Question:

What is the difference between an MDMA and a GHB?

Answer:

MDMA creates a more euphoric experience lasting around 3 - 5 hours. GHB has a more drowsy hallucination effect lasting around 1.5 - 2.5 hours. Both are dangerous to experiment with.3 - 51.5 - 2.5

More Info:


Gamma-Hydroxybutyric acid

InChI=1S/C4H8O3/c5-3-1-2-4(6)7/h5H,1-3H2,(H,6,7)Yes 
Key:SJZRECIVHVDYJC-UHFFFAOYSA-NYes  γ-Hydroxybutyric acid (GHB), also known as 4-hydroxybutanoic acid, is a naturally occurring substance found in the human central nervous system, as well as in wine, beef, small citrus fruits, and almost all animals in small amounts. It is also categorized as an illegal drug in many countries. It is currently regulated in Australia and New Zealand, Canada, most of Europe and in the US. GHB as the sodium salt, known as sodium oxybate (INN) or by the trade name Xyrem, is used to treat cataplexy and excessive daytime sleepiness in patients with narcolepsy. GHB has been used in a medical setting as a general anesthetic, to treat conditions such as insomnia, clinical depression, narcolepsy, and alcoholism, and to improve athletic performance. It is also used as an intoxicant (illegally in many jurisdictions) or as a date rape drug. GHB is naturally produced in the human body's cells and is structurally related to the ketone body beta-hydroxybutyrate. As a supplement or drug, it is used most commonly in the form of a salt, such as sodium gamma-hydroxybutyrate (Na.GHB, sodium oxybate, or Xyrem) or potassium gamma-hydroxybutyrate (K.GHB, potassium oxybate). GHB is also produced as a result of fermentation, and so is found in small quantities in some beers and wines. Succinic semialdehyde dehydrogenase deficiency is a disease that causes GHB to accumulate in the blood. The only common medical applications for GHB today are in the treatment of narcolepsy and more rarely alcoholism. GHB is the active ingredient in the prescription medication sodium oxybate (Xyrem). Sodium oxybate is approved by the U.S. Food and Drug Administration (FDA) for the treatment of cataplexy associated with narcolepsy and excessive daytime sleepiness (EDS) associated with narcolepsy. GHB has been shown to reliably increase slow-wave sleep. GHB is a central nervous system depressant used as an intoxicant. It has many street names, including "Georgia Home Boy","Lollipops", "Juice", "Liquid Ecstasy", "Mils", "G", "Liquid X", and "Liquid G", as well as "Fantasy". Its effects have been described anecdotally as comparable with alcohol and ecstasy use, such as euphoria, disinhibition, enhanced sensuality and empathogenic states. At higher doses, GHB may induce nausea, dizziness, drowsiness, agitation, visual disturbances, depressed breathing, amnesia, unconsciousness, and death. The effects of GHB can last from 1.5 to 3 hours, or even longer if large doses have been consumed. Consuming GHB with alcohol is dangerous as it can lead to vomiting in combination with unrouseable sleep, a potentially lethal combination. In general, the doses used recreationally are between 500 mg and 3,000 mg. When used as a recreational drug, GHB may be found as the sodium or potassium salt, which is a white crystalline powder, or as GHB salt dissolved in water to form a clear solution. The sodium salt of GHB has a salty taste. Other salt forms such as calcium GHB and magnesium GHB have also been reported, but the sodium salt is by far the most common. Some chemicals convert to GHB in the stomach and blood stream. GBL, or -butyrolactonegamma, is one such prodrug. Other prodrugs include 1,4-butanediol. There may be additional toxicity concerns with these precursors. 1,4-B and GBL are normally found as pure liquids, though they may be mixed with other more harmful solvents when intended for industrial use, e.g., as paint stripper or varnish thinner. GHB can be easily manufactured at home with very little knowledge of chemistry, as it only involves the mixing of its two precursors, GBL and an alkali hydroxide (such as sodium hydroxide) to form the resulting GHB salt. Due to the ease of manufacture and the availability of its precursors, its production is not done in relatively few illicit laboratories like most other synthetic drugs, but in private homes by low level producers instead. While available as a prescription for rare and severe forms of sleep disorders such as narcolepsy in some other countries, notably most of Europe, GHB was banned (in the U.S.) by the FDA in 1990. However, on 17 July 2002, GHB was approved for treatment of cataplexy, often associated with narcolepsy. GHB is "colourless and odorless". GHB is often taken because users find that it enhances their experiences of being in a club, party, or rave; small doses of GHB can act as a stimulant and aphrodisiac. GHB is sometimes referred to as liquid ecstasy, lollipops, liquid X or liquid E due to its tendency to produce euphoria and sociability and its use in the dance party scene. Despite this nickname, GHB has entirely separate chemical and pharmacological modes of action compared to MDMA (ecstasy). Some athletes also use GHB, as GHB has been shown to elevate human growth hormone in vivo. One study found that it doubled growth hormone secretion in normal young males. The growth hormone elevating effects of GHB are mediated through muscarinic acetylcholine receptors and can be prevented by prior administration of pirenzepine, a muscarinic acetylcholine receptor blocking agent. As certain succinate salts have been shown to elevate growth hormone in vitro, and because GHB is metabolized into succinate some people have suggested this may play a role in the growth hormone elevations from GHB. There is however currently no evidence to show that succinate plays any role in the growth hormone elevations from GHB. Like alcohol and potent benzodiazepines such as flunitrazepam (Rohypnol), GHB has been labeled as a date rape drug. The sodium form of GHB has an extremely salty taste but, as it is colourless and odorless, it has been described as "very easy to add to drinks" that mask the flavor. GHB produced as a sodium salt (sodium oxybate) may provide a noticeable salty character to the drink, though individual sensitivity to the taste of salt varies. GHB can also be produced as different salts, some of which may not have a taste as distinctive as the sodium salt (e.g., magnesium oxybate), or much less commonly in the unstable free-acid form. Allegedly, GHB has been used in cases of drug-related sexual assault, usually when the victim is vulnerable due to intoxication with a sedative, generally alcohol. It is difficult to establish how often GHB is used to facilitate rape as it is difficult to detect in a urine sample after a day, and many victims may not recall the rape until some time after this, although GHB can be detected in hair. Hair testing can be a useful tool in court cases and/or for the victim's own information. Over-the-counter urine test kits only test for date rape drugs that are benzodiazepines, which GHB is not. To detect GHB in urine, the sample must be taken within 8–12 hours of GHB ingestion, and cannot be tested at home. GHB can be detected in hair for months after GHB ingestion. Other drugs, such as muscle relaxers (Carisoprodol for example), are sometimes mixed with GHB. Therefore, it can be beneficial to request that the hair sample be tested for multiple drugs. There have been several high profile cases of GHB as a date rape drug that received national attention in the United States. In early 1999 a 15-year old girl, Samantha Reid of Rockwood, MI, died from GHB poisoning. Reid’s death inspired the legislation titled the "Hillory J. Farias and Samantha Reid Date-Rape Drug Prohibition Act of 2000." This is the law that made GHB a schedule 1 controlled substance. In humans, GHB has been shown to inhibit the elimination rate of alcohol. This may explain the respiratory arrest that has been reported after ingestion of both drugs. A review of the details of 194 deaths attributed to or related to GHB over a ten-year period found that most were from respiratory depression caused by interaction with alcohol or other drugs. One report has suggested that sodium oxybate overdose may be fatal, based on deaths of three patients who had been prescribed the drug. However, for two of the three cases, post-mortem GHB concentrations were 141 and 110 mg/L, which is within the expected range of concentrations for GHB after death, and the third case was a patient with a history of intentional drug overdose. One publication has investigated 226 deaths attributed to GHB. Of 226 deaths included, 213 suffered cardiorespiratory arrest and 13 suffered fatal accidents. Seventy-one deaths (34%) had no co-intoxicants. Postmortem blood GHB was 18–4400 mg/L (median=347) in deaths negative for co-intoxicants. GHB is produced in the body in very small amounts, and blood levels may climb after death to levels in the range of 30–50 mg/L. Levels higher than this are found in GHB deaths. Levels lower than this may be due to GHB or to postmortem endogenous elevations. A UK parliamentary committee commissioned report found the use of GHB to be less dangerous than tobacco and alcohol in social harms, physical harm and addiction. Overdose of GHB can be difficult to treat because of its multiple effects on the body. GHB tends to cause rapid unconsciousness at doses above 3500 mg, with single doses over 7000 mg often causing life-threatening respiratory depression, and higher doses still inducing bradycardia and cardiac arrest. Other side-effects include convulsions (especially when combined with stimulants), and nausea/vomiting (especially when combined with alcohol). The greatest life threat due to GHB overdose (with or without other substances) is respiratory arrest. Other relatively common causes of death due to GHB ingestion include aspiration of vomitus, positional asphyxia, and trauma sustained while intoxicated (e.g., motor vehicle accidents while driving under the influence of GHB).][ The risk of aspiration pneumonia and positional asphyxia risk can be reduced by laying the patient down in the recovery position. People are most likely to vomit as they become unconscious, and as they wake up. It is important to keep the patient/friend awake and moving, plus do not allow them to be alone as death through vomiting can easily happen. Frequently they will be in a good mood but this does not mean they are not in danger. GHB overdose is a medical emergency and immediate assessment in an emergency department is needed. Convulsions from GHB can be treated with diazepam or lorazepam, even though these are also CNS depressants they are GABAA agonists, whereas GHB is primarily a GABAB agonist, so the benzodiazepines do not worsen CNS depression as much as might be expected.][ Because of the faster and more complete absorption of GBL relative to GHB, its dose-response curve is steeper, and overdoses of GBL tend to be more dangerous and problematic than overdoses involving only GHB or 1,4-B. Any GHB/GBL overdose is a medical emergency and should be cared for by appropriately trained personnel. A newer synthetic drug SCH-50911, which acts as a selective GABAB antagonist, quickly reverses GHB overdose in mice. However, this treatment has yet to be tried in humans, and it is unlikely that it will be researched for this purpose in humans due to the illegal nature of clinical trials of GHB, and the lack of medical indemnity coverage inherent in using an untested treatment for a life-threatening overdose.][ GHB may be quantitated in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients, provide evidence in an impaired driving arrest or to assist in a medicolegal death investigation. Blood or plasma GHB concentrations are usually in a range of 50–250 mg/L in persons receiving the drug therapeutically (during general anesthesia), 30–100 mg/L in those arrested for impaired driving, 50–500 mg/L in acutely intoxicated patients and 100–1000 mg/L in victims of fatal overdosage. Urine is often the preferred specimen for routine drug abuse monitoring purposes. Both gamma-butyrolactone (GBL) and 1,4-butanediol are converted to GHB in the body. In multiple studies, GHB has been found to impair spatial and working learning and memory in rats with chronic administration. These effects are associated with decreased NMDA receptor expression in the cerebral cortex and possibly other areas as well. Pedraza et al. (2009) found that repeated administration of GHB to rats for 15 days drastically reduced the number of neurons and non-neuronal cells in the CA1 region of the hippocampus and in the prefrontal cortex. With doses of 10 mg/kg of GHB, they were decreased by 61% in the CA1 region and 32% in the prefrontal cortex, and with 100 mg/kg, they were decreased by 38% and 9%, respectively. It is interesting to note that GHB has biphasic effects on neuronal loss, with lower doses (10 mg/kg) producing the most neurotoxicity, and higher doses (100 mg/kg) producing less. Pretreatment with NCS-382, a GHB receptor antagonist, prevents both learning/memory deficits and neuronal loss in GHB-treated animals, suggesting that GHB's neurotoxic actions are mediated via activation of the GHB receptor. In addition, the neurotoxicity appears to be caused by oxidative stress. Although there have been reported fatalities due to GHB withdrawal, reports are inconclusive and further research is needed. Addiction occurs when repeated drug use disrupts the normal balance of brain circuits that control rewards, memory and cognition, ultimately leading to compulsive drug taking. Colombo reports that rats forced to consume massive doses of GHB will intermittently prefer GHB solution to water, but notes that "no rat showed any sign of withdrawal when GHB was finally removed at the end of the 20-week period" or during periods of voluntary abstinence. GHB has also been associated with a withdrawal syndrome of insomnia, anxiety, and tremor that usually resolves within three to twenty-one days. The withdrawal syndrome can be severe producing acute delirium and may require hospitalization in an intensive care unit for management. The mainstay of treatment for severe withdrawal is supportive care and benzodiazepines for control of acute delirium, but larger doses are often required compared to acute delirium of other causes (e.g. > 100 mg/d of diazepam). Baclofen has been suggested as an alternative or adjunct to benzodiazepines based on anecdotal evidence and some animal data. However, there is less experience with the use of baclofen for GHB withdrawal, and additional research in humans is needed. Baclofen was first suggested as an adjunct because benzodiazepines do not affect GABAB receptors and thus have no cross-tolerance with GHB while baclofen, which works via GABAB receptors, is cross-tolerant with GHB and may be more effective in alleviating withdrawal effects of GHB. GHB withdrawal is not widely discussed in text books and some psychiatrists, general practitioners, and even hospital emergency physicians may not be familiar with this withdrawal syndrome. Cells produce GHB by reduction of succinic semialdehyde via the enzyme succinic semialdehyde dehydrogenase. This enzyme appears to be induced by cAMP levels, meaning substances that elevate cAMP, such as forskolin and vinpocetine, may increase GHB synthesis and release. People with the disorder known as succinic semialdehyde dehydrogenase deficiency, also known as gamma-hydroxybutyric aciduria, have elevated levels of GHB in their urine, blood plasma and cerebrospinal fluid. The precise function of GHB in the body is not clear. It is known, however, that the brain expresses a large amount of receptors that are activated by GHB. These receptors are excitatory and not responsible for the sedative effects of GHB – they have been shown to elevate the principal excitatory neurotransmitter—glutamate. The benzamide antipsychotics—amisulpride, sulpiride—have been shown to bind to this receptor in vivo. Other antipsychotics were tested and were not found to have an affinity for this receptor. It is a precursor to GABA, glutamate, and glycine in certain brain areas. GHB has neuroprotective properties and has been found to protect cells from hypoxia. GHB is also produced as a result of fermentation and so is found in small quantities in some beers and wines, in particular fruit wines. However, the amount of GHB found in wine is insignificant and not sufficient to produce any effects. GHB has at least two distinct binding sites in the central nervous system. GHB is an agonist at the newly characterized GHB receptor, which is excitatory, and it is a weak agonist at the BGABA receptor, which is inhibitory. GHB is a naturally occurring substance that acts in a similar fashion to some neurotransmitters in the mammalian brain. GHB is probably synthesized from GABA in GABAergic neurons, and released when the neurons fire. If taken orally, GABA itself does not effectively cross the blood-brain-barrier. GHB induces the accumulation of either a derivative of tryptophan or tryptophan itself in the extracellular space, possibly by increasing tryptophan transport across the blood–brain barrier. The blood content of certain neutral amino-acids, including tryptophan, is also increased by peripheral GHB administration. GHB-induced stimulation of tissue serotonin turnover may be due to an increase in tryptophan transport to the brain and in its uptake by serotonergic cells. As the serotonergic system may be involved in the regulation of sleep, mood, and anxiety, the stimulation of this system by high doses of GHB may be involved in certain neuropharmacological events induced by GHB administration. However, at therapeutic doses, GHB reaches much higher concentrations in the brain and activates GABAB receptors, which are primarily responsible for its sedative effects. GHB's sedative effects are blocked by GABAB antagonists. The role of the GHB receptor in the behavioural effects induced by GHB is more complex. GHB receptors are densely expressed in many areas of the brain, including the cortex and hippocampus, and these are the receptors that GHB displays the highest affinity for. There has been somewhat limited research into the GHB receptor; however, there is evidence that activation of the GHB receptor in some brain areas results in the release of glutamate, the principal excitatory neurotransmitter. Drugs that selectively activate the GHB receptor cause absence seizures in high doses, as do GHB and GABA(B) agonists. Activation of both the GHB receptor and GABA(B) is responsible for the addictive profile of GHB. GHB's effect on dopamine release is biphasic. Low concentrations stimulate dopamine release via the GHB receptor. Higher concentrations inhibit dopamine release via GABA(B) receptors as do other GABA(B) agonists such as baclofen and phenibut. After an initial phase of inhibition, dopamine release is then increased via the GHB receptor. Both the inhibition and increase of dopamine release by GHB are inhibited by opioid antagonists such as naloxone and naltrexone. Dynorphin may play a role in the inhibition of dopamine release via kappa opioid receptors. This explains the paradoxical mix of sedative and stimulatory properties of GHB, as well as the so-called "rebound" effect, experienced by individuals using GHB as a sleeping agent, wherein they awake suddenly after several hours of GHB-induced deep sleep. That is to say that, over time, the concentration of GHB in the system decreases below the threshold for significant GABAB receptor activation and activates predominantly the GHB receptor, leading to wakefulness. Recently, analogs of GHB, such as 4-hydroxy-4-methylpentanoic acid have been synthesised and tested on animals, in order to gain a better understanding of GHB's mode of action. Analogues of GHB such as 3-methyl-GHB, 4-methyl-GHB and 4-phenyl-GHB have been shown to produce similar effects to GHB in some animal studies, but these compounds are even less well researched than GHB itself. Of these analogues, only 4-methyl-GHB (γ-hydroxyvaleric acid, GHV) and its prodrug form gamma-valerolactone (GVL) have been reported as drugs of abuse in humans, and on the available evidence seem to be less potent but more toxic than GHB, with a particular tendency to cause nausea and vomiting. Other prodrug ester forms of GHB have also rarely been encountered by law enforcement, including 1,4-diacetoxybutane, methyl-4-acetoxybutanoate, and ethyl-4-acetoxybutanoate, but these are, in general, covered by analogue laws in jurisdictions where GHB is illegal, and little is known about them beyond their delayed onset and longer duration of action. The intermediate compound 4-hydroxybutaldehyde is also a prodrug for GHB; however, as with all aldehydes this compound is caustic and is strong-smelling and foul-tasting; actual use of this compound as an intoxicant is likely to be unpleasant and result in severe nausea and vomiting. Also note that both of the metabolic breakdown pathways shown for GHB can run in either direction, depending on the concentrations of the substances involved, so the body can make its own GHB either from GABA or from succinic semialdehyde. Under normal physiological conditions, the concentration of GHB in the body is rather low, and the pathways would run in the reverse direction to what is shown here to produce endogenous GHB. However, when GHB is consumed for recreational or health promotion purposes, its concentration in the body is much higher than normal, which changes the enzyme kinetics so that these pathways operate to metabolise GHB rather than producing it. Synthesis of the chemical GHB was first reported in 1874 by Alexander Zaytsev, but the first major research into its use in humans was conducted in the early 1960s by Dr. Henri Laborit to use in studying the neurotransmitter GABA. It quickly found a wide range of uses due to its minimal side-effects and short duration of action, the only difficulties being the narrow therapeutic dosage range and the dangers presented by its combination with alcohol and other nervous system depressants. GHB was widely used in France, Italy, and other European countries for several decades as a sleeping agent and an anesthetic in childbirth but problems with its abuse potential and development of newer drugs have led to a decrease in legitimate medical use of GHB in recent times. In the Netherlands, GHB could be bought as aphrodisiac and euphoriant in a smartshop for several years, until several incidents caused it to become regulated. The only common medical applications for GHB today are in the treatment of narcolepsy and more rarely alcoholism. In the typical scenario, GHB has been synthesized from γ-butyrolactone (GBL) by adding sodium hydroxide (lye) in ethanol or water. A popular children's toy, Bindeez (also known as Aqua Dots, in the United States), produced by Melbourne company Moose, was banned in Australia in early November 2007 when it was discovered that 1,4-butanediol (1,4-B), which is metabolized into GHB, had been substituted for the non-toxic plasticiser 1,5-pentanediol in the bead manufacturing process. Three young children were hospitalized as a result of ingesting a large number of the beads, and the toy was recalled. In the United States, it was placed on Schedule I of the Controlled Substances Act in March 2000. However, when sold as sodium oxybate, it is considered a Schedule III substance but with Schedule I trafficking penalties, one of several drugs that are listed in multiple schedules. On 20 March 2001, the Commission on Narcotic Drugs placed GHB in Schedule IV of the 1971 Convention on Psychotropic Substances. In the UK it was made a class C drug in June 2003. In Hong Kong, GHB is regulated under Schedule 1 of Hong Kong's Chapter 134 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 fined HK$10000. The penalty for trafficking or manufacturing the substance is a HK$150,000 fine and life imprisonment. Possession of the substance for consumption without license from the Department of Health is illegal with a HK$100,000 fine and/or 5 years of jail time. In New Zealand and Australia, GHB, 1,4-B and GBL are all Class B illegal drugs, along with any possible esters, ethers and aldehydes. GABA itself is also listed as an illegal drug in these jurisdictions, which seems unusual given its failure to cross the blood–brain barrier, but there was a perception among legislators that all known analogues should be covered as far as this was possible. Attempts to circumvent the illegal status of GHB have led to the sale of derivatives such as 4-methyl-GHB (gamma-hydroxyvaleric acid, GHV) and its prodrug form gamma-valerolactone (GVL), but these are also covered under the law by virtue of their being "substantially similar" to GHB or GBL and; so importation, sale, possession and use of these compounds is also considered to be illegal. In Chile, GHB is a controlled drug under the law "Ley de substancias psicotropicas y estupefacientes" (psychotropic substances and narcotics). In Norway and in Switzerland, GHB is considered a narcotic and is only available by prescription under the trade name Xyrem (Union Chimique Belge S.A.). Sodium oxybate is also used therapeutically in Italy under the brand name Alcover for treatment of alcohol withdrawal and dependence. Note: See the receptor PAMsAGABA navbox for a full list of GABAA positive allosteric modulators. Dopamine M: PNS anat (h/r/t/c/b/l/s/a)/phys (r)/devp/prot/nttr/nttm/ntrp noco/auto/cong/tumr, sysi/epon, injr proc, drug (N1B)

