Methamphetamine, "meth" is a medication by itself. This is a generic name given to the drug. Some brands of methamphetamine are Desoxyn, Desoxyn, and Gradumet.
(USAN) , also known as metamfetamine
, clouds crystal
, 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.
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
. 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-
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)
dsrd (o, p, m, p, a, d, s), sysi/epon, spvo
proc (eval/thrp), drug (N5A/5B/5C/6A/6B/6D)
cof, enz, met
noco, nuvi, sysi/epon, met
Desbutal was a brand name drug by Abbott containing 5 mg Desoxyn (methamphetamine hydrochloride) and 30 mg Nembutal (pentobarbital sodium); an amphetamine combined with a barbiturate in the same capsule.
It came in bottles of 100 and 1000, and is no longer marketed today.
; sold as Vyvanse
) is a psychostimulant prodrug of the phenethylamine and amphetamine chemical classes. Its molecular structure consists of dextroamphetamine coupled with the essential amino acid -lysineL
Lisdexamfetamine itself is inactive and acts as a prodrug to dextroamphetamine upon cleavage of the lysine portion of the molecule. It was developed for the intention of creating a longer-lasting and less easily abused version of dextroamphetamine, as the requirement of conversion into dextroamphetamine via enzymes in the red blood cells increases its duration, regardless of the route of ingestion. The drug lisdexamfetamine dimesylate is the first prodrug of its kind. Studies conducted show that lisdexamfetamine dimesylate may have less abuse potential than d-amphetamine and an abuse profile similar to diethylpropion at dosages that are FDA-approved for treatment of ADHD, but still has a high abuse potential when this dosage is exceeded by over 100%. There is no increased onset or effect as occurs with IV administration of dextroamphetamine compared to oral use of the same. Intravenously administered lisdexamfetamine produced likability effects similar to placebo, therefore affirming the drug's ability to reduce abuse potential.
Lisdexamfetamine is indicated for the treatment of attention deficit hyperactivity disorder (ADHD) in children six to twelve years and in adults as an integral part of a total treatment program that may include other measures (i.e., psychological, educational, social). The safety and the efficacy of lisdexamfetamine dimesylate in patients three to five years old have not been established. Important side effects of therapeutic lisdexamfetamine include stunted growth in young people and, occasionally, a psychosis can occur at therapeutic doses during chronic therapy as a treatment emergent side effect. When abused at high doses the risk of experiencing and the severity of side effects increase.
As opposed to Adderall, which contains roughly 75% dextroamphetamine and 25% levoamphetamine, lisdexamfetamine is a single-enantiomer (dextro) amphetamine formula. While this pure formulation may reduce side effects, certain individuals still exhibit a better clinical response to the mixed isomer preparation.
Vyvanse is also being investigated for possible treatment of Major Depressive Disorder, cognitive impairment associated with Schizophrenia, Excessive Daytime Sleepiness, and Binge Eating Disorder.
Lisdexamfetamine is marketed under the brand name Vyvanse. Vyvanse comes in several dosages (see table below). These are usually labeled to be taken once daily.
25 mg of Vyvanse is molecularly equivalent to 10 mg of Dexedrine (resulting in or including 7.37 mg versus 7.50 mg dextroamphetamine, respectively), although a 25 mg Vyvanse capsule is not commercially available. However, the molecular equivalence ratio does not mean that the respective doses of Vyvanse and Dexedrine SR (Spansule) are bioequivalent because the two formulations have slightly different pharmacokinetic profiles. For example, while the area under the curve for the aforementioned pharmaceuticals is equivalent, the peak exposure (Cmax
) to the active compound dextroamphetamine is about 50% higher for Vyvanse than for Dexedrine SR. The conversion rate of lisdexamfetamine to dextroamphetamine base is 0.2948, meaning that each milligram of lisdexamfetamine is equivalent to 0.2948 mg of dextroamphetamine base.
Because lisdexamphetamine is active in the human brain as amphetamine, its mechanism of action is identical to that of amphetamine.
