First Clinical Trial: Social Anxiety in Autistic Adults Successfully Treated with MDMA Therapy

The first clinical trial in adults on the autism spectrum investigating MDMA, or any psychedelic substance for that matter, was published in Psychopharmacology this week [1]. This groundbreaking research looked at whether MDMA combined with psychotherapy could help with the severe social anxiety that autistic adults commonly experience.

The drug-therapy combo wasn’t intended to be a treatment for autism itself but was evaluated to see if it could possibly relieve some of the symptoms that limit social adaptability and often affect quality of life.

Twelve study participants were given MDMA or placebo during two all-day therapy sessions with additional non-drug preparatory and integrative therapy sessions. The main findings of this pilot study showed marked improvements in social anxiety and less avoidance of social interactions for the group that received MDMA. Most importantly, limited doses of MDMA in the controlled clinical setting was safe and well tolerated in adults on the autism spectrum.

91% of participants reported “increased feelings of empathy/connectedness” and 86% experienced “ease of communication” during MDMA/Ecstasy that persisted after use

The rationale for this double-blind study came after a review of accounts in online discussion forums of unsolicited anecdotal reports of MDMA/Ecstasy use in autistic adults in non-medical settings suggested that some had better overall functioning and others had reduced symptoms of anxiety [2].

For her dissertation research, Dr. Alicia Danforth conducted interviews and collected survey data about the MDMA experiences of autistic adults. The survey found that 91% of participants reported “increased feelings of empathy/connectedness” and 86% experienced “ease of communication” during MDMA/Ecstasy that persisted after use.

In 2014, these findings supported the Multidisciplinary Association for Psychedelic Studies (MAPS)’s commitment to sponsor a Phase 2 randomized controlled trial of MDMA-assisted psychotherapy. Dr. Danforth and Dr. Charles Grob, a long-established researcher of psychedelic substances, led the trial at the Los Angeles BioMedical Research Institute at the Harbor-UCLA Medical Center and worked together as a co-therapy team for participants in MDMA-assisted psychotherapy.

The trial design was similar to methods used for MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD), but included some variations to meet the specific needs of the autistic population. Dr. Danforth said, “This study was the first of its kind, and one of the success factors was working with autistic consultants from protocol development through writing the findings paper. As a result, the investigators had a well-supported rationale for focusing on social anxiety and were able to create a setting that would feel safe and comfortable for a population that often struggles with novel situations and sensory overstimulation.”

For example, to assess whether autistic participants experienced similar subjective effects that would constitute a therapeutic window without becoming overwhelmed, the first four participants received MDMA in the initial session at a dose lower (75 mg) than the typical full dose in PTSD trials (100-125 mg). There were no issues with the 75 mg dose, therefore the dose was escalated to 100-125 mg for the rest of the sessions and participants.

The researchers also wove in mindfulness-based therapy since this approach has previously been shown useful for autistic adults and other populations who struggle with emotion regulation, relationships, and tolerance of distress. Unlike the PTSD trials that require the participant to stay overnight in clinic after MDMA sessions, participants in this study would leave after the session ended with a trusted Study Support Partner who would remain with them at home. This adaptation was made to best accommodate autistic adults who may have elevated anxiety from staying in a clinic setting overnight.

One month after the second experimental session (MDMA or placebo given during 8-hour psychotherapy sessions), the primary measure for gauging social anxiety, the Leibowitz Social Anxiety Scale (LSAS), showed that the group that received MDMA had significantly more improvement in social functioning and less distress in social situations than the placebo group. The large therapeutic effects remained six-months later.

One individual said, “Being a participant in the study affected me in many ways. My self-esteem increased, my social anxiety decreased, love flooded in, my heart healed, and I’m more resilient” [1].

Change in LSAS Total Scores

Baseline to One Month Post Second MDMA/Placebo Session
LSAS evaluates impact of social anxiety on areas of a person’s life

Beyond just changes in study measure scores, participants and their Study Support Partner reported tangible gains in both family and romantic relationships, with two participants feeling confident enough to start dating for the first time. A participant described this as, “… I have been able to sustain flirtatious conversations for a longer time. In these conversations, I realized communication is not just about talking. Now, I take time to notice my emotions and others’ emotions before talking” [1].

Another two participants felt more at ease talking about and reflecting on gender identity, and overall participants were more adept and comfortable in interactions with friends, family, and the therapy team.

The effects lasted long after MDMA, with remarkable reductions of anxiety in triggering situations, such as entering a new social setting or speaking on the telephone. The investigators noted that they observed, “emergence of apparently intact latent social skills (e.g., ease of initiating and sustaining conversation) that manifested and became apparent to observers during experimental sessions with MDMA when participants relaxed” [1].

Dr. Lisa Jerome, one of the researchers on the team, elaborated on this idea about MDMA by saying, “These findings show that MDMA and psychotherapy can help people, maybe by giving people a whole new set of experiences with social interactions. MDMA isn’t giving people something they didn’t have already, it’s helping them use what they had all along.”

This pilot study was successful in establishing that MDMA-assisted psychotherapy can be used safely in adults on the autism spectrum, and is helpful in relieving severe social anxiety in this population. When asked if new trials would be started soon, Dr. Danforth said, “We hope that the good safety profile and encouraging reduction in social anxiety symptoms will inspire funding for new and larger studies. It remains to be seen how the mainstream autism science community will respond to the new data.”

More clinical trials are needed in a much larger sample of autistic adults before FDA could approve this treatment, but the initial findings are compelling to expand research into this novel approach. “We are looking forward to sharing what we learned with other researchers and communities who are committed to improving the quality of care for autistic adults and other populations who struggle with social anxiety” says Danforth.

Until more data is generated in clinical trials of MDMA in autistic populations, Dr. Danforth strongly encourages autistic individuals to “wait until this type of therapy is more widely available in controlled settings with qualified therapists”. She goes on to say, “In the meantime, we saw an indication that mindfulness-based therapy can also improve social anxiety symptoms. That has certainly been the case in my private practice, where I also have to wait patiently until I can provide MDMA-assisted therapy outside of a clinical trial.”

Read the full text, open-access article here.

  1. Danforth, Alicia L., Charles S. Grob Christopher M. Struble, Allison A. Feduccia, Nick Walker, Lisa Jerome, Berra Yazar-Klosinski, and Amy Emerson. “Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: A randomized, double-blind, placebo-controlled pilot study.” Psychopharmacology (2018): 1-12.
  2. Danforth, Alicia L., Christopher M. Struble, Berra Yazar-Klosinski, and Charles S. Grob. “MDMA-assisted therapy: a new treatment model for social anxiety in autistic adults.” Progress in Neuro-Psychopharmacology and Biological Psychiatry 64 (2016): 237-249.