3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy (tablet form), and molly (crystal form), is an empathogen–entactogenic drug with

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

and minor psychedelic properties. In studies, it has been used alongside

psychotherapy Psychotherapy (also psychological therapy, talk therapy, or talking therapy) is the use of Psychology, psychological methods, particularly when based on regular Conversation, personal interaction, to help a person change behavior, increase hap ...

in the treatment of

post-traumatic stress disorder Post-traumatic stress disorder (PTSD) is a mental disorder that develops from experiencing a Psychological trauma, traumatic event, such as sexual assault, domestic violence, child abuse, warfare and its associated traumas, natural disaster ...

(PTSD) and

social anxiety Social anxiety is the anxiety and fear specifically linked to being in social settings (i.e., interacting with others). Some categories of disorders associated with social anxiety include anxiety disorders, mood disorders, autism spectrum dis ...

autism spectrum disorder Autism, also known as autism spectrum disorder (ASD), is a neurodevelopmental disorder characterized by differences or difficulties in social communication and interaction, a preference for predictability and routine, sensory processing di ...

. The purported pharmacological effects that may be prosocial include altered sensations, increased energy, empathy, and pleasure. When taken by mouth, effects begin in 30 to 45 minutes and last three to six hours. MDMA was first synthesized in 1912 by Merck chemist Anton Köllisch. It was used to enhance psychotherapy beginning in the 1970s and became popular as a street drug in the 1980s. MDMA is commonly associated with dance parties,

rave A rave (from the verb: '' to rave'') is a dance party at a warehouse, club, or other public or private venue, typically featuring performances by DJs playing electronic dance music. The style is most associated with the early 1990s dance mus ...

s, and

electronic dance music Electronic dance music (EDM), also referred to as dance music or club music, is a broad range of percussive electronic music genres originally made for nightclubs, raves, and List of electronic dance music festivals, festivals. It is generally ...

. Tablets sold as ecstasy may be mixed with other substances such as

ephedrine Ephedrine is a central nervous system (CNS) stimulant and sympathomimetic agent that is often used to prevent hypotension, low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred ...

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

, and

methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...

. In 2016, about 21 million people between the ages of 15 and 64 used ecstasy (0.3% of the world population). This was broadly similar to the percentage of people who use

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

s, but lower than for

cannabis ''Cannabis'' () is a genus of flowering plants in the family Cannabaceae that is widely accepted as being indigenous to and originating from the continent of Asia. However, the number of species is disputed, with as many as three species be ...

opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...

s. In the United States, as of 2017, about 7% of people have used MDMA at some point in their lives and 0.9% have used it in the last year. The lethal risk from one dose of MDMA is estimated to be from 1 death in 20,000 instances to 1 death in 50,000 instances. Short-term adverse effects include grinding of the teeth, blurred vision, sweating, and a rapid heartbeat, and extended use can also lead to addiction, memory problems,

paranoia Paranoia is an instinct or thought process that is believed to be heavily influenced by anxiety, suspicion, or fear, often to the point of delusion and irrationality. Paranoid thinking typically includes persecutory beliefs, or beliefs of co ...

, and difficulty sleeping. Deaths have been reported due to increased body temperature and dehydration. Following use, people often feel depressed and tired, although this effect does not appear in clinical use, suggesting that it is not a direct result of MDMA administration. MDMA acts primarily by increasing the release of the neurotransmitters

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

, and

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

in parts of the brain. It belongs to the

substituted amphetamine Substituted amphetamines, or simply amphetamines, are a chemical class, class of compounds based upon the amphetamine structure; it includes all derivative (chemistry), derivative compounds which are formed by replacing, or substitution reacti ...

classes of drugs. MDMA is structurally similar to

mescaline Mescaline, also known as mescalin or mezcalin, and in chemical terms 3,4,5-trimethoxyphenethylamine, is a natural product, naturally occurring psychedelic drug, psychedelic alkaloid, protoalkaloid of the substituted phenethylamine class, found ...

(a psychedelic), methamphetamine (a stimulant), as well as

endogenous Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell. For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...

monoamine neurotransmitter Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines ...

s such as serotonin, norepinephrine, and dopamine. MDMA has limited approved medical uses in a small number of countries, but is illegal in most jurisdictions. In the United States, the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) is evaluating the drug for clinical use . Canada has allowed limited distribution of MDMA upon application to and approval by

Health Canada Health Canada (HC; )Health Canada is the applied title under the Federal Identity Program; the legal title is Department of Health (). is the Structure of the Canadian federal government#Departments, with subsidiary units, department of the Gove ...

. In Australia, it may be prescribed in the treatment of PTSD by specifically authorised psychiatrists.

Uses

Recreational

MDMA is often considered the drug of choice within the

culture and is also used at clubs, festivals, and house parties. In the rave environment, the sensory effects of music and lighting are often highly

synergistic Synergy is an interaction or cooperation giving rise to a whole that is greater than the simple sum of its parts (i.e., a non-linear addition of force, energy, or effect). The term ''synergy'' comes from the Attic Greek word συνεργία ' f ...

with the drug. The psychedelic

quality of MDMA offers multiple appealing aspects to users in the rave setting. Some users enjoy the feeling of mass communion from the inhibition-reducing effects of the drug, while others use it as party fuel because of the drug's stimulatory effects. MDMA is used less often than other stimulants, typically less than once per week. MDMA is sometimes taken in conjunction with other psychoactive drugs such as LSD, psilocybin mushrooms, 2C-B, and

ketamine Ketamine is a cyclohexanone-derived general anesthetic and NMDA receptor antagonist with analgesic and hallucinogenic properties, used medically for anesthesia, depression, and pain management. Ketamine exists as its S- (esketamine) a ...

. The combination with LSD is called "candy-flipping". The combination with 2C-B is called "nexus flipping". For this combination, most people take the MDMA first, wait until the peak is over, and then take the 2C-B. MDMA is often co-administered with

alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

, and prescription drugs such as SSRIs with which MDMA has several drug-drug interactions. Three life-threatening reports of MDMA co-administration with ritonavir have been reported; with ritonavir having severe and dangerous drug-drug interactions with a wide range of both psychoactive, anti-psychotic, and non-psychoactive drugs.

Medical

As of 2023, MDMA therapies have only been approved for research purposes, with no widely accepted medical indications, although this varies by jurisdiction. Before it was widely banned, it saw limited use in psychotherapy. In 2017 the

United States Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) granted breakthrough therapy designation for MDMA-assisted psychotherapy for

(PTSD), with some preliminary evidence that MDMA may facilitate psychotherapy efficacy for PTSD. Pilot studies indicate that MDMA-assisted psychotherapy may be beneficial in treating

in autistic adults. In these pilot studies, the vast majority of participants reported increased feelings of empathy that persisted after the therapy sessions. Some have proposed that psychedelics in general may act as active "super

placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

s" used for therapeutic purposes.

Others

Small doses of MDMA are used by some religious practitioners as an

entheogen Entheogens are psychoactive substances used in spiritual and religious contexts to induce altered states of consciousness. Hallucinogens such as the psilocybin found in so-called "magic" mushrooms have been used in sacred contexts since ancie ...

to enhance prayer or meditation. MDMA has been used as an adjunct to

New Age New Age is a range of Spirituality, spiritual or Religion, religious practices and beliefs that rapidly grew in Western world, Western society during the early 1970s. Its highly eclecticism, eclectic and unsystematic structure makes a precise d ...

spiritual practices.

Forms

MDMA has become widely known as ecstasy (shortened "E", "X", or "XTC"), usually referring to its tablet form, although this term may also include the presence of possible adulterants or diluents. The UK term "mandy" and the US term "molly" colloquially refer to MDMA in a crystalline powder form that is thought to be free of adulterants. MDMA is also sold in the form of the hydrochloride salt, either as loose crystals or in gelcaps. MDMA tablets can sometimes be found in a shaped form that may depict characters from

popular culture Popular culture (also called pop culture or mass culture) is generally recognized by members of a society as a set of cultural practice, practices, beliefs, artistic output (also known as popular art

f. pop art F is the sixth letter of the Latin alphabet. F may also refer to: Science and technology Mathematics * F or f, the number 15 (number), 15 in hexadecimal and higher positional systems * ''p'F'q'', the hypergeometric function * F-distributi ...

or mass art, sometimes contraste ...