Although the precise mechanism of action by which amphetamines improve the symptoms of ADHD remains unknown. However, it is thought that amphetamines decrease ADHD symptoms due to their effects on the central nervous system. Amphetamines act as releasing agents on the monoamine neurotransmitters dopamine and norepinephrine, thus causing massive extracellular levels on these two neurotransmitters. Amphetamines are also known to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and therefore increase their availability into the extraneuronal space.
Lisdexamfetamine (LDX) is a therapeutically inactive molecule. After oral ingestion, LDX is broken down by enzymes to form l-lysine, a naturally occurring essential amino acid, and active d-amphetamine, which is responsible for the drug’s activity. The conversion of LDX to d-amphetamine is not affected by gastrointestinal pH and is unlikely to be affected by alterations in normal gastrointestinal transit times. LDX was developed with the goal of providing a long duration of effect that is consistent throughout the day, with reduced potential for abuse-related liking. The attachment of the amino acid lysine slows down the relative amount of d-amphetamine available to the blood stream. Because no free d-amphetamine is present in LDX capsules, d-amphetamine does not become available through mechanical manipulation, such as crushing or simple extraction. A relatively sophisticated biochemical process is needed to obtain d-amphetamine from LDX.
Vyvanse was developed by New River Pharmaceuticals, who were bought by Shire Pharmaceuticals shortly before lisdexamfetamine began being marketed. Vyvanse is approved by the U.S. Food and Drug Administration (FDA) for the treatment of attention-deficit hyperactivity disorder.
On April 23, 2008, Vyvanse received FDA approval for the adult population. In a randomized, double-blind, four-week phase III trial in adult patients with ADHD, dosages of 30, 50 or 70 mg/day of oral lisdexamfetamine caused a significantly greater improvement in ADHD-Rating Scale total score than placebo.
On February 19, 2009, Health Canada approved 30 mg and 50 mg capsules of lisdexamfetamine for treatment of ADHD.
On February 8, 2012, Vyvanse received FDA approval for maintenance treatment of adult ADHD.
Lisdexamfetamine has less potential for misuse than its active metabolite (dextroamphetamine) due to being initially inactive upon consumption via all methods, and the drug level of the active metabolite dextroamphetamine reaching a plateau within a therapeutic dosage range (both results of being a prodrug).
Common side effects (side effects that have average rates of presentation; usually presenting in >5% of patients) of lisdexamfetamine use may include:
Other side effects can be caused by lisdexamfetamine; these potentially serious reactions may include:
dsrd (o, p, m, p, a, d, s), sysi/epon, spvo
proc (eval/thrp), drug (N5A/5B/5C/6A/6B/6D)
Strawberry Quik meth was a drug scare from 2007. Drug dealers were allegedly using coloring and flavoring to disguise methamphetamine as Strawberry Quik, thus making them more appealing to children. The story was widely reported in the media, but no cases of children using flavored meth have been verified.
Emails reported that drug dealers were using pop rocks to disguise the taste of meth and market it to children.
Emails began to circulate, claiming that meth was being disguised as candy and given to unsuspecting children. Snopes has reported that while colored crystal meth exists, and flavored meth may exist, there is no evidence of it being given to children. It is notable to point out that drug dealers seek clients with a regular source of income, which precludes many children.
Sometimes meth labs will try to brand their crystal meth product by coloring it in order to make it seem unique and to give it more market appeal. Police and drug enforcement officials have conjectured that the idea for "strawberry meth" may have come from such a process.
Law enforcement and treatment providers in Nevada and California have reported the distribution and/or use of flavored methamphetamine.
Strawberry-flavored meth was seized in an apartment in Carson City, Nevada in January 2007.
(INN) ) is a psychostimulant drug typically used for the treatment of attention deficit-hyperactivity disorder (ADHD) and narcolepsy.
Dextroamphetamine is the dextrorotatory, or "right-handed"
, enantiomer of the amphetamine molecule. The amphetamine molecule has two stereoisomers; levoamphetamine and dextroamphetamine. Names for dextroamphetamine include d-amphetamine
, and (S)-(+)-amphetamine
. Dextroamphetamine is available as a generic drug or under several brand names, including Dexedrine
Dextroamphetamine is also an active metabolite of the prodrug lisdexamfetamine (Vyvanse), as well as of several older N-substituted amphetamine prodrugs used as anorectics, such as clobenzorex (Asenlix), benzphetamine (Didrex), and amphetaminil (Aponeuron).
