MDMA was first synthesized in 1912 at Merck pharmacuteicals by the German chemist Anton Köllisch, who was trying to develop a drug to treat abnormal bleeding (3). In the 1950s the US military began testing on mescaline and it’s analogs, including MDMA. The first drug recipe for MDMA was published in a Polish language scientific journal in the 1960s with mass production from various laboratories becoming more common moving into the 1970s.

In the late 1970s, American psychopharmacologist Alexander Shulgin synthesized MDMA and tried it himself 1978 (4), afterward MDMA propagated through his social circle and psychotherapists began using it with their clients, noting that it seemed to decrease fear and increase communication and empathy.   MDMA accelerated therapy, (5) and had a number of applications including treating Depression, substance abuse, relationship problems, premenstrual syndrome, and autism(6).

Since 1985, MDMA has been a schedule 1 drug in the U.S and has similar classifications around the world (7). Most of MDMA’s history has not been medical and for the most part, this drug has been popularized by rave and festival scenes. However, in recent years as more clinical research has taken place, MDMA has gained a reputation as a therapeutic tool for a range of conditions.

Researchers have been granted more funding and freedom to research MDMA for the treatment of conditions including PTSD, social anxiety, and depression. People being treated with MDMA are under the supervision of a qualified psychotherapist to help guide them through the experience and maximize healing potential.

According to personal accounts, MDMA-assisted therapy can act as a catalyst for healing when a person comes with a  prepared and attentive attitude, and is focused on gaining insights.  The outcome depends on an individual’s set or intention (8). 

Posttraumatic stress disorder (PTSD) may develop after exposure to a single traumatic event or from repeated stressful experiences, such as rape, childhood abuse, or childhood abuse, to name a few. PTSD causes long-lasting, debilitating symptoms in a person’s life.  It is estimated that 40-60% of patients do not respond to current therapies (9). 

Studies show that MDMA administered to people with PTSD, under the guidance of a trained therapist (known as MDMA-assisted psychotherapy), improved PTSD symptoms.   MDMA and psychotherapy together, may allow for reprocessing of traumatic memories, and may be more effective than psychotherapy alone.

• Six randomized double-blind controlled trials were conducted from 2004-2017 on MDMA and PTSD (10). Doses of MDMA varying between 75-125 mg were given to a total of 72 participants.. These individuals with PTSD were also partaking in two or three psychotherapy sessions per month with the assistance of a medical professional guiding them through the MDMA experience. The results of these trials showed that MDMA-assisted psychotherapy was well-tolerated and significantly decreased markers of PTSD such as depressive symptoms compared to controls.
• The majority of patients with previously severe PTSD ,who were unresponsive to existing treatments, had symptomatic long-term relief lasting 17 months -3.5 years after completion of MDMA-assisted psychotherapy (11).
• Pure crystal MDMA is in phase III clinical trials for treating PTSD and the Food and Drug Administration (FDA) has granted MDMA “Breakthrough Therapy” status due to its efficacy for PTSD (12).

Preliminary results from several studies show MDMA could potentially help treat social anxiety in adults with autism. Whether MDMA will help with generalized social anxiety in people that don’t have autism is still unknown.

• In one randomized, double-blind, placebo-controlled pilot study on autistic adults, MDMA was shown to reduce social anxiety (13). Eight adults were given between 75-125 mg of MDMA, and four were given an inactive placebo of 0 mg during two 8 hour psychotherapy sessions. Results showed improvements in social anxiety scores in the MDMA group after completing the active treatment. In the six month follow up, social anxiety remained the same or continued to slightly improve in most participants from the MDMA group.

Current pharmacotherapies for depression typically take around six weeks to take full effect. The potential of MDMA to help is promising, as it’s a rapid-onset therapy that doesn’t require frequent administration like SSRIs (antidepressants).  Cognitive-behavioral therapy (CBT) is a proven form of psychotherapy for depression. MDMA in conjunction with CBT could prove to be even more effective than CBT alone.

• According to a review on MDMA as a treatment for mood disorders, the fact that MDMA is being successfully used for treating anxiety disorders may mean MDMA could help with depression too (14).
• MDMA increases 5-hydroxytryptamine (5-HT) rapidly when consumed, which mimics the actions of antidepressants, and may, therefore, offer instantaneous relief for depressive symptoms (15).

Most negative outcomes from MDMA come from consuming a mixture of other drugs, either intentionally or unintentionally, as well as dehydration (16, 17, 18).  Accidental deaths have been reported from taking other compounds being presented “MDMA” (19).  In a harm assessment performed on 20 popular drugs, Ecstasy was ranked overall as the 4th least harmful drug on the list (20).

Do NOT Take MDMA If You’re

• Unsure whether the MDMA you have is pure
• Feeling pressured to take MDMA because of others
• Pregnant or there’s a chance you are
• Do not trust the person who is giving you MDMA

Avoid MDMA If You Have

• Cardiovascular disease
• Severe hypertension
• Hyperthermia
• Susceptibility to seizures
• Liver problems
• Cerebrovascular disease

Pharmacological Contraindications

Avoid stimulants that increase your heart rate such as:

• Caffeine
• Amphetamines

Avoid consuming MDMA with other psychoactive substances such asLSD and psilocybin, as animal research has shown mixing these substances may increase neurotoxicity (21).

Do not use MDMA if you have taken monoamine oxidase inhibitors (MAOIs) in the last two to three weeks (such as Nardil, Parnate, Marplan, and Ayahuasca), as doing so can cause adverse effects (22).

You can read more about potential adverse drug interactions here.

Keep in mind that even though some reports claim no danger by combining SSRIs and MDMA, to be safe, it’s best to avoid combining SSRIs with MDMA. Do NOT stop taking antidepressants to take MDMA without the permission of your doctor.

Addiction Potential

There is a risk of dependence with MDMA, however it is not as addictive as other stimulant or depressants (23).  Preclinical evidence suggests MDMA is a less potent reinforcing drug compared to other well-known addictive substances like cocaine (24), and is estimated to have a lower physical dependence than cannabis (25). Increased tolerance to MDMA and withdrawal has been reported, such as fatigue, decreased appetite, loss of concentration, and feeling ‘down’ (26). 

Research has not confirmed whether self-reported ‘withdrawal’ is the same withdrawal seen with nicotine and cocaine use that reinforces addictive behavior. 

Long-Term Effects

There isn’t any evidence showing that acute and sparing doses of MDMA (e.g once per year) cause long-term damage such as neurotoxicity.

However, regular use (e.g once per week) can cause adverse effects. In one review, researchers concluded that heavier MDMA use is associated with significant mood changes when not under the influence of MDMA, as well as cognitive deficits (27). One potential adverse effect of MDMA abuse is ‘serotonergic dysfunction’, a condition characterized by low serotonin levels, which is linked to depression.

Harm Reduction Measures

• MDMA that isn’t from a reliable source may be cut with other drugs like methamphetamine, and PCP. Always use a testing kit to ensure purity. Testing kits are inexpensive, easy to use, and for a few dollars can save your life.
• MDMA should not be used for therapeutic purposes without guidance from a trained psychotherapist experienced with MDMA-assisted psychotherapy.
• Appropriate doses of MDMA should be used to avoid potential side effects and neurotoxicity.
• “Less is more”, You enhance the benefits and minimize harm by using lower doses, less often, and reduce the risk of neurotoxicity and depression (28).
• Staying hydrated when under the influence of MDMA is important to prevent potential dehydration and hyperthermia.

One man’s journey with MDMA-assisted psychotherapy

Book: Ecstasy: The Complete Guide