. These are sometimes collectively referred to as "fun tablets". Partly due to the global supply shortage of sassafras oil—a problem largely assuaged by use of improved or alternative modern methods of synthesis—the purity of substances sold as molly have been found to vary widely. Some of these substances contain

methylone Methylone, also known as 3,4-methylenedioxy-''N''-methylcathinone (MDMC), is an entactogen and stimulant drug of the amphetamine, cathinone, and benzodioxole families related to 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy"). It is th ...

, ethylone, MDPV, mephedrone, or any other of the group of compounds commonly known as bath salts, in addition to, or in place of, MDMA. Powdered MDMA ranges from pure MDMA to crushed tablets with 30–40% purity. MDMA tablets typically have low purity due to bulking agents that are added to dilute the drug and increase profits (notably lactose) and binding agents. Tablets sold as ecstasy sometimes contain 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxyethylamphetamine (MDEA), other amphetamine derivatives, caffeine, opiates, or painkillers. Some tablets contain little or no MDMA. The proportion of seized ecstasy tablets with MDMA-like impurities has varied annually and by country. The average content of MDMA in a preparation is 70 to 120mg with the purity having increased since the 1990s. MDMA is usually consumed by mouth. It is also sometimes snorted.

Effects

In general, MDMA users report feeling the onset of subjective effects within 30 to 60 minutes of oral consumption and reaching peak effect at 75 to 120 minutes, which then plateaus for about 3.5 hours. The desired short-term psychoactive effects of MDMA have been reported to include: *

Euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...

– a sense of general

well-being Well-being is what is Intrinsic value (ethics), ultimately good for a person. Also called "welfare" and "quality of life", it is a measure of how well life is going for someone. It is a central goal of many individual and societal endeavors. ...

and happiness * Increased self-confidence, sociability, and perception of facilitated communication *

Entactogen Entactogens, also known as empathogens or connectogens, are a class of psychoactive drugs that induce the production of experiences of emotional communion, oneness, connectedness, emotional openness—that is, empathy—as particularly observe ...

ic effects—increased

empathy Empathy is generally described as the ability to take on another person's perspective, to understand, feel, and possibly share and respond to their experience. There are more (sometimes conflicting) definitions of empathy that include but are ...

or feelings of closeness with others and oneself * Dilated pupils * Relaxation and reduced anxiety * Increased emotionality * A sense of inner peace * Mild hallucination * Enhanced sensation, perception, or sexuality * Altered sense of time The experience elicited by MDMA depends on the dose, setting, and user. The variability of the induced altered state is lower compared to other psychedelics. For example, MDMA used at parties is associated with high motor activity, reduced sense of identity, and poor awareness of surroundings. Use of MDMA individually or in small groups in a quiet environment and when concentrating, is associated with increased lucidity, concentration, sensitivity to aesthetic aspects of the environment, enhanced awareness of emotions, and improved capability of communication. In psychotherapeutic settings, MDMA effects have been characterized by infantile ideas, mood lability, and memories and moods connected with childhood experiences. MDMA has been described as an "empathogenic" drug because of its empathy-producing effects. Results of several studies show the effects of increased empathy with others. When testing MDMA for medium and high doses, it showed increased hedonic and arousal continuum. The effect of MDMA increasing sociability is consistent, while its effects on empathy have been more mixed.

Side effects

Short-term

Acute adverse effects are usually the result of high or multiple doses, although single dose toxicity can occur in susceptible individuals. The most serious short-term physical health risks of MDMA are

hyperthermia Hyperthermia, also known as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme te ...

and

dehydration In physiology, dehydration is a lack of total body water that disrupts metabolic processes. It occurs when free water loss exceeds intake, often resulting from excessive sweating, health conditions, or inadequate consumption of water. Mild deh ...

. Cases of life-threatening or fatal

hyponatremia Hyponatremia or hyponatraemia is a low concentration of sodium in the Serum (blood), blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symp ...

(excessively low sodium concentration in the blood) have developed in MDMA users attempting to prevent dehydration by consuming excessive amounts of water without replenishing

electrolytes An electrolyte is a substance that conducts electricity through the movement of ions, but not through the movement of electrons. This includes most soluble salts, acids, and bases, dissolved in a polar solvent like water. Upon dissolving, t ...

. The immediate adverse effects of MDMA use can include: *

Bruxism Bruxism is excessive teeth grinding or jaw clenching. It is an oral Parafunctional habit, parafunctional activity; i.e., it is unrelated to normal function such as eating or talking. Bruxism is a common behavior; the global prevalence of brux ...

(grinding and clenching of the teeth) *

Dehydration In physiology, dehydration is a lack of total body water that disrupts metabolic processes. It occurs when free water loss exceeds intake, often resulting from excessive sweating, health conditions, or inadequate consumption of water. Mild deh ...

Diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

Erectile dysfunction Erectile dysfunction (ED), also referred to as impotence, is a form of sexual dysfunction in males characterized by the persistent or recurring inability to achieve or maintain a Human penis, penile erection with sufficient rigidity and durat ...

Hyperthermia Hyperthermia, also known as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme te ...

* Increased wakefulness or

insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

* Increased perspiration and sweating * Increased

heart rate Heart rate is the frequency of the cardiac cycle, heartbeat measured by the number of contractions of the heart per minute (''beats per minute'', or bpm). The heart rate varies according to the body's Human body, physical needs, including the nee ...

and

blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...

* Increased psychomotor activity * Loss of

appetite Appetite is the desire to eat food items, usually due to hunger. Appealing foods can stimulate appetite even when hunger is absent, although appetite can be greatly reduced by satiety. Appetite exists in all higher life-forms, and serves to reg ...

* Nausea and vomiting * Visual and auditory hallucinations (rarely) Other adverse effects that may occur or persist for up to a week following cessation of moderate MDMA use include: ; Physiological * Insomnia * Loss of appetite * Tiredness or lethargy * Trismus (lockjaw) ;Psychological * Anhedonia * Anxiety or paranoia * Depression * Impulsiveness * Irritability * Memory impairment * Restlessness

Long-term

, the long-term effects of MDMA on human brain structure and function have not been fully determined. However, there is consistent evidence of structural and functional deficits in MDMA users with high lifetime exposure. These structural or functional changes appear to be dose dependent and may be less prominent in MDMA users with only a moderate (typically <50 doses used and <100 tablets consumed) lifetime exposure. Nonetheless, moderate MDMA use may still be

neurotoxic Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifical ...

and what constitutes moderate use is not clearly established. Furthermore, it is not clear yet whether "typical" recreational users of MDMA (1 to 2 pills of 75 to 125mg MDMA or analogue every 1 to 4 weeks) will develop neurotoxic brain lesions. Long-term exposure to MDMA in humans has been shown to produce marked

neurodegeneration A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their cell death, death. Neurodegenerative diseases include amyotrophic lateral sc ...

in striatal, hippocampal, prefrontal, and occipital serotonergic

axon terminal Axon terminals (also called terminal boutons, synaptic boutons, end-feet, or presynaptic terminals) are distal terminations of the branches of an axon. An axon, also called a nerve fiber, is a long, slender projection of a Neuron, nerve cell tha ...

s. Neurotoxic damage to serotonergic axon terminals has been shown to persist for more than two years. Elevations in brain temperature from MDMA use are positively correlated with MDMA-induced neurotoxicity. However, most studies on MDMA and serotonergic neurotoxicity in humans focus more on heavy users who consume as much as seven times or more the amount that most users report taking. The evidence for the presence of serotonergic neurotoxicity in casual users who take lower doses less frequently is not conclusive. However, adverse neuroplastic changes to brain microvasculature and

white matter White matter refers to areas of the central nervous system that are mainly made up of myelinated axons, also called Nerve tract, tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distr ...

have been observed to occur in humans using low doses of MDMA. Reduced gray matter density in certain brain structures has also been noted in human MDMA users. Global reductions in gray matter volume, thinning of the parietal and orbitofrontal cortices, and decreased hippocampal activity have been observed in long term users. The effects established so far for recreational use of ecstasy lie in the range of moderate to severe effects for serotonin transporter reduction. Impairments in multiple aspects of cognition, including attention, learning, memory, visual processing, and sleep, have been found in regular MDMA users. The magnitude of these impairments is correlated with lifetime MDMA usage and are partially reversible with abstinence. Several forms of memory are impaired by chronic ecstasy use; however, the effects for memory impairments in ecstasy users are generally small overall. MDMA use is also associated with increased impulsivity and depression. Serotonin depletion following MDMA use can cause depression in subsequent days. In some cases, depressive symptoms persist for longer periods. Some studies indicate repeated recreational use of ecstasy is associated with depression and anxiety, even after quitting the drug. Depression is one of the main reasons for cessation of use. At high doses, MDMA induces a neuroimmune response that, through several mechanisms, increases the permeability of the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

, thereby making the brain more susceptible to environmental toxins and

pathogen In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory of d ...

s. In addition, MDMA has immunosuppressive effects in the

peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of Bilateria, bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside t ...

and pro-inflammatory effects in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

. MDMA may increase the risk of cardiac valvulopathy in heavy or long-term users due to activation of serotonin 5-HT_2B receptors. MDMA induces cardiac epigenetic changes in

DNA methylation DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter (genetics), promoter, DNA methylati ...