Common side effects include dry mouth, insomnia and headache. A study has found temporary reduction in growth rate in pediatric use.]
Dextroamphetamine is used for the treatment of ADHD and narcolepsy.
Side effects of amphetamine salts include dry mouth, insomnia, drowsiness, dizziness, nervousness, headache and weight loss, diarrhea, as well as faster heartbeat combined with lower blood pressure.
A study on comparative effects between amphetamine mixed salts (commonly known as adderall) and methylphenidate in children who have been treated for a year or more have shown a temporary decrease in growth rate that does not affect final adult height. Change in weight was reported as slightly greater for amphetamine mixed salts and authors concluded that the result may be clinically insignificant.
Studies on rats show long-term neurological and behavioral changes resulting from prenatal and early postnatal exposure to amphetamines. Warnings from the Patient Medication Guide for Adderall include serious cardiovascular events, sudden deaths, stroke, emergence of new psychotic or manic symptoms, aggression and blurred vision.
Prolonged high doses of amphetamines followed by an abrupt cessation can result in extreme fatigue, insomnia, irritability, weight gain, mental depression, urination problems (sometimes mistaken for a urinary tract infection), and bloody stools. Chronic abuse of amphetamines can result in the manifestation of amphetamine psychosis; occasionally this psychosis can occur at therapeutic doses during chronic therapy as a treatment emergent side effect.
The U.S. Air Force uses dextroamphetamine as one of its "go pills", given to pilots on long missions to help them remain focused and alert. The Tarnak Farm incident was linked by media reports to the use of this drug on long term fatigued pilots. The military did not accept this explanation, citing the lack of similar incidents. Newer stimulant medications or awakeness promoting agents with different side effect profiles, such as modafinil are being investigated and sometimes issued for this reason.
Though such use remains out of the mainstream, dextroamphetamine has been successfully applied in the treatment of certain categories of depression as well as other psychiatric syndromes. Such alternate uses include reduction of fatigue in cancer patients, antidepressant treatment for HIV patients with depression and debilitating fatigue, and early-stage physiotherapy for severe stroke victims. If physical therapy patients take dextroamphetamine while they practice their movements for rehabilitation, they may learn to move much faster than without dextroamphetamine, and in practice sessions with shorter lengths.
Physical effects can include anorexia, dilated pupils, vasoconstriction or vasodilation, tachycardia or bradycardia, hypertension or hypotension, blood shot eyes, flushing, erectile dysfunction, restlessness, dry mouth, bruxism, headache, tachypnea, fever, diaphoresis, diarrhea, constipation, blurred vision, dizziness, reduced seizure threshold, insomnia, numbness, palpitations, arrhythmias, tics, dry and/or itchy skin, acne, and pallor. Effects of extremely high doses can include coma, rhabdomyolysis, adrenergic storm, and stereotypy. Dangerous physical side effects are exceedingly rare in typical pharmaceutical doses.
Recent studies by the FDA indicate that, in children, young adults, and adults, there is no association
between serious adverse cardiovascular events (sudden death, myocardial infarction, and stroke) and the use of dextroamphetamine or other ADHD stimulants.
Psychological effects can include euphoria, anxiety, increased libido, alertness, concentration, increased energy, increased self-esteem and self-confidence, sociability, irritability, aggressiveness, grandiosity, hallucinations, repetitive and obsessive behaviors, paranoia, and with chronic and/or high doses, amphetamine psychosis can occur; occasionally this psychosis can occur at therapeutic doses during chronic therapy as a treatment emergent side effect.
Although withdrawal symptoms of Dextroamphetamine are rare, Withdrawal symptoms of dextroamphetamine primarily consist of fatigue, depression and an 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 dextroamphetamine used. Withdrawal symptoms may also include anxiety, irritability, headaches, agitation, seizures, vomiting, akathisia, hypersomnia (excessive sleeping), vivid or lucid dreams, deep REM sleep and suicidal ideation.
