorable. The DEA's relatively firm stance on this issue is in contrast to that of the Federal Bureau of Investigation, which, in 2005, considered relaxing its hiring policy relevant to individual drug use history. The DEA Aviation Division or Office of Aviation Operations (OA) (formerly Aviation Section) is an airborne division based in Fort Worth Alliance Airport, Texas. The current OA fleet consists of 106 aircraft and 124 DEA pilots. The DEA shares a communications system with the Department of Defense for communication with state and regional enforcement independent of the Department of Justice and police information systems and is coordinated by an information command center called the El Paso Intelligence Center (EPIC) near El Paso, Texas. As of January 2010, FAST fields five teams. One team is always stationed in Afghanistan conducting Counter Narcotics (CN), Counter Terrorism (CT), Direct Action (DA) missions. The remaining four teams are stationed at Marine Corps Base Quantico, Virginia. FAST originally was created to solely conduct missions in Afghanistan but has evolved into a global action arm for the US Department of Justice and DEA. Selection for FAST is extremely difficult; attrition rates are usually above 50%. Selection is rumored to last 8 weeks where events such as timed runs, timed ruck sack marches, land navigation and many other events are conducted daily. Once selection is complete, advanced training begins with emphasis in small unit tactics, and close quarters battle. The 1998 DEA budget was directed toward three of five major goals of U.S. drug eradication: DEA agents' primary service weapons are the Glock 22 and Glock 23 in .40 S&W caliber ammunition, and agents can also qualify to use the Glock 27 and SIG Pro in .40 S&W, and they also have the option of using the newly appointed Smith & Wesson M&P series pistol. Special Agents may qualify with their own personally-owned handguns and certain handguns are allowed to be used with permission from the DEA Firearms office in Quantico, VA, but they are required to qualify on all assigned weapons quarterly. Trained to use shoulder-launched weapon, the H&K UMP40 is the standard SMG of DEA, although the Colt 9mm SMG may also be issued. They are issued a LWRCI M6A2 carbine as their new personal duty service rifle and also the Rock River Arms CAR-15 and shotguns such as the Remington 870 are one of the weapons trained. The DEA has a registration system in place which authorizes medical professionals, researchers and manufacturers access to "Schedule I" drugs, as well as Schedules 2, 3, 4 and 5. Authorized registrants apply for and, if granted, receive a "DEA number". An entity that has been issued a DEA number is authorized to manufacture (drug companies), distribute, research, prescribe (doctors, nurse practitioners and physician assistants, etc.) or dispense (pharmacy) a controlled substance. Many problems associated with drug abuse are the result of legitimately-manufactured controlled substances being diverted from their lawful purpose into the illicit drug traffic. Many of the analgesics, depressants and stimulants manufactured for legitimate medical use can often carry potential for dependence or abuse. Therefore those scheduled substances have been brought under legal control for prevention and population safety. The goal of controls is to ensure that these "controlled substances" are readily available for medical use, while preventing their distribution for illicit distribution and non-medical use. This can be a difficult task, sometimes providing difficulty for legitimate patients and healthcare providers while circumventing illegal trade and consumption of scheduled drugs. Under federal law, all businesses which manufacture or distribute controlled drugs, all health professionals entitled to dispense, administer or prescribe them, and all pharmacies entitled to fill prescriptions must register with the DEA. Registrants must comply with a series of regulatory requirements relating to drug security, records accountability, and adherence to standards. All of these investigations are conducted by Diversion Investigators (DIs). DIs conduct investigations to uncover and investigate suspected sources of diversion and take appropriate civil and administrative actions. Prescription Database Management Programs (PDMP) aid and facilitate investigation and surveillance.][ In 1985 MDMA and its analogues were under review by the American government as a drug for potential of abuse. During this time, several public hearings on the new drug were held by the DEA. Based on all of the evidence and facts presented at the time, the DEA's administrative law judge did not see MDMA and its analogues as being of large concern and recommended that they be placed in Schedule III. The DEA administrator, expressing concern for abuse potential, overruled the recommendation and ruled that MDMA be put in Schedule I, the Controlled Substances Act's most restrictive category. The DEA has been criticized for placing highly restrictive schedules on a few drugs which researchers in the fields of pharmacology and medicine regard as having medical uses. Critics assert that some such decisions are motivated primarily by political factors stemming from the U.S. government's War on Drugs, and that many benefits of such substances remain unrecognized due to the difficulty of conducting scientific research. A counterpoint to that criticism is that under the Controlled Substances Act it is the Department of Health and Human Services (through the Food and Drug Administration and the National Institute on Drug Abuse), not the DEA, which has the legal responsibility to make scientific and medical determinations with respect to drug scheduling; no drug can be scheduled if the Secretary of Health and Human Services recommends against it on a scientific or medical basis, and no drug can be placed in the most restrictive schedule (Schedule I) if DHHS finds that the drug has an accepted medical use. Jon Gettman's essay Science and the End of Marijuana Prohibition describes the DEA as "a fall guy to deflect responsibility from the key decision-makers" and opines, "HHS calls the shots when it comes to marijuana prohibition, and the cops at DEA and the general over at ONDCP take the heat." The DEA is also criticized for focusing on the operations from which it can seize the most money, namely the organized cross-border trafficking of marijuana. Some individuals contemplating the nature of the DEA's charter advise that, based on danger, the DEA should be most focused on cocaine. Others suggest that, based on opiate popularity, the DEA should focus much more on prescription opiates used recreationally, which critics contend comes first before users switch to heroin. Practitioners who legally prescribe medicine however must possess a valid DEA license. According to federal law the budget of the entire DEA is to be paid by these license fees. In 1984 a three-year license cost $25. In 2009 the fee for a three-year license was $551. Some have likened this approach to license fees unreasonable, "like making pilot licenses support the entire Federal Aviation Authority (FAA) budget." The total cost of the DEA from 1972 to 2009 according to the agency website was $536,367,800,000.00 with 10,784 employees in 2009. For the data available for the years 1986 to 2009, the average cost per arrest made was $9,893.09. Others, such as the Cato Institute and the Drug Policy Alliance criticize the very existence of the DEA and the War on Drugs as both hostile, and contrary, to the concept of civil liberties by arguing that anybody should be free to put any substance they choose into their own bodies for any reason, particularly when legal drugs such as alcohol, tobacco and prescription drugs are also open to abuse, and that any harm caused by a drug user or addict to the general public is a case of conflicting civil rights. Recurrently, billions of dollars are spent yearly, focusing largely on criminal law and demand reduction campaigns, which has resulted in the imprisonments of thousands of U.S. citizens. Demand for recreational drugs is somewhat static as the market for most illegal drugs has been saturated, forcing the cartels to expand their market to Europe and other areas than the United States.][ United States federal law registers cannabis as a Schedule I drug, yet it is common for illicit drugs such as cannabis to be widely available in most urban, suburban, and even rural areas in the United States, which leads drug legalization proponents to claim that drug laws have little effect on those who choose not to obey them, and that the resources spent enforcing drug laws are wasted. As it relates to the DEA specifically, the vast majority of individual arrests stemming from illegal drug possession and distribution are narrow and more local in scope and are made by local law enforcement officers, while the DEA tends to focus on larger, interstate and international distribution networks and the higher-ranking members of such organizations in addition to operating in conjunction with other local, state, and federal law enforcement agencies along U.S. borders.][ Some groups advocate legalization of certain controlled substances under the premise that doing so may reduce the volume of illicit trafficking and associated crime as well as yield a valuable tax source, although some of the results of drug legalization have raised doubt about some of these beliefs. For example, marijuana is now available as a palliative agent, in Canada, with a medical prescription. Yet 86% of Canadians with HIV/AIDS, eligible for a prescription, continue to obtain marijuana illegally (AIDS Care. 2007 Apr;19(4):500-6.) However, this could be due to the availability or quality of illegal cannabis compared to provisions by government sources. Bureaucratic impediments may also discourage patients