Author: John Carter

How psychedelic drugs may help with depression National Institutes of Health NIH

Similar MDMA doses to those in the present study have been safely used in previous PTSD trials (28, 30). The rationale of the supplemental dose is to increase the durability of the psychoactive effects. As this is a feasibility study, we are interested in obtaining a preliminary impression of how MDD patients can be recruited to an MDMA-AT study, and to what extent the patient remains in the study as a proxy for the acceptability of the treatment. The safety analysis included all participants who were given at least one dose of the study drug or placebo.

Side-effects of mdma-assisted psychotherapy: a systematic review and meta-analysis

In Phase 2 studies, the odds of experiencing any side effect in the 7 days following medication sessions were higher in the MDMA-AP group compared with controls. In total, 46% of MDMA-AP participants versus 31% of controls reported side effects in the 7 days following medication sessions. No specific side effects in the 7 days following medication sessions reached significance (Table S3).

Data extraction

The results of the study would also be presented at scientific conferences and in the media. Had full access to all of the data in the study and take responsibility for the integrity of the data and for the accuracy of the data analysis. M.O.G., B.P., W.G., S.Q., C.P., I.G., R.W., J.M.M., S.S., G.W., B.V.D.K., C.M., Y.G., S.S.K., E.H., S.A., M.B., R.A., Y.W., C.N., R.B. J.M.M., B.Y.-K., A.D.B., M.B., A.L., C.H., S.K., K.P.-G., A.C., S.H., R.D., J.B.W., B.V.D.K., M.O.G., W.G., C.P., I.G., C.N., M.M., S.C., B.P., G.W., S.S.K., E.H., A.E., J.D.W., S.S., Y.G., S.A., R.W.

Psychedelic medicine

  1. Cohen’s kappa was calculated for overall bias to determine agreement between reviewers.
  2. The primary objective of this pilot study is to explore the proof of principle and safety of open-label MDMA-AT with a flexible dose of MDMA in participants with MDD, and provide an initial assessment of treatment effectiveness.
  3. Participants were instructed to withhold their opinion on treatment group assignment from independent raters and to refrain from sharing details regarding the study design and their number of completed visits.
  4. Based on dose-dependent reports 38, 41, jaw clenching may be more likely to occur when receiving a higher dose (125 or 150 mg).
  5. A prescription version of ketamine, called esketamine, given through a nasal spray, was approved by the FDA in 2019 for patients with treatment-resistant depression.

Major depressive disorder (MDD) is a world-leading cause of disability. The available treatments are not effective in all patients, and there is a significant need for more effective treatment options. Here we present the protocol for an investigator-initiated and publicly funded trial of MDMA-assisted therapy (MDMA-AT) for MDD. This single-site, open-label study investigates the proof of principle and safety of MDMA-AT in participants with MDD and provides an initial impression of treatment effectiveness. MDMA-assisted therapy may facilitate recall of negative or threatening memories with greater self-compassion27 and less PTSD-related shame and anger28. Additionally, the acute prosocial and interpersonal effects of MDMA25,29 may support the quality of the therapeutic alliance, a potentially important factor relating to PTSD treatment adherence30 and outcome31.

MDMA, Depression, and Anxiety: Does It Harm or Help?

The funders had no role in study design, data collection and analysis, or in decision to publish or manuscript preparation. Statistical analysis plan by T-MK in collaboration with the hospital’s statistician. Input to study rationale by DR. All authors contributed to the article and approved the submitted version. The goals of the integrative sessions are to help the participant continue to process emerging material and provide support if any challenges arise during this process, and invite the participant to apply any new insights, perspective and attitudes to daily life. During the preparatory period, the therapists begin establishing an effective therapeutic alliance, addressing any questions or concerns the participant may have, as well as familiarizing them with the therapeutic approach.

As MDMA temporarily increases interpersonal trust, while also reducing avoidance and psychological defenses, it might be helpful in the processing of memories and emotions in MDD same as in PTSD (42). Furthermore, MDMA-AT allows for an experience of safety, trust and collaboration with the therapists (43). Overall, MDMA-AT holds promise as a catalyst to the therapeutic process and enhancer of the therapeutic alliance. Each experimental session was followed by three 90-min integration sessions that were spaced ~1 week apart to allow the participant to understand and incorporate their experience.

In Phase 2 studies, MDMA-AP participants had 1.7 times greater odds of experiencing any side effect during medication sessions than placebo participants, and 1.6 greater odds of side effects in the 7 days following. These results, however, were based on ‘spontaneously reported reactions’ data, defined as a subset of adverse events that could be expected based on findings in healthy volunteers 28. It is therefore unsurprising that an effect was detected, albeit a small one 49.

Side effects—during medication sessions

Approximately 4.7 million US veterans report a service-related disability34, costing the US government approximately $73 billion per year35. Researchers are still unsure of the long-term effects of MDMA on the brain, though. MDMA can produce harmful side effects in people, and it may have a negative effect on mental health and worsen existing depression.

Study arms were not significantly different in terms of race, ethnicity, sex, age, dissociative subtype, disability or CAPS-5 score (Table 1). The mean duration of PTSD diagnosis was 14.8 (s.d. 11.6) years and 13.2 (s.d. 11.4) years in the MDMA and placebo groups, respectively. Of note, six participants in the MDMA group and 13 participants in the placebo group had the dissociative subtype according to CAPS-5 score. Ongoing research is looking into the effects of MDMA on the brain to determine whether it could be a treatment for depression.