MDMA

MDMA was first synthesized in 1912 by Merck chemist Anton Köllisch.^[23] It was used to enhance psychotherapy beginning in the 1970s and became popular as a street drug in the 1980s.^[21][22] MDMA is commonly associated with dance parties, raves, and electronic dance music.^[24] Tablets sold as ecstasy may be mixed with other substances such as ephedrine, amphetamine, and methamphetamine.^[21] In 2016, about 21 million people between the ages of 15 and 64 used ecstasy (0.3% of the world population).^[25] This was broadly similar to the percentage of people who use cocaine or amphetamines, but lower than for cannabis or opioids.^[25] 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.^[26] 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.^[27]


Short-term adverse effects include grinding of the teeth, blurred vision, sweating and a rapid heartbeat,^[21] and extended use can also lead to addiction, memory problems, paranoia 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.^[21][28] MDMA acts primarily by increasing the release of the neurotransmitters serotonin, dopamine and noradrenaline in parts of the brain.^[21][22] It belongs to the substituted amphetamine classes of drugs.^[9][29] MDMA is structurally similar to mescaline (a psychedelic), methamphetamine (a stimulant), as well as endogenous monoamine neurotransmitters such as serotonin, norepinephrine, and dopamine.^[30]


MDMA has limited approved medical uses in a small number of countries,^[31] but is illegal in most jurisdictions.^[32] In the United States, the Food and Drug Administration is evaluating the drug for clinical use as of 2021.^[33] Canada has allowed limited distribution of MDMA upon application to and approval by Health Canada.^[34][35] In Australia, it may be prescribed in the treatment of PTSD by specifically authorised psychiatrists.^[36]

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.^[37] The desired short-term psychoactive effects of MDMA have been reported to include:


The experience elicited by MDMA depends on the dose, setting, and user.^[7] 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.^[13][39] In psychotherapeutic settings, MDMA effects have been characterized by infantile ideas, mood lability, and memories and moods connected with childhood experiences.^[39][40]


MDMA has been described as an "empathogenic" drug because of its empathy-producing effects.^[41][42] Results of several studies show the effects of increased empathy with others.^[41] When testing MDMA for medium and high doses, it showed increased hedonic and arousal continuum.^[43][44] The effect of MDMA increasing sociability is consistent, while its effects on empathy have been more mixed.^[45]

Interactions

A number of drug interactions can occur between MDMA and other drugs, including serotonergic drugs.^[14][113] MDMA also interacts with drugs which inhibit CYP450 enzymes, like ritonavir (Norvir), particularly CYP2D6 inhibitors.^[14] Life-threatening reactions and death have occurred in people who took MDMA while on ritonavir.^[114] Concurrent use of MDMA high dosages with another serotonergic drug can result in a life-threatening condition called serotonin syndrome.^[7][14] Severe overdose resulting in death has also been reported in people who took MDMA in combination with certain monoamine oxidase inhibitors,^[7][14] such as phenelzine (Nardil), tranylcypromine (Parnate), or moclobemide (Aurorix, Manerix).^[115] Serotonin reuptake inhibitors such as citalopram (Celexa), duloxetine (Cymbalta), fluoxetine (Prozac), and paroxetine (Paxil) have been shown to block most of the subjective effects of MDMA.^[116] Norepinephrine reuptake inhibitors such as reboxetine (Edronax) have been found to reduce emotional excitation and feelings of stimulation with MDMA but do not appear to influence its entactogenic or mood-elevating effects.^[116]