from actually attempting to receive it from the government. An April 2012 DEA raid on a California home led to the incarceration of Daniel Chong for several days under conditions of neglect. The 23 year-old student attending the University of California, San Diego was taken into custody along with eight other people when the DEA executed a raid on a suspected MDMA distribution operation at a residence that he was visiting to celebrate the April 20 cannabis "holiday" known as "420". According to Chong, the DEA agents questioned him and told him that he could go home, one even offering him a ride home, but instead he was transferred to a holding cell and confined for five days without any food or water, although Chong said he ingested a powdery substance that was left for him, which was later found to be methamphetamine. After five days and two failed suicide attempts, DEA agents found Chong. He was taken to the hospital, where he spent three days in intensive care, because his kidneys were close to failing. No criminal charges were filed against Chong. A DEA spokesperson stated that the extended detention was accidental and the acting special agent in charge of the San Diego DEA office issued an apology to Chong. Chong disputes the claim of accidental neglect, saying that DEA personnel ignored his calls for help. His attorney stated an intent to file a claim against the federal government and some members of California's delegation to the Congress called for further investigation of the incident. The DEA was accused in 2005 by the Venezuelan government of collaborating with drug traffickers, after which President Hugo Chávez decided to end any collaboration with the agency. In 2007, after the U.S. State Department criticized Venezuela in its annual report on drug trafficking, the Venezuelan Minister of Justice reiterated the accusations: "A large quantity of drug shipments left the country through that organization,...[]..We were in the presence of a new drug cartel." The government of Bolivia has also taken similar steps to ban the DEA from operating in the country. In September 2008, Bolivia and the US drastically reduced diplomatic ties with one another, each withdrawing ambassadors from the other country. This occurred soon after Bolivian president Evo Morales expelled all DEA agents from the country due to a revolt in the traditional coca-growing Chapare Province. The Bolivian government claimed that it could not protect the agents, and Morales further accused the agency of helping incite the violence, which claimed 30 lives. National agencies were to take over control of drug management. Three years later, Bolivia and the US began to restore full diplomatic ties. However, Morales maintained that the DEA would remain unwelcome in the country, characterising it as an affront to Bolivia's "dignity and sovereignty". In the Netherlands, both the Dutch government and the DEA have been criticized for violations of Dutch sovereignty in drug investigations. According to Peter R. de Vries, a Dutch journalist present at the 2005 trial of Henk Orlando Rommy, the DEA has admitted to activities on Dutch soil. Earlier, then Minister of Justice Piet Hein Donner, had denied to the Dutch parliament that he had given permission to the DEA for any such activities, which would have been a requirement by Dutch law in order to allow foreign agents to act within the territory. The DEA has taken a particularly strong stance on enforcement of the Controlled Substances Act on persons and organizations acting within state laws that allow medical cannabis cultivation and distribution. "The people of California and the County of Santa Cruz have overwhelmingly supported the provision of medical marijuana for people who have serious illnesses," county Supervisor Mardi Wormhoudt told the San Francisco Gate. "These people (blocking the road) are people with AIDS and cancer and other grave illnesses. To attack these people, who work collectively and have never taken money for their work, is outrageous." As a result, the Wo/Men's Alliance for Medical Marijuana, with the City and County of Santa Cruz, has sued the DEA, Attorney General Michael Mukasey, and the ONDCP. The most recent court decision rejected the government's motion to dismiss, which allows discovery to move forward. The American Civil Liberties Union hailed the decision as "a first-of-its-kind ruling. " More recently, the DEA has escalated its enforcement efforts on the recently-proliferated Los Angeles area medical cannabis collectives. On July 25, 2007, the DEA raided the California Patients Group, Hollywood Compassionate Collective, and Natural Hybrid (NHI Caregivers) in Hollywood, California.][ Earlier that day, the operators of those collectives participated in a press conference with LA City Council members announcing the City's intention to regulate the collectives and asking the DEA to halt raids on collectives while the City drafted regulations.][ The dispensary operator of Natural Hybrid (NHI Caregivers) was forced to close down the collective due to the tremendous loss caused by the DEA conducted joint task force raid against them.][ In 1999, the DEA opened the Drug Enforcement Administration Museum in Arlington, Virginia. The original permanent exhibit - Illegal Drugs in America: A Modern History - remains the museum's centerpiece. The exhibit features "the more than 150 year history of drugs and drug abuse and the DEA," including a considerable collection of drug paraphernalia and an image of a smiling drug vendor under the heading "Jimmy's Joint." An audio tour is available at the front desk of the museum on a small MP3 device and headphones from the late 1990s/early 2000s. A second exhibition gallery was opened in 2002, and features a changing exhibit. The current exhibit is titled "Good Medicine, Bad Behavior: Drug Diversion in America." According to the museum's website, its mission is to "educate the American public on the history of drugs, drug addiction and drug law enforcement in the United States through engaging and state-of-the-art exhibits, displays, interactive stations and educational outreach programs." Some have noted that the museum's educational mission is inhibited by its relative inaccessibility and appearance of propaganda. While "Admission is free!!", the museum is only open to the public from 10:00am – 4:00pm, Tuesday - Friday. The number of annual visitors is relatively low compared with other museums in the Washington Metropolitan Area. The gift shop at the DEA museum sells items such as small stuffed K9 dogs and the annual DEA Holiday ornament. However, the gift shop is sometimes closed during the museum's normal operating hours.
Physiological tolerance or drug tolerance is commonly encountered in pharmacology, when a subject's reaction to a specific drug and concentration of the drug is progressively reduced, requiring an increase in concentration to achieve the desired effect. Drug tolerance can involve both psychological drug tolerance and physiological factors. The following are characteristics of drug tolerance: it is reversible, the rate depends on the particular drug, dosage and frequency of use, differential development occurs for different effects of the same drug. Physiological tolerance also occurs when an organism builds up a resistance to the effects of a substance after repeated exposure. This can occur with environmental substances, such as salt or pesticides. A rapid drug tolerance is termed tachyphylaxis. Tachyphylaxis is a sudden onset drug tolerance which is not dose dependent. Pharmacokinetic Tolerance - Also known as Dispositional tolerance: occurs because of a decreased quantity of the substance reaching the site it affects. This may be caused by an increase in induction of the enzymes required for degradation of the drug e.g. CYP450 enzymes. This is most commonly seen with substances such as ethanol, barbiturates, benzodiazapines and opiates. Pharmacodynamic Tolerance - Also known as Reduced responsiveness: the response to the substance is decreased by cellular mechanisms. This may be caused by a down regulation of receptor numbers. Tolerance: reduced response to repeated administration of the same dose or increase in the dose are required to produce the same magnitude of response. Tolerance to the analgesic effects of morphine is fairly rapid. There are several hypotheses about how tolerance develops, including opioid receptor phosphorylation (which would change the receptor conformation), functional decoupling of receptors from G-proteins (leading to receptor desensitization), mu-opioid receptor internalization and/or receptor down-regulation (reducing the number of available receptors for morphine to act on), and upregulation of the cAMP pathway (a counterregulatory mechanism to opioid effects) (For a review of these processes, see Koch and Hollt.) CCK might mediate some counter-regulatory pathways responsible for opioid tolerance. CCK-antagonist drugs, specifically proglumide, have been shown to slow the development of tolerance to morphine or any other kind of drug, including alcohol. Significant involvement of the intracellular Beta-arrestin-2 protein expression in the agonist-mediated desensitization of G protein-coupled receptors, such as the μ-opioid receptor (MOR), has been elucidated. It was reported that VTA dopamine neurons in rats remain increased for at least 3 days after a single morphine exposure. Within this limited window of time, the VTA dopamine neurons failed to respond to additional morphine challenge. Indicating a transient morphine tolerance in VTA DA neuron activity in rats was developed with a single dose of morphine treatment. It further demonstrated that this acute morphine tolerance was associated with impairment of opiate receptor-G protein coupling, indicating that down regulation of G-protein activation may contribute to acute morphine tolerance.
