Psilocybin provides ‘noticeable’ relief in severe depression

Psilocybin, the psychedelic compound in “magic mushrooms,” rapidly improves symptoms and produces remission in as little as two sessions for patients with major depression, new research suggests.

The results of a small randomized trial showed that psilocybin treatment was associated with a greater than 50% reduction in depressive symptoms in 67% of study participants. Furthermore, 71% showed improvement at 4 weeks of follow-up, and more than 50% achieved remission.

“The finding that most of the people we treated showed efficacy was quite a remarkable and rewarding finding and really sets the stage for psilocybin as a treatment for major depression,” said lead researcher Roland Griffiths, PhD, Oliver Lee McCabe III, professor of Neuropsychopharmacology of Consciousness, Johns Hopkins University School of Medicine, Baltimore, Maryland said in a statement.

“Perhaps the most exciting aspect of this as a new therapy is that psilocybin works as a therapeutic intervention with a single session or a few sessions, and then the effects are long-lasting. By contrast, most conventional treatments for depression. .. they are administered chronically and also have chronic side effects, “added Griffiths, who is also director of the Johns Hopkins Center for Consciousness and Psychedelic Research.

The study was published online November 4 at JAMA Psychiatry.

Growing evidence base

As previously reported, psilocybin improves depressive symptoms in cancer patients. However, these patients could be considered to have “reactive depression” to their life-threatening illness, Griffiths said.

“This study built on that earlier research by asking the question, is psilocybin effective in patients who have major depressive disorder, [which is] a much larger population? “, said.

Also, previous studies of psilocybin-assisted therapy did not have a control group, said lead author Alan Davis, PhD, an adjunct assistant professor in the Johns Hopkins University Psychedelic Research Unit. Medscape Medical News.

The researchers created a control condition by randomly assigning 24 individuals (mean age, 39.8 years[SD, 12.2 years]; 67% women) who were experiencing a moderate or severe major depressive episode to receive immediate treatment (IT) (n = 13) or delayed treatment (DT) (n = 11).

Participants had long-term depression, averaging 22.4 months in the current depressive episode. They were asked to avoid the use of other antidepressants for 4 weeks prior to evaluation and up to 4 months after enrollment.

The patients also had to be medically stable; has no personal / family history of psychotic or bipolar disorders; no alcohol, substance, or nicotine use disorder from the prior year; and no substantial lifetime or recent use of ketamine or classic hallucinogens.

Depression was measured using the Structured Clinical Interview for the DSM-5 and the GRID-Hamilton Depression Rating Scale (GRID-HAMD). A baseline score of ≥17 was required for enrollment.

Participants received eight preparatory meetings with two session facilitators before the first psilocybin session and after 2 to 3 hours of follow-up meetings after the psilocybin sessions. In addition, they received 13 sessions of psychotherapy.

After completing these preparatory sessions, they underwent two psilocybin sessions, administered an average of 1.6 weeks apart.

Participants in the DT group were evaluated weekly for depressive symptoms for 8 weeks before entering the treatment protocol.

“Surprising” findings

Participants in the IT group showed significantly lower depression scores on the GRID-HAMD 1 and 4 weeks after the second psilocybin session compared to patients in the DT group during the corresponding weeks.

Also, the effect sizes at weeks 5 and 8 were ‘large’ (d = 2.2, 95% CI, 1.4-3.0, and d = 2.6, 95% CI, 1.7 – 3.6, respectively).

An analysis of the results showed that for the 24 participants, 1 and 4 weeks after the psilocybin intervention, 67% and 71% of the participants, respectively, had a “clinically significant response” in depressive symptoms; 60% and 56%, respectively, met the remission criteria.

Intra-individual t-tests also revealed significant decreases in depression scores from baseline to 1 and 4 week follow-ups (P <0.001; d = 3.6; 95% CI 2.2-5.0; Y P <0.001; d = 3.6 95% CI, 2.2 - 4.9, respectively).

Importantly, the participants did not experience serious adverse effects.

Griffiths said he was “surprised” by the findings. “We knew that psilocybin would be effective in reactive depression of the type associated with the disease, but we did not know that this would be the case in the large number of people who qualify for MDD. [major depressive disorder],” he said.

Davis said the finding “represents a large effect of this treatment among people with major depressive disorder, an effect about 4 times greater compared to studies of antidepressant medications.”

Davis noted that psychotherapy was an “essential” component of the study protocol. “It is likely that the combination of psychotherapy and psilocybin is what makes this treatment effective and that this treatment will always have a psychotherapy component and will not be approved by the FDA as a standalone drug.”

Inflection point

Comment on the study of Medscape Medical NewsCollin Reiff, MD, clinical assistant professor, Department of Psychiatry, New York University Grossman School of Medicine, New York City, noted that because psychedelics “are still stigmatized,” the publication of this study in ” one of the most impactful journals in all of psychiatry suggests that psychedelic research is now mainstream and that the academic psychiatry research community is paying close attention to what is happening. ” He described this as a “turning point.”

Reiff, who was not involved in the study, noted that research had been done on psychedelic compounds until the 1960s, “when they left the research lab and went mainstream, leading to the closure and subsequent inactivity of the research for the next few years. 30 to 30 years “. 40 years.”

Psychedelic research is “undergoing a renaissance and is no longer viewed with such skepticism, but it is important to take our time doing this research so we don’t repeat what happened in the 1960s,” Reiff said.

In an accompanying editorial, Charles F. Reynolds III, MD, professor of geriatric psychiatry at the University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, asked “for whom is psychedelic-assisted psychotherapy appropriate (or not), particularly in patients with depression who are suicidal or have a history of suicide attempts. “

Reynolds, who is also director of the UPMC Institute on Aging, who was not involved in the study, wrote, “Personalizing the management of depression has to involve an understanding of the multiple contexts in which depression occurs, including genetics, development, psychosocial, cultural, medical, neurocognitive and spiritual “.

The study was supported by a crowdsourcing campaign organized by Tim Ferris, as well as grants from the Riverstyx Foundation. The Center for Psychedelic Research and Consciousness is funded by the Steven and Alexandra Cohen Foundation and is supported by Tim Ferriss, Matt Mullenweg, Craig Nerenberg, and Blake Mycoskie. It is also supported by grants from the National Institute on Drug Abuse. Davis received support from the National Institute on Drug Abuse. Griffiths was partially supported by a grant from NIDA. Disclosures for the other authors are listed in the original article. Reiff reports that he owns shares in Compass Pathways. Reynolds reports having no relevant financial conflicts of interest.

JAMA Psychiatry. Published online November 4, 2020. Full Text, Editorial

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