Methaqualone
InChI=1S/C16H14N2O/c1-11-7-3-6-10-15(11)18-12(2)17-14-9-5-4-8-13(14)16(18)19/h3-10H,1-2H3Yes 
Key:JEYCTXHKTXCGPB-UHFFFAOYSA-NYes  Methaqualone (; brand name Quaalude ) is a sedative-hypnotic drug that is similar in effect to barbiturates, a general central nervous system depressant. The sedative-hypnotic activity was first noted by Indian researchers in the 1950s and in 1962 methaqualone itself was patented in the US by Wallace and Tiernan. Its use peaked in the early 1970s as a hypnotic, for the treatment of insomnia, and as a sedative and muscle relaxant. It has also been used illegally as a recreational drug. Clandestinely produced methaqualone is seized by government agencies and police forces around the world. Methaqualone was first synthesized in India in 1951 by Indra Kishore Kacker and Syed Hussain Zaheer, and was soon introduced to Japanese and European consumers as a safe barbiturate substitute.][ By 1965 it was the most commonly prescribed sedative in Britain, where it has been sold legally under the names Malsed, Malsedin, and Renoval. In 1965 a Methaqualone/antihistamine combination was sold as the sedative drug Mandrax, by Roussel Laboratories (now part of Sanofi-Aventis). In 1972 it was the sixth-bestselling sedative in the USA, where it was legal under the brand name Quaalude. Methaqualone is a depressant that increases the activity of the GABA receptors in the brain and nervous system. When GABA activity is increased, blood pressure drops and the breathing and pulse rates slow, leading to a state of deep relaxation. These properties explain why methaqualone was originally mainly prescribed for insomnia, most commonly in 300 mg dosage. Methaqualone peaks in the bloodstream within several hours, its effects generally lasting four to eight hours. Regular users build up a physical tolerance, requiring larger doses for the same effect. Overdose can lead to nervous system shut down, coma and death. Methaqualone is not recommended for use while pregnant and is in pregnancy category D. Methaqualone is available in Canada by prescription as a Schedule III drug][. Methaqualone became increasingly popular as a recreational drug in the late 1960s and early 1970s, known variously as 'ludes or sopers (also soapers) in the U.S. and mandrakes and mandies in Great Britain. The drug was sometimes used during sexual activity due to heightened sensitivity and lowered inhibition coupled with relaxation and euphoria.][ The drug was often used by people who went dancing at glam rock clubs in the early 1970s and at discos in the late 1970s. (One slang term for Quaalude was disco biscuits.) In the mid-1970s there were bars in Manhattan called juice bars that only served non-alcoholic drinks that catered to people who liked to dance on methaqualone. Smoking methaqualone, either by itself or as an adulterant added to various legal and illegal smoking mixtures, gained popularity in the US among a few during the mid-1970s. Because the various binders and inert ingredients that were contained in the pill form were toxic when smoked, this practice was roundly decried by the medical community as a serious health risk. Smoking methaqualone pills can lead to emphysema and other chronic lung disorders, most notably talcosis. The drug was more tightly regulated in Britain under the Misuse of Drugs Act 1971 and in the U.S. from 1973. It was withdrawn from many developed markets in the early 1980s. In the United States it was withdrawn in 1982 and made a Schedule I drug in 1984. Gene Haislip, the former head of the Chemical Control Division of the Drug Enforcement Agency (DEA), told the PBS documentary program Frontline: "We beat 'em." By working with governments and manufacturers around the world, the DEA was able to halt production and, Haislip says, "eliminated the problem". Methaqualone was manufactured in the United States under the name Quaalude by the pharmaceutical firms Rorer and "Lemmon" with the numbers 714 stamped on the tablet, so people often referred to Quaalude as 714s, "Lemmons", or "Lemmon 7s". Methaqualone was also manufactured in the USA under the trade names Sopor and Parest. After the legal manufacture of the drug ended in the United States in 1982, underground laboratories in Mexico continued illegal manufacture of methaqualone all through the 1980s, continuing the use of the "714" stamp, until their popularity waned in the early 1990s. Bristol Myers manufactured this drug until taken out of the market in 1982 as well.][ Methaqualone is one of the most commonly used drugs in South Africa. Commonly known as Mandrax, M-pills, buttons, or smarties, it is not taken orally but is crushed and mixed in a pipe with cannabis. The drug's price of ][ (about ) together with readily available cheap, low-grade marijuana, makes methaqualone one of the preferred hard drugs of the lower-income, mid and upper sections of South African society. Effects can include euphoria, drowsiness, reduced heart rate, reduced respiration, increased sexual arousal (aphrodisia), and paresthesias (numbness of the fingers and toes). Larger doses can bring about respiratory depression, slurred speech, headache, and photophobia (a symptom of excessive sensitivity to light). An overdose can cause delirium, convulsions, hypertonia, hyperreflexia, vomiting, renal failure, coma, and death through cardiac or respiratory arrest. It resembles barbiturate poisoning, but with increased motor difficulties and a lower incidence of cardiac or respiratory depression. Urine drug test of gas-liquid chromatography (GLC) confirmation up to 72 hours after the last intake is a practical way of detecting methaqualone use in individuals. To avoid a false positive Substance Abuse and Mental Health Services Administration (SAMHSA) determined the initial cut off level of 300 ng/ml for forensic and workplace drug testing of methaqualone. Only after the confirmatory test of 200 ng/ml will a person be considered positive and possibly face penalties or workplace disciplinary action. As reported by Quest Diagnostics in 2011, methaqualone had a 0% positive drug testing rate in the US, making it one of the least abused drugs in that year. Note: See the receptor PAMsAGABA navbox for a full list of GABAA positive allosteric modulators.

