Impact of Psilocybin on Peripheral Cytokine Production

Psilocybin is a psychedelic drug with potential therapeutic effects in patients with mood and substance use disorders. Little is known about its impact on the immune system.

Multiplex immunoassay pro-inflammatory cytokine panels (Meso-Scale Discovery, Rockville, MD) were used to examine the serum from participants in three separate randomized controlled clinical trials (randomized controlled trials [RCTs]) wherein a range of doses of psilocybin were administered (methods reported previously). Participants represented a range of clinical histories including those with no-known health problems/long-term meditation practice (n = 35), depression (n = 25), anxiety, and cancer (various types; n = 31). Linear mixed models with random effects for each participant were fit to determine relative cytokine levels both immediately before and at various time points after psilocybin administration, adjusted for multiple comparisons. Serum extracted during a waitlist, where applicable, was not included.

Sera from 91 participants were included from our three prior RCTs. In our linear models of pooled data, sera collected ≤1-week postpsilocybin revealed increased levels of interleukin (IL)-8 (β = 0.164, 95% confidence interval [0.10 to 0.23]; p = 0.042). At ≥4-week time points compared to baseline, there were no changes in cytokine levels. In our linear models of individual studies, no changes in cytokine levels at each time point were observed.

This preliminary study suggests that a transient increase in cytokine production ≤1-week postpsilocybin may be found, although not consistently across patient populations. More broadly, peripheral cytokine production is possibly altered by psilocybin administration. ClinicalTrials.gov Identifier: NCT01988311.