Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences

• Published in: Psychopharmacology 2018-02, Vol.235 (2), p.521-534
• Main Authors: Carbonaro, Theresa M., Johnson, Matthew W., Hurwitz, Ethan, Griffiths, Roland R.
• Format: Article
• Language: English
• Subjects: Adult; Altered states of consciousness; Biomedical and Life Sciences; Biomedicine; Blood pressure; Blood Pressure - drug effects; Blood Pressure - physiology; Comparative analysis; Comparative studies; Complications and side effects; Dextromethorphan; Dextromethorphan - administration & dosage; Dose-Response Relationship, Drug; Double-Blind Method; Double-blind studies; Drug dosages; Expectancy; Female; Hallucinations - chemically induced; Hallucinations - psychology; Hallucinogenic drugs; Hallucinogens; Hallucinogens - administration & dosage; Heart rate; Heart Rate - drug effects; Heart Rate - physiology; Humans; Male; Music - psychology; Mysticism - psychology; Nausea; Neurosciences; Original Investigation; Pharmacology/Toxicology; Physiological effects; Physiology; Psilocybin; Psilocybin - administration & dosage; Psychedelic drugs; Psychiatry; Psychopharmacology; Receptor mechanisms; Substance-Related Disorders - drug therapy; Surveys and Questionnaires; Visual effects; Vomiting; Young Adult
• ISSN: 0033-3158; 1432-2072; 1432-2072
• DOI: 10.1007/s00213-017-4769-4

Rationale Although psilocybin and dextromethorphan (DXM) are hallucinogens, they have different receptor mechanisms of action and have not been directly compared. Objective This study compared subjective, behavioral, and physiological effects of psilocybin and dextromethorphan under conditions that minimized expectancy effects. Methods Single, acute oral doses of psilocybin (10, 20, 30 mg/70 kg), DXM (400 mg/70 kg), and placebo were administered under double-blind conditions to 20 healthy participants with histories of hallucinogen use. Instructions to participants and staff minimized expectancy effects. Various subjective, behavioral, and physiological effects were assessed after drug administration. Results High doses of both drugs produced similar increases in participant ratings of peak overall drug effect strength, with similar times to maximal effect and time-course. Psilocybin produced orderly dose-related increases on most participant-rated subjective measures previously shown sensitive to hallucinogens. DXM produced increases on most of these same measures. However, the high dose of psilocybin produced significantly greater and more diverse visual effects than DXM including greater movement and more frequent, brighter, distinctive, and complex (including textured and kaleidoscopic) images and visions. Compared to DXM, psilocybin also produced significantly greater mystical-type and psychologically insightful experiences and greater absorption in music. In contrast, DXM produced larger effects than psilocybin on measures of disembodiment, nausea/emesis, and light-headedness. Both drugs increased systolic blood pressure, heart rate, and pupil dilation and decreased psychomotor performance and balance. Conclusions Psilocybin and DXM produced similar profiles of subjective experiences, with psilocybin producing relatively greater visual, mystical-type, insightful, and musical experiences, and DXM producing greater disembodiment.