InChI=1S/C10H15N/c1-9(11-2)8-10-6-4-3-5-7-10/h3-7,9,11H,8H2,1-2H3 
Key:MYWUZJCMWCOHBA-UHFFFAOYSA-N  Methamphetamine (USAN) , also known as metamfetamine (INN), meth, ice, clouds crystal, glass, tik, N-methylamphetamine, methylamphetamine, and desoxyephedrine, is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs. Methamphetamine occurs in two enantiomers, dextrorotary and levorotary. Dextromethamphetamine is a stronger psychostimulant, but levomethamphetamine has a longer half-life and is CNS-active with weaker (approx. one-tenth) effects on striatal dopamine and shorter psychodynamic effects. At high doses, both enantiomers of methamphetamine can induce stereotypy and psychosis, but levomethamphetamine is less desired by drug abusers because of its weaker pharmacodynamic profile. Although rarely prescribed, methamphetamine hydrochloride is approved by the U.S. Food and Drug Administration (FDA) for the treatment of attention deficit hyperactivity disorder and obesity under the trade name Desoxyn. Illicitly, methamphetamine may be sold either as pure dextromethamphetamine or in a racemic mixture. Both dextromethamphetamine and racemic methamphetamine are Schedule II controlled substances in the United States, and similarly the production, distribution, sale, and possession of methamphetamine is restricted or illegal in many jurisdictions. Internationally, methamphetamine has been placed in Schedule II of the United Nations Convention on Psychotropic Substances treaty. Contrary to popular misconception, methamphetamine in both powder and crystal form is a hydrochloride salt. The freebase form of methamphetamine (as well as amphetamine) is an oily liquid. The misconception started with the fact that heroin and cocaine are injected or snorted as salts, but they are smoked in freebase form. See also: crack cocaine. In low dosages, methamphetamine can increase alertness, concentration, and energy in fatigued individuals. In higher doses, it can induce mania with accompanying euphoria, feelings of self-esteem and increased libido. Methamphetamine has a high potential for abuse and addiction, activating the psychological reward system by triggering a cascading release of dopamine in the brain characterized as Amphetamine/Stimulant psychosis. Chronic abuse may also lead to post-withdrawal syndrome, a result of methamphetamine-induced neurotoxicity to dopaminergic neurons. Post-withdrawal syndrome can persist beyond the withdrawal period for months, and sometimes up to a year. In addition to psychological harm, physical harm – primarily consisting of cardiovascular damage – may occur with chronic use or acute overdose. Methamphetamine has found use as both a medicinal and recreational drug. In United States, Methamphetamine has been approved by the Food and Drug Administration (FDA) in treating ADHD and exogenous obesity (obesity originating from factors outside of the patient's control) in both adults and children. Methamphetamine is a drug that is under the Controlled Substances Act which is listed under Schedule II in the United States and is sold under the name Desoxyn trademarked by the Danish pharmaceutical company Lundbeck. Because methamphetamine is highly abused for negative purposes such as selling the prescription to others, or overdosing (which contributes to very dangerous side effects) than using the medication medically, it is a tightly controlled substance under federal law. The minimum dosage prescribed is 5 milligrams. Desoxyn may be prescribed off-label for the treatment of narcolepsy and treatment-resistant depression. Methamphetamine's levorotary form is available in many over-the-counter nasal decongestant products. Methamphetamine is used as a recreational drug for its euphoric and stimulant properties. Physical effects can include anorexia, hyperactivity, dilated pupils, flushed skin, excessive sweating, restlessness, dry mouth and bruxism (leading to "meth mouth"), headache, accelerated heartbeat, slowed heartbeat, irregular heartbeat, rapid breathing, high blood pressure, low blood pressure, high body temperature, diarrhea, constipation, blurred vision, dizziness, twitching, insomnia, numbness, palpitations, tremors, dry and/or itchy skin, acne, pallor, and – with chronic and/or high doses – convulsions, heart attack, stroke, and death. Psychological effects can include euphoria, anxiety, increased libido, alertness, concentration, increased energy, increased self-esteem, self-confidence, sociability, irritability, aggressiveness, psychosomatic disorders, psychomotor agitation, dermatillomania (compulsive skin picking), hair pulling, delusions of grandiosity, hallucinations, excessive feelings of power and invincibility, repetitive and obsessive behaviors, paranoia, and – with chronic use and/or high doses – amphetamine psychosis. Withdrawal symptoms of methamphetamine primarily consist of fatigue, depression, and increased appetite. Symptoms may last for days with occasional use and weeks or months with chronic use, with severity dependent on the length of time and the amount of methamphetamine used. Withdrawal symptoms may also include anxiety, irritability, headaches, agitation, restlessness, excessive sleeping, vivid or lucid dreams, deep REM sleep, and suicidal ideation. Methamphetamine use has a high association with depression and suicide as well as serious heart disease, amphetamine psychosis, anxiety, and violent behaviors. Methamphetamine also has a very high addiction risk. Methamphetamine is not directly neurotoxic but long-term use can have neurotoxic side-effects. Its use is associated with an increased risk of Parkinson's disease due to the fact that uncontrolled dopamine release is neurotoxic. Long-term dopamine upregulation occurring as a result of Methamphetamine abuse can cause neurotoxicity, which is believed to be responsible for causing persisting cognitive deficits, such as memory loss, impaired attention, and decreased executive function. Similar to the neurotoxic effects on the dopamine system, methamphetamine can also result in neurotoxicity to the serotonin system. As a result of methamphetamine-induced neurotoxicity to dopaminergic neurons, chronic abuse may also lead to post acute withdrawals which persist beyond the withdrawal period for months, and even up to a year. A study performed on female Japanese prison inmates suffering from methamphetamine addiction showed that 49% experienced "flashbacks" afterward and 21% experienced a psychosis resembling schizophrenia which persisted for longer than six months post-methamphetamine use; this amphetamine psychosis could be resistant to traditional treatment. Other studies in Japan show that those who experience methamphetamine-induced psychosis are much more likely to experience psychotic symptoms again if they use methamphetamine.][ In addition to psychological harm, physical harm – primarily consisting of cardiovascular damage – may occur with chronic use or acute overdose. As with other amphetamines, tolerance to methamphetamine is not completely understood but is known to be sufficiently complex that it cannot be explained by any single mechanism. The extent of tolerance and the rate at which it develops vary widely between individuals, and even within one person. It is highly dependent on dosage, duration of use, and frequency of administration. Tolerance to the awakening effect of amphetamines does not readily develop, making them suitable for the treatment of narcolepsy. Short-term tolerance can be caused by depleted levels of neurotransmitters within the synaptic vesicles available for release into the synaptic cleft following subsequent reuse (tachyphylaxis). Short-term tolerance typically lasts until neurotransmitter levels are fully replenished; because of the toxic effects on dopaminergic neurons, this can be greater than 2–3 days. Prolonged overstimulation of dopamine receptors caused by methamphetamine may eventually cause the receptors to downregulate in order to compensate for increased levels of dopamine within the synaptic cleft. To compensate, larger quantities of the drug are needed in order to achieve the same level of effects. Reverse tolerance or sensitization can also occur. The effect is well established, but the mechanism is not well understood. Methamphetamine is highly addictive. While the withdrawal itself may not be dangerous, withdrawal symptoms are common with heavy use and relapse is common. Methamphetamine-induced hyperstimulation of pleasure pathways can lead to anhedonia months after use has been discontinued. Investigation of treatments targeting dopamine signalling such as bupropion, or psychological treatments that raise hedonic tone, such as behavioral activation