In an open-label trial, twenty patients with severe, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, one week apart) in a supportive setting. Depressive symptoms dropped markedly within the first five weeks, with large effect sizes (Cohen's d = 2.2 at week 1 and 2.3 at week 5). Nine patients responded and four achieved remission at week 5. Improvements remained significant at three and six months (Cohen's d = 1.5 and 1.4). No one sought conventional antidepressants within five weeks. The quality of the acute psychedelic experience predicted symptom reductions at five weeks. Tolerability was good, and psilocybin appears promising for unresponsive depression, though double-blind trials are needed.
A single dose of LSD increased brain entropy—the unpredictability of neural activity—across sensory and higher-order networks in 19 healthy adults. These entropy shifts, measured during resting-state fMRI, predicted lasting increases in the personality trait openness two weeks later. The predictive effect was strongest when participants listened to music and reported experiences of ego dissolution during the drug's acute effects. The findings suggest that psychedelic-induced changes in brain dynamics and subjective experience can forecast enduring personality change.