MDMA, aka ecstasy, is proving itself as an effective tool in the treatment of PTSD, but how long does MDMA last? — here’s what you should know about its pharmacokinetic effects.
3,4-methylenedioxymethamphetamine (MDMA), commonly called “Molly” or “ecstasy,” is a recreational drug that is particularly popular among rave scene enthusiasts, largely due to its stimulating and euphoriant properties.
Ecstasy typically refers to MDMA in pressed pill or tablet form, whereas Molly (a term more prevalent in the U.S.) typically refers to MDMA in crystal or powder form.
In contrast with other central nervous stimulants, which primarily stimulate the release of the neurotransmitters noradrenaline and dopamine, MDMA also possesses high serotonergic activity.
MDMA’s distinct pharmacology is likely responsible for its unique subjective effects, sharing some that are typical of stimulant drugs and others that are more psychedelic.
Large-scale distribution and ever-increasing detection by U.S. authorities in the ‘70s and ‘80s provoked the eventual banning of MDMA. In 1985, ecstasy was placed in schedule I of the Controlled Substances Act, meaning it has a high potential for abuse and no accepted medical use.
However, the ongoing clinical trials conducted by the Multidisciplinary Association for Psychedelic Studies (MAPS) investigating MDMA’s potential to aid in the treatment of post-traumatic stress disorder (PTSD) are demonstrating that this empathy-producing substance fails to satisfy at least one of these criteria.
The unprecedented results of MAPS’ trials mean that MDMA-assisted psychotherapy is expected to become a legal medicine by the end of 2023.
MDMA is commonly thought of as a psychedelic, but its effects differ in important ways from those of the classic psychedelics (mescaline, LSD, psilocybin, and DMT). Though there is some overlap in subjective effects, MDMA belongs more so to a distinct class of drugs called “entactogens” or “empathogens,” two interchangeably used terms used to describe the fascinating ability of these drugs to boost emotional empathy and promote prosocial behavior.
In total, the subjective effects of a typical MDMA dose (between 80 and 150mg) last 3-6 hours, setting in approximately 30–60 minutes subsequent to consumption. A brief come-up period of 15-30 minutes first ensues, before peak effects lasting 1.5-2.5 hours take hold.
The effects of the drug begin to wear off slowly during an offset period that lasts approximately 1-1.5 hours. It is common for therapists to administer a supplementary half-dose to patients during the peak to prolong the experience — a practice that is also widely employed by recreational users.
The quality of one’s MDMA experience is largely dependent on the dose, as well as the person’s mental state and the physical and social environment in which it is consumed (this is known as set and setting). One is more likely to experience negative effects when ecstasy is taken in uncontrolled, recreational contexts.
Conversely, no serious adverse effects have been observed in the last 20 years of using MDMA in clinical contexts.
Subjective effects of MDMA may include:
The amount of time that MDMA is present at its maximum concentration in serum (tmax) is typically observed at 2 hours after ingestion. The length of time required for the concentration of MDMA to decrease to half of its starting dose in the body (elimination half-life) is about 8–9 hours.
MDMA can be detected in blood and saliva for up to 2 days, in urine for up to 4 days, and in hair for up to 90 days. However, the detection window depends on several factors, including the route of administration, frequency of use, quantity consumed, physical characteristics, and the type of drug test used.
One’s chosen method of administration can affect how long MDMA will be detectable. Generally speaking, the faster a drug is absorbed into the bloodstream, the shorter the detection window.
Accordingly, MDMA is detectable for shorter periods when it is snorted in crystal or powder form, versus when pressed pills or tablets are orally consumed.
One less-than-ideal consequence of prohibition is that scheduled recreational drugs like MDMA are not manufactured as a standard dose. MDMA is synthesized in clandestine labs and is mostly sold in pills or powder form of highly variable dosages, often containing adulterants such as methylone, ephedrine, methamphetamine, benzylpiperazine, and dextromethorphan, each of which has their own effects. This, too, can influence how long the drug stays in the body.
Continuous use over prolonged periods, or consuming large doses at a time is more likely to prolong the presence of MDMA in one’s system. People who use MDMA in moderation, for example, once every few months — as is advised by medical professionals to mitigate its potentially toxic effects — will typically have a shorter detection window than more regular users.
Studies have demonstrated that the pharmacokinetics of MDMA in the range of recreational doses may be nonlinear (i.e. the length of time it takes for MDMA to be absorbed, distributed in the body, metabolized, and excreted may not be related to the quantity of MDMA consumed).
Some potential mechanisms have been proposed to explain the nonlinear kinetics of MDMA. These include the saturation of enzymes responsible for metabolizing it, and the formation of a temporary molecule called an enzyme-substrate complex which causes the enzyme to undergo a temporary change in shape.
Metabolism of MDMA involves N-demethylation to 3,4-methylenedioxyamphetamine (MDA). Both MDMA and MDA are then further O-demethylenated to 3,4-dihydroxymethamphetamine (HHMA) and 3,4-dihydroxyamphetamine (HHA), and both HHMA and HHA are subsequently O-methylated mainly to 4-hydroxy-3-methoxy-methamphetamine (HMMA) and 4-hydroxy-3-methoxy-amphetamine (HMA). The elimination half-life of these metabolites is significantly longer than that of MDMA.
Metabolism can also be affected by the following factors:
The presence of certain substances can produce a false-positive drug test result. To help prevent this from happening, those taking a test must inform testing agencies of all drugs and supplements that they have been using. For instance, the antidepressant medication Trazadone has produced false positives on a test that detects MDMA in urine.
Likewise, if a person is worried or confused after having received a false positive result, they should ensure that agencies are fully informed as additional confirmatory tests can be carried out to resolve these issues.
As a consequence of MDMA’s tendency to deplete the brain of serotonin, effects that occur during the “comedown” of an ecstasy experience can generally feel quite negative, especially in comparison to the euphoric, love-enhancing effects experienced during the peak.
The comedown or post-trip “crash,” which can be mild, severe, or in some cases, non-existent, usually lasts 12-72 hours but may last up to a week.
The effects of an MDMA comedown typically include:
However, new research suggests that MDMA can be comedown free, particularly when used in a clinical setting. The study, led by Dr. Ben Sessa, addiction psychiatrist and co-founder of biotech company Awakn Life Sciences, offers some initial evidence that comedowns previously associated with the substance may be explained by factors relating to recreational use, such as drug impurity, alcohol consumption, excessive dancing, poor diet, overheating, and dehydration.
The researchers analyzed data collected from 14 people diagnosed with alcohol use disorder who had undergone 10 psychotherapy sessions. In 2 of these sessions, participants received 125 mg of MDMA followed by a top-up dose of 62.5 mg two hours later. Participants’ mood was assessed for 7 days after each MDMA-assisted psychotherapy session, all maintaining a positive overall mood.
Instead of a miserable, depression-dyed comedown, participants enjoyed somewhat of an afterglow effect.
That said, it is important to keep in mind that this was a very small pilot study with no control group, meaning participants knew they would be receiving MDMA and not placebo. Also, in MAPS trials of MDMA-assisted psychotherapy for PTSD, which are controlled and have much bigger sample sizes, several effects consistent with an MDMA comedown occurred transiently in some participants in the week post-session.
As a result, the findings of Dr. Sessa and colleagues, although interesting, and certainly worthy of further exploration, would best be regarded as preliminary.
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