MDMA
InChI=1S/C11H15NO2/c1-8(12-2)5-9-3-4-10-11(6-9)14-7-13-10/h3-4,6,8,12H,5,7H2,1-2H3Yes 
Key:SHXWCVYOXRDMCX-UHFFFAOYSA-NYes  MDMA (3,4-methylenedioxy-N-methylamphetamine) is an empathogenic drug of the phenethylamine and amphetamine classes of drugs. MDMA has become widely known as "ecstasy" (shortened to "E", "X", or "XTC"), usually referring to its street pill form, although this term may also include the presence of possible adulterants. The term "mandy" or "molly" colloquially refers to MDMA in powder or crystalline form, usually implying a higher level of purity. MDMA can induce euphoria, a sense of intimacy with others, and diminished anxiety. Many studies, particularly in the fields of psychology and cognitive therapy, have suggested MDMA has therapeutic benefits and facilitates therapy sessions in certain individuals, a practice for which it had been formally used in the past. Clinical trials are now testing the therapeutic potential of MDMA for post-traumatic stress disorder, anxiety associated with terminal cancer and addiction. MDMA is criminalized in most countries (though some civil society initiatives—such as the Global Commission on Drug Policy—consider educating the public about the drug more important than curtailing supply) and its possession, manufacture, or sale may result in criminal prosecution. Some limited exceptions exist for scientific and medical research. For 2008, the UN estimated between 10 and 25 million people globally used MDMA at least once in the past year. This was broadly similar to the number of cocaine, amphetamine, and opioid users, but far fewer than the global number of cannabis users. It is taken in a variety of contexts far removed from its roots in psychotherapeutic settings, and is commonly associated with dance parties (or "raves") and electronic dance music. Regulatory authorities in several locations around the world have approved scientific studies administering MDMA to humans to examine its therapeutic potential and its effects. MDMA has long been suggested as possibly useful in psychotherapy, facilitating self-examination with reduced fear. Indeed, some therapists, including Leo Zeff, Claudio Naranjo, George Greer, Joseph Downing, and Philip Wolfson, used MDMA in their practices until it was made illegal. George Greer synthesized MDMA in the lab of Alexander Shulgin and administered it to about 80 of his clients over the course of the remaining years preceding MDMA's Schedule I placement in 1985. In a published summary of the effects, the authors reported patients felt improved in various mild psychiatric disorders and experienced other personal benefits, especially improved intimate communication with their significant others. In a subsequent publication on the treatment method, the authors reported one patient with severe pain from terminal cancer experienced lasting pain relief and improved quality of life. Recently, two randomized, controlled trials of MDMA-assisted psychotherapy for post-traumatic stress disorder were published. Although small, these trials are consistent with earlier results. The patients treated with two or three sessions of MDMA-psychotherapy showed greater improvement than the ones treated by placebo-psychotherapy or placebo-inactive dose of MDMA. This improvement was generally maintained on a follow-up several years later. Small doses of MDMA are used as an entheogen to enhance prayer or meditation by some religious practitioners. MDMA is often considered the drug of choice within the rave culture and is also used at clubs, festivals and parties. In the rave environment, the sensorial effects from the music and setup such as lasers are often highly synergistic with the drug. The psychedelic amphetamine quality of MDMA lends it to variable reasons as to why it appeals to users in the rave setting. Some find ego-melting mass communion while others use it as party fuel. MDMA is occasionally known for being taken in conjunction with psychedelic drugs, such as LSD or psilocybin mushrooms, or even common drugs such as cannabis. As this practice has become more prevalent, most of the more common combinations have been given nicknames, such as "candy flipping" for MDMA combined with LSD, "hippy flipping" for MDMA with psilocybin mushrooms, or "kitty flipping" for MDMA with ketamine. The term "flipping" may come from the subjective effects of using MDMA with a psychedelic in which the user may shift rapidly between a more lucid state and a more psychedelic state several times during the course of their experiences. Many users use mentholated products while taking MDMA for its cooling sensation while experiencing the drug's effects. Examples include menthol cigarettes, Vicks VapoRub, NyQuil, and lozenges. The primary effects attributable to MDMA consumption are predictable and fairly consistent among users. In general, users begin reporting subjective effects within 30–60 minutes of consumption, hitting a peak at about 75–120 minutes, reaching a plateau that lasts about 3.5 hours. This is followed by a comedown of a few hours. After the drug has run its course, many users report feeling fatigue. The following subjective effects of MDMA were statistically significant in a placebo-controlled trial, using Altered States of Consciousness rating scale: derealization, depersonalization, altered perception of space and time, positive basic mood, mania-like experience, anxious derealization, thought disorder, fears of loss of thought or body control, visual hallucinations or pseudo-hallucinations, synesthesia, changed meaning of percepts, facilitated recollection or imagination. On an Adjective Mood rating scale, the following measurements were significantly increased: self-confidence, heightened mood, apprehension-anxiety, thoughtfulness-contemplativeness, extroversion, dazed state, sensitivity and emotional excitation. In January 2001, an overview of the subjective side effects of MDMA based on clinical research conducted over several years involving 74 healthy volunteers. The researchers found a number of common side effects, and many of the effects seemed to occur in different amounts based on the sex of the user. The top side effects reported were difficulty concentrating, jaw clenching, grinding of the teeth during sleep, lack of appetite, and dry mouth/thirst (all occurring in more than 50% of the 74 volunteers). They also measured some of the test subjects for blood pressure, heart rate, and body temperature against a placebo control, but no statistically significant changes were seen. A 2008 study found a slight but significant correlation of cognitive deficiency in MDMA users, but admitted these data may be confounded by other illicit drug use. The significant finding of the article was the serotonergic neurotoxicity in stacked doses and a lasting decrease in serotonin reuptake (SERT) binding. In rats, high doses and in high temperatures, serotonergic neurotoxicity is limited and dopaminergic neurotoxicity occurs. However, rats may not be a generalizable model for human neurotoxicity studies. A 2010 study found changes in EEG measured brain activity believed to confirm neurotoxicity to serotonergic neurotransomission systems, and noted that the recorded brain activity data were "in line with the observation of attentional and memory impairments in Ecstasy users with moderate to high misuse". However, a 2011 study found no signs of cognitive impairment due to MDMA use, and it did not decrease mental ability. The report also raised concerns that previous methods used to conduct that research on the drug had been flawed, and the experiments overstated the cognitive differences between users and nonusers. Effects reported by some users once the acute effects of MDMA have worn off include: A slang term given to the depressive period following MDMA consumption is Tuesday Blues (or "Suicide Tuesday"), referring to the low mood that can be experienced midweek by depleted serotonin levels following MDMA use on the previous Friday or Saturday when raves or dance concerts were frequently scheduled. Some users reported consuming 5-HTP, L-tryptophan and vitamins the day after use can reduce the depressive effect by replenishing serotonin levels (magnesium supplements are also used prior to or during use, in an attempt to prevent jaw/muscle clenching). Upon overdose, the potentially serious serotonin syndrome, stimulant psychosis, and/or hypertensive crisis, among other dangerous adverse reactions, may come to prominence, the symptoms of which can include: Some studies indicate repeated recreational users of MDMA have increased rates of depression and anxiety, even after quitting the drug. Other meta analyses have reported possibility of impairment of executive functioning. Despite these findings, many factors, including total lifetime MDMA consumption, the duration of abstinence between uses, dosage, the environment of use, multiple drug use/abuse, quality of mental health, various lifestyle choices, and predispositions to develop clinical depression and other disorders, have made the results of many studies difficult to verify. A study that attempted to eliminate these confounding factors found few differences in the cognitive functioning of MDMA-using ravers versus non-MDMA-using ravers, "In a study designed to minimize limitations found in many prior investigations, we failed to demonstrate marked residual cognitive effects in ecstasy users. This finding contrasts with many previous findings-including our own-and emphasizes the need for continued caution in interpreting field studies of cognitive function in illicit ecstasy users." MDMA use has been occasionally associated with liver damage, excessive wear of teeth, and (very rarely) hallucinogen persisting perception disorder. Short-term physical health risks of MDMA consumption include hyperthermia, and hyponatremia. Continuous activity without sufficient rest or rehydration may cause body temperature to rise to dangerous levels, and loss of fluid via excessive perspiration puts the body at further risk as the stimulatory and euphoric qualities of the drug may render the user oblivious to their energy expenditure for quite some time. Diuretics such as alcohol may exacerbate these risks further.][ MDMA causes a reduction in the concentration of serotonin transporters in the brain. The rate at which the brain recovers from serotonergic changes is unclear. One study demonstrated lasting serotonergic changes in some animals exposed to MDMA. Other studies have suggested that the brain may recover from serotonergic damage. Some studies show MDMA may be neurotoxic in humans. Other studies, however, suggest that any potential brain damage may be at least partially reversible following prolonged abstinence from MDMA. Depression and deficits in memory have been shown to occur more frequently in long-term MDMA users. However, some recent studies have suggested MDMA use may not be associated with chronic depression. One study on MDMA toxicity, by George A. Ricaurte of Johns Hopkins School of Medicine, which claimed a single recreational dose of MDMA could cause Parkinson's disease in later life due to severe dopaminergic stress, was actually retracted by Ricaurte himself after he discovered his lab had administered not MDMA but methamphetamine, which is known to cause dopaminergic changes similar to the serotonergic changes caused by MDMA. Ricaurte blamed this mistake on a labeling error by the chemical supply company that sold the material to his lab, but the supply company responded there was no evidence of a labeling error on their end. Most studies have found the levels of the dopamine transporter (or other markers of dopamine function) in MDMA users deserve further study or are normal. Several studies have indicated a possible mechanism for neurotoxicity of a metabolite of MDMA, through the reaction of alpha-methyldopamine, a principal metabolite, and glutathione, the major antioxidant in the human body. One possible product of this reaction, 2,5-bis-(glutathion-S-yl)-alpha-methyldopamine, has been demonstrated to produce the same toxic effects observed in MDMA, while MDMA, and alpha-methyldopamine themselves have been shown to be non-neurotoxic. It is, however, impossible to avoid the metabolism of MDMA in the body, and the production of this toxic metabolite. Some studies have demonstrated possible ways to minimize the production of this particular metabolite, though evidence at this point is sparse at best. Another concern associated with MDMA use is toxicity from chemicals other than MDMA in ecstasy tablets. Due to its near-universal illegality, the purity of a substance sold as ecstasy is unknown to the typical user. The MDMA content of tablets varies widely between regions and different brands of pills and fluctuates somewhat each year. Pills may contain other active substances meant to stimulate in a way similar to MDMA, such as amphetamine, mephedrone, methamphetamine, ephedrine, caffeine, all of which may be comparatively cheap to produce and can help to boost overall profits. In some cases, tablets sold as ecstasy do not even contain any MDMA. Instead they may contain an assortment of undesirable drugs and substances, such as paracetamol, ibuprofen, talcum powder, etc. A number of deaths have been attributed to -methoxyamphetamine (PMA)para, a hallucinogenic amphetamine, being sold as ecstasy. PMA is unique in its ability to quickly elevate body temperature and heart rate at relatively low doses, especially in comparison to MDMA. Hence, users believing they are consuming two 120-mg pills of MDMA could actually be consuming a dose of PMA that is potentially lethal, depending on the purity of the pill. Not only does PMA cause the release of serotonin, but it also acts as a monoamine oxidase inhibitor. When combined with an MDMA or an MDMA-like substance, serotonin syndrome can result. Combining