The Evidence for Psychedelic Medicine

The United States is experiencing a long-standing mental health crisis. One in five U.S. adults experience mental illness each year, and 17 percent of individuals experience mental illness before reaching adulthood. The need for effective, long-term relief is clear, yet there has been limited progress in effective pharmacologic treatment for most behavioral health conditions in the past 30 years and many existing medications fail to help many patients who try them. However, evidence is mounting that psychedelics hold promise for the treatment of a wide range of mental health and substance use disorders, including major depressive disorder, alcoholism, and PTSD among many others.

In March 2021, BrainFutures undertook a multi-part initiative to review the evidence for psychedelic-assisted therapy, outline key challenges and milestones along the path to patient access, and document the approach to the psychotherapeutic aspect of PAT among leading practitioners and pioneers in the field.

BrainFutures recently released its first issue brief of this initiative: Psychedelic Medicine: A Review of Clinical Research for a Class of Rapidly Emerging Behavioral Health Interventions. Our report provides an in-depth assessment of the current state of clinical research into the efficacy, effectiveness, and safety of this class of interventions, including evidence for psilocybin, ketamine, MDMA, LSD, DMT (ayahuasca), ibogaine, and mescaline. It is the most thorough review of this body of research to date.

Already, three psychedelic compounds are in the final phases of clinical trials and many more are in earlier stages of development. In academic and clinical trial settings, research findings show that some of these compounds have great potential to be both safer and more effective at treating certain mental health and substance use disorders compared to treatment as usual. BrainFutures’ clear, thorough review of this research serves as a tool for educating policymakers, healthcare payers, insurers, regulators, and the public about the promise of psychedelics.

Read on for some of the most recent highlights of clinical research on psychedelics and BrainFutures’ recommendations, or read our full report here.

Recent Research Highlights:

A Phase 2 trial found psilocybin was efficacious in treating major depressive disorder, with a clinically significant response in 71 percent of participants and remission from depression in 54 percent at four weeks post treatment.

After two PAT sessions with psilocybin, at least 70 percent of participants with cancer-related psychiatric distress showed clinically significant reductions in symptoms in more than one study.

Ketamine indicated effectiveness for treatment-resistant depression, with response rates over 60 percent within 24 hours, and lasting up to four weeks after end of treatment for a portion of patients.

A single infusion of ketamine rapidly reduced symptoms of refractory anxiety within one hour, lasting up to seven days.

The world’s first FDA Phase 3 trial using MDMA to treat PTSD found that after three MDMA-assisted therapy sessions, 67 percent of participants no longer qualified for a PTSD diagnosis, and 88 percent experienced a clinically significant reduction in symptoms.

BrainFutures’ Recommendations

Given the evidence outlined in our report for psychedelic-assisted therapy, limitations of treatment as usual for many mental health and substance use disorders, and the growing need for effective interventions, BrainFutures makes the following recommendations:

Certain PAT interventions with sufficient evidence levels for safety and efficacy should be rapidly adopted once approved by the FDA. BrainFutures believes a core segment of the rapidly evolving PAT field shows promising efficacy and safety, and should be made available as treatments as soon as regulatorily-required studies prove continued safety and efficacy outcomes. Specifically, BrainFutures recommends fast and wide­spread adoption for PAT therapies, including psilocybin- and MDMA-assisted therapies, upon FDA approval. In the short term, BrainFutures also recommends that the DEA re­lease safeguards ensuring that the immunity protec­tions of state and federal Right to Try Acts extend to investigational Schedule I substances for those with qualifying life-threatening illnesses.

Reimbursable and equitable access to approved psychedelic therapies is essential and all payers should adequately cover PAT treatments. Payers should cover all aspects of PAT for ketamine-assisted therapy and, eventually, MDMA- and psilocybin-assisted therapies, including assessment, therapeutic preparation, medication/dosing session (including compound, therapy, and observation), and integration therapy.

Public research dollars should be invested in advancing the field. Since the Schedule 1 classification of psychedelic compounds in 1970, the advancement of therapeutic clinical research has been largely dependent on private philanthropy. Given the demonstrated outcomes to date, public monies in this field are a much-needed investment to stem the tide of today’s mental health crisis.