Microdosing MDMA and the Future of MDMA Treatments for Mental Health

Plenty of studies have explored the effects of high dose MDMA — and, of course, there are numerous anecdotal reports.

Yet research has not investigated the effects of microdosing MDMA. As such, there’s no official data on the potential side effects of taking very low amounts of MDMA.

“The only information we have is completely anecdotal. It’s all just conjecture,” said Jennifer Mitchell, PhD, a professor in the departments of neurology and psychiatry and behavioral sciences at the Weill Institute for Neurosciences at the University of California, San Francisco.

That said, research involving lower doses of MDMA could indicate the potential effects of microdosing.

For instance, a series of five small studies, sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS), involved giving various groups of participants with post-traumatic stress disorder (PTSD) different amounts of MDMA across two sessions held 1 month apart.

Some participants were given low (but not micro) doses of MDMA at 25 milligrams (mg), 30 mg, or 40 mg. Others were given full doses at 75 mg, 100 mg, or 125 mg.

All doses produced some negative effects. People who took lower doses were more likely to report headaches and fatigue than those who took full doses. Other common symptoms included lack of appetite and nausea and dizziness.

Many participants who took lower doses also experienced anxiety, which is not surprising, said Mitchell.

“Lower amounts of MDMA can be anxiogenic [anxiety-inducing],” she explained.

It’s also unclear what effects microdoses taken over an extended period may have on the brain.

“MDMA has this history, whether rightly so or not, as a neurotoxin at high doses,” Mitchell said. “The concern would be that small doses over a long period of time could eventually build up in some way and impact neural function.”

Essentially, a microdose “should be small enough that it doesn’t generate any sort of perceptual or subjective changes,” she said. But “no one’s figured out the appropriate microdosing schedule for MDMA, at least not scientifically.”

During the 1960s, some psychiatrists experimented with MDMA as a potential treatment for mental health concerns. This practice stopped when the drug became illegal. But that could be about to change.

In recent years, clinical studies have explored the potential of using MDMA to treat mental health issues such as PTSD and anxiety. Researchers can obtain permits to use the drug in some scientific research settings.

However, the doses used in such studies are not microdoses but macrodoses, which are medium to high amounts of the drug.

MDMA as a PTSD treatment

For instance, MAPS recently concluded a phase 3 trial, led by Mitchell.

In the trial, participants with PTSD received either a placebo or MDMA at a medium to high dose (80–180 mg), followed by a lower supplemental dose (40–60 mg), in three separate sessions 1 month apart.

After each MDMA session, participants had a 90-minute therapy session where they could discuss their experiences.

Researchers found that participants taking MDMA experienced a “significant” reduction in PTSD symptoms and associated functional impairment.

Following the trial’s success, MAPS is requesting Food and Drug Administration (FDA) approval to use three macrodoses of MDMA — alongside therapy sessions — to treat people with PTSD.

MAPS has also found that taking MDMA had a lower dropout rate than taking selective serotonin reuptake inhibitors (SSRIs), a class of antidepressant medication.

“It will be submitted to the FDA in October of this year, and the FDA has 6 months in which to respond,” Mitchell said.

This means that, if approved, MDMA could be officially recognized as a treatment by March 2024.

But you won’t be able to self-administer: You need to take the drug in a supervised medical setting.

A psychiatrist, psychologist, nurse practitioner, or family therapist will always be involved, said Mitchell. “Nobody’s going to take the drugs at home,” she said.

If MDMA treatment is FDA approved, you might wonder whether you could request to take a lower dose of MDMA than recommended. But this isn’t advisable.

“If we find a dosing strategy that really works, and has been proven to work, people should stick to that and not tinker,” Mitchell said.

Using MDMA to treat other mental health conditions

PTSD is not the only mental health condition that may benefit from macrodoses of MDMA.

In a small U.K. study involving 14 people with alcohol use disorder, researchers gave them 187.5 mg of MDMA twice over 8 weeks. In addition, participants received psychological support before, during, and after each MDMA session.

Participants did not experience unexpected adverse effects. Nine months later, their average alcohol consumption dropped from 130.6 units to 18.7 units per week.

Other research indicates macrodoses of MDMA may help relieve anxiety symptoms.

In a 2020 study, researchers gave a small group of people with life threatening illnesses experiencing anxiety a 125-mg dose of MDMA alongside therapy. Compared with the placebo group, those given MDMA said they had lower levels of anxiety afterward.

Meanwhile, another small study from 2018 included 12 autistic participants. They received either a placebo or 75–125 mg of MDMA during two 8-hour psychotherapy sessions. Those in the MDMA group “demonstrated rapid and durable improvement in social anxiety symptoms.”

Again, it’s vital to note that all these MDMA doses were given in controlled and supervised clinical settings. MDMA shouldn’t be used to self-treat in any circumstances.

Some people should not take any dose of MDMA, even if it’s medically supervised.

“I would strongly caution anyone that has a family history of any sort of psychotic disorder to not take psychedelics,” Mitchell said. “We simply don’t know under which circumstances and which psychedelics potentiate the psychosis, but we have reason to believe that they do.”

People with cardiovascular health issues should also avoid MDMA. For instance, “we know that blood pressure does go up when you take these drugs,” Mitchell said.

Finally, many people with mental health diagnoses take prescription medications, such as SSRIs. It’s unclear how these medications interact with MDMA.

In the phase 3 trial led by Mitchell, all participants taking SSRIs tapered off the medications before taking MDMA — but the association needs to be explored.

“Undoubtedly, there are interactions that we need to know about to make clinical recommendations,” Mitchell said.

Some studies have explored the effects of microdosing certain psychedelics, such as psilocybin, but no research has investigated the effects of microdosing MDMA.

Further studies are needed to explore the effects of MDMA at different doses.

Although clinical trials are investigating the drug’s potential in treating mental health conditions, MDMA remains an illegal substance in the United States.

It might be tempting to take MDMA at home to enhance mental well-being. But it’s important to remember that MDMA and other psychedelics have serious risks.

If you are having difficulty managing your mental health, reach out to a qualified mental health professional for support.