MAO inhibitors with certain legal prescription and over-the-counter medications can also lead to (potentially fatal) serotonin syndrome. The UK study placed great weight on the risk for acute physical harm, the propensity for physical and psychological dependency on the drug, and the negative familial and societal impacts of the drug. They did not evaluate or rate the negative impact of 'ecstasy' on the cognitive health of ecstasy users, e.g., impaired memory and concentration. Based on these factors, the study placed MDMA at number 18 in the list of 20 harmful drugs. David Nutt, a former chairman of the UK Advisory Council on the Misuse of Drugs, stated in the Journal of Psychopharmacology in January 2009, that 'ecstasy' use compared favorably with horse riding in terms of risk, with the drug leading to around 30 deaths a year in the UK compared to about 10 from horse riding, and "acute harm to person" occurring in about one in 10,000 episodes of 'ecstasy' use compared to about one in 350 episodes of horse riding. Dr. Nutt noted the lack of a balanced risk assessment in public discussions of MDMA: The general public, especially the younger generation, are disillusioned with the lack of balanced political debate about drugs. This lack of rational debate can undermine the trust in government in relation to drug misuse and thereby undermining the government's message in public information campaigns. The media in general seem to have an interest in scare stories about illicit drugs, though there are some exceptions (Horizon, 2008). A telling review of 10-year media reporting of drug deaths in Scotland illustrates the distorted media perspective very well (Forsyth, 2001). During this decade, the likelihood of a newspaper reporting a death from paracetamol was in [sic] per 250 deaths, for diazepam it was 1 in 50, whereas for amphetamine it was 1 in 3 and for ecstasy every associated death was reported. A spokesperson for the ACMD said, "The recent article by Professor David Nutt published in the Journal of Psychopharmacology was done in respect of his academic work and not as chair of the ACMD." The most carefully designed study so far, compared the effect on cognitive skills in 52 'ecstasy' users against 59 very closely matched nonusers. The study eliminated potential confounding factors such as the use of other drugs and history of drug use. The study found no short- or long-term differences in cognitive skills in the test group (users) versus the control group (nonusers). A number of reported potentially dangerous possible interactions occur between MDMA and other drugs, including serotonergic drugs. Several cases have been reported of death in individuals who ingested MDMA while taking ritonavir (Norvir), which inhibits multiple CYP450 enzymes. Toxicity or death has also been reported in people who took MDMA in combination with certain monoamine oxidase inhibitors, such as phenelzine (Nardil), tranylcypromine (Parnate), or moclobemide (Aurorix, Manerix). Conversely, BMAO inhibitors such as selegiline (Deprenyl; Eldepryl, Zelapar, Emsam) do not seem to carry these risks when taken at selective doses, and have been used to completely block neurotoxicity in rats. Commercial sassafras oil generally is a byproduct of camphor production in Asia or comes from related trees in Brazil. Safrole is a precursor for the clandestine manufacture of MDMA, and as such, its transport is monitored internationally. Roots of Sassafras can also be steeped to make tea and were used in the flavoring of traditional root beer until being banned for mass production by the FDA. Laboratory animals that were given oral doses of sassafras tea or sassafras oil that contained large doses of safrole developed permanent liver damage or various types of cancer. In humans, liver damage can take years to develop, and it may not have obvious signs.][ While sassafras oil is an important ingredient in clandestine manufacture of MDMA, MDMA itself does not contain any sassafras oil. Safrole, a colorless or slightly yellow oily liquid, extracted from the root-bark or the fruit of the sassafras tree is the primary precursor for all manufacture of MDMA. There are numerous synthetic methods available in the literature to convert safrole into MDMA via different intermediates. One common route is via the MDP2P (3,4-methylenedioxyphenyl-2-propanone, also known as piperonyl acetone) intermediate, which can be produced in at least two different ways. One method is to isomerize safrole to isosafrole in the presence of a strong base, and then oxidize isosafrole to MDP2P. Another, reportedly better,][ method is to make use of the Wacker process to oxidize safrole directly to the MDP2P (3,4-methylenedioxy phenyl-2-propanone) intermediate. This can be done with a palladium catalyst. Once the MDP2P intermediate has been prepared, a reductive amination leads to MDMA, a racemate {1:1 mixture of (R)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine and (S)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine}. Another method for the synthesis of racemic MDMA is addition of hydrogen bromide to safrole and reaction of the adduct with methylamine. Safrole is not required for MDMA production, and other precursor chemicals are often used instead, for example piperonal. Relatively small quantities of essential oil are required to make large amounts of MDMA. The essential oil of Ocotea cymbarum typically contains between 80 and 94% safrole. This would allow 500 ml of the oil, which retails at between $20 and $100, to be used to produce between 150 and 340 grams of MDMA. MDMA acts as a releasing agent of serotonin, norepinephrine, and dopamine. It enters neurons via carriage by the monoamine transporters. Once inside, MDMA inhibits the vesicular monoamine transporter, which results in increased concentrations of serotonin, norepinephrine, and dopamine in the cytoplasm, and induces their release by reversing their respective transporters through a process known as phosphorylation. MDMA has been identified as a potent agonist of TAAR1, a newly discovered GPCR important for regulation of monoaminergic systems in the brain. Activation of TAAR1 increases cAMP production via adenylyl cyclase activation and inhibits transporter function. These effects increase monoamine efflux and prolong the amount of time monoamines remain in the synapse. It also acts as a weak 15-HT and receptor25-HT agonist, and its more efficacious metabolite MDA likely augments this action. MDMA's unusual entactogenic effects have been hypothesized to be, at least partly, the result of indirect oxytocin secretion via activation of the serotonin system. Oxytocin is a hormone released following events such as hugging, orgasm, and childbirth, and is thought to facilitate bonding and the establishment of trust. Based on studies in rats, MDMA is believed to cause the release of oxytocin, at least in part, by both directly and indirectly agonizing the serotonin receptor1A5-HT. A placebo-controlled study in 15 human volunteers found 100 mg MDMA increased blood levels of oxytocin, and the amount of oxytocin increase was correlated with the subjective prosocial effects of MDMA. Three neurobiological mechanisms for the therapeutic effects of MDMA have been suggested: "1) MDMA increases oxytocin levels, which may strengthen the therapeutic alliance; 2) MDMA increases ventromedial prefrontal activity and decreases amygdala activity, which may improve emotional regulation and decrease avoidance, and 3) MDMA increases norepinephrine (NE) release and circulating cortisol levels, which may facilitate emotional engagement and enhance extinction of learned fear associations." MDMA reaches maximal concentrations in the blood stream between 1.5 and 3 hr after ingestion. It is then slowly metabolized and excreted, with levels of MDMA and its metabolites decreasing to half their peak concentration over approximately 8 hours. Thus, there are still high MDMA levels in the body when the experiential effects have mostly ended, indicating acute tolerance has developed to the actions of MDMA. Taking additional supplements of MDMA at this point, therefore, produces higher concentrations of MDMA in the blood and brain than might be expected based on the perceived effects. Metabolites of MDMA that have been identified in humans include 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxy-methamphetamine (HMMA), 4-hydroxy-3-methoxyamphetamine (HMA), 3,4-dihydroxyamphetamine (DHA) (also called alpha-methyldopamine (α-Me-DA)), 3,4-methylenedioxyphenylacetone (MDP2P), and 3,4-Methylenedioxy-N-hydroxyamphetamine (MDOH). The contributions of these metabolites to the psychoactive and toxic effects of MDMA are an area of active research. Sixty-five percent of MDMA is excreted unchanged in the urine (in addition, 7% is metabolized into MDA) during the 24 hours after ingestion. MDMA is known to be metabolized by two main metabolic pathways: (1) O-demethylenation followed by -methyltransferaseOcatechol- (COMT)-catalyzed methylation and/or glucuronide/sulfate conjugation; and (2) N-dealkylation, deamination, and oxidation to the corresponding benzoic acid derivatives conjugated with glycine. The metabolism may be primarily by cytochrome P450 (CYP450) enzymes (CYP2D6 (in humans, but CYP2D1 in mice), and CYP3A4) and COMT. Complex, nonlinear pharmacokinetics arise via autoinhibition of CYP2D6 and CYP2D8, resulting in zeroth order kinetics at higher doses. It is thought that this can result in sustained and higher concentrations of MDMA if the user takes consecutive doses of the drug. Because the enzyme CYP2D6 is deficient or totally absent in some people, it was once hypothesized that these people might have elevated risk when taking MDMA. However, there is still no evidence for this theory and available evidence argues against it. It is now thought that the contribution of CYP2D6 to MDMA metabolism in humans is less than 30% of the metabolism. Indeed, an individual lacking CYP2D6 was given MDMA in a controlled clinical setting and a larger study gave MDMA to healthy volunteers after inhibiting CYP2D6 with paroxetine. Lack of the enzyme caused a modest increase in drug exposure and decreases in some metabolites, but physical effects did not appear appreciably elevated. While there is little or no evidence that low CYP2D6 activity increases risks from MDMA, it is likely that MDMA-induced CYP2D inhibition will increase risk of those prescription drugs that are metabolized by this enzyme. MDMA-induced CYP2D inhibition appears to last for up to a week after MDMA exposure. MDMA and metabolites are primarily excreted as conjugates, such as sulfates and glucuronides. MDMA is a chiral compound and has been almost exclusively administered as a racemate. However, the two enantiomers have been shown to exhibit different kinetics. (S)-MDMA is more effective in eliciting 5-HT, NE, and DA release, while (D)-MDMA is overall less effective, and more selective for 5-HT and NE release (having only a very faint efficacy on DA release). The disposition of MDMA may also be stereoselective, with the S-enantiomer having a shorter elimination half-life and greater excretion than the R-enantiomer. Evidence suggests that the area under the blood plasma concentration versus time curve (AUC) was two to four times higher for the (R)-enantiomer than the (S)-enantiomer after a 40 mg oral dose in human volunteers. Likewise, the plasma half-life of (R)-MDMA was significantly longer than that of the (S)-enantiomer (5.8 ± 2.2 hours vs 3.6 ± 0.9 hours). However, because MDMA excretion and metabolism have nonlinear kinetics, the half-lives would be higher at more typical doses (100 mg is sometimes considered a typical dose). Given as the racemate MDMA has a half-life of around 8 hours. MDMA and MDA may be quantitated in blood, plasma or urine to monitor for use, confirm a diagnosis of poisoning or assist in the forensic investigation of a traffic or other criminal violation or a sudden death. Some drug abuse screening programs rely on hair, saliva, or sweat as specimens. Most commercial amphetamine immunoassay screening tests cross-react significantly with MDMA or its major metabolites, but chromatographic techniques can easily distinguish and separately measure each of these substances. The concentrations of MDA in the blood or urine of a person who has taken only MDMA are, in general, less than 10% those of the parent drug. MDMA was first synthesized in 1912 by Merck chemist Anton Köllisch. At the time, Merck was interested in developing substances that stopped abnormal bleeding. Merck wanted to evade an existing patent, held by Bayer, for one such compound: hydrastinine. At the behest of his superiors Walther Beckh and Otto Wolfes, Köllisch developed a preparation of a hydrastinine analogue, methylhydrastinine. MDMA was an intermediate compound in the synthesis of methylhydrastinine, and Merck was not interested in its properties at the time. On 24 December 1912, Merck filed two patent applications that described the synthesis of MDMA and its subsequent conversion to methylhydrastinine. Merck records indicate that its researchers returned to the compound sporadically. In 1927, Max Oberlin studied the pharmacology of MDMA and observed that its effects on blood sugar and smooth muscles were similar to ephedrine's. Researchers at Merck conducted experiments with MDMA in 1952 and 1959. In 1953 and 1954, the United States Army commissioned a study of toxicity and behavioral effects in animals of injected mescaline and several analogues, including MDMA. The Army experimented with MDMA as an interrogation tool in Project MKUltra. These originally classified investigations were declassified and published in 1973. The first scientific paper on MDMA appeared in 1958 in Yakugaku Zasshi, the Journal of the Pharmaceutical Society of Japan. In this paper, Yutaka Kasuya described the synthesis