, particularly hypermethylation changes.

Reinforcement disorders

Approximately 60% of MDMA users experience withdrawal symptoms when they stop taking MDMA. Some of these symptoms include fatigue, loss of appetite, depression, and trouble concentrating. Tolerance to some of the desired and adverse effects of MDMA is expected to occur with consistent MDMA use. A 2007 delphic analysis of a panel of experts in pharmacology, psychiatry, law, policing and others estimated MDMA to have a psychological dependence and physical dependence potential roughly three-fourths to four-fifths that of cannabis.
Lay summary: MDMA has been shown to induce ΔFosB in the

nucleus accumbens The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for ' nucleus adjacent to the septum') is a region in the basal forebrain rostral to the preoptic area of the hypo ...

. Because MDMA releases dopamine in the

striatum The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...

, the mechanisms by which it induces ΔFosB in the nucleus accumbens are analogous to other dopaminergic psychostimulants. Therefore, chronic use of MDMA at high doses can result in altered brain structure and

drug addiction Addiction is a neuropsychological disorder characterized by a persistent and intense urge to use a drug or engage in a behavior that produces natural reward, despite substantial harm and other negative consequences. Repetitive drug use can ...

that occur as a consequence of ΔFosB overexpression in the nucleus accumbens. MDMA is less addictive than other stimulants such as methamphetamine and cocaine. Compared with amphetamine, MDMA and its metabolite MDA are less reinforcing. One study found approximately 15% of chronic MDMA users met the

DSM-IV The ''Diagnostic and Statistical Manual of Mental Disorders'' (''DSM''; latest edition: ''DSM-5-TR'', published in March 2022) is a publication by the American Psychiatric Association (APA) for the classification of mental disorders using a com ...

diagnostic criteria for

substance dependence Substance dependence, also known as drug dependence, is a biopsychological situation whereby an individual's functionality is dependent on the necessitated re-consumption of a psychoactive substance because of an adaptive state that has develop ...

. However, there is little evidence for a specific diagnosable MDMA dependence syndrome because MDMA is typically used relatively infrequently. There are currently no medications to treat MDMA addiction.

During pregnancy

MDMA is a moderately teratogenic drug (i.e., it is toxic to the fetus). In utero exposure to MDMA is associated with a neuro- and cardiotoxicity and impaired motor functioning. Motor delays may be temporary during infancy or long-term. The severity of these developmental delays increases with heavier MDMA use. MDMA has been shown to promote the survival of fetal dopaminergic neurons in culture.

Overdose

MDMA overdose symptoms vary widely due to the involvement of multiple organ systems. Some of the more overt overdose symptoms are listed in the table below. The number of instances of fatal MDMA intoxication is low relative to its usage rates. In most fatalities, MDMA was not the only drug involved. Acute toxicity is mainly caused by

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain Serotonin, serotonergic medications or Recreational drug use, drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild c ...

and sympathomimetic effects. Sympathomimetic side effects can be managed with carvedilol. MDMA's toxicity in overdose may be exacerbated by caffeine, with which it is frequently cut in order to increase volume. A scheme for management of acute MDMA toxicity has been published focusing on treatment of hyperthermia, hyponatraemia, serotonin syndrome, and multiple organ failure.

Interactions

A number of drug interactions can occur between MDMA and other drugs, including serotonergic drugs. MDMA also interacts with drugs which inhibit CYP450 enzymes, like ritonavir (Norvir), particularly CYP2D6 inhibitors. Life-threatening reactions and death have occurred in people who took MDMA while on ritonavir. Bupropion, a strong CYP2D6 inhibitor, has been found to increase MDMA exposure with administration of MDMA. Concurrent use of MDMA high dosages with another serotonergic drug can result in a life-threatening condition called

. Severe overdose resulting in death has also been reported in people who took MDMA in combination with certain

monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a drug class, class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressa ...

s (MAOIs), such as

phenelzine Phenelzine, sold under the brand name Nardil among others, is a non-selective and irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine family which is primarily used as an antidepressant and anxiolytic to treat depression and a ...

(Nardil),

tranylcypromine Tranylcypromine, sold under the brand name Parnate among others, is a monoamine oxidase inhibitor (MAOI). More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used a ...

(Parnate), or

moclobemide Moclobemide, sold under the brand names Amira, Aurorix, Clobemix, Depnil and Manerix among others, is a reversible inhibitor of monoamine oxidase A (RIMA) drug primarily used to treat Clinical depression, depression and social anxiety. It is not ...

(Aurorix, Manerix). Serotonin reuptake inhibitors (SRIs) such as

citalopram Citalopram, sold under the brand name Celexa among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive compulsive disorder, panic disorder, and soci ...

(Celexa), duloxetine (Cymbalta), fluoxetine (Prozac), and paroxetine (Paxil) have been shown to block most of the subjective effects of MDMA. Norepinephrine reuptake inhibitors (NRIs) such as reboxetine (Edronax) have been found to reduce emotional excitation and feelings of

stimulation Stimulation is the encouragement of development or the cause of activity in general. For example, "The press provides stimulation of political discourse." An interesting or fun activity can be described as "stimulating", regardless of its physic ...

with MDMA but do not appear to influence its

entactogen Entactogens, also known as empathogens or connectogens, are a class of psychoactive drugs that induce the production of experiences of emotional communion, oneness, connectedness, emotional openness—that is, empathy—as particularly observe ...

ic or mood-elevating effects. MDMA induces the release of monoamine neurotransmitters and thereby acts as an indirectly acting sympathomimetic and produces a variety of cardiostimulant effects. It dose-dependently increases

, and cardiac output. SRIs like citalopram and paroxetine, as well as the

5-HT_2A receptor

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.ketanserin, have been found to partially block the increases in heart rate and blood pressure with MDMA. It is notable in this regard that

serotonergic psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluci ...

s such as

psilocybin Psilocybin, also known as 4-phosphoryloxy-''N'',''N''-dimethyltryptamine (4-PO-DMT), is a natural product, naturally occurring tryptamine alkaloid and Investigational New Drug, investigational drug found in more than List of psilocybin mushroom ...

, which act as serotonin 5-HT_2A receptor agonists, likewise have sympathomimetic effects. The NRI reboxetine and the

serotonin–norepinephrine reuptake inhibitor Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant medications used to treat major depressive disorder (MDD), anxiety disorders, social phobia, chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopaus ...

(SNRI) duloxetine block MDMA-induced increases in heart rate and blood pressure. Conversely, bupropion, a

norepinephrine–dopamine reuptake inhibitor A norepinephrine–dopamine reuptake inhibitor (NDRI) is a type of drug that inhibits the reuptake of the monoamine neurotransmitters norepinephrine and dopamine and thereby increases extracellular levels of these neurotransmitters and nor ...

(NDRI) with only weak

dopaminergic Dopaminergic means "related to dopamine" (literally, "working on dopamine"), a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic pathways, Dopaminergic brain pathways facil ...

activity, reduced MDMA-induced heart rate and circulating

increases but did not affect MDMA-induced blood pressure increases. On the other hand, the robust NDRI

methylphenidate Methylphenidate, sold under the brand names Ritalin ( ) and Concerta ( ) among others, is a central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It may be taken Oral adm ...