The Physician's 1991 Drug Handbook
reports: "Symptoms of overdose include restlessness, tremor, hyperreflexia, tachypnea, confusion, aggressiveness, hallucinations, and panic." Dilated pupils are common with high doses. Repeated high doses may lead to manifestations of acute psychosis. Additionally at least one case report identifies rhabdomyolysis as an associated side effect of dextroamphetamine in the presence of other risk factors.
The fatal dose in humans is not precisely known, but in various species of rat generally ranges between 50 and 100 mg/kg, or a factor of 100 over what is required to produce noticeable psychological effects. Although the symptoms seen in a fatal overdose are similar to those of methamphetamine, their mechanisms are not identical, as some substances which inhibit dextroamphetamine toxicity do not do so for methamphetamine.
An extreme symptom of overdose is amphetamine psychosis, characterized by vivid visual, auditory, and sometimes tactile hallucinations. Many of its symptoms are identical to the psychosis-like state which follows long-term sleep deprivation, so it remains unclear whether these are solely the effects of the drug, or due to the long periods of sleep deprivation which are often undergone by the chronic user. Amphetamine psychosis, however, is extremely rare in individuals taking oral amphetamines at therapeutic doses; it is usually seen in cases of prolonged or high-dose intravenous (IV) for non-medicinal uses.
Dextroamphetamine is the dextrorotatory stereoisomer of the amphetamine molecule, which can take two different forms. It is a slightly polar, weak base and is lipophilic.
In the United States, an instant-release (IR) tablet preparation of the salt dextroamphetamine sulfate is available]
[ under the brand names Dexedrine
, in 5 mg and 10 mg strengths]
[, and generic formulations from Teva Pharmaceutical Industries and recently Wilshire Pharmaceuticals. It is also available as a capsule preparation of controlled-release (CR) dextroamphetamine sulfate, under the brand names Dexedrine SR
and Dexedrine Spansule
, in the strengths of 5 mg, 10 mg, and 15 mg. A bubblegum flavored oral solution is available under the brand name ProCentra
, manufactured by FSC Pediatrics, which is designed to be an easier method of administration in children who have difficulty swallowing tablets, each 5 mL contains 5 mg dextroamphetamine.
In Australia, dextroamphetamine is available in bottles of 100 under the generic name dexamphetamine
] as 5 mg instant release sulfate tablets., or slow release dexamphetamine preparations may be compounded by individual chemists. Similarly, in the United Kingdom it is only available in 5 mg instant release sulfate tablets under the generic name dexamfetamine sulphate
] having had been available under the brand name Dexedrine
prior to UCB Pharma disinvesting the product to another pharmaceutical company (Auden Mckenzie).
Dextroamphetamine is the active metabolite of the prodrug lisdexamfetamine (L-lysine-d-amphetamine), available by the trademark name Vyvanse. Lisdexamfetamine is metabolised in the gastrointestinal tract, while dextroamphetamine's metabolism is hepatic. Lisdexamfetamine is therefore an inactive compound until it is converted into an active compound by the digestive system. Although still rated as a Schedule II drug by the U.S. Drug Enforcement Administration, lisdexamfetamine has a slower onset and its route of administration is limited to being taken orally, unlike dextroamphetamine, Adderall, and methylphenidate, which can be insufflated to achieve a faster onset with a higher bioavailability]
[. Vyvanse is marketed as once-a-day dosing as it provides a slow release of dextroamphetamine into the body. Vyvanse is available as capsules, and in six strengths; 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg. The conversion rate of lisdexamfetamine to dextroamphetamine base is 0.2948, thus a 30 mg-strength Vyvanse capsule is molecularly equivalent to 8.844 mg dextroamphetamine base.
Another pharmaceutical that contains dextroamphetamine is Adderall. The drug formulation of Adderall (both controlled and instant release forms) is:
Adderall is roughly three-quarters dextroamphetamine, with it accounting for 72.7% of the amphetamine base in Adderall (the remaining percentage is levoamphetamine).