of MDMA, a part of his research on antispasmodics. MDMA was being used recreationally in the United States by 1970. In the mid-1970s, Alexander Shulgin, then at University of California, Berkeley, heard from his students about unusual effects of MDMA; among others, the drug had helped one of them to overcome his stutter. Intrigued, Shulgin synthesized MDMA and tried it himself in 1976. Two years later, he and David E. Nichols published the first report on the drug's psychotropic effect in humans. They described "altered state of consciousness with emotional and sensual overtones" that can be compared "to marijuana, and to psilocybin devoid of the hallucinatory component". Shulgin took to occasionally using MDMA for relaxation, referring to it as "my low-calorie martini", and giving the drug to his friends, researchers, and other people whom he thought could benefit from it. One such person was psychotherapist Leo Zeff, who had been known to use psychedelics in his practice. Zeff was so impressed with the effects of MDMA that he came out of his semi-retirement to proselytize for it. Over the following years, Zeff traveled around the U.S. and occasionally to Europe, training other psychotherapists in the use of MDMA. Among underground psychotherapists, MDMA developed a reputation for enhancing communication during clinical sessions, reducing patients' psychological defenses, and increasing capacity for therapeutic introspection. In the early 1980s in the U.S., MDMA rose to prominence as "Adam" in trendy nightclubs and gay dance clubs in the Dallas area. From there, use spread to raves in major cities around the country,][ and then to mainstream society. The drug was first proposed for scheduling by the Drug Enforcement Administration (DEA) in July 1984 and was classified as a Schedule I controlled substance in the U.S. on 31 May 1985. In the late 1980s MDMA, known by that time as "ecstasy", began to be widely used in the UK and other parts of Europe, becoming an integral element of rave culture and other psychedelic-influenced music scenes. Spreading along with rave culture, illicit MDMA use became increasingly widespread among young adults in universities and later in high schools. MDMA became one of the four most widely used illicit drugs in the U.S., along with cocaine, heroin, and cannabis. According to some estimates as of 2004, only marijuana attracts more first time users in the U.S. After MDMA was criminalized, most medical use stopped, although some therapists continued to prescribe the drug illegally. Later Charles Grob initiated an ascending-dose safety study in healthy volunteers. Subsequent legally approved MDMA studies in humans have taken place in the U.S. in Detroit (Wayne State University), Chicago (University of Chicago), San Francisco (UCSF and California Pacific Medical Center), Baltimore (NIDA–NIH Intramural Program), and South Carolina, as well as in Switzerland (University Hospital of Psychiatry, Zürich), the Netherlands (Maastricht University), and Spain (Universitat Autònoma de Barcelona). In 2010, the BBC reported that use of MDMA had decreased in the UK in previous years. This is thought to be due to increased seizures and decreased production of the precursor chemicals used to manufacture MDMA. Unwitting substitution with other drugs, such as mephedrone and methamphetamine, as well as legal alternatives to MDMA, such as BZP, MDPV, and methylone, are also thought to have contributed to its decrease in popularity. MDMA is legally controlled in most of the world under the UN Convention on Psychotropic Substances and other international agreements, although exceptions exist for research and limited medical use. In general, the unlicensed use, sale or manufacture of MDMA are all criminal offenses. MDMA was made illegal in 1977 by a modification order to the existing Misuse of Drugs Act 1971. Although MDMA was not named explicitly in this legislation, the order extended the definition of Class A drugs to include various ring-substituted phenethylamines, thereby making it illegal to sell, buy, or possess the drug without a licence. Penalties include a maximum of seven years and/or unlimited fine for possession; life and/or unlimited fine for production or trafficking. See list of drugs illegal in the UK for more information. In February 2009 an official independent scientific advisory board to the UK government recommended that MDMA be re-classified to Class B, but this recommendation was immediately rejected by the government. This 2009 report on MDMA stated: In 2000, the UK Police Foundation issued the Runciman Report, which reviewed the medical and social harms of MDMA and recommended: "Ecstasy and related compounds should be transferred from Class A to Class B." In 2002, the Home Affairs Committee of the UK House of Commons, issued a report, The Government's Drugs Policy: Is it working?, which also recommended that MDMA should be reclassified to a Class B drug. The UK government rejected both recommendations, saying that re-classification of MDMA would not be considered without a recommendation from the Advisory Council on the Misuse of Drugs, the official UK scientific advisory board on drug abuse issues. In February 2009, the UK Advisory Council on the Misuse of Drugs issued A review of MDMA ('ecstasy'), its harms and classification under the Misuse of Drugs Act 1971, which recommended that MDMA be re-classified in the UK from a class A drug to a class B drug. From the Discussion section of the ACMD report on MDMA: Physical harms: (10.2) Use of MDMA is undoubtedly harmful. High doses may lead to death: by direct toxicity, in situations of hyperthermia/dehydration, excessive water intake, or for other reasons. However, fatalities are relatively low given its widespread use, and are substantially lower than those due to some other Class A drugs, particularly heroin and cocaine. Although it is no substitute for abstinence, the risks can be minimised by following advice such as drinking appropriate amounts of water (see Annex E). (10.3) Some people experience acute medical consequences as a result of MDMA use, which can lead to hospital admission, sometimes with the requirement for intensive care. MDMA poisonings are not currently increasing in number and are less frequent than episodes due to cocaine. (10.4) MDMA appears not to have a high propensity for dependence or withdrawal reactions, although a number of users seek help through treatment services. (10.5) MDMA appears to have little acute or enduring effect on the mental health of the average user, and, unlike amphetamines and cocaine, it is seldom implicated in significant episodes of paranoia. (10.6) There is at the present time little evidence of longer-term harms to the brain in terms of either its structure or its function. However, there is evidence for some small decline in a variety of domains, including verbal memory, even at low cumulative dose. The magnitude of such deficits appears to be small and their clinical relevance is unclear. The evidence shows that MDMA has been misused in the UK for 20 years, but it should be noted that long-term effects of use cannot be ruled out. (10.7) Overall, the ACMD judges that the physical harms of MDMA more closely equate with those of amphetamine than of heroin or cocaine. Societal harms: (10.8) MDMA use seems to have few societal effects in terms of intoxication-related harms or social disorder. However, the ACMD notes the very small proportion of cases where ‘ecstasy’ use has been implicated in sexual assault. (10.9) Disinhibition and impulsive, violent or risky behaviours are not commonly seen under the influence of MDMA, unlike with cocaine, amphetamines, heroin and alcohol. (10.10) The major issue for law enforcement is ‘ecstasy's’ position, alongside other Class A drugs, as a commodity favoured by organised criminal groups. It is therefore generally associated with a range of secondary harms connected with the trafficking of illegal drugs. The UK Home Office rejected the recommendation of its independent scientific advisory board to downgrade MDMA to Class B, "saying it is not prepared to send a message to young people that it takes ecstasy less seriously". The government's veto was criticized in scientific publications. Colin Blakemore, Professor of Neuroscience, Oxford, stated in the British Medical Journal, "The government's decisions compromise its commitment to evidence based policy". Also in response, an editorial in the New Scientist noted "A much larger percentage of people suffer a fatal acute reaction to peanuts than to MDMA.... Sadly, perspective is something that is generally lacking in the long and tortuous debate over illegal drugs." In the U.S., MDMA was legal and unregulated until 31 May 1985, at which time it was emergency scheduled to DEA Schedule I, for drugs deemed to have no medical uses and a high potential for abuse. During DEA hearings to schedule MDMA, most experts recommended DEA Schedule III prescription status for the drug, due to beneficial usage of MDMA in psychotherapy. The Administrative Law Judge (ALJ) overseeing the hearings, Francis Young, also recommended that MDMA be placed in Schedule III. The DEA however classified MDMA as Schedule I. However, in Grinspoon v. Drug Enforcement Administration, 828 F.2d 881 (1st Cir. 1987), the First Circuit Court of Appeals remanded the scheduling determination for reconsideration by the DEA. MDMA was temporarily removed from Schedule I. Ultimately, in 1988, the DEA re-evaluated its position on remand and subsequently placed MDMA into Schedule I of the Controlled Substances Act. In 2001, responding to a mandate from the U.S. Congress, the U.S. Sentencing Commission, resulted in an increase in the penalties for MDMA by nearly 3,000%. The increase in penalties was opposed by the Federation of American Scientists. The increase makes 1 gram of MDMA (four pills at 250 mg per pill's total weight regardless of purity, standard for Federal charges) equivalent to 1 gram of heroin (approximately fifty doses) or 2.2 pounds (1.00 kg) of cannabis for sentencing purposes at the federal level. See also the RAVE Act of 2003. In a 2011 federal court hearing the American Civil Liberties Union successfully argued that the sentencing guideline for MDMA/ecstasy is based on outdated science, leading to excessive prison sentences. The Expert Committee on the List (Expertcommissie Lijstensystematiek Opiumwet) of the Netherlands issued a report in June 2011 which discussed the evidence for harm and the legal status of MDMA. From the English-language summary: As regards MDMA, better known as XTC, the committee concludes that investigations show that damage to the health of the individual in the long term is less serious than was initially assumed. But the extent of the illegal production and involvement of organised crime leads to damage to society, including damage to the image of the Netherlands abroad. This argues in favour of maintaining MDMA on List I. The Committee noted that research had found the health risks of MDMA were less serious than previously assumed (citing the 2009 UK ACMD report), and so they considered moving MDMA out of the Dutch List I ('hard drugs') to List II ('soft drugs' such as cannabis), but this was not acceptable because the criminal black market would continue to produce all the MDMA. Note, the Committee did not discuss permitting legally regulated production of MDMA for non-medical use because this is not allowed under the UN 1971 Convention on Psychotropic Substances (See Drug decriminalization vs. legalization). Listed as a Schedule 1 as it is an analogue of amphetamine. The CDSA was updated as a result of the Safe Streets Act changing amphetamines from Schedule 3 to Schedule 1. In 1985 the World Health Organization's Expert Committee on Drug Dependence recommended that MDMA be placed in Schedule I of the 1971 Convention on Psychotropic Substances, despite noting: The decision to recommend scheduling of MDMA was not unanimous: The 1971 Convention has a provision in Article 7(a) that allows use of Schedule I drugs for "scientific and very limited medical purposes." The committee's report stated: Demand for safrole, a substance used in the manufacture of MDMA, is causing rapid and illicit harvesting of the Cinnamomum parthenoxylon tree in Southeast Asia, in particular the Cardamom Mountains in Cambodia. Demand for safrole, mostly for industrial use but also for MDMA production, depletes around 500,000 trees per year in China, Brazil, Cambodia, Vietnam, and Laos.][ In 2008 alone, Australian and Cambodian authorities blocked and destroyed the export of 33 tons of safrole, capable of producing 245 million ecstasy tablets with a street value of 7.6 billion dollars. Only a small proportion of illicitly harvested safrole is going toward MDMA production, as over 90% of the global safrole supply (approx 2000 metric tons per year) is used to manufacture pesticides, fragrances, and other chemicals. Sustainable harvesting of safrole is possible from leaves and sticks of certain plants. Safrole is not required for MDMA production, and other precursor chemicals are often used instead. The European Monitoring Centre for Drugs and Drug Addiction notes that, although there are some reports of tablets being sold for as little as €1, most countries in Europe now report typical retail prices in the range of €3 to €9 per tablet. The United Nations Office on Drugs and Crime claimed in its 2008 World Drug Report that typical U.S. retail prices are US$20 to $25 per tablet, or from $3 to $10 per tablet if bought in batches. MDMA is expensive in Australia, costing A$20–A$30 per tablet. In terms of purity data for Australian MDMA, the average is around 34%, ranging from less than 1% to about 85%. The majority of tablets contain 70–85 mg of MDMA. Most MDMA enters Australia from the Netherlands, the UK, Asia, and the U.S. Notes