, which has sympathomimetic effects of its own, has been found to augment the cardiovascular effects and increases in circulating norepinephrine and

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...

levels induced by MDMA. The non-selective

beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms ( arrhythmia), and to protect the heart from a second heart attack after a first heart attack ( secondary prevention ...

pindolol blocked MDMA-induced increases in heart rate but not blood pressure. The α₂-adrenergic receptor

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

clonidine did not affect the cardiovascular effects of MDMA, though it reduced blood pressure. The α₁-adrenergic receptor antagonists

doxazosin Doxazosin, sold under the brand name Cardura among others, is a medication used to treat symptoms of benign prostatic hyperplasia (enlarged prostate), hypertension (high blood pressure), and post-traumatic stress disorder (PTSD). For high bloo ...

and prazosin blocked or reduced MDMA-induced blood pressure increases but augmented MDMA-induced heart rate and cardiac output increases. The dual α₁- and β-adrenergic receptor blocker carvedilol reduced MDMA-induced heart rate and blood pressure increases. In contrast to the cases of serotonergic and noradrenergic agents, the

D₂ receptor antagonist haloperidol did not affect the cardiovascular responses to MDMA. Due to the theoretical risk of "unopposed α-stimulation" and possible consequences like coronary vasospasm, it has been suggested that dual α₁- and β-adrenergic receptor antagonists like carvedilol and labetalol, rather than selective beta blockers, should be used in the management of stimulant-induced sympathomimetic

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacteria, bacterium, or plant, as well as the effect o ...

, for instance in the context of

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Retrieved on September 20, 2014.

Pharmacology

Pharmacodynamics

MDMA is an

or empathogen, as well as a

, euphoriant, and weak psychedelic. It is a substrate of the monoamine transporters (MATs) and acts as a monoamine releasing agent (MRA). The drug is specifically a well-balanced serotonin–norepinephrine–dopamine releasing agent (SNDRA). To a lesser extent, MDMA also acts as a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI). MDMA enters monoaminergic

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

s via the MATs and then, via poorly understood

mechanism Mechanism may refer to: *Mechanism (economics), a set of rules for a game designed to achieve a certain outcome **Mechanism design, the study of such mechanisms *Mechanism (engineering), rigid bodies connected by joints in order to accomplish a ...

s, reverses the direction of these transporters to produce efflux of the

s rather than the usual reuptake. Induction of monoamine efflux by

s in general may involve

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

Na⁺ and Ca²⁺ elevation and PKC and CaMKIIα activation. MDMA also acts on the vesicular monoamine transporter 2 (VMAT2) on

synaptic vesicle In a neuron, synaptic vesicles (or neurotransmitter vesicles) store various neurotransmitters that are exocytosis, released at the chemical synapse, synapse. The release is regulated by a voltage-dependent calcium channel. Vesicle (biology), Ves ...

s to increase the

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

ic concentrations of the monoamine neurotransmitters available for efflux. By inducing release and reuptake inhibition of

, and

, MDMA increases levels of these neurotransmitters in the

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

and periphery. In addition to its actions as an SNDRA, MDMA directly but more modestly interacts with a number of monoamine and other

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

s. It is a low- potency

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

of the serotonin 5-HT₂ receptors, including of the serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors. The drug also interacts with α₂-adrenergic receptors, with the

sigma Sigma ( ; uppercase Σ, lowercase σ, lowercase in word-final position ς; ) is the eighteenth letter of the Greek alphabet. In the system of Greek numerals, it has a value of 200. In general mathematics, uppercase Σ is used as an operator ...

σ₁ and σ₂ receptors, and with the imidazoline I₁ receptor. It is thought that agonism of the serotonin 5-HT_2A receptor by MDMA may mediate the weak psychedelic effects of the drug in humans. However, findings in this area appear to be conflicting. Likewise, findings on MDMA and induction of the head-twitch response (HTR), a behavioral proxy of psychedelic-like effects, are contradictory in animals, and MDMA does not substitute for or generalize with psychedelics like LSD or DOM in animal drug discrimination tests. Along with the preceding receptor interactions, MDMA is a potent partial agonist of the rodent trace amine-associated receptor 1 (TAAR1). Conversely however, it is far weaker in terms of potency as an agonist of the human TAAR1. Moreover, MDMA acts as a weak partial agonist or

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.efficacious Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as ''effectiveness'', and it has often been used synonymously, although in pharmacology a distinction is now often made between ...

agonist. In relation to the preceding, MDMA has been said to be inactive as a human TAAR1 agonist. TAAR1 activation is thought to auto-inhibit and constrain the effects of amphetamines that possess TAAR1 agonism, for instance MDMA in rodents. Elevation of serotonin, norepinephrine, and dopamine levels by MDMA is believed to mediate most of the drug's effects, including its entactogenic, stimulant, euphoriant, hyperthermic, and sympathomimetic effects. The entactogenic effects of MDMA, including increased sociability,

, feelings of closeness, and reduced aggression, are thought to be mainly due to induction of serotonin release. The exact serotonin receptors responsible for these effects are unclear, but may include the serotonin 5-HT_1A receptor, 5-HT_1B receptor, and 5-HT_2A receptor, as well as 5-HT_1A receptor-mediated

oxytocin Oxytocin is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. Present in animals since early stages of evolution, in humans it plays roles in behavior that include Human bonding, ...

release and consequent activation of the oxytocin receptor. Induction of dopamine release is thought to be importantly involved in the stimulant and euphoriant effects of MDMA, while induction of norepinephrine release and serotonin 5-HT_2A receptor stimulation are believed to mediate its sympathomimetic effects. MDMA has been associated with a unique subjective "magic" or

euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...

that few or no other known entactogens are said to fully reproduce. The mechanisms underlying this property of MDMA are unknown, but it has been theorized to be due to a very specific mixture and balance of pharmacological activities, including combined serotonin, norepinephrine, and dopamine release and direct serotonin receptor agonism. Repeated activation of serotonin 5-HT_2B receptors by MDMA is thought to result in risk of valvular heart disease (VHD) and primary pulmonary hypertension (PPH). MDMA has been associated with serotonergic neurotoxicity. This may be due to formation of toxic MDMA

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

s and/or induction of simultaneous serotonin and dopamine release, with consequent uptake of dopamine into serotonergic neurons and breakdown into toxic species. MDMA is a

racemic mixture In chemistry, a racemic mixture or racemate () is a mixture that has equal amounts (50:50) of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as r ...

of two

enantiomers In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...

, (''S'')-MDMA and (''R'')-MDMA. (''S'')-MDMA is much more potent as an SNDRA ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'' and in producing MDMA-like subjective effects in humans than (''R'')-MDMA. By contrast, (''R'')-MDMA acts as a lower-potency serotonin–norepinephrine releasing agent (SNRA) with weak or negligible effects on dopamine. Relatedly, (''R'')-MDMA shows weak or negligible stimulant-like and rewarding effects in animals. Both (''S'')-MDMA and (''R'')-MDMA produce entactogen-type effects in animals and humans. In addition, both (''S'')-MDMA and (''R'')-MDMA are weak agonists of the serotonin 5-HT₂ receptors. (''R'')-MDMA is more potent and efficacious as a serotonin 5-HT_2A and 5-HT_2B receptor agonist than (''S'')-MDMA, whereas (''S'')-MDMA is somewhat more potent as an agonist of the serotonin 5-HT_2C receptor. Despite its greater serotonin 5-HT_2A receptor agonism however, (''R'')-MDMA did not produce more psychedelic-like effects than (''S'')-MDMA in humans. MDMA produces 3,4-methylenedioxyamphetamine (MDA) as a minor active metabolite. Peak levels of MDA are about 5 to 10% of those of MDMA and total exposure to MDA is almost 10% of that of MDMA with

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or ora ...

MDMA administration. As a result, MDA may contribute to some extent to the effects of MDMA. MDA is an entactogen, stimulant, and weak psychedelic similarly to MDMA. Like MDMA, it acts as a potent and well-balanced SNDRA and as a weak serotonin 5-HT₂ receptor agonist. However, MDA shows much more potent and efficacious serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C receptor agonism than MDMA. Accordingly, MDA produces greater psychedelic effects than MDMA in humans and might particularly contribute to the mild psychedelic-like effects of MDMA. On the other hand, MDA may also be importantly involved in

of MDMA, such as cardiac valvulopathy. The duration of action of MDMA (3–6hours) is much shorter than its

elimination half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

(8–9hours) would imply. In relation to this, MDMA's duration and the offset of its effects appear to be determined more by rapid acute tolerance rather than by circulating drug concentrations. Similar findings have been made for

and

. One mechanism by which tolerance to MDMA may occur is internalization of the serotonin transporter (SERT). Although MDMA and serotonin are not significant TAAR1 agonists in humans, TAAR1 activation by MDMA may result in SERT internalization.