An experiment with rats suggested Adderall's inclusion of levoamphetamine provides the pharmaceutical with a quicker onset and longer clinical effect compared to pharmaceuticals exclusively formulated of dextroamphetamine. One study has shown that although the human brain usually has a preference for dextroamphetamine over levoamphetamine, certain children have a better clinical response to levoamphetamine.
Amphetamine exists as two stereoisomers that differ in effects. The l- enantiomer (levoamphetamine) produces more cardiovascular and peripheral effects than the d- enantiomer (dextroamphetamine). At low doses, levoamphetamine produces greater arousal than dextroamphetamine, acting primarily on norepinephrine. At higher doses, dextroamphetamine has stimulant properties that are three to four times as potent as those of levoamphetamine, and acts primarily on dopamine, although few clinical studies of ADHD have documented differences among d-, l- and racemic amphetamine.
Just as dextroamphetamine has greater central effects and fewer peripheral effects than levoamphetamine, methamphetamine, which is equipotent to dextroamphetamine in producing behavioral stimulant effects, has even fewer peripheral effects and greater central effects than dextroamphetamine.
In relation to other over-the-counter ADD/ADHD pharmaceuticals, the d- isomer of racemic amphetamine is superior in bioavailibility and CNS stimulation.
Scientific findings have established that dextroamphetamine administration increases the activity of the phosphoinositol cycle via an indirect release of dopamine and Norepinephrine. These results are the first time that this has been confirmed in humans. Because dextroamphetamine is a substrate analog at monoamine transporters, at all doses, dextroamphetamine prevents the re-uptake of these neurotransmitters by competing with endogenous monoamines for uptake. Transporter inhibition causes monoamines to remain in the synaptic cleft for a prolonged period (amphetamine inhibits monoamine reuptake in rats with a norepinephrine to dopamine ratio (NE:DA) of 1:1 and a norepinephrine to 5-hydroxytryptamine ratio (NE:5-HT) of about 100:1).
At higher doses, when the concentration of dextroamphetamine is sufficient, the drug can trigger direct release of norepinephrine and dopamine from the cytoplasmic transmitter pool, that is, dextroamphetamine will cause norepinephrine and dopamine efflux via transporter proteins, functionally reversing transporter action, which triggers a cascading release of catecholamines. This inversion leads to a release of large amounts of these neurotransmitters from the cytoplasm of the presynaptic neuron into the synapse, causing increased stimulation of post-synaptic receptors, inducing euphoria. Dextroamphetamine releases monoamines in rats with selectivity ratios of about NE:DA = 1:3.5 and NE:5-HT = 1:250, meaning that NE and DA are readily released, but release of 5-HT occurs at a 1/4 ration than of NE:DA.
Dextroamphetamine increases dopamine release in the prefrontal cortex; activation of the dopamine-2 receptors inhibits glutamate release in the prefrontal cortex. Activation of the dopamine-1 receptors in the prefrontal cortex, however, results in elevated glutamate levels in the nucleus accumbens. An increase of the glutamate levels in the nucleus accumbens is the reason that dextroamphetamine has an ability to increase locomotor activity in rats. Serotonin also plays a role in dextroamphetamine's effect on glutamate levels; however, at therapeutic doses, dextroamphetamine has minuscule effect on the serotonin transporter (SERT).
On average, about one half of a given dose is eliminated unchanged in the urine, while the other half is broken down into various metabolites (mostly benzoic acid). However, the drug's half-life is highly variable because the rate of excretion is very sensitive to urinary pH. Under alkaline conditions, direct excretion is negligible and 95%+ of the dose is metabolized. Having an alkaline stomach will cause the drug to be absorbed faster through the stomach resulting in a higher blood level concentration of amphetamine. Having an alkaline bladder causes dextroamphetamine to be excreted more slowly from the blood and into the urine. Alkalinization of the urine can decrease the renal elimination of amphetamines, both potentiating the strength and prolonging the mechanism of action, especially when ingested with sodium bicarbonate.
The main metabolic pathway is:
Another pathway, mediated by enzyme CYP2D6, is:
Although p-hydroxyamphetamine is a minor metabolite (~5% of the dose), it may have significant physiological effects as a norepinephrine analogue.