Methylenedioxyethylamphetamine
MDEA (3,4-methylenedioxy-N-ethylamphetamine; MDE, "Eve") is a psychedelic and entactogenic drug of the phenethylamine and amphetamine chemical classes. Like MDA, MDEA acts as a serotonin, norepinephrine, and dopamine releasing agent. The subjective effects of MDEA are very similar to those of MDMA. However, the euphoric and "loved up" feelings associated with MDMA are not as pronounced in comparison. The effects of MDEA are also not as stimulating as MDMA, as it is said to be somewhat stoning in high doses and may be responsible for rumors of heroin-laced "ecstasy" tablets.

2C-B
2-(4-bromo-2,5-dimethoxyphenyl)ethanamine COC1=C(Br)C=C(OC)C(CCN)=C1 InChI=1S/C10H14BrNO2/c1-13-9-6-8(11)10(14-2)5-7(9)3-4-12/h5-6H,3-4,12H2,1-2H3Yes 
Key: YMHOBZXQZVXHBM-UHFFFAOYSA-NYes  InChI=1/C10H14BrNO2/c1-13-9-6-8(11)10(14-2)5-7(9)3-4-12/h5-6H,3-4,12H2,1-2H3
Key: YMHOBZXQZVXHBM-UHFFFAOYAK 4-bromo-2,5-dimethoxyphenethylamine (2C-B) is a psychedelic drug of the 2C family. It was first synthesized by Alexander Shulgin in 1974. In Shulgin's book PiHKAL, the dosage range is listed as 16–24 mg. 2C-B is sold as a white powder sometimes pressed in tablets or gel caps and is referred to on the street as 'Rusko', 'Spectrum', 'Venus', 'B's', 'CB's', or 'Nexus'. The drug is usually taken orally, but can also be insufflated or vaporized. 2C-B was synthesized from 2,5-dimethoxybenzaldehyde by Alexander Shulgin in 1974. It first saw use among the psychiatric community as an aid during therapy. It was considered one of the best drugs for this purpose because of its short duration, relative absence of side effects, and comparably mild nature. Shortly after becoming popular in the medical community, it became popular recreationally. 2C-B was first sold commercially as an aphrodisiac under the trade name "Eros", which was manufactured by the German pharmaceutical company Drittewelle. For several years, it was available in Dutch smart shops under the name "Nexus" as predosed tablets. However, it was later placed on List I of the Opium Law after being sold without any incidents occurring. 2C-B was subsequently replaced by other phenethylamine psychedelics, such as 2C-I, 2C-T-2 and 2C-T-7, which were not controlled substances in the Netherlands at the time. Those compounds were banned later by the Dutch government, after being sold in smartshops for short periods. Internationally, 2C-B is a Schedule II drug under the Convention on Psychotropic Substances. In the Netherlands, 2C-B became a list I substance of the Opium Law, after being legally sold in smartshops, and which led to the follow-up by other, at that time, legal phenethylamines. The Netherlands was the first country in the world to subsequently ban 2C-B (as well as 2C-I, 2C-T-2 and 2C-T-7). In the United States, a notice of proposed rulemaking published on December 20, 1994 in the Federal Register (59 FR 65521) and after a review of relevant data, the Deputy Administrator of the Drug Enforcement Administration (DEA) proposed to place 4-bromo-2,5-DMPEA into Schedule I, making 2C-B illegal in the United States. This became permanent law on July 2, 1995. 2C-B first became popularized in the United States as a short-lived legal substitute for the street drug Ecstasy when MDMA became illegal in 1985. Many 2C-B users are young adults who attend raves. Though 2C-B is still used in the rave subculture, commonly mistaken for and/or sold as Ecstasy, its intentional use has become more common. Intentional consumption of 2C-B is concentrated among a relatively small and knowledgeable group of users. In recent years, 2C-B has emerged as the drug of choice for club drug users in Colombia. Street prices range between $10–30 per tablet in the United States when bought in small quantities. Larger retail purchases cost between $200 and $500 per gram. Wholesale purchases of 2C-B can lower the price to a range of $100 to $300 per gram. The September 1998 Journal of Analytical Toxicology reported that very little data exists about the pharmacological properties, metabolism, and toxicity of 2C-B. The relationship between its use and death are unknown. The common oral recreational dose is around 15–25 mg, at which visual and auditory effects are experienced. Severe adverse reactions are extremely rare, but use of 2C-B has been linked to significant injury in one case where the dosage is unknown, and the purity/identity of the chemical was not verified. When sold as "Ecstasy", tablets containing 2C-B often contain about 5 mg of the drug, an amount which produces stimulatory effects that mimick the effects of MDMA; in contrast, tablets marketed as 2C-B have larger quantities of the drug (10–20 mg) which cause hallucinogenic effects. Street purity of 2C-B, when tested, has been found to be relatively high. Researchers in Spain found that 2C-B samples in the country doubled between 2006 and 2009, switched from primarily powder form to tablets, and exhibited "low falsification rates". An analysis of street samples in the Netherlands found impurities "in small percentages"; only one of the impurities, the N-acetyl derivative of 2C-B, could be identified and comprised 1.3% of the sample. The authors suggested that this compound was a by-product of 2C-B synthesis. Little or no academic research has been conducted on the effects of 2C-B in humans. The information available is largely anecdotal and limited. The effects of 2C-B include: The visuals ‘waver’ or come and go in a carousel-like pattern meaning that when the effect is strong then dies down, users may feel that the trip is over, only for it to come back stronger. The duration as a whole, though is only about 2–5 hours depending on dosage. The following effects are highly dose-dependent. 15–20 mg 21–35 mg >35 mg Unknown 2-7 Hours 13–19 mg 20–30 mg >31 mg 2-5 Hours The lethal dosage is unknown. Alexander Shulgin reported a 100 mg oral dose taken without apparent harm. Unlike most hallucinogens, 2C-B has been shown to be a low efficacy serotonin receptor2A5-HT partial agonist or even full antagonist. This suggests that the receptor2C5-HT is primarily responsible for mediating the effects experienced by users of 2C-B, although functional antagonism of 5-HT2A or activation of the 5-HT2A-coupled phospholipase D pathway may also play a role. The rank order of receptor antagonist potency for this family of drugs is 2C-I > 2C-B > 2C-D > 2C-H.][][ Research suggests that 2C-B increases dopamine levels in the brains of rats, which may contribute to its psychoactivity. 2C-B has been shown to be metabolized by liver hepatocytes resulting in deamination and demethylation that produces several products. Oxidative deamination results in the 2-(4-bromo-2,5-dimethoxyphenyl)-ethanol (BDMPE) and 4-bromo-2,5-dimethoxyphenylacetic acid (BDMPAA) metabolites. Additionally, 4-bromo-2,5-dimethoxybenzoic acid (BDMBA) can be produced also by oxidative deamination. Further metabolism of BDMPE and BDMPAA may occur by demethylation. Alternatively, the later metabolites can be generated by demethylation of 2C-B followed by oxidative deamination.][ There is species differentiation in the metabolism of 2C-B. Mice hepatocytes produce 4-bromo-2,5-dimethoxy-phenol (BDMP) a previously unknown metabolite. 2-(4-bromo-2-hydroxy-5-methoxyphenyl)-ethanol (B-2-HMPE) was produced by hepatocytes from human, monkey and rabbit but not by dog, rat and mouse. 2C-B also reduces aggressor responses in drugged rats. A variety of N-substituted derivatives of 2CB have been tested, including N-methyl-2CB, N,N-dimethyl-2CB, N-ethyl-2CB and N-benzyl-2CB. Most simple alkyl derivatives were considerably less potent than 2CB, with N-ethyl-2CB for instance having around 40x lower affinity at the 5-HT2A receptor. The N-benzyl derivative however was found to have higher binding affinity than 2CB itself, with N-(4-bromobenzyl)-2CB binding even more tightly again. This initial research did not include functional assays of activity, but later led to the development of potent substituted N-benzyl derivatives such as 25B-NBOMe. 2C-B is used as entheogen by the Sangoma, Nyanga, and Amagqirha people over their traditional plants, they refer to the chemical as Ubulawu Nomathotholo, which roughly translates to "Medicine of the Singing Ancestors". The UN Commission on Narcotic Drugs added 2C-B to Schedule II of the Convention on Psychotropic Substances in March 2001. LSD, psilocybin, and mescaline are in the more restrictive Schedule I. Although still available through online stores in some countries as a "research chemical" not for human consumption, 2C-B is scheduled as a drug in most jurisdictions. The following is a partial list of territories where the substance has been scheduled.

