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

Matthew W Johnson, R Andrew Sewell, Roland R. Griffiths

Drug and Alcohol Dependence June 1, 2012 DOI: 10.1016/j.drugalcdep.2011.10.029 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Double-blind study Peer reviewed
Sample size 18
Population Healthy volunteers
Intervention Psilocybin
Dose 0, 5, 10, 20, and 30 mg/70 kg
Topics Psilocybin
Keywords Temporary side effect Common effect Dose-dependent effect Transient Not severe Not disabling Headache characteristics: headaches Delayed onset Healthy volunteers Various doses Future research
Citations 121
Key points Psilocybin frequently causes dose-dependent, transient, delayed-onset headaches that are neither severe nor disabling.

Abstract

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. 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. 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. 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.

Comparable studies

Other randomized controlled trials on psilocybin, most cited first.

Study Year Design Participants
Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety 2016 Randomized controlled trial n = 51
Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression 2016 Double-blind, placebo-controlled, crossover trial n = 29
Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Hallucinogen-naïve adults reporting regular participation in religious or spiritual... 2006 Double-blind study n = 36
Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression 2021 Randomized controlled trial
Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... 2020 Randomized controlled trial n = 24

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