therapy, have been suggested. It is possible that daily administration of the amino acids L-tyrosine and -5HTPL/tryptophan can aid in the recovery process by making it easier for the body to reverse the depletion of dopamine, norepinephrine, and serotonin.][ Although studies involving the use of these amino acids have shown some success, this method of recovery has not been shown to be consistently effective.][ It is shown that taking ascorbic acid prior to using methamphetamine may help reduce acute toxicity to the brain, as rats given the human equivalent of 5–10  grams of ascorbic acid 30 minutes prior to methamphetamine dosage had toxicity mediated, yet this will likely be of little avail in solving the other serious behavioral problems associated with methamphetamine use and addiction that many users experience. Large doses of ascorbic acid also lower urinary pH, reducing methamphetamine's elimination half-life and thus decreasing the duration of its actions. To combat addiction, doctors are beginning to use other forms of stimulants such as dextroamphetamine, the dextrorotatory (right-handed) isomer of the amphetamine molecule, to break the addiction cycle in a method similar to the use of methadone in the treatment of heroin addicts. There are no publicly available drugs comparable to naloxone, which blocks opiate receptors and is therefore used in treating opiate dependence, for use with methamphetamine problems. However, experiments with some monoamine reuptake inhibitors such as indatraline have been successful in blocking the action of methamphetamine. There are studies indicating that fluoxetine, bupropion and imipramine may reduce craving and improve adherence to treatment. Research has also suggested that modafinil can help addicts quit methamphetamine use, as can Topiramate. Methamphetamine addiction is one of the most difficult forms of addictions to treat. Bupropion, aripiprazole, and baclofen have been employed to treat post-withdrawal cravings, although the success rate is low. Modafinil is somewhat more successful, but this is a Class IV scheduled drug. Adrafinil is the prodrug of Modafinil, being metabolized by the body to Modafinil in 45–60 minutes, and is not a controlled substance.][ Ibogaine has been used with success in Europe, where it is a Class I drug and available only for scientific research. Mirtazapine has been reported useful in some small-population studies. As the phenethylamine phentermine is a constitutional isomer of methamphetamine, it has been suggested that it may be effective in treating methamphetamine addiction. Phentermine is a central nervous system stimulant that acts on dopamine and norepinephrine. When comparing (+)-amphetamine, (+/-)-ephedrine, and phentermine, one key difference among the three drugs is their selectivity for norepinephrine (NE) release vs. dopamine (DA) release. The NE/DA selectivity ratios for these drugs as determined in vitro [(EC(50) NE(-1))/(EC(50) DA(-1))] are (+/-)-ephedrine (18.6) > phentermine (6.7) > (+)-amphetamine (3.5). Abrupt interruption of chronic methamphetamine use results in the withdrawal syndrome in almost 90% of the cases.][ The mental depression associated with methamphetamine withdrawal lasts longer and is more severe than that of cocaine withdrawal. Methamphetamine users and addicts may lose their teeth abnormally quickly, a condition informally known as meth mouth. According to the American Dental Association, meth mouth "is probably caused by a combination of drug-induced psychological and physiological changes resulting in xerostomia (dry mouth), extended periods of poor oral hygiene, frequent consumption of high-calorie, carbonated beverages and bruxism (teeth grinding and clenching)". Some reports have also speculated that the caustic nature of the drug is a contributing factor. Methamphetamine also has the potential to cause excessive cigarette smoking for users already smoking. This combined with the methamphetamine can perpetuate the "meth mouth". Similar, though far less severe, symptoms have been reported in clinical use of regular amphetamine, where effects are not exacerbated by extended periods of poor oral hygiene. Short-term exposure to high concentrations of chemical vapors that may exist in black market methamphetamine laboratories can cause severe health problems or even result in death. Exposure to these substances can occur from volatile air emissions, spills, fires, and explosions. Such methamphetamine labs are often discovered when fire fighters respond to a blaze. Methamphetamine cooks, their families, and first responders are at highest risk of acute health effects from chemical exposure, including lung damage and chemical burns to the body. Following a seizure of a methamphetamine lab, there is often a low exposure risk to chemical residues, however this contamination should be sanitized. Chemical residues and lab wastes that are left behind at a former methamphetamine lab can result in severe health problems for people who use the property, therefore local health departments should thoroughly assess the property for hazards prior to allowing it to be reinhabited, especially by children. Those seeking home ownership in heavy meth use areas should be especially careful while house hunting and be sure to have properties inspected before purchasing. Methamphetamine present in a mother's bloodstream passes through the placenta to a fetus, and is also secreted into breast milk. Infants born to methamphetamine-abusing mothers were found to have a significantly smaller gestational age-adjusted head circumference and birth weight measurements. Methamphetamine exposure was also associated with neonatal withdrawal symptoms of agitation, vomiting and tachypnea. This withdrawal syndrome is relatively mild and only requires medical intervention in approximately 4% of cases. Men who use methamphetamine, cocaine, MDMA, and ketamine, are twice as likely to have unprotected sex than those who do not use such drugs, according to British research. American psychologist Perry N. Halkitis performed an analysis using data collected from community-based participants among gay and bisexual men to examine the associations between their methamphetamine use and sexual risk taking behaviors. Methamphetamine use was found to be related to higher frequencies of unprotected sexual intercourse in both HIV-positive and unknown casual partners in the study population. The association between methamphetamine use and unprotected acts were also more pronounced in HIV-positive participants. These findings suggested that methamphetamine use and engagement in unprotected anal intercourse are co-occurring risk behaviors that potentially heighten the risk of HIV transmission among gay and bisexual men. Methamphetamine allows users of both sexes to engage in prolonged sexual activity, which may cause genital sores and abrasions. Methamphetamine can also cause sores and abrasions in the mouth via bruxism (teeth clenching and grinding), which can turn typically low-risk sex acts, such as oral sex, into high-risk sexual activity. As with the injection of any drug, if a group of users share a common needle, blood-borne diseases, such as HIV or hepatitis, can be transmitted. The level of needle sharing among methamphetamine users is similar to that among other drug injection users. Following oral administration, methamphetamine is readily absorbed into the bloodstream, with peak plasma concentrations achieved in approximately 3.13 to 6.3 hours post ingestion. The amphetamine metabolite peaks at 10 to 24 hours. Methamphetamine is also well absorbed following inhalation and following intranasal administration. It is distributed to most parts of the body. Methamphetamine is known to produce central effects similar to the other stimulants, but at smaller doses, with fewer peripheral effects. Methamphetamine's high lipophilicity also allows it to cross the blood brain barrier faster than other stimulants, where it is more stable against degradation by monoamine oxidase (MAO). Methamphetamine is metabolized in the liver with the main metabolites being amphetamine (active) and 4-hydroxymethamphetamine (pholedrine); other minor metabolites include 4-hydroxyamphetamine, norephedrine, and 4-hydroxynorephedrine. Other drugs metabolized to amphetamine and methamphetamine include benzphetamine, furfenorex, and famprofazone. Selegiline (marketed as Deprenyl, EMSAM, and others) is metabolized into levomethamphetamine which in turn is metabolized into levoamphetamine. Although only the D-Isomer of selegiline will metabolize into active metabolites, both isomers may cause a positive result for methamphetamine and amphetamine on a drug test, in certain