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.
Inhaled salvinorin A, the active ingredient in Salvia divinorum, produces transient psychotomimetic and perceptual alterations including dissociative and somaesthetic effects, increases plasma cortisol and prolactin, and reduces resting electroencephalogram spectral power. It does not cause euphoria, cognitive deficits, or changes in vital signs, and the effects are not dose-related. The substance is very well-tolerated without acute or delayed adverse effects, and its lack of euphoric effects suggests a low addictive potential similar to other hallucinogens.
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.
The balance between excitatory and inhibitory (E/I) activity in the brain is important for normal function, and its disruption is linked to psychiatric disorders. In a randomized, double-blind, placebo-controlled study, healthy volunteers received low doses of ketamine (which shifts E/I balance toward excitation) and thiopental (which shifts it toward inhibition) while their brain activity was recorded with EEG. The drugs altered the aperiodic exponent of the power spectrum in opposite directions, matching computational predictions. Changes in the exponent correlated with subjective and cognitive effects, suggesting that this measure could serve as a noninvasive EEG biomarker for transient shifts in cortical E/I balance.