Christopher Gottschalk
Yale University, Neurology, Faculty Member
Objective: Using a patient-informed regimen, we conducted an exploratory randomized, double-blind, placebo-controlled study to systematically investigate the effects of psilocybin in cluster headache. Background: Sustained reductions in... more
Objective: Using a patient-informed regimen, we conducted an exploratory randomized, double-blind, placebo-controlled study to systematically investigate the effects of psilocybin in cluster headache.
Background: Sustained reductions in cluster headache burden after limited quantities of psilocybin-containing mushrooms are anecdotally reported, though there are no controlled studies investigating these effects.
Methods: Subjects were randomized to receive psilocybin (0.143 mg/kg) or placebo (microcrystalline cellulose) in a pulse of 3 doses approximately 5 days apart each. Subjects maintained headache diaries starting two weeks before and continuing through eight weeks after the first drug session. Fourteen subjects were included in the final analysis.
Results: In the three weeks after the start of the pulse regimen, cluster attack frequency was +0.03 (95% Confidence Interval: -2.6 to 2.6) attacks/week with placebo and -3.2 (-8.3 to 1.9) attacks/week with psilocybin (p = 0.251). Group difference in change from baseline had a moderate effect size (d = 0.69), though was not statistically significant (p = 0.251). The effect size in episodic subjects was small (d = 0.35), but large in chronic subjects (d = 1.25), which remained over the entire 8-week period measured (d = 0.81). Changes in cluster attack frequency were not correlated with the intensity of acute psychotropic effects during psilocybin administration. Psilocybin was well-tolerated without any unexpected or serious adverse events.
Conclusions: Findings from this initial, exploratory study provide valuable information for the development of larger, more definitive studies. The separation of acute psychotropic effects and lasting therapeutic effects underscores the need for further investigation into the mechanism(s) of action of psilocybin in headache disorders. Clinicaltrials.gov: NCT02981173
Background: Sustained reductions in cluster headache burden after limited quantities of psilocybin-containing mushrooms are anecdotally reported, though there are no controlled studies investigating these effects.
Methods: Subjects were randomized to receive psilocybin (0.143 mg/kg) or placebo (microcrystalline cellulose) in a pulse of 3 doses approximately 5 days apart each. Subjects maintained headache diaries starting two weeks before and continuing through eight weeks after the first drug session. Fourteen subjects were included in the final analysis.
Results: In the three weeks after the start of the pulse regimen, cluster attack frequency was +0.03 (95% Confidence Interval: -2.6 to 2.6) attacks/week with placebo and -3.2 (-8.3 to 1.9) attacks/week with psilocybin (p = 0.251). Group difference in change from baseline had a moderate effect size (d = 0.69), though was not statistically significant (p = 0.251). The effect size in episodic subjects was small (d = 0.35), but large in chronic subjects (d = 1.25), which remained over the entire 8-week period measured (d = 0.81). Changes in cluster attack frequency were not correlated with the intensity of acute psychotropic effects during psilocybin administration. Psilocybin was well-tolerated without any unexpected or serious adverse events.
Conclusions: Findings from this initial, exploratory study provide valuable information for the development of larger, more definitive studies. The separation of acute psychotropic effects and lasting therapeutic effects underscores the need for further investigation into the mechanism(s) of action of psilocybin in headache disorders. Clinicaltrials.gov: NCT02981173