cases. It is excreted by the kidneys, with the rate of excretion into the urine heavily influenced by urinary pH. Between 30-54% of an oral dose is excreted in urine as unchanged methamphetamine and 10-23% as unchanged amphetamine. Following an intravenous dose, 45% is excreted as unchanged parent drug and 7% amphetamine. The half-life of methamphetamine is variable with a mean value of between 9 and 12 hours. Methamphetamine and amphetamine are often measured in urine, sweat or saliva as part of a drug-abuse testing program, in plasma or serum to confirm a diagnosis of poisoning in hospitalized victims, or in whole blood to assist in a forensic investigation of a traffic or other criminal violation or a case of sudden death. Chiral techniques may be employed to help distinguish the source of the drug, whether obtained legally (via prescription) or illicitly, or possibly as a result of formation from a prodrug such as famprofazone or selegiline. Chiral separation is needed to assess the possible contribution of l-methamphetamine (Vicks Inhaler) toward a positive test result. In 2011, researchers at John Jay College of Criminal Justice reported that dietary zinc supplements can mask the presence of methamphetamine and other drugs in urine.][ Similar claims have been made in web forums on that topic. A member of the family of phenethylamines, methamphetamine is chiral, with two isomers, levorotatory and dextrorotatory. The levorotatory form, called levomethamphetamine, is an over-the-counter drug used in inhalers for nasal decongestion. Methamphetamine is a potent central nervous system stimulant that affects neurochemical mechanisms responsible for regulating heart rate, body temperature, blood pressure, appetite, attention, mood and emotional responses associated with alertness or alarming conditions. The acute physical effects of the drug closely resemble the physiological and psychological effects of an epinephrine-provoked fight-or-flight response, including increased heart rate and blood pressure, vasoconstriction (constriction of the arterial walls), bronchodilation, and hyperglycemia (increased blood sugar). Users experience an increase in focus, increased mental alertness, and the elimination of fatigue, as well as a decrease in appetite. It is known to produce central effects similar to the other stimulants, but at smaller doses, with fewer peripheral effects. Methamphetamine's fat solubility also allows it to enter the brain faster than other stimulants, where it is more stable against degradation by monoamine oxidase (MAO). The methyl group is responsible for the potentiation of effects as compared to the related compound amphetamine, rendering the substance more lipid-soluble, enhancing transport across the blood–brain barrier, and more stable against enzymatic degradation by monoamine oxidase (MAO). Methamphetamine causes the norepinephrine, dopamine, and serotonin (5HT) transporters to reverse their direction of flow. This inversion leads to a release of these transmitters from the vesicles to the cytoplasm and from the cytoplasm to the synapse (releasing monoamines in rats with ratios of about NE:DA = 1:2, NE: 5HT = 1:60), causing increased stimulation of post-synaptic receptors. Methamphetamine also indirectly prevents the reuptake of these neurotransmitters, causing them to remain in the synaptic cleft for a prolonged period (inhibiting monoamine reuptake in rats with ratios of about: NE:DA = 1:2.35, NE:5HT = 1:44.5). Methamphetamine also interacts with TAAR1 to trigger phosphorylation of PKA and PKC, ultimately resulting in the internalization of dopamine transporters. The presynaptic cell is less able to effectively remove dopamine from the synapse. The binding of methamphetamine to TAAR1 also activates adenylyl cyclase, which allows for increased intracellular cAMP. Taken together, the binding of methamphetamine to TAAR1 results in a massive efflux of neurogenic monoamines with a sustained synaptic presence. Methamphetamine is a potent neurotoxin, shown to cause dopaminergic degeneration. High doses of methamphetamine produce losses in several markers of brain dopamine and serotonin neurons. Dopamine and serotonin concentrations, dopamine and 5HT uptake sites, and tyrosine and tryptophan hydroxylase activities are reduced after the administration of methamphetamine. It has been proposed that dopamine plays a role in methamphetamine-induced neurotoxicity, because experiments that reduce dopamine production or block the release of dopamine decrease the toxic effects of methamphetamine administration. When dopamine breaks down, it produces reactive oxygen species such as hydrogen peroxide. It is likely that the approximate twelvefold increase in dopamine levels and subsequent oxidative stress that occurs after taking methamphetamine mediates its neurotoxicity. The lab of David Sulzer and colleagues at Columbia University developed a technique known as "intracellular patch electrochemistry" to measure concentrations of dopamine in the cytosol, and found massive increases following methamphetamine, leading to the "cytosolic dopamine hypothesis" of neurotoxicity, in which dopamine oxidation, particularly close to synaptic vesicles, produce oxidative stress that in turn leads to exacerbation of autophagy that can destroy axons and dendrites. Recent research published in the Journal of Pharmacology And Experimental Therapeutics (2007) indicates that methamphetamine binds to and activates a G protein-coupled receptor called TAAR1. TAARs are a newly discovered receptor family whose members are activated by a number of amphetamine-like molecules called trace amines, thyronamines, and certain volatile odorants. It has been demonstrated that a high core temperature is correlated with an increase in the neurotoxic effects of methamphetamine. Methamphetamine has been reported to occur naturally in Acacia berlandieri, and possibly Acacia rigidula, trees that grow in West Texas. Methamphetamine and amphetamine were long thought to be strictly human-synthesized, but Acacia trees contain these and numerous other psychoactive compounds (e. g., mescaline, nicotine, dimethyltryptamine), and the related compound β-phenethylamine is known to occur from numerous Acacia species. The findings, however, have never been confirmed or repeated, leading some researchers to believe the results were the result of cross-contamination.][ Studies have shown that the subjective pleasure of drug use (the reinforcing component of addiction) is proportional to the rate at which the blood level of the drug increases. These findings suggest the route of administration used affects the potential risk for psychological addiction independently of other risk factors, such as dosage and frequency of use. Intravenous injection is the fastest route of drug administration, causing blood concentrations to rise the most quickly, followed by smoking, suppository (anal or vaginal insertion), insufflation (snorting), and ingestion (swallowing). Ingestion does not produce a rush, an acute transcendent state of euphoria as forerunner to the high experienced with the use of methamphetamine, which is most pronounced with the intravenous route of administration. While the onset of the rush induced by injection can occur in as little as a few seconds, the oral route of administration requires approximately half an hour before the high sets in. Injection carries relatively greater risks than other methods of administration. The hydrochloride salt of methamphetamine is soluble in water. Intravenous users may use any dose range, from less than 100 milligrams to over one gram, using a hypodermic needle, although it should be noted that typically street methamphetamine is “cut,” or diluted, with a water-soluble cutting material, which constitutes a significant portion of a given street methamphetamine dose. Intravenous users risk developing pulmonary embolism (PE), a blockage of the main artery of the lung or one of its branches, and commonly develop skin rashes (also known as "speed bumps") or infections at the site of injection. As with the injection of any drug, if a group of users share a common needle without sterilization procedures, blood-borne diseases, such as HIV or hepatitis, can be transmitted. Smoking amphetamines refers to vaporizing it to inhale the resulting fumes, not burning it to inhale the resulting smoke. It is commonly smoked in glass pipes made from glassblown Pyrex tubes and light bulbs. It can also be smoked off aluminium foil, which is heated underneath by a flame. This method is also known as "chasing the white dragon" (whereas smoking heroin is known as "chasing the dragon"). There is little evidence that methamphetamine