Subjective effects are increased by larger doses, however, over the course of a given dose there is a noticeable divergence between such effects and drug concentration in the blood. In particular, mental effects peak before maximal blood levels are reached, and decline as blood levels remain stable or even continue to increase. This indicates a mechanism for development of acute tolerance, perhaps distinct from that seen in chronic use. The long-term effects of amphetamines use on neural development in children has not been well established.
Racemic amphetamine was first synthesized under the chemical name "phenylisopropylamine" in Berlin, 1887 by the Romanian chemist Lazar Edeleanu. It was not widely marketed until 1932, when the pharmaceutical company Smith, Kline & French (now known as GlaxoSmithKline) introduced it in the form of the Benzedrine inhaler for use as a bronchodilator. Notably, the amphetamine contained in the Benzedrine inhaler was the liquid free-base, not a chloride or sulfate salt.
Three years later, in 1935, the medical community became aware of the stimulant properties of amphetamine, specifically dextroamphetamine, and in 1937 Smith, Kline, and French introduced tablets under the tradename Dexedrine. In the United States, Dexedrine was approved to treat narcolepsy, attention disorders, depression, and obesity. In Canada, epilepsy and parkinsonism were also approved indications. Dextroamphetamine was marketed in various other forms in the following decades, primarily by Smith, Kline, and French, such as several combination medications including a mixture of dextroamphetamine and amobarbital (a barbiturate) sold under the tradename Dexamyl and, in the 1950s, an extended release capsule (the "Spansule").
It quickly became apparent that dextroamphetamine and other amphetamines had a high potential for misuse, although they were not heavily controlled until 1970, when the Comprehensive Drug Abuse Prevention and Control Act was passed by the United States Congress. Dextroamphetamine, along with other sympathomimetics, was eventually classified as Schedule II, the most restrictive category possible for a drug with a government-sanctioned, recognized medical use. Internationally, it has been available under the names AmfeDyn (Italy), Curban (US), Obetrol (Switzerland), Simpamina (Italy), Dexedrine/GSK (US & Canada), Dexedrine/UCB (United Kingdom), Dextropa (Portugal), and Stild (Spain).
In October 2010, GlaxoSmithKline sold the rights for Dexedrine Spansule to Amedra Pharmaceuticals (a subsidiary of CorePharma).
dsrd (o, p, m, p, a, d, s), sysi/epon, spvo
proc (eval/thrp), drug (N5A/5B/5C/6A/6B/6D)
The production, distribution, and sale of methamphetamine is restricted or illegal in many jurisdictions.
As a Schedule 8 drug, the medical use of Methamphetamine is recognized in Australia, although it is never prescribed as there are no pharmaceutical companies in Australia that manufacture it.
Methamphetamine is not approved for medical use in Canada. As of 2005, methamphetamine has been moved to Schedule I of the Controlled Drugs and Substances Act, which provides access to the highest maximum penalties. The maximum penalty for production and distribution of methamphetamine has increased from 10 years to life in prison.
In the Czech republic the law prohibits possession of amount of a drug, which is "larger than small". The Government mandates which amount is regarded as "larger than small". Nowadays possession of up to 2 grams of Methamphetamine is considered to be a misdemeanour rather than a crime and such possession can be fined up to 15,000 CZK (approximately $800). However, production and distribution is illegal. In 2009 police raided 340 Methamphetamine laboratories in the Czech republic, which is the most among EU countries. Government changed policy of sale of legal drugs, which contain substances needed for meth production - the buyer must have medical prescription, must identify himself by ID card and can obtain only a few packages. Due to this Czech meth producers are buying out the drugs with Pseudoephedrine in Poland, where there are no restrictions to it.
The Czech penal code penalizes possession (of more than 2 grams) by 1 – 8 years of imprisonment (penalty is differentiated by the amount of drug); production and distribution by up to 5 years, or up to 10 years (if conducted as a member of organized group, in large scale, against a child, or if it led to a large profit). Penal code also punishes spoofing or propagation of drugs (up to 5 years of imprisonment by different circumstances, up to 8 if against a child).
