When I first heard that the psychedelic, MDMA, was part of a clinical trial for the treatment of Post Traumatic Stress Disorder (PTSD) 4 years ago, I was very surprised and a bit confused. MDMA (aka Ecstasy) had been demonized as a party drug for several decades associated with a lot of negative consequences. I treated several patients in drug rehabilitation that were hooked on MDMA and they were suffering greatly with severe depression, paranoid thinking and impaired functioning. There was an article published in Science magazine twenty years ago that reinforced those negative connotations: MDMA was dangerous and could kill nerve cells and lead to permanent depression and Parkinson’s Disease. Ironically, the same Science magazine published in 2021 that a study on MDMA assisted therapy for PTSD was in their top ten breakthrough discoveries of 2021. So what is the truth about MDMA? In this article, I will unravel this paradox about MDMA and its implications for treating psychiatric problems.
3-4-Methylenedioxymethamphetamine (MDMA) was first synthesized in 1912 and patented by the pharmaceutical company Merck in 1914 as part of a research program on clotting agents. At the time, there was no awareness of what practical use it could have and it was pretty much forgotten about. MDMA was never part of the drug culture of the 1960s and for that reason was never banned like other psychedelics in the early 1970s. MDMA was “rediscovered’ in the 1970s and began to be used as an adjunct to psychotherapy. By the 1980s, many psychotherapists adapted MDMA as part of their practice due to its ability to accelerate the therapeutic process. Although there were no clinical trials nor government approval, MDMA-Assisted Therapy (MDMA-AT) was legally used for couples counseling, relationship problems, depression, anxiety, substance use disorders, premenstrual syndrome, and autism, among several other psychiatric disorders.
In the mid-1980s, there were heightened concerns amid the crack cocaine-dominated headlines, so at that point MDMA raised the attention of the Drug Enforcement Agency (DEA). Due to the growing recreational use of MDMA, the DEA designated MDMA as having “no currently acceptable medical use” in 1985. Due to the extensive hurdles involved with DEA approval and public funding, clinical research was stunted but medical researchers still believed MDMA had therapeutic potential, particularly among people with PTSD and depression. In 1986, the nonprofit Multidisciplinary Association for Psychedelic Studies (MAPS) was founded to secure private funding for clinical trials despite these barriers with the goal of making MDMA an FDA approved medicine.
By contrast, the National Institute of Health spent two decades funding research that suggested MDMA is neurotoxic and often lethal. There had been research stating that MDMA caused brain damage in rats but that may have been a bit misleading since the study never noted the significantly large and frequent intravenous doses given to the rats. The study published in Science in 2002 showing MDMA killed nerve cells in primates was later redacted once the lab was found to have been injecting methamphetamine instead of MDMA. The other confusing aspect is that several related derivatives of MDMA and not MDMA itself are known to cause extensive destruction of serotonergic nerve terminals in the CNS. Nevertheless, MDMA can produce selective, long-lasting damage to serotonergic nerve terminals in animals due to its metabolites but we still don’t know if the levels of MDMA metabolites in humans after the usual doses of MDMA suffice to produce lasting damage. So far, human trial participants have shown no evidence of neurotoxic effects in controlled doses. Obviously, with recreational use of MDMA which relies on street drugs that are often cut with all kinds of adulterants there can be many potential adverse health effects: dehydration, kidney failure, heart failure, seizures, and loss of consciousness.
MDMA is estimated to be the next psychedelic FDA-approved in late 2023/early 2024 for PTSD. The use of MDMA alongside psychotherapy allows participants to revisit past distressful memories in a state of emotional security and empathic self-reflection. MDMA typically lets a person engage in active and open discussion about traumatic experiences without becoming emotionally overwhelmed. MDMA is an experiential medicine so its therapeutic effects are influenced by the setting in which it is administered. The participant is lying on a bed, listens to a predetermined setlist of emotionally evocative music, engages in mindful use of touch as appropriate, and engages in conversation with the therapists. The current protocol involves 3 MDMA-AT (Assisted Therapy) sessions spaced 4 weeks apart. Each treatment session involves the therapists work with the participant six to eight hours or until the drug’s psychedelic effects have worn off. As the MDMA subsides, therapists may talk with the participant more extensively about what they experienced during the session. In addition to the three 8 hour MDMA-AT sessions there are twelve 90 minute sessions; that’s 42 hours of therapy in total over a 3 month period.
PTSD is a common and debilitating condition with immeasurable social and economic costs that affects the lives of hundreds of millions of people annually. Although there are several therapies that are effective for treating PTSD, many people fail to respond and continue to have significant symptoms. Novel cost-effective treatments are needed, especially for those for whom comorbidities such as dissociation, depression, substance use, and childhood trauma confer treatment resistance. According to MAPS founder Rick Doblin, if MDMA is approved by early 2024, he predicts that by the end of this decade there will be 25,000 certified therapists, one million MDMA sessions, and a half million patients that will have received this treatment. Clearly, there is a lot of hope and optimism about MDMA’s healing potential but I would also urge caution. With any new treatment, we never truly understand the whole story, the unforeseen benefits and risks, about a medication until it’s used in the clinical setting in large numbers over time.