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.
Users of hallucinogenic drugs report less harm from classic hallucinogens like LSD and psilocybin compared to MDMA, cannabis, ketamine, and alcohol. Over 600 web-based survey responses indicated benefits including help with mood disorders, addictions, and migraines, along with long-term wellbeing improvements. Symptoms of hallucinogen persisting perceptual disorder were most associated with LSD, though few users found them troubling. Eighty-one percent reported a spiritual experience on a hallucinogen, and over 90% considered access to the unconscious mind a specific property of classic hallucinogens. These findings cautiously support calls for systematic investigation of the therapeutic potential of classic hallucinogens.