Methamphetamine is regulated under Schedule 1 of Hong Kong's Dangerous Drugs Ordinance. It can only be used legally by health professionals and for university research purposes. The substance can be given by pharmacists under a prescription. Anyone who supplies the substance without prescription can be punished with 15 years imprisonment and a fine of $100,000 (HKD). The penalty for trafficking or manufacturing the substance is a $5,000,000 (HKD) fine and life imprisonment. Possession or use of the substance without license from the Department of Health is liable to a $1,000,000 (HKD) fine and/or 7 years of imprisonment.
Methamphetamine is not approved for medical use in Italy, except for an extremely small number of case-approved, strictly controlled experimental therapies, and it is listed in the Tabella 1 ("Schedule One") of the Psychotropic Substances List of the Italian Ministry of Health. Production, traffic and/or sale of methamphetamine can be punished with a sentence of imprisonment ranging from six to twenty years, and with a fine ranging from 26,000 to 260,000 Euros, according to the severity of the felony. As for any other drugs, the consumption of methamphetamine and the possession of the substance for "personal use" (under a certain quantity) is not illegal in Italy, although law enforcement and health authorities keep files on known users and addicts, who are often forced to undergo treatment.][ However, methamphetamine is not a particularly common or popular substance in Italy, surpassed by cocaine, heroin, and ecstasy, even if its popularity is growing.
Methamphetamine is not approved for medical use in The Netherlands. It falls under Schedule I of the Opium Act. Although production and distribution of this drug are prohibited, few people who were caught with a small amount for personal use have been prosecuted.][
Methamphetamine is a Class "A" or Schedule 1 controlled drug under the Misuse of Drugs Act 1975. The maximum penalty for production and distribution is imprisonment for life. While in theory a doctor could prescribe it for an appropriate indication, this would require case-by-case approval by the director-general of public health. High purity methamphetamine is most commonly referred to by the uniquely New Zealand street name of P, for "pure".
Under the Misuse of Drugs Act in Singapore, methamphetamine is a Class A — Schedule I controlled drug. Under the Section 17 of the Misuse of Drugs Act, any person who carries 250 or more grammes of the drug shall be presumed to possess them for the purpose of drug trafficking, which is punishable by death. Unless authorized by the government, the possession, consumption, manufacturing, import, export, or trafficking of methamphetamine in any amount are illegal.
In South Africa, methamphetamine is classified as a Schedule 7 drug, and is listed as Undesirable Dependence-Producing Substances in Part III of Schedule 2 of the Drugs and Drug Trafficking Act, 1992. It is predominantly used by people in the Cape Flats areas.
As of 18 January 2007, methamphetamine is classified as a Class A drug in the UK under the Misuse of Drugs Act 1971 following a recommendation made by the Advisory Council on the Misuse of Drugs in June 2006. It had previously been classified as a Class B drug, except when prepared for injection.
Methamphetamine is classified as a Schedule II substance by the Drug Enforcement Administration under the UN Convention on Psychotropic Substances. It is available by prescription under the trade name Desoxyn, manufactured by Ovation Pharma. While there is technically no difference between the laws regarding methamphetamine and other controlled stimulants, most medical professionals are averse to prescribing it due to its notoriety.
In addition to federal laws, some states have placed additional restrictions on the sale of precursor chemicals commonly used to synthesize methamphetamine, particularly pseudoephedrine, a common over-the-counter decongestant. In 2005, the DEA seized 2,148.6 kg(4,736.8 lbs) of methamphetamine. In 2005, the Combat Methamphetamine Epidemic Act of 2005 was passed as part of the USA PATRIOT Act, putting restrictions on the sale of methamphetamine precursors. Various state governments have passed even more stringent laws to regulate the sale of pseudoephedrine decongestants.
On November 7, 2006, the US Department of Justice declared that November 30, 2006 be Methamphetamine Awareness Day.