Pharmacokinetics

Main metabolic pathways of MDMA in humans

The MDMA

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'', ...

in the blood stream starts to rise after about 30 minutes, and reaches its maximal

in the blood stream between 1.5 and 3 hours after ingestion. It is then slowly metabolized and excreted, with levels of MDMA and its metabolites decreasing to half their peak concentration over the next several hours. The duration of action of MDMA is about 3 to 6hours. Brain serotonin levels are depleted after MDMA administration but serotonin levels typically return to normal within 24 to 48hours.

Metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

s of MDMA that have been identified in humans include 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (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 Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

effects of MDMA are an area of active research. 80% of MDMA is metabolised in the liver, and about 20% is excreted unchanged in the

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

. MDMA is known to be metabolized by two main

metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell (biology), cell. The reactants, products, and Metabolic intermediate, intermediates of an enzymatic reaction are known as metabolites, which are ...

s: (1) ''O''-demethylenation followed by catechol-''O''-methyltransferase (COMT)-catalyzed methylation or glucuronide/sulfate conjugation; and (2) ''N''-dealkylation, deamination, and oxidation to the corresponding

benzoic acid Benzoic acid () is a white (or colorless) solid organic compound with the formula , whose structure consists of a benzene ring () with a carboxyl () substituent. The benzoyl group is often abbreviated "Bz" (not to be confused with "Bn," which ...

derivatives conjugated with

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (G ...

. The metabolism may be primarily by

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

(CYP450)

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

s CYP2D6 and

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

and COMT. Complex, nonlinear

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific su ...

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

s of MDMA if the user takes consecutive doses of the drug. MDMA and metabolites are primarily excreted as conjugates, such as sulfates and glucuronides. MDMA is a

chiral Chirality () is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek language, Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is dist ...

compound and has been almost exclusively administered as a

racemate In chemistry, a racemic mixture or racemate () is a mixture that has equal amounts (50:50) of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as r ...

. However, the two enantiomers have been shown to exhibit different kinetics. 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 Blood plasma is a light Amber (color), amber-colored liquid component of blood in which blood cells are absent, but which contains Blood protein, proteins and other constituents of whole blood in Suspension (chemistry), suspension. It makes up ...

concentration versus time curve (AUC) was two to four times higher for the (''R'')-enantiomer than the (''S'')-enantiomer after a 40mg 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 (100mg is sometimes considered a typical dose).

Chemistry

MDMA is in the substituted methylenedioxyphenethylamine and

classes of chemicals. As a free base, MDMA is a colorless oil insoluble in water. The most common salt of MDMA is the hydrochloride salt; pure MDMA hydrochloride is water-soluble and appears as a white or off-white powder or crystal.

Synthesis

There are numerous methods available to synthesize MDMA via different intermediates. The original MDMA synthesis described in Merck's patent involves brominating safrole to 1-(3,4-methylenedioxyphenyl)-2-bromopropane and then reacting this adduct with methylamine. Most illicit MDMA is synthesized using MDP2P (3,4-methylenedioxyphenyl-2-propanone) as a precursor. MDP2P in turn is generally synthesized from piperonal, safrole or isosafrole. One method is to isomerize safrole to isosafrole in the presence of a strong base, and then oxidize isosafrole to MDP2P. Another method uses the Wacker process to oxidize safrole directly to the MDP2P intermediate with a

palladium Palladium is a chemical element; it has symbol Pd and atomic number 46. It is a rare and lustrous silvery-white metal discovered in 1802 by the English chemist William Hyde Wollaston. He named it after the asteroid Pallas (formally 2 Pallas), ...

catalyst. Once the MDP2P intermediate has been prepared, a reductive amination leads to

racemic In chemistry, a racemic mixture or racemate () is a mixture that has equal amounts (50:50) of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as r ...

MDMA (an equal parts mixture of (''R'')-MDMA and (''S'')-MDMA). Relatively small quantities of essential oil are required to make large amounts of MDMA. The essential oil of '' Ocotea cymbarum'', for example, typically contains between 80 and 94% safrole. This allows 500mL of the oil to produce between 150 and 340 grams of MDMA.

Detection in body fluids

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.

History

Early research and use

MDMA was first synthesized and

patent A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an sufficiency of disclosure, enabling discl ...

ed in 1912 by Merck chemist Anton Köllisch. At the time, Merck was interested in developing substances that stopped abnormal bleeding. Merck wanted to avoid an existing patent held by

Bayer Bayer AG (English: , commonly pronounced ; ) is a German multinational pharmaceutical and biotechnology company and is one of the largest pharmaceutical companies and biomedical companies in the world. Headquartered in Leverkusen, Bayer' ...

for one such compound: hydrastinine. Köllisch developed a preparation of a hydrastinine analogue, methylhydrastinine, at the request of fellow lab members, Walther Beckh and Otto Wolfes. MDMA (called methylsafrylamin, safrylmethylamin or N-Methyl-a-Methylhomopiperonylamin in Merck laboratory reports) was an intermediate compound in the synthesis of methylhydrastinine. Merck was not interested in MDMA itself at the time. On 24 December 1912, Merck filed two patent applications that described the synthesis and some chemical properties of MDMA and its subsequent conversion to methylhydrastinine. Merck records indicate its researchers returned to the compound sporadically. A 1920 Merck patent describes a chemical modification to MDMA. MDMA's analogue 3,4-methylenedioxyamphetamine (MDA) was first synthesized in 1910 as a

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

adrenaline Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...

. Gordon A. Alles, the discoverer of the psychoactive effects of

, also discovered the psychoactive effects of MDA in 1930 in a self-experiment in which he administered a high dose (126mg) to himself. However, he did not subsequently describe these effects until 1959. MDA was later tested as an

appetite suppressant An anorectic is a drug that reduces appetite, resulting in lower food consumption, leading to weight loss. These substances work by affecting the central nervous system or certain neurotransmitters to create a feeling of fullness or reduce the desi ...

Smith, Kline & French Smith, Kline & French (SKF) was an American pharmaceutical company that is now a part of the British group GSK plc. History In 1830, John K. Smith opened a drugstore in Philadelphia, and his younger brother, George, joined him in 1841 to form ...

and for other uses by other groups in the 1950s. In relation to the preceding, the psychoactive effects of MDA were discovered well before those of MDMA. In 1927, Max Oberlin studied the pharmacology of MDMA while searching for substances with effects similar to

, the latter being structurally similar to MDMA. Compared to ephedrine, Oberlin observed that it had similar effects on

vascular smooth muscle Vascular smooth muscle is the type of smooth muscle that makes up most of the walls of blood vessels. Structure Vascular smooth muscle refers to the particular type of smooth muscle found within, and composing the majority of the wall of blood v ...

tissue, stronger effects at the uterus, and no "local effect at the eye". MDMA was also found to have effects on

blood sugar The blood sugar level, blood sugar concentration, blood glucose level, or glycemia is the measure of glucose concentrated in the blood. The body tightly regulates blood glucose levels as a part of metabolic homeostasis. For a 70 kg (1 ...

levels comparable to high doses of ephedrine. Oberlin concluded that the effects of MDMA were not limited to the

sympathetic nervous system The sympathetic nervous system (SNS or SANS, sympathetic autonomic nervous system, to differentiate it from the somatic nervous system) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous sy ...

. Research was stopped "particularly due to a strong price increase of safrylmethylamine", which was still used as an intermediate in methylhydrastinine synthesis. Albert van Schoor performed simple toxicological tests with the drug in 1952, most likely while researching new stimulants or circulatory medications. After pharmacological studies, research on MDMA was not continued. In 1959, Wolfgang Fruhstorfer synthesized MDMA for pharmacological testing while researching stimulants. It is unclear if Fruhstorfer investigated the effects of MDMA in humans. Outside of Merck, other researchers began to investigate MDMA. In 1953 and 1954, the

United States Army The United States Army (USA) is the primary Land warfare, land service branch of the United States Department of Defense. It is designated as the Army of the United States in the United States Constitution.Article II, section 2, clause 1 of th ...

commissioned a study of

and behavioral effects in animals injected with

and several analogues, including MDMA. Conducted at the

University of Michigan The University of Michigan (U-M, U of M, or Michigan) is a public university, public research university in Ann Arbor, Michigan, United States. Founded in 1817, it is the oldest institution of higher education in the state. The University of Mi ...

