Archives of General Psychiatry
September 1, 2005
John H. Krystal, Edward Perry, Ralitza Gueorguieva et al.
323 citations
Ketamine and amphetamine produce different patterns of psychotic and cognitive effects in healthy people. Ketamine causes perceptual changes, negative symptoms, and memory disruption, while amphetamine triggers hostility, grandiosity, and somatic concern. Both drugs produce positive symptoms and euphoria, but their interaction reveals three patterns: amphetamine reduces ketamine-induced working memory impairment; the drugs additively increase thought disorder, arousal, and euphoria; and their combined effect on psychosis is less than additive. These results suggest that glutamate and dopamine systems contribute differently to psychosis, thought disorder, and euphoria, and that boosting prefrontal dopamine may help cognitive problems linked to glutamate dysfunction.
Journal of Psychopharmacology
March 20, 2023
Jordan Sloshower, Hamideh Safi-Aghdam, Surbhi Pathania et al.
153 citations
In a small exploratory study, 19 adults with moderate-to-severe major depression received placebo first, then 4 weeks later a single dose of psilocybin (0.3 mg/kg), both embedded in psychotherapy. Depression and anxiety improved after both placebo and psilocybin, with no statistically significant difference between the two conditions. However, antidepressant effect sizes were larger after psilocybin (d′ = 1.02–2.27) than after placebo (d′ = 0.65–0.99), and 66.7% of participants responded and 46.7% remitted following psilocybin. Improvements lasted about 2 months on average. The intensity of mystical-type experience during psilocybin did not correlate with antidepressant effects. The authors conclude that expectancy and therapy effects complicate interpretation but support further study of psilocybin for depression.
Headache The Journal of Head and Face Pain
November 1, 2022
Christina Luddy, Yutong Zhu, Hayley Lindsey et al.
75 citations
In an exploratory randomized, double-blind, placebo-controlled trial, a pulse regimen of three doses of psilocybin (0.143 mg/kg) given about five days apart did not significantly reduce cluster headache attack frequency compared to placebo. Over three weeks, attack frequency changed by −3.2 attacks per week with psilocybin (baseline 9.6) and 0.03 attacks per week with placebo (baseline 8.9), a difference that was not statistically significant. The overall effect size was moderate (d = 0.69), but large in chronic participants (d = 1.25) and small in episodic participants (d = 0.35). Changes in attack frequency were not linked to the intensity of acute psychedelic effects. Psilocybin was well-tolerated with no serious adverse events.
Biological Psychiatry Cognitive Neuroscience and Neuroimaging
February 1, 2024
Friederike Holze, Nirmal Singh, Matthias E. Liechti et al.
50 citations
Psychedelic compounds such as psilocybin, LSD, DMT, 5-MeO-DMT, and mescaline, all serotonin 2A receptor agonists, are under investigation as potential treatments. This review summarizes current clinical research on these five compounds, covering mechanisms of action, pharmacokinetics, pharmacodynamics, efficacy, and safety. Evidence for therapeutic indications remains scarce except for psilocybin for depression. No differences in psychedelic effects were noted beyond effect duration, and it is unclear whether different receptor profiles contribute to therapeutic potential. More research is needed to differentiate these compounds for various therapeutic uses.
Journal of Psychopharmacology
June 30, 2023
Jordan Sloshower, Hamideh Safi-Aghdam, Surbhi Pathania et al.
47 citations
A single dose of psilocybin (0.3 mg/kg) doubled electroencephalographic theta power—a marker of neuroplasticity—in the auditory cortex of people with major depressive disorder two weeks later, while placebo produced no such change. Greater increases in theta power correlated with greater reductions in depression symptoms measured by the GRID-HAM-D-17 scale. These results provide evidence that psilocybin can induce sustained changes in human brain plasticity, and the theta-power increase may serve as an EEG biomarker for its antidepressant effects.
Neurology
April 7, 2025
Emmanuelle A. D. Schindler, Christopher Gottschalk, Deepak Cyril D’souza
2 citations
In clinical trials of psilocybin for migraine and cluster headache, the strength of acute psychedelic effects did not predict reductions in headache frequency. Improvements in mental health measures were also not consistently linked to headache relief. The findings suggest that the therapeutic benefits of psilocybin on headache disorders may operate through mechanisms separate from its psychedelic or mood-altering properties.