1,3-Benzodioxolyl-N-methylbutanamine
InChI=1S/C12H17NO2/c1-3-10(13-2)6-9-4-5-11-12(7-9)15-8-14-11/h4-5,7,10,13H,3,6,8H2,1-2H3
Key:USWVWJSAJAEEHQ-UHFFFAOYSA-N MBDB (N-methyl-1,3-benzodioxolylbutanamine), MDMB, 3,4-Methylenedioxy-N-methyl-butanphenamine is an entactogen of the phenethylamine chemical class. MBDB is a closely related chemical analogue of MDMA, with the only difference between the two molecules being an ethyl group instead of a methyl group attached to the alpha carbon. It has IC50 values of 5-HT 784 nM dopamine 7825 nM norepinephrine 1233 nM. MBDB was first synthesized by David E. Nichols][, a leading pharmacologist and medicinal chemist, and later tested by Alexander Shulgin and described in his book, PiHKAL: A Chemical Love Story. MBDB's dosage, according to PiHKAL, is 180–210 mg; the proper dosage relative to body mass seems unknown. Its duration is 4–6 hours, with noticeable after-effects lasting for 1–3 hours. MBDB was initially developed as a non-psychedelic entactogen. It has lower effects on the dopamine system in comparison to other entactogens such as MDMA. MBDB causes many mild, MDMA-like effects, such as lowering of social barriers and inhibitions, pronounced sense of empathy and compassion, mood lift, and mild euphoria are all present. MBDB tends to produce less euphoria, psychedelia, and stimulation in comparison. Many users declare that MBDB is a "watered-down" version of MDMA. Despite these features which make MBDB less desirable as a recreational drug, it has been suggested that the drug may have greater therapeutic potential than MDMA. Unlike MDMA, MBDB is not internationally scheduled under the United Nations Convention on Psychotropic Substances. The thirty-second meeting of the WHO Expert Committee on Drug Dependence (September 2000) evaluated MBDB and recommended against scheduling. From the WHO Expert Committee assessment of MBDB:

