In cancer patients with life-threatening diagnoses and symptoms of depression or anxiety, a high dose of psilocybin (22 or 30 mg/70 kg) produced large decreases in depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety, compared with a very low placebo-like dose (1 or 3 mg/70 kg). At 6-month follow-up, about 80% of participants continued to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life, mood, relationships, and spirituality to the high-dose experience, with over 80% endorsing moderately or greater increased well-being or life satisfaction. The mystical-type experience during the session mediated the effect of dose on therapeutic outcomes.
High doses of the cough suppressant dextromethorphan (DXM) produce perceptual changes, mystical-type experiences, and physiological effects similar to those of classic hallucinogens like psilocybin. In a double-blind study, 12 healthy volunteers with histories of hallucinogen use received single oral doses of DXM ranging from 100 to 800 mg/70 kg, triazolam, or placebo. DXM dose-dependently increased blood pressure, heart rate, and emesis, and elicited observer-rated hallucinogen-like effects such as visual distortions and joy. After 400 mg/70 kg DXM, 11 of 12 participants thought they had received a classic hallucinogen. At a 1-month follow-up, volunteers reported lasting positive changes in spirituality, attitudes, and mood attributed to the session.
Acute high doses of dextromethorphan (DXM) impair attention, working memory, episodic memory, and metacognition in healthy volunteers with histories of hallucinogen use. Impairments from 100–300 mg/70 kg DXM were generally smaller than those from 0.5 mg/70 kg triazolam. Doses needed to match triazolam's impairment exceeded 10–30 times the therapeutic dose. Supratherapeutic doses caused impairments on all tasks, indicating a broad therapeutic window for over-the-counter DXM when used appropriately, but relevance to high-dose abuse.