inhalation results in greater toxicity than any other route of administration. Lung damage has been reported with long-term use, but manifests in forms independent of route (pulmonary hypertension (PH)), or limited to injection users (pulmonary embolism (PE)). Another popular route of administration to intake methamphetamine is insufflation (snorting). This method allows methamphetamine to be absorbed through the soft tissue of the mucous membrane in the sinus cavity, and then directly into the bloodstream, bypassing first-pass metabolism. Suppository (anal or vaginal insertion) is a less popular method of administration used in the community with comparatively little research into its effects. Information on its use is largely anecdotal with reports of increased sexual pleasure and the effects of the drug lasting longer, though as methamphetamine is centrally active in the brain, these effects are likely experienced through the higher bioavailability of the drug in the bloodstream (second to injection) and the faster onset of action (than insufflation). Nicknames for the route of administration within some methamphetamine communities include a "butt rocket", a "booty bump", "potato thumping", "turkey basting", "plugging", "boofing", "suitcasing", "hooping", "keistering", "shafting", "bumming", and "shelving" (vaginal). Shortly after the first synthesis of amphetamine in 1887, methamphetamine was synthesized from ephedrine in 1893 by Japanese chemist Nagai Nagayoshi. The term "methamphetamine" was derived from elements of the chemical structure of this new compound: ylmeth lphaa-ethylm enylph hylet amine. In 1919, crystallized methamphetamine was synthesized by pharmacologist Akira Ogata via reduction of ephedrine using red phosphorus and iodine. One of the earliest uses of methamphetamine was during World War II, when it was used by Axis and Allied forces. The company Temmler produced methamphetamine under the trademark Pervitin and so did the German and Finnish militaries. It was also dubbed "Pilot's chocolate" or "Pilot's salt". It was widely distributed across rank and division, from elite forces to tank crews and aircraft personnel, with many millions of tablets being distributed throughout the war. Its use by German Panzer crews also led to it being known as "Panzerschokolade" ("Panzer chocolate" or "tankers' chocolate"). More than 35 million three-milligram doses of Pervitin were manufactured for the German army and air force between April and July 1940. From 1942 until his death in 1945, Adolf Hitler was given intravenous injections of methamphetamine by his personal physician Theodor Morell. It is possible that it was used to treat Hitler's speculated Parkinson's disease, or that his Parkinson-like symptoms that developed from 1940 onwards resulted from using methamphetamine. In Japan, methamphetamine was sold under the registered trademark of Philopon (ヒロポン hiropon) by Dainippon Pharmaceuticals (present-day Dainippon Sumitomo Pharma [DSP]) for civilian and military use. As with the rest of the world at the time, the side effects of methamphetamine were not well studied, and regulation was not seen as necessary. In the 1940s and 1950s the drug was widely administered to Japanese industrial workers to increase their productivity. Methamphetamine and amphetamine were given to Allied bomber pilots during World War II to sustain them by fighting off fatigue and enhancing focus during long flights. The experiment failed because soldiers became agitated, could not channel their aggression and showed impaired judgment. Rather, dextroamphetamine (Dexedrine) became the drug of choice for American bomber pilots, being used on a voluntary basis by roughly half of the U.S. Air Force pilots during the Persian Gulf War, a practice which came under some media scrutiny in 2003 after a mistaken attack on Canadian troops. Following the use of amphetamine (such as Benzedrine, introduced 1932) in the 1930s for asthma, narcolepsy, and symptoms of the common cold, in 1943, Abbott Laboratories requested U.S. FDA approval of methamphetamine for treatment of narcolepsy, mild depression, postencephalitic parkinsonism, chronic alcoholism, cerebral arteriosclerosis, and hay fever, which was granted in December 1944.][ Sale of the massive postwar surplus of methamphetamine in Europe, North America, and Japan stimulated civilian demand. After World War II, a large Japanese military stockpile of methamphetamine, known by its trademark Philopon, flooded the market. Post-war Japan experienced the first methamphetamine epidemic, which later spread to Guam, the U. S. Marshall Islands, and to the U. S. West Coast. In 1948, the Philopon trademark came under a well-publicized lawsuit by Philips Corporation. Philips, under its Koninklijke division, filed suit against Dainippon Pharmaceuticals to cease using Philipon as the commercial name for methamphetamine. Philips claimed the exclusive right to use the trademark as a portmanteau of Philips and Nippon, the Japanese name of the country. DSP's attorneys challenged Philips' standing to sue as a foreign (Dutch) corporation. The matter was ultimately settled out of court in 1952, with Dainippon Pharmaceuticals agreeing to pay Philips a 5% royalty on worldwide sales of methamphetamines sold by DSP under the Philopon label. The Japanese Ministry of Health banned production less than a year later. In the 1950s, there was a rise in the legal prescription of methamphetamine to the American public. In the 1954 edition of Pharmacology and Therapeutics, conditions treatable by methamphetamine included "narcolepsy, postencephalitic parkinsonism, alcoholism, certain depressive states, and in the treatment of obesity." Methamphetamine constituted half of the amphetamine salts for the original formulation for the diet drug Obetrol, which later became the ADHD drug Adderall. Methamphetamine was also marketed for sinus inflammation or for non-medicinal purposes as "pep pills" or "bennies". In 1950 the Japanese Ministry of Health banned stimulant production, but drug companies continued to produce stimulants and they wound up on the black market. From 1951 to 1954 a series of acts were passed by the Japanese government to try to stop production and sale of stimulants; however, the production and sale of stimulant drugs continued through criminal syndicates such as Yakuza criminal organizations. On the streets, it is also known as S, Shabu, and Speed, in addition to its old trademarked name. The 1960s saw the start of significant use of clandestinely manufactured methamphetamine, most of which was produced by motorcycle gangs. It was also prescribed by San Franciscan drug clinics to treat heroin addiction. Beginning in the 1990s, the production of methamphetamine in users' own homes for personal and recreational use became popular. In 1970, methamphetamine was regulated in the Controlled Substances Act in the U. S., and a public education campaign was mounted against it. By the 2000s, the only two FDA approved marketing indications remaining for methamphetamine were for attention-deficit hyperactivity disorder (ADHD) and the short-term management of exogenous obesity, although the drug is clinically established as effective in the treatment of narcolepsy. The production, distribution, sale, and possession of methamphetamine is restricted or illegal in many jurisdictions. Methamphetamine has been placed in Schedule II of the United Nations Convention on Psychotropic Substances treaty. North Korea might be facing one of the world's worst meth epidemics. Although the secrecy of the North Korean government means that any report may be only approximate, there have been an increasing number of signs that meth is very widespread throughout the country, used both recreationally and as medicine. Methamphetamine is called Bingdu (Hangul: ; Hanja: ; "ice poison") in the Korean language. In 1983, laws were passed in the United States prohibiting possession of precursors and equipment for methamphetamine production. This was followed a month later by a bill passed in Canada enacting similar laws. In 1986, the U.S. government passed the Federal Controlled Substance Analogue Enforcement Act in an attempt to curb the growing use of designer drugs. Despite this, use of methamphetamine expanded from its initial base in California throughout the rural United States, especially through the Midwest and South. Government officials in many U.S. counties now report that meth is their most serious drug problem. Meth use is said to be particularly common in the American western states, where the substance is in high demand. States like Montana, South Dakota, Idaho, Colorado and Arizona have all launched extensive