Ann Arbor Ann Arbor is a city in Washtenaw County, Michigan, United States, and its county seat. The 2020 United States census, 2020 census recorded its population to be 123,851, making it the List of municipalities in Michigan, fifth-most populous cit ...

, these investigations were declassified in October 1969 and published in 1973. A 1960 Polish paper by Biniecki and Krajewski describing the synthesis of MDMA as an intermediate was the first published scientific paper on the substance. MDA appeared as a

recreational drug Recreational drug use is the use of one or more psychoactive drugs to induce an altered state of consciousness, either for pleasure or for some other casual purpose or pastime. When a psychoactive drug enters the user's body, it induces an Sub ...

in the mid-1960s. MDMA may have been in non-medical use in the western United States in 1968. An August 1970 report at a meeting of crime laboratory chemists indicates MDMA was being used recreationally in the Chicago area by 1970. MDMA likely emerged as a substitute for MDA, a drug at the time popular among users of psychedelics which was made a Schedule 1 controlled substance in the United States in 1970.

Shulgin's research

American chemist and psychopharmacologist Alexander Shulgin reported he synthesized MDMA in 1965 while researching methylenedioxy compounds at Dow Chemical Company, but did not test the psychoactivity of the compound at this time. Around 1970, Shulgin sent instructions for N-methylated MDA (MDMA) synthesis to the founder of a Los Angeles chemical company who had requested them. This individual later provided these instructions to a client in the Midwest. Shulgin may have suspected he played a role in the emergence of MDMA in Chicago. Shulgin first heard of the psychoactive effects of N-methylated MDA around 1975 from a young student who reported "amphetamine-like content". Around 30 May 1976, Shulgin again heard about the effects of N-methylated MDA, this time from a graduate student in a medicinal chemistry group he advised at

San Francisco State University San Francisco State University (San Francisco State, SF State and SFSU) is a Public university, public research university in San Francisco, California, United States. It was established in 1899 as the San Francisco State Normal School and is ...

who directed him to the University of Michigan study. She and two close friends had consumed 100mg of MDMA and reported positive emotional experiences. Following the self-trials of a colleague at the

University of San Francisco The University of San Francisco (USF) is a Private university, private Society of Jesus, Jesuit university in San Francisco, California, United States. Founded in 1855, it has nearly 9,000 students pursuing undergraduate and graduate degrees ...

, Shulgin synthesized MDMA and tried it himself in September and October 1976. Shulgin first reported on MDMA in a presentation at a conference in Bethesda, Maryland in December 1976. In 1978, he and David E. Nichols published a report on the drug's psychoactive effect in humans. They described MDMA as inducing "an easily controlled altered state of consciousness with emotional and sensual overtones" comparable "to marijuana, to

devoid of the hallucinatory component, or to low levels of MDA". While not finding his own experiences with MDMA particularly powerful, Shulgin was impressed with the drug's disinhibiting effects and thought it could be useful in therapy. Believing MDMA allowed users to strip away habits and perceive the world clearly, Shulgin called the drug ''window''. Shulgin occasionally used MDMA for relaxation, referring to it as "my low-calorie martini", and gave the drug to friends, researchers, and others who he thought could benefit from it. One such person was Leo Zeff, a psychotherapist who had been known to use psychedelic substances in his practice. When he tried the drug in 1977, Zeff was impressed with the effects of MDMA and came out of his semi-retirement to promote its use in therapy. Over the following years, Zeff traveled around the United States and occasionally to Europe, eventually training an estimated four thousand psychotherapists in the therapeutic use of MDMA. Zeff named the drug ''Adam'', believing it put users in a state of primordial innocence. Psychotherapists who used MDMA believed the drug eliminated the typical fear response and increased communication. Sessions were usually held in the home of the patient or the therapist. The role of the therapist was minimized in favor of patient self-discovery accompanied by MDMA induced feelings of empathy. Depression, substance use disorders, relationship problems, premenstrual syndrome, and autism were among several psychiatric disorders MDMA assisted therapy was reported to treat. According to psychiatrist George Greer, therapists who used MDMA in their practice were impressed by the results. Anecdotally, MDMA was said to greatly accelerate therapy. According to David Nutt, MDMA was widely used in the western US in couples counseling, and was called ''empathy''. Only later was the term ''ecstasy'' used for it, coinciding with rising opposition to its use.

Rising recreational use

In the late 1970s and early 1980s, "Adam" spread through personal networks of psychotherapists, psychiatrists, users of psychedelics, and yuppies. Hoping MDMA could avoid criminalization like LSD and mescaline, psychotherapists and experimenters attempted to limit the spread of MDMA and information about it while conducting informal research. Early MDMA distributors were deterred from large scale operations by the threat of possible legislation. Between the 1970s and the mid-1980s, this network of MDMA users consumed an estimated 500,000 doses. A small recreational market for MDMA developed by the late 1970s, consuming perhaps 10,000 doses in 1976. By the early 1980s MDMA was being used in Boston and New York City nightclubs such as

Studio 54 Studio 54 is a Broadway theatre, Broadway theater and former nightclub at 254 West 54th Street (Manhattan), 54th Street in the Midtown Manhattan neighborhood of New York City, New York, U.S. Opened as the Gallo Opera House in 1927, it served ...

and

Paradise Garage Paradise Garage, also known as "the Garage" or the "Gay-rage", was a New York City discotheque notable in the history of dance and pop music, as well as LGBT and nightclub cultures. The club was founded by sole proprietor Michael Brody, and ...

. Into the early 1980s, as the recreational market slowly expanded, production of MDMA was dominated by a small group of therapeutically minded

Boston Boston is the capital and most populous city in the Commonwealth (U.S. state), Commonwealth of Massachusetts in the United States. The city serves as the cultural and Financial centre, financial center of New England, a region of the Northeas ...

chemists. Having commenced production in 1976, this "Boston Group" did not keep up with growing demand and shortages frequently occurred. Perceiving a business opportunity, Michael Clegg, the Southwest distributor for the Boston Group, started his own "Texas Group" backed financially by Texas friends. In 1981, Clegg had coined "Ecstasy" as a slang term for MDMA to increase its marketability. Starting in 1983, the Texas Group mass-produced MDMA in a Texas lab or imported it from California and marketed tablets using pyramid sales structures and toll-free numbers. MDMA could be purchased via credit card and taxes were paid on sales. Under the brand name "Sassyfras", MDMA tablets were sold in brown bottles. The Texas Group advertised "Ecstasy parties" at bars and discos, describing MDMA as a "fun drug" and "good to dance to". MDMA was openly distributed in Austin and Dallas–Fort Worth area bars and nightclubs, becoming popular with yuppies, college students, and gays. Recreational use also increased after several cocaine dealers switched to distributing MDMA following experiences with the drug. A California laboratory that analyzed confidentially submitted drug samples first detected MDMA in 1975. Over the following years the number of MDMA samples increased, eventually exceeding the number of MDA samples in the early 1980s. By the mid-1980s, MDMA use had spread to colleges around the United States.

Media attention and scheduling

United States

In an early media report on MDMA published in 1982, a

Drug Enforcement Administration The Drug Enforcement Administration (DEA) is a Federal law enforcement in the United States, United States federal law enforcement agency under the U.S. Department of Justice tasked with combating illicit Illegal drug trade, drug trafficking a ...

