Psilocybin Side Effects Found to be Tolerable, Resolve Within 2 Days

Over the last several years, research examining the therapeutic benefits of psilocybin has increased substantially. The psychoactive compound is a classic psychedelic that’s found in different mushroom species around the globe. It has proven to be effective in treating a variety of psychiatric conditions, including depression, anxiety, end-of-life mood disorders, and substance use disorders.¹

Side effects of psilocybin appear to be tolerable and resolve within 48 hours / Cannbis_Pic - stock.adobe.com

However, the majority of these studies have focused on psilocybin’s efficacy and there is a current lack of systematic reviews on the psychedelic’s safety. But a recent meta-analysis found that side effects from single-use psilocybin were tolerable and appeared to resolve within 2 days.²

The results were presented at the American Pharmacists Association Annual Meeting & Exposition, held March 22-25 in Orlando, Florida.

READ MORE: Psilocybin Analog for Treatment of Depression Receives FDA Breakthrough Therapy Designation

A team of investigators from the University of Georgia College of Pharmacy conducted a meta-analysis to examine the side effects of psilocybin. The meta-analysis included 5 studies found through a systematic review of ClinicalTrials.gov, Medline via PubMed, and Web of Science. The studies were all published from between January 2012 and December 2022.

The inclusion criteria were randomized controlled trials that compared psilocybin to placebo or other comparators—such as niacin or escitalopram—to treat depression and anxiety. Doses of psilocybin in the included trials were separated into 3 categories: low: 1-3 mg; moderate: 10-20 mg; and high: 20-30 mg.

Of the 5 included studies, there were 7 reported side effects. The most statistically significant side effects were nausea (RR=9.02; 95% CI [3.22-25.30]), anxiety (RR=3.74; 95% CI [1.05-13.35]), and dizziness (RR=5.81; 95% CI [1.02-33.04]). A non-statistical increased risk was found for headache (RR=1.78; 95% CI [0.96-3.32]), paranoia (RR=2.95; 95% CI [0.31-27.68]), transient thought disorder (RR=5.50; 95% CI [0.65-46.69]) and elevated blood pressure (RR=7.32; 95% CI [0.17-316.76]).

Investigators found the majority of side effects lasted for between 24 to 48 hours. Additionally, none of the side effects were reported as serious.

“The side effect profile of single-use psilocybin at this time appears to be tolerable and resolve within 48 hours,” the authors concluded. “However, more studies are needed to evaluate if any dose related response exists and medication management of side effects.”

Read more of our coverage from the 2024 APhA Annual Meeting & Exposition here.

References

1. Ziff S, Stern B, Lewis G, Majeed M, Gorantla VR. Analysis of Psilocybin-Assisted Therapy in Medicine: A Narrative Review. Cureus. 2022;14(2):e21944. Published 2022 Feb 5. doi:10.7759/cureus.21944

2. Yerubandi A, Bhuiya MA, Thomas JE, et al. Psilocybin and Side Effects: A Meta-analysis of Randomized Controlled Trials. Presented at: American Pharmacists Association Annual Meeting & Exposition; March 22-25, 2024; Orlando, Fl. Poster 1186.