efforts – both private and public – to stop meth use. Methamphetamine is most structurally similar to methcathinone and amphetamine. Synthesis is relatively simple, but entails risk with flammable and corrosive chemicals, particularly the solvents used in extraction and purification; therefore, illicit production is often discovered by fires and explosions caused by the improper handling of volatile or flammable solvents. The six major routes of production begin with either phenyl-2-propanone (P2P) or with one of the isomeric compounds pseudoephedrine and ephedrine. One procedure uses the reductive amination of phenyl-2-propanone (phenylacetone) with methylamine, P2P was usually obtained from phenylacetic acid and acetic anhydride, though many other methods have been considered, and phenylacetic acid might arise from benzaldehyde, benzylcyanide, or benzylchloride. Methylamine is crucial to all such methods, and is produced from the model airplane fuel nitromethane, or formaldehyde and ammonium chloride, or methyl iodide with hexamine. This was once the preferred method of production by motorcycle gangs in California, until DEA restrictions on the chemicals made the process difficult. Pseudoephedrine, ephedrine, phenylacetone, and phenylacetic acid are currently DEA list I and acetic anhydride is list II on the DEA list of chemicals subject to regulation and control measures. This method can involve the use of mercuric chloride and leaves behind mercury and lead environmental wastes. The methamphetamine produced by this method is racemic, consisting partly of the less-desired levomethamphetamine isomer. The alternative Leuckart route also relies on P2P to produce a racemic product, but proceeds via methylformamide in formic acid to an intermediate N-formyl-methamphetamine, which is then decarboxylated with hydrochloric acid. Two infrequently used reductive amination routes have also been reported. The "nitropropene route", in which benzaldehyde is condensed with nitroethane to produce 1-phenyl-2-nitropropene, which is subsequently reduced by hydrogenation of the double bond and reduction of the nitro group using hydrogen over a palladium catalyst or lithium aluminum hydride. The "oxime route" reacts phenyl-2-propanol with hydroxylamine to produce an oxime intermediate which likewise is hydrogenated using hydrogen over a palladium catalyst or lithium aluminum hydride. Illicit methamphetamine is more commonly made by the reduction of ephedrine or pseudoephedrine, which produces the more active d-methamphetamine isomer. The maximum conversion rate for ephedrine and pseudoephedrine is 92%, although typically, illicit methamphetamine laboratories convert at a rate of 50% to 75%. Most methods of illicit production involve protonation of the hydroxyl group on the ephedrine or pseudoephedrine molecule. Though dating back to the discovery of the drug, the Nagai route did not become popular among illicit manufacturers until ca. 1982, and comprised 20% of production in Michigan in 2002 It involves red phosphorus and hydrogen iodide (also known as hydroiodic acid or iohydroic acid). (The hydrogen iodide is replaced by iodine and water in the "Moscow route") The hydrogen iodide is used to reduce either ephedrine or pseudoephedrine to methamphetamine. On heating the precursor is rapidly iodinated by the hydrogen iodide to form iodoephedrine. The phosphorus assists in the second step, by consuming iodine to form phosphorus triiodide (which decomposes in water to phosphorous acid, regenerating hydrogen iodide). Because hydrogen iodide exists in a chemical equilibrium with iodine and hydrogen, the phosphorus reaction shifts the balance toward hydrogen production when iodine is consumed. In Australia, criminal groups have been known to substitute "red" phosphorus with either hypophosphorous acid or phosphorous acid (the "Hypo route"). This is a hazardous process for amateur chemists because phosphine gas, a side-product from in situ hydrogen iodide production, is extremely toxic to inhale. The reaction can also create toxic, flammable white phosphorus waste. Methamphetamine produced in this way is usually more than 95% pure. The conceptually similar Emde route involves reduction of ephedrine to chloroephedrine using thionyl chloride (SOCl2), followed by catalytic hydrogenation. The catalysts for this reaction are palladium or platinum. The Rosenmund route also uses hydrogen gas and a palladium catalyst poisoned with barium sulfate (Rosenmund reduction), but uses perchloric acid instead of thionyl chloride. The Birch reduction, also called the "Nazi method", became popular in the mid-to-late 1990s and comprised the bulk of methamphetamine production in Michigan in 2002. It reacts pseudoephedrine with liquid anhydrous ammonia and an alkali metal such as sodium or lithium. The reaction is allowed to stand until the ammonia evaporates. However, the Birch reduction is dangerous because the alkali metal and ammonia are both extremely reactive, and the temperature of liquid ammonia makes it susceptible to explosive boiling when reactants are added. It has been the most popular method in Midwestern states of the U. S. because of the ready availability of liquid ammonia fertilizer in farming regions. In recent years, a simplified "Shake 'n Bake" one-pot synthesis has become more popular. The method is suitable for such small batches that pseudoephedrine restrictions are less effective, it uses chemicals that are easier to obtain (though no less dangerous than traditional methods), and it is so easy to carry out that some addicts have made the drug while driving. It involves placing crushed pseudoephedrine tablets into a nonpressurized container containing ammonium nitrate, water, and a hydrophobic solvent such as Coleman fuel or automotive starting fluid, to which lye and lithium (from lithium batteries) is added. Hydrogen chloride gas produced by a reaction of salt with sulfuric acid is then used to recover crystals for purification. The container needs to be "burped" periodically to prevent failure under accumulating pressure, as exposure of the lithium to the air can spark a flash fire; thus an abandoned reaction becomes a severe hazard to firefighters. The battery lithium can react with water to shatter a container and potentially start a fire or explosion. Producing methamphetamine in this fashion can be extremely dangerous and has been linked to several fatalities. Because users frequently carry out the reaction in a two-liter bottle held close to their bodies, which can explode if the cap is removed too soon or if it accidentally perforates, the procedure has led to a large number of severe burns — for example, approximately 70 in Indiana during 2010 and 2011. As 90% of these cases in the United States lack health insurance, and the average cost for their treatment is $130,000 (60% more than the average), which is only partially compensated by Medicaid, this method of synthesis has been blamed for the closure of hospital burn units and a cost to taxpayers of tens or hundreds of millions of dollars. Until the early 1990s, methamphetamine for the U.S. market was made mostly in labs run by drug traffickers in Mexico and California. Indiana state police found 1,260 labs in 2003, compared to just 6 in 1995, although this may be partly a result of increased police activity. As of 2007, drug and lab seizure data suggests that approximately 80 percent of the methamphetamine used in the United States originates from larger laboratories operated by Mexican-based syndicates on both sides of the border and that approximately 20 percent comes from small toxic labs (STLs) in the United States. Mobile and motel-based methamphetamine labs have caught the attention of both the U.S. news media and the police. Such labs can cause explosions and fires and expose the public to hazardous chemicals. Those who manufacture methamphetamine are often harmed by toxic gases. Many police departments have specialized task forces with training to respond to cases of methamphetamine production. The National Drug Threat Assessment 2006, produced by the Department of Justice, found "decreased domestic methamphetamine production in both small and large-scale laboratories", but also that "decreases in domestic methamphetamine production have been offset by increased production in Mexico." The report concluded that "methamphetamine availability is not likely to decline in the near term. " Methamphetamine labs can give off noxious fumes, such as phosphine gas, methylamine gas, solvent vapors, acetone or chloroform, iodine vapors, white phosphorus, anhydrous ammonia, hydrogen chloride/muriatic acid, hydrogen iodide, lithium and sodium gases, ether, or methamphetamine