(DEA) spokesman stated the agency would ban the drug if enough evidence for abuse could be found. By mid-1984, MDMA use was becoming more noticed. Bill Mandel reported on "Adam" in a 10 June

San Francisco Chronicle The ''San Francisco Chronicle'' is a newspaper serving primarily the San Francisco Bay Area of Northern California. It was founded in 1865 as ''The Daily Dramatic Chronicle'' by teenage brothers Charles de Young and M. H. de Young, Michael H. ...

article, but misidentified the drug as methyloxymethylenedioxyamphetamine (MMDA). In the next month, the World Health Organization identified MDMA as the only substance out of twenty phenethylamines to be seized a significant number of times. After a year of planning and data collection, MDMA was proposed for scheduling by the DEA on 27 July 1984, with a request for comments and objections. The DEA was surprised when a number of psychiatrists, psychotherapists, and researchers objected to the proposed scheduling and requested a hearing. In a

Newsweek ''Newsweek'' is an American weekly news magazine based in New York City. Founded as a weekly print magazine in 1933, it was widely distributed during the 20th century and has had many notable editors-in-chief. It is currently co-owned by Dev P ...

article published the next year, a DEA pharmacologist stated that the agency had been unaware of its use among psychiatrists. An initial hearing was held on 1 February 1985 at the DEA offices in Washington, D.C., with administrative law judge Francis L. Young presiding. It was decided there to hold three more hearings that year: Los Angeles on 10 June, Kansas City, Missouri on 10–11 July, and Washington, D.C., on 8–11 October. Sensational media attention was given to the proposed criminalization and the reaction of MDMA proponents, effectively advertising the drug. In response to the proposed scheduling, the Texas Group increased production from 1985 estimates of 30,000 tablets a month to as many as 8,000 per day, potentially making two million ecstasy tablets in the months before MDMA was made illegal. By some estimates the Texas Group distributed 500,000 tablets per month in Dallas alone. According to one participant in an ethnographic study, the Texas Group produced more MDMA in eighteen months than all other distribution networks combined across their entire histories. By May 1985, MDMA use was widespread in California, Texas, southern Florida, and the northeastern United States. According to the DEA there was evidence of use in twenty-eight states and Canada. Urged by Senator Lloyd Bentsen, the DEA announced an emergency Schedule I classification of MDMA on 31 May 1985. The agency cited increased distribution in Texas, escalating street use, and new evidence of MDA (an analog of MDMA) neurotoxicity as reasons for the emergency measure. The ban took effect one month later on 1 July 1985 in the midst of

Nancy Reagan Nancy Davis Reagan (; born Anne Frances Robbins; July 6, 1921 – March 6, 2016) was an American film actress who was the first lady of the United States from 1981 to 1989, as the second wife of President Ronald Reagan. Reagan was born in ...

's " Just Say No" campaign. As a result of several expert witnesses testifying that MDMA had an accepted medical usage, the administrative law judge presiding over the hearings recommended that MDMA be classified as a Schedule III substance. Despite this, DEA administrator John C. Lawn overruled and classified the drug as Schedule I. Harvard psychiatrist Lester Grinspoon then sued the DEA, claiming that the DEA had ignored the medical uses of MDMA, and the federal court sided with Grinspoon, calling Lawn's argument "strained" and "unpersuasive", and vacated MDMA's Schedule I status. Despite this, less than a month later Lawn reviewed the evidence and reclassified MDMA as Schedule I again, claiming that the expert testimony of several psychiatrists claiming over 200 cases where MDMA had been used in a therapeutic context with positive results could be dismissed because they were not published in medical journals. In 2017, the FDA granted breakthrough therapy designation for its use with psychotherapy for PTSD. However, this designation has been questioned and problematized.

United Nations

While engaged in scheduling debates in the United States, the DEA also pushed for international scheduling. In 1985, the

World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...

's Expert Committee on Drug Dependence recommended that MDMA be placed in Schedule I of the 1971 United Nations

Convention on Psychotropic Substances The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as amphetamine-type stimulants, barbiturates, benzodiazepines, and psychedelics signed in Vienna, Austria on 21 February ...

. The committee made this recommendation on the basis of the pharmacological similarity of MDMA to previously scheduled drugs, reports of illicit trafficking in Canada, drug seizures in the United States, and lack of well-defined therapeutic use. While intrigued by reports of psychotherapeutic uses for the drug, the committee viewed the studies as lacking appropriate methodological design and encouraged further research. Committee chairman Paul Grof dissented, believing international control was not warranted at the time and a recommendation should await further therapeutic data. The Commission on Narcotic Drugs added MDMA to Schedule I of the convention on 11 February 1986.

Post-scheduling

The use of MDMA in Texas clubs declined rapidly after criminalization, but by 1991, the drug became popular among young middle-class whites and in nightclubs. In 1985, MDMA use became associated with

acid house Acid house (also simply known as just " acid") is a subgenre of house music developed around the mid-1980s by DJs from Chicago. The style is defined primarily by the squelching sounds and basslines of the Roland TB-303 electronic bass synt ...

on the Spanish island of

Ibiza Ibiza (; ; ; #Names and pronunciation, see below) or Iviza is a Spanish island in the Mediterranean Sea off the eastern coast of the Iberian Peninsula. It is 150 kilometres (93 miles) from the city of Valencia. It is the third largest of th ...

. Thereafter, in the late 1980s, the drug spread alongside rave culture to the United Kingdom and then to other European and American cities. Illicit MDMA use became increasingly widespread among young adults in universities and later, in high schools. Since the mid-1990s, MDMA has become the most widely used amphetamine-type drug by college students and teenagers. MDMA became one of the four most widely used illicit drugs in the US, along with

heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is a morphinan opioid substance synthesized from the Opium, dried latex of the Papaver somniferum, opium poppy; it is mainly used as a recreational drug for its eupho ...

, and

. According to some estimates as of 2004, only marijuana attracts more first time users in the United States. 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 FDA-approved MDMA studies in humans have taken place in the United States in Detroit (

Wayne State University Wayne State University (WSU) is a public university, public research university in Detroit, Michigan, United States. Founded in 1868, Wayne State consists of 13 schools and colleges offering approximately 375 programs. It is Michigan's third-l ...

), Chicago (

University of Chicago The University of Chicago (UChicago, Chicago, or UChi) is a Private university, private research university in Chicago, Illinois, United States. Its main campus is in the Hyde Park, Chicago, Hyde Park neighborhood on Chicago's South Side, Chic ...

), San Francisco (UCSF and California Pacific Medical Center),

Baltimore Baltimore is the most populous city in the U.S. state of Maryland. With a population of 585,708 at the 2020 census and estimated at 568,271 in 2024, it is the 30th-most populous U.S. city. The Baltimore metropolitan area is the 20th-large ...

( NIDA– NIH Intramural Program), and

South Carolina South Carolina ( ) is a U.S. state, state in the Southeastern United States, Southeastern region of the United States. It borders North Carolina to the north and northeast, the Atlantic Ocean to the southeast, and Georgia (U.S. state), Georg ...

. Studies have also been conducted in Switzerland (University Hospital of Psychiatry,

Zürich Zurich (; ) is the list of cities in Switzerland, largest city in Switzerland and the capital of the canton of Zurich. It is in north-central Switzerland, at the northwestern tip of Lake Zurich. , the municipality had 448,664 inhabitants. The ...

), the Netherlands (

Maastricht University Maastricht University (abbreviated as UM; ) is a public university, public research university in Maastricht, Netherlands. Founded in 1976, it is the second youngest of the thirteen List of universities in the Netherlands, Dutch universities. In ...

), and Spain ( Universitat Autònoma de Barcelona). "Molly", short for 'molecule', was recognized as a slang term for crystalline or powder MDMA in the 2000s. In 2010, the BBC reported that use of MDMA had decreased in the UK in previous years. This may be due to increased seizures during use and decreased production of the precursor chemicals used to manufacture MDMA. Unwitting substitution with other drugs, such as mephedrone and

, as well as legal alternatives to MDMA, such as BZP, MDPV, and

, are also thought to have contributed to its decrease in popularity. In 2017, it was found that some pills being sold as MDMA contained pentylone, which can cause very unpleasant agitation and paranoia. According to David Nutt, when safrole was restricted by the United Nations in order to reduce the supply of MDMA, producers in China began using anethole instead, but this gives para-methoxyamphetamine (PMA, also known as "Dr Death"), which is much more toxic than MDMA and can cause overheating, muscle spasms, seizures, unconsciousness, and death. People wanting MDMA are sometimes sold PMA instead. In 2025, the BBC reported on a study of 650 survivors from the Nova music festival massacre. Two-thirds were under the influence of recreational drugs (MDMA, LSD, marijuana or psilocybin) when

Hamas The Islamic Resistance Movement, abbreviated Hamas (the Arabic acronym from ), is a Palestinian nationalist Sunni Islam, Sunni Islamism, Islamist political organisation with a military wing, the Qassam Brigades. It has Gaza Strip under Hama ...

attacked the festival on October 7, 2023. MDMA appeared to have a protective effect against later problems with sleeping and emotional distress.

Society and culture

Legal status

MDMA is legally controlled in most of the world under the UN

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 offences.