DEA El Paso Intelligence Center data is showing a distinct downward trend in the seizure of clandestine drug labs for the illicit manufacture of methampetamine from a high of 18,091 in 2004. This trend has reversed as of 2008. Lab seizure data for the United States is available from EPIC beginning in 1999 when 7,438 labs were reported to have been seized during that calendar year. These figures include methamphetamine lab, "dumpsite" and "chemical and glassware" seizures.
See ephedrine and pseudoephedrine for legal restrictions in place as a result of their use as precursors in the clandestine manufacture of methamphetamine.
Cycloalkylamines are chemical compounds featuring a cycloalkyl group and an amine. Some examples include propylhexedrine, cyclopentamine, cypenamine, and tranylcypromine.
Methamphetamine (USAN) //, also known as metamfetamine (INN), N-methylamphetamine, methylamphetamine, and desoxyephedrine, is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs. Euphoriants
Monoamine oxidase inhibitors (MAOIs) are chemicals which inhibit the activity of the monoamine oxidase enzyme family. They have a long history of use as medications prescribed for the treatment of depression. They are particularly effective in treating atypical depression.]citation needed[ They are also used in the treatment of Parkinson's Disease and several other disorders.
Because of potentially lethal dietary and drug interactions, monoamine oxidase inhibitors have historically been reserved as a last line of treatment, used only when other classes of antidepressant drugs (for example selective serotonin reuptake inhibitors and tricyclic antidepressants) have failed. New research into MAOIs indicate that much of the concern over their dangerous dietary side effects stems from misconceptions and misinformation, and that despite proven effectiveness of this class of drugs, it is underutilized and misunderstood in the medical profession. New research also questions the validity of the perceived severity of dietary reactions, which has historically been based on outdated research. Pharmacology
The production, distribution, and sale of methamphetamine is restricted or illegal in many jurisdictions.
As a Schedule 8 drug, the medical use of Methamphetamine is recognized in Australia, although it is never prescribed as there are no pharmaceutical companies in Australia that manufacture it.
Meth mouth is a dental condition characterized by severe decay and loss of teeth, as well as fracture, enamel erosion, and other oral problems symptomatic of extended use of the drug methamphetamine (meth). The specific cause of the condition is unknown, although drug-induced xerostomia (dry mouth) and bruxism (grinding of the teeth) are thought to be involved. Other frequently cited factors are poor nutrition and lack of dental hygiene, common among long-term users of the drug. The legitimacy of meth mouth as a unique condition has been questioned because of the similar effects of some other drugs on teeth. Advocates of its status as a unique condition cite the pattern and scope of the decay as distinguishing factors.
Treating meth mouth is difficult, and it can be medically dangerous for active methamphetamine users because of the cardiac problems that can result from the interaction of local anesthetic with the drug. To treat patients with the condition, dentists prescribe fluoride to fight tooth decay (dental caries) and drugs that increase saliva for dry mouth; they also educate patients about nutrition and dental hygiene. Meth mouth has become widespread in some areas, and it has strained public health budgets because of the high cost of its treatment. Images of diseased mouths are often used in anti-drug campaigns. Methamphetamine
A dopamine agonist is a compound that activates dopamine receptors in the absence of dopamine. Dopamine agonists activate signaling pathways through the dopamine receptor and trimeric G-proteins, ultimately leading to changes in gene transcription.
Some medical drugs act as dopamine agonists and can treat hypodopaminergic (low dopamine) conditions; they are typically used for treating Parkinson's disease, attention deficit/hyperactivity disorder (in the form of stimulants) and certain pituitary tumors (prolactinoma), and may be useful for restless legs syndrome (RLS). Both Requip (Ropinirole) and Mirapex (Pramipexole) are FDA-approved for the treatment of RLS. There is also an ongoing clinical trial to test the effectiveness of the dopamine agonist Requip (ropinirole) in reversing the symptoms of SSRI-induced sexual dysfunction and Post-SSRI sexual dysfunction (PSSD). Additionally, a systematic review and meta-analysis concluded that prophylactic treatment with cabergoline reduces the incidence, but not the severity, of ovarian hyperstimulation syndrome (OHSS), without compromising pregnancy outcomes, in females undergoing stimulated cycles of in vitro fertilization (IVF). Health Medical Pharma