Study Demonstrates Potential of Psilocybin as an Antidepressant Compared with Non-Psychoactive Drugs

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Over the past ten years, the global rate of depression has increased by 20%, with around 300 million cases reported. Even though there are a variety of medications currently available to treat depression, it is common for those taking them to experience adverse reactions and little symptom relief.

Over the past 20 years, psilocybin, a psychedelic prodrug compound that is found in hundreds of mushroom species, has been researched as a potential treatment for depression. Citing psilocybin’s different mechanism of action, there is belief that it might improve the treatment response rate. To achieve a better understanding, the authors of a study published by The BMJ conducted a meta-analysis aimed at determining how effective psilocybin is as a treatment for depression compared to placebo or non-psychoactive drugs.

For the study, researchers collected data from five electronic databases and four databases of unpublished and international literature. After collecting the data, it was synthesized through a random effects meta-analysis model on 436 participants between the 36 and 60 years of age across the studies. The results indicated that there was a significant benefit when using psilocybin (Hedges’ g=1.64, 95% confidence interval (CI) 0.55 to 2.73, P<0.001) in treating depression. A response was defined as a 50% decrease in symptom severity and remission according to questionnaire scores.¹

These findings follow significant progress in the area of psychedelic research for mental health issues. Earlier this year, Cybin Inc. received FDA Breakthrough Therapy Designation (BTD) for CYB003, a novel deuterated psilocybin analog in development for the treatment of major depressive disorder. According to the company, the BTD was based on positive topline results from a Phase II study of CYB003 in major depressive disorder. The positive four-month efficacy data showed that 60% of patients on 12 mg and 75% on 16 mg were in remission from depression following two doses of CYB003.²

“It is a testament to the hard work and dedication of the entire Cybin team that we have accomplished so much so quickly. The granting of Breakthrough Therapy Designation by the FDA underscores the potential of CYB003 to fill a gap in the treatment landscape for MDD and serves to expedite and de-risk our development program going forward,” said Doug Drysdale, CEO, Cybin, in a press release. “This designation provides for a streamlined review process and enhanced engagement with the FDA. With the robust durability data from our Phase II study in hand, we are ready to move forward expeditiously. We are grateful for the opportunity to accelerate the development and regulatory review process that this designation affords, as we prepare to advance CYB003 toward a Phase III pivotal trial around mid-year.”

Common adverse effects (AEs) reported in The BMJ study were minor, with cases of anxiety, short increases in blood pressure, and headaches being the most frequently reported AEs. However, there was one case of insomnia and abnormal dreams. This lines up with CYB003, which also reported minor AEs, no incidents of suicidal ideation, and no discontinuations related to AEs.^1,2

“In our meta-analysis we found that psilocybin use showed a significant benefit on change in depression scores compared with placebo. This is consistent with other recent meta-analyses and trials of psilocybin as a standalone treatment for depression or in combination with psychological support,” wrote the authors of the study.

Moving forward, the investigators suggest that more randomized trials with long follow-up are needed to fully understand psilocybin’s treatment potential. The authors suggest recruiting a more diverse population that includes patients who have used commonly prescribed serotonergic antidepressants. Doing so would give researchers the ability to understand how psilocybin interacts with commonly prescribed drugs for depression.

The authors also believe that future studies should focus on psilocybin’s exact mechanism of treatment effectiveness, showcasing how all of its factors interact to produce a synergistic antidepressant effect.¹

“This review’s findings on psilocybin’s efficacy in reducing symptoms of depression are encouraging for its use in clinical practice as a drug intervention for patients with primary or secondary depression, particularly when combined with psychological support and administered in a supervised clinical environment. However, the highly standardized treatment setting, high cost, and lack of regulatory guidelines and legal safeguards associated with psilocybin treatment need to be dealt with before it can be established in clinical practice,” concluded the study authors.

References

1. Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis. BMJ 2024; 385 doi: https://doi.org/10.1136/bmj-2023-078084

2. Cybin Receives FDA Breakthrough Therapy Designation for its Novel Psychedelic Molecule CYB003 and Announces Positive Four-Month Durability Data in Major Depressive Disorder. Cybin. March 13, 2024. Accessed May 10, 2024. https://ir.cybin.com/investors/news/news-details/2024/Cybin-Receives-FDA-Breakthrough-Therapy-Designation-for-its-Novel-Psychedelic-Molecule-CYB003-and-Announces-Positive-Four-Month-Durability-Data-in-Major-Depressive-Disorder/default.aspx