Australia

In Australia, MDMA was rescheduled on 1 July 2023 as a schedule 8 substance (available on prescription) when used in the treatment of PTSD, while remaining a schedule 9 substance (prohibited) for all other uses. For the treatment of PTSD, MDMA can only be prescribed by psychiatrists with specific training and authorisation. In 1986, MDMA was declared an illegal substance because of its allegedly harmful effects and potential for misuse. Any non-authorised sale, use or manufacture is strictly prohibited by law. Permits for research uses on humans must be approved by a recognized ethics committee on human research. In

Western Australia Western Australia (WA) is the westernmost state of Australia. It is bounded by the Indian Ocean to the north and west, the Southern Ocean to the south, the Northern Territory to the north-east, and South Australia to the south-east. Western Aust ...

under the Misuse of Drugs Act 1981 4.0g of MDMA is the amount required determining a court of trial, 2.0g is considered a presumption with intent to sell or supply and 28.0g is considered trafficking under Australian law. The

Australian Capital Territory The Australian Capital Territory (ACT), known as the Federal Capital Territory until 1938, is an internal States and territories of Australia, territory of Australia. Canberra, the capital city of Australia, is situated within the territory, an ...

passed legislation to decriminalise the possession of small amounts of MDMA, which took effect in October 2023.

Canada

In Canada, MDMA is listed as a Schedule 1 as it is an analogue of amphetamine. The

Controlled Drugs and Substances Act Control may refer to: Basic meanings Economics and business * Control (management), an element of management * Control, an element of management accounting * Comptroller (or controller), a senior financial officer in an organization * Controll ...

was updated as a result of the Safe Streets and Communities Act changing amphetamines from Schedule III to Schedule I in March 2012. In 2022, the federal government granted

British Columbia British Columbia is the westernmost Provinces and territories of Canada, province of Canada. Situated in the Pacific Northwest between the Pacific Ocean and the Rocky Mountains, the province has a diverse geography, with rugged landscapes that ...

a 3-year exemption, legalizing the possession of up to of MDMA in the province from February 2023 until February 2026.

Netherlands

In 2024, a Dutch state commission issued a report advocating for MDMA to be made available to patients with PTSD. In June 2011, the Expert Committee on the List (Expertcommissie Lijstensystematiek Opiumwet) issued a report which discussed the evidence for harm and the legal status of MDMA, arguing in favor of maintaining it on List I.

United Kingdom

In the United Kingdom, 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. The drug is therefore illegal to sell, buy, or possess without a licence in the UK. Penalties include a maximum of seven years and/or unlimited fine for possession; life and/or unlimited fine for production or trafficking. Some researchers such as David Nutt have criticized the scheduling of MDMA, which he determined to be a relatively harmless drug. An editorial he wrote in the '' Journal of Psychopharmacology'', where he compared the risk of harm for

horse riding Equestrianism (from Latin , , , 'horseman', 'horse'), commonly known as horse riding ( Commonwealth English) or horseback riding (American English), includes the disciplines of riding, driving, and vaulting. This broad description includes the ...

(1 adverse event in 350) to that of ecstasy (1 in 10,000) resulted in his dismissal, leading to the resignation of several of his colleagues from the ACMD.

United States

In the United States, MDMA is listed in Schedule I of the

Controlled Substances Act The Controlled Substances Act (CSA) is the statute establishing federal government of the United States, federal drug policy of the United States, U.S. drug policy under which the manufacture, importation, possession, use, and distribution of ...

. In a 2011 federal court hearing, the

American Civil Liberties Union The American Civil Liberties Union (ACLU) is an American nonprofit civil rights organization founded in 1920. ACLU affiliates are active in all 50 states, Washington, D.C., and Puerto Rico. The budget of the ACLU in 2024 was $383 million. T ...

successfully argued that the sentencing guideline for MDMA/ecstasy is based on outdated science, leading to excessive prison sentences. Other courts have upheld the sentencing guidelines. The United States District Court for the Eastern District of Tennessee explained its ruling by noting that "an individual federal district court judge simply cannot marshal resources akin to those available to the Commission for tackling the manifold issues involved with determining a proper drug equivalency."

Demographics

In 2014, 3.5% of 18-to-25-year-olds had used MDMA in the United States. In the European Union as of 2018, 4.1% of adults (15–64 years old) have used MDMA at least once in their life, and 0.8% had used it in the last year. Among young adults, 1.8% had used MDMA in the last year. In Europe, an estimated 37% of regular club-goers aged 14 to 35 used MDMA in the past year according to the 2015 European Drug report. The highest one-year prevalence of MDMA use in Germany in 2012 was 1.7% among people aged 25 to 29 compared with a population average of 0.4%. Among adolescent users in the United States between 1999 and 2008, girls were more likely to use MDMA than boys.

Economics

Europe

In 2008 the European Monitoring Centre for Drugs and Drug Addiction noted that although there were some reports of tablets being sold for as little as €1, most countries in Europe then reported typical retail prices in the range of €3 to €9 per tablet, typically containing 25–65mg of MDMA. By 2014 the EMCDDA reported that the range was more usually between €5 and €10 per tablet, typically containing 57–102mg of MDMA, although MDMA in powder form was becoming more common.

North America

The

United Nations Office on Drugs and Crime The United Nations Office on Drugs and Crime (UNODC; French language, French: ''Office des Nations unies contre la drogue et le crime'') is a United Nations office that was established in 1997 as the Office for Drug Control and Crime Prevention ...

stated in its 2014 World Drug Report that US ecstasy retail prices range from US$1 to $70 per pill, or from $15,000 to $32,000 per kilogram. A new research area named Drug Intelligence aims to automatically monitor distribution networks based on image processing and machine learning techniques, in which an Ecstasy pill picture is analyzed to detect correlations among different production batches. These novel techniques allow police scientists to facilitate the monitoring of illicit distribution networks. , most of the MDMA in the United States is produced in British Columbia, Canada and imported by Canada-based Asian transnational criminal organizations. The market for MDMA in the United States is relatively small compared to

, and

. In the United States, about 0.9 million people used ecstasy in 2010.

Australia

MDMA is particularly expensive in Australia, costing A$15–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 70–85mg of MDMA. Most MDMA enters Australia from the Netherlands, the UK, Asia, and the US.

Corporate logos on pills

A number of ecstasy manufacturers brand their pills with a logo, often being the logo of an unrelated corporation. Some pills depict logos of products or media popular with children, such as Shaun the Sheep.

Research

A 2014 review of the safety and efficacy of MDMA as a treatment for various disorders, particularly

(PTSD), indicated that MDMA has therapeutic efficacy in some patients. Four clinical trials provide moderate evidence in support of this treatment. Some authors have concluded that because of MDMA's potential to cause lasting harm in humans (e.g., serotonergic neurotoxicity and persistent memory impairment), "considerably more research must be performed" on its efficacy in PTSD treatment to determine if the potential treatment benefits outweigh its potential to harm a patient. Other authors have argued that the neurotoxic effects of MDMA are dose-dependent, with lower doses exhibiting lower neurotoxicity or even neuroprotection, and that MDMA assisted psychotherapy is considerably safer than current treatments. Animal models suggest that postnatal exposure may ameliorate social impairments in autism. Recent evidence suggests the safe and potentially effective use of MDMA to treat the negative symptoms of schizophrenia. Unlike other treatments for mental illness, MDMA would be intended to be used infrequently and alongside psychotherapy in treatment.

References

External links

A Multi-Site Phase 3 Study of MDMA-Assisted Therapy for PTSD (MAPP2)
* {{Authority control 5-HT1A agonists 5-HT2A agonists 5-HT2B agonists 5-HT2C agonists Alexander Shulgin Aphrodisiacs Entactogens Entheogens Euphoriants Experimental antidepressants Experimental entactogens German inventions Methamphetamines Methylenedioxyphenethylamines Psychedelic phenethylamines Serotonin-norepinephrine-dopamine releasing agents Serotonin receptor agonists Stimulants TAAR1 agonists TAAR1 antagonists VMAT inhibitors Articles containing video clips Wikipedia medicine articles ready to translate

Uses

Recreational

Medical

Others

Forms

Effects

Side effects

Short-term

Long-term

Reinforcement disorders

During pregnancy

Overdose

Interactions

Pharmacology

Pharmacodynamics

Pharmacokinetics

Chemistry

Synthesis

Detection in body fluids

History

Early research and use

Shulgin's research

Rising recreational use

Media attention and scheduling

United States

United Nations

Post-scheduling

Society and culture

Legal status

Australia

Canada

Netherlands

United Kingdom

United States

Demographics

Economics

Europe

North America

Australia

Corporate logos on pills

Research

See also

References

External links