vapors. If performed by amateurs, manufacturing methamphetamine can be extremely dangerous. If the red phosphorus overheats, because of a lack of ventilation, phosphine gas can be produced. This gas is highly toxic and, if present in large quantities, is likely to explode upon autoignition from diphosphine, which is formed by overheating phosphorus.][ In July 2007, Mexican officials at the port of Lázaro Cárdenas seized a ship carrying 19 tons of pseudoephedrine, a raw material needed for methamphetamine. The shipment originated in Hong Kong and passed through the United States at the port of Long Beach prior to its arrival in Mexico. The Australian Crime Commission's illicit drug data report for 2011–2012 was released in western Sydney, Australia on 20 May 2013 and revealed that the average strength of crystal methamphetamine doubled in most Australian jurisdictions within a 12-month period and the majority of domestic laboratory closures involved small "addict-based" operations. In Japan, methamphetamine seizures are usually white crystals of high purity, but contain impurities that vary according to the means of production, and are sometimes adulterated. Diagnostic impurities are the naphthalenes 1-benzyl-methylnaphthalene and 1,3-dimethyl-2-phenylnaphthalene, arising in the Nagai and Leuckart routes, and cis- or trans- 1,2-dimethyl-3-phenylaziridine, ephedrine, or erythro-3,4-dimethyl- 5-phenyloxazolidine, arising in the Nagai and Emde routes; these are absent in the reductive amination route. Characteristic impurities of the Birch route include N-methyl-1-(1-(1,4-cyclohexadienyl))-2-propanamine. Methamphetamine produced by the Birch route contains phenyl-2-propanone, the precursor for the reductive amination route, as a degradation product. However, specific diagnostic impurities are not very reliable in practice, and it is generally preferable for forensic technicians to evaluate a larger profile of trace compounds. A common adulterant is dimethyl sulfone, a solvent and cosmetic base without known effect on the nervous system; other adulterants include dimethylamphetamine HCl, ephedrine HCl, sodium thiosulfate, sodium chloride, sodium glutamate, and a mixture of caffeine with sodium benzoate. In the United States, illicit methamphetamine comes in a variety of forms with prices varying widely over time. Most commonly, it is found as a colorless crystalline solid. Impurities may result in a brownish or tan color. Colorful flavored pills containing methamphetamine and caffeine are known as yaa baa (Thai for "crazy medicine"). An impure form of methamphetamine is sold as a crumbly brown or off-white rock, commonly referred to as "peanut butter crank". It may be diluted or cut with non-psychoactive substances like inositol, isopropylbenzylamine or dimethylsulfone. Another popular method is to combine methamphetamine with other stimulant substances, such as caffeine or cathine, into a pill known as a "Kamikaze", which can be particularly dangerous due to the synergistic effects of multiple stimulants. Reports in 2007 of the appearance of flavored "Strawberry Quik meth" circulated in the media and local law enforcement, but were debunked in 2010 by the DEA, although meth of varying colors has been seized. Rarely, the impure reaction mixture from the hydrogen iodide/red phosphorus route is used without further modification, usually by injection; it is called "ox blood". "Meth oil" refers to the crude methamphetamine base produced by several synthesis procedures. Ordinarily it is purified by exposure to hydrogen chloride, as a solution or as a bubbled gas, and extraction of the resulting salt occurs by precipitation and/or recrystallization with ether/acetone. Slang terms for methamphetamine, especially common among illicit users, are numerous and vary from region to region. Some names are "crystal meth", "meth", "speed", "crystal", "clavo", "ice", "shards", "shabu/shaboo", "glass", "jib", "crank", "batu/batunas", "scanté", "schizznit", "gack", "tweak", "rizz", "rock", "tina" and "cold". Some terms vary by region or subculture. Some regional terms are based on the original trade names; thus "필로폰" ("Pilopon") in South Korea, "Пико" for pure methamphetamine in Bulgaria or "piko" in the Czech Republic, Slovakia, and Poland after the trade name "Pervitin". Also "peří" ("feathers", phonetically similar to "Pervitin") and "perník" ("gingerbread", phonetically similar to "Pervitin" in the Czech Republic. In New Zealand it is called "P". Other local names include “冰毒” (Bīng Dú, Chinese for "Ice drug") in China, "ya ba" (Thai for "Crazy Medicine", Thailand), "ya ice" (Thai for "Ice drug", Thailand), "đá" (Vietnamese for "ice", Vietnam), "batu kilat" (Malaysian for "shining rocks", Malaysia), "bato" (Filipino for "rock" or "stone", Philippines) "شیشه" (in translation "Glass", transliterate to "Shishe", Iran), "tik" (South Africa), "dimineata speciala aurie" ("Special golden morning", Romania), "bala" in Brazilian Portuguese, "tjäck" in Swedish, "ספיד" in Israel and "Teeft" United Kingdom. "Vint", Russian for "a screw", specifically refers to a very impure homemade form of methamphetamine in Russia. The name originally comes from "Pervitin," a pharmaceutical trademark. The DSM IV has amphetamine defined in two ways: Amphetamine dependence (304.40) and Amphetamine abuse (305.70) M: PSO/PSI mepr dsrd (o, p, m, p, a, d, s), sysi/epon, spvo proc (eval/thrp), drug (N5A/5B/5C/6A/6B/6D) M: NUT cof, enz, met noco, nuvi, sysi/epon, met drug (A8/11/12)
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Personal life is the course of an individual's life, especially when viewed as the sum of personal choices contributing to one's personal identity. It is a common notion in modern existence—although more so in more prosperous parts of the world such as Western Europe and North America.]citation needed[ In these areas, there are service industries which are designed to help people improve their personal lives via counselling or life coaching.

In the past, before modern technology largely alleviated the problem of economic scarcity in industrialised countries, most people spent a large portion of their time attempting to provide their basic survival needs, including water, food, and protection from the weather. Survival skills were necessary for the sake of both self and community; food needed to be harvested and shelters needed to be maintained. There was little privacy in a community, and people were identified by their social role. Jobs were assigned out of necessity rather than personal choice.

Drug prohibition law is prohibition-based law by which governments prohibit, except under licence, the production, supply, and possession of many, but not all, substances which are recognised as drugs, and which corresponds to international treaty commitments in the Single Convention on Narcotic Drugs 1961, the Convention on Psychotropic Substances 1971, and the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances 1988.

When produced, supplied or possessed under licence, otherwise prohibited drugs are known as controlled drugs. The aforementioned legislation is the cultural institution and social fact that de facto divides world drug trade as illegal vs legal, according to geopolitical issues. The United Nations has its own drug control programme, as part of the United Nations Office on Drugs and Crime (UNODC), which was formerly called the United Nations Office for Drug Control and Crime Prevention (ODCCP), and the Commission on Narcotic Drugs is the central drug policy-making body within the United Nations system.

Doping

A drug test is a technical analysis of a biological specimen – for example urine, hair, blood, breath air, sweat, or oral fluid / saliva – to determine the presence or absence of specified parent drugs or their metabolites. Major uses of drug testing are to detect the presence of performance enhancing steroids in sport or for drugs prohibited by laws, such as cannabis, cocaine and heroin.

A "10-panel urine screen" consists of 10 of the following:

In journalism, a human interest story is a feature story that discusses a person or people in an emotional way. It presents people and their problems, concerns, or achievements in a way that brings about interest, sympathy or motivation in the reader or viewer.

Human interest stories may be "the story behind the story" about an event, organization, or otherwise faceless historical happening, such as about the life of an individual soldier during wartime, an interview with a survivor of a natural disaster, a random act of kindness or profile of someone known for a career achievement.

Social Issues

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