Empathogen-entactogen
The terms empathogen and entactogen are used to describe a class of psychoactive drugs that produce distinctive emotional and social effects similar to those of MDMA (ecstasy). Putative members of this class include 2C-B, 2C-I(at 2-14mg), MDMA, MDA, MDEA, MBDB and 6-APB among others. The chemical structure of many entactogens contains a substituted amphetamine core, and most belong to the phenethylamine class of psychoactive drugs, although several (AET and AMT) are tryptamines. When referring to MDMA and its counterparts, the term 'MDxx' is often used with the exception of MDPV. Entactogens are sometimes incorrectly referred to as major hallucinogens or stimulants, which is often thought to be incorrect although their effects are often somewhat similar.
The term "empathogen" was coined in 1983 by Ralph Metzner to denote chemical agents inducing feelings of empathy. "Entactogen" was coined by David E. Nichols as an alternative to "empathogen", attempting to avoid the potential for improper association of the latter with negative connotations related to the Greek root "pathos" (suffering); Nichols also thought the word was limiting, and did not cover other therapeutic uses for the drugs that go beyond instilling feelings of empathy. The word "entactogen" is derived from the roots "en" (Greek: ), "tactus" (Latin: ) and "gen" (Greek: produce) (Nichols 1986: 308). Neither term is dominant in usage, and, despite their difference in connotation, they are essentially interchangeable, as they refer to precisely the same chemicals. These drugs appear to produce a different spectrum of psychological effects from major stimulants such as methamphetamine and amphetamine or from major psychedelic drugs such as LSD or psilocybin. As implied by the category names, users of entactogens say the drugs often produce feelings of empathy, love, and emotional closeness to others. However, there have been only very preliminary comparisons of these different drugs in humans in properly-controlled laboratory studies. The chemicals below have a varying degree of entactogenic effects. Some of the chemicals have a minimal entactogenic effect while others may have a strong entactogenic effect. These substances possess other effects including serenic effects, stimulant effects, antidepressant effects, anxiolytic effects, and psychedelic effects. 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: PSO/PSI mepr dsrd (o, p, m, p, a, d, s), sysi/epon, spvo proc (eval/thrp), drug (N5A/5B/5C/6A/6B/6D)
Sedatives Entheogens MDMA Neuropsychology Chemistry
Gamma-Hydroxybutyric acid

InChI=1S/C4H8O3/c5-3-1-2-4(6)7/h5H,1-3H2,(H,6,7)YYes 
Key:SJZRECIVHVDYJC-UHFFFAOYSA-NYYes 

γ-Hydroxybutyric acid (GHB), also known as 4-hydroxybutanoic acid, is a naturally occurring substance found in the human central nervous system, as well as in wine, beef, small citrus fruits, and almost all animals in small amounts. It is also categorized as an illegal drug in many countries. It is currently regulated in Australia and New Zealand, Canada, most of Europe and in the US. GHB as the sodium salt, known as sodium oxybate (INN) or by the trade name Xyrem, is used to treat cataplexy and excessive daytime sleepiness in patients with narcolepsy.

The effects of MDMA (or ecstasy) on the human brain and body are complex. The biochemical effects induced include serotonin, dopamine, and norepinephrine release, and can act directly on a number of receptors, including α2-adrenergic (adrenaline) and 5-HT2A (serotonin) receptors. (DHEA), and the antidiuretic hormone vasopressin (which may be important in its occasional production of water intoxication or hyponatremia).

It is not understood how the chemical effects of MDMA induce its psychoactive effects. Most explanations focus on serotonin release. MDMA causes serotonin vesicles in the neurons to release quantities of serotonin into the synapses. Studies using pretreatment with an SSRI to block the ability of MDMA to release serotonin in volunteers suggest serotonin release is necessary for most psychoactive effects of MDMA in humans. Released serotonin stimulates several receptors that are believed to contribute to the experiential effects of MDMA. Laboratory rodent experiments have shown MDMA to activate oxytocin-containing neurons in the hypothalamus by stimulating 5-HT1A receptors. This appears to contribute to some of the social effects of MDMA: upon administering a drug that blocked brain receptors for oxytocin, the effects of the drug on social behavior were reduced. A second serotonin receptor, 5-HT2A receptors (which are important for the effects of hallucinogens), makes mild contributions to MDMA effects. When the receptor was blocked, volunteers given MDMA reported decreases in MDMA-induced perceptual changes, emotional excitation, and acute adverse responses. In contrast, blocking these 5-HT2A receptors had little effect on MDMA-induced positive mood, well-being, extroversion, and most short-term sequelae. One possible explanation for some of these 5-HTA-mediated effects is that 5-HT2A stimulation inhibits dopamine release.

Amphetamines Euphoriants Neurochemistry
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