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Randomized Controlled Trial
. 2012 Jun 1;123(1-3):132-40.
doi: 10.1016/j.drugalcdep.2011.10.029. Epub 2011 Nov 29.

Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers

Matthew W Johnson  1 , R Andrew Sewell, Roland R Griffiths
Affiliations
Randomized Controlled Trial

Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers

Matthew W Johnson et al. Drug Alcohol Depend. .

Abstract

Background: Psilocybin is a well-characterized classic hallucinogen (psychedelic) with a long history of religious use by indigenous cultures, and nonmedical use in modern societies. Although psilocybin is structurally related to migraine medications, and case studies suggest that psilocybin may be efficacious in treatment of cluster headache, little is known about the relationship between psilocybin and headache.

Methods: This double-blind study examined a broad range of psilocybin doses (0, 5, 10, 20, and 30 mg/70 kg) on headache in 18 healthy participants.

Results: Psilocybin frequently caused headache, the incidence, duration, and severity of which increased in a dose-dependent manner. All headaches had delayed onset, were transient, and lasted no more than a day after psilocybin administration.

Conclusions: Possible mechanisms for these observations are discussed, and include induction of delayed headache through nitric oxide release. These data suggest that headache is an adverse event to be expected with the nonmedical use of psilocybin-containing mushrooms as well as the administration of psilocybin in human research. Headaches were neither severe nor disabling, and should not present a barrier to future psilocybin research.

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Figures

Fig. 1
Fig. 1
Top panel: Incidence of headache across dose conditions. Bars show percent of participants reporting headache after each dose condition. Asterisks indicate a significant difference between that condition and the placebo (0 mg/70 kg) condition (Tukey post-hoc tests). Middle panel: Mean headache duration among those reporting headache. Bottom panel: Percent of participants with headache reporting analgesic use. Number of volunteers reporting headache (indicated by n) increased across dose conditions for all panels.
Fig. 2
Fig. 2
Ratings of headache severity among those reporting headache for each dose condition. Percents of participants reporting “mild” and “moderate” severity are shown for each dose condition. No participant rated any headache as “severe.” The number of volunteers reporting headache (indicated by n) increased across dose conditions.
Fig. 3
Fig. 3
Individual participant data showing the incidence, timing (including onset time and duration), and severity of headaches for each dose condition. The y-axis shows the different dose conditions categorically. Each bar horizontal bar shows data for the participant number listed to right of the y-axis. Data are not shown for sessions without reported headache and sessions with missing data.
See this image and copyright information in PMC

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