When researchers recruit participants for studies involving psychedelic drugs, they are often looking for people who continue to suffer from mental health conditions even after trying current treatments—and there are many people who fall into that category.
An estimated 40%–60% of people with posttraumatic stress disorder (PTSD) do not respond to the selective serotonin reuptake inhibitors (SSRIs) that are first-line medications for the condition, and many do not respond to trauma-focused psychotherapies (Brady, K., et al., JAMA, Vol. 283, No. 14, 2000; Steenkamp, M. M., et al., JAMA, Vol. 314, No. 5, 2015). About a third of people diagnosed with major depressive disorder experience treatment-resistant depression (Zhdanava, M., et al., Journal of Clinical Psychiatry, Vol. 82, No. 2, 2021).
While small studies in recent years started to show promising results, regulatory agencies required larger randomized, multisite clinical trials to evaluate the safety and therapeutic efficacy of psychedelic drugs. Now the results are in on the largest studies to date of psilocybin (the compound in “magic” mushrooms) and MDMA (3,4-methylenedioxymethamphetamine, also called Ecstasy or Molly). In response to an application from Lykos Therapeutics, the U.S. Food and Drug Administration (FDA) targeted August 2024 to decide whether MDMA in combination with therapy to treat PTSD would be the first type of psychedelic-assisted therapy approved in the United States.
On Aug. 10, the FDA ruled to reject MDMA for assisted psychotherapy for PTSD, citing insufficient evidence and the need for more research. The ruling is consistent with a letter APA sent the FDA earlier this year that stated that a review of the literature on MDMA-assisted psychotherapy by a multidisciplinary panel of experts determined that there is insufficient evidence to be able to recommend MDMA-assisted psychotherapy for patients with PTSD.
The APA Services Inc. comments to the FDA drew on the expertise and recommendations of the experts who are currently updating APA’s 2017 Clinical Practice Guideline for the Treatment of PTSD in Adults. The comments also pointed out that more high-quality research is needed on MDMA-assisted psychotherapy to clarify the balance of potential benefits versus potential harms.
Larger studies have also supported the benefits of psilocybin for treatment-resistant depression, and researchers suspect this drug could be the next in line for FDA approval. Evidence is also mounting that psychedelics, which typically produce an altered state of consciousness, could help people suffering from substance use disorders, racial trauma, obsessive-compulsive disorder, and other conditions.
“If we rely on antidepressants for treatment, it can take several weeks before people experience amelioration of symptoms, if at all,” said Nora Volkow, MD, director of the National Institute on Drug Abuse. “Psychedelics may offer the opportunity to get a very fast and lasting response, and with some conditions, this could be lifesaving.” The latest research findings are also uncovering the potential neurobiological mechanisms that might make it possible for these controlled substances to produce mental health benefits.
While the latest evidence is encouraging, scientists are concerned that the hype in the public is ahead of the evidence. Recent data suggest that the number of people using magic mushrooms recreationally is increasing: Law enforcement seizures of the substance tripled from 2017 to 2022, and calls to U.S. poison control centers related to psilocybin use for adolescents tripled between 2018 and 2022 (Palamar, J. J., et al., Drug and Alcohol Dependence, 2024, in press; Farah, R., et al., Journal of Adolescent Health, 2024, in press). “I worry that people think they can self-medicate with these drugs,” said Joshua Gordon, MD, PhD, director of the National Institute of Mental Health (NIMH). “Existing studies have been conducted with guided psychotherapy along with the treatment, though more research is needed to understand how crucial therapy is in the process.”
In one survey of more than 2,300 people who used psilocybin in real-world settings for self-exploration, 11% of the respondents reported persisting negative effects, such as mood fluctuations and depressive symptoms, weeks or sometimes months after using the drug (Nayak, S. M., et al., Frontiers in Psychiatry, Vol. 14, 2023). Psychedelics are also not recommended for people who have a predisposition to or family history of psychotic disorders or bipolar mood. The drugs, which can increase heart rate and blood pressure, are also contraindicated for people with cardiovascular conditions.
Psychologists have played a critical role in clinical studies on psychedelics through their work as clinicians who prepare participants for the “trip,” or the experience with the drug, which often lasts many hours, and “integration,” or incorporating the key insights gained during the experience into their lives in the weeks and months after the trip. To equip licensed professionals to responsibly incorporate psychedelic medicine into the clinical setting, psychologists are developing education programs focused on the latest research and evidence-based practices. For now, these clinical settings are restricted to research studies, but that could change soon if the FDA approves MDMA-assisted therapy.
link