Subjective features of the psilocybin experience that may account for its self-administration by humans: a double-blind comparison of psilocybin and dextromethorphan



Although both psilocybin and dextromethorphan (DXM) produce psychedelic-like subjective effects, rates of non-medical use of psilocybin are consistently greater than DXM.


New data are presented from a study of psilocybin and DXM relevant to understanding the features of psilocybin subjective effects that may account for its higher rates of non-medical use.


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.


High doses of both drugs produced similar time courses and increases in participant ratings of peak overall drug effect strength. Nine subjective effect domains are proposed to be related to the reinforcing effects of psilocybin: liking, visual effects, positive mood, insight, positive social effects, increased awareness of beauty (both visual and music), awe/amazement, meaningfulness, and mystical experience. For most ratings, (1) psilocybin and DXM both produced effects significantly greater than placebo; (2) psilocybin showed dose-related increases; 3, DXM was never significantly higher than psilocybin; (4) the two highest psilocybin doses were significantly greater than DXM. These differences were consistent with two measures of desire to take the drug condition again.


This analysis provides new information about domains of psilocybin subjective effects proposed to be related to its reinforcing effects (alternatively described as the “motivation” to use). Observed differences on these domains between psilocybin and DXM are consistent with the relative rates of non-medical use of psilocybin and DXM.

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We thank Frederick Barrett, Ph.D. for contributing to the study design, Mary Cosimano, M.S.W, Ethan Hurwitz, Taylor Marcus, and 6 other staff members for their roles as session monitors, Dr. Annie Umbricht for medical management, Lisa Schade for technical assistance, Linda Felch for statistical assistance, and the pharmacy and medical staff. We also thank David Nichols, Ph.D., for synthesizing the psilocybin.


Conduct of this research was supported by NIH grants R01DA03889 and T32 DA07209, the Heffter Research Institute, Tim Ferriss, Matt Mullenweg, Craig Nerenberg, Blake Mycoskie, and the Steven and Alexandra Cohen Foundation.

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Correspondence to Roland R. Griffiths.

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The study was conducted in compliance with US laws.

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Roland Griffiths is on the Board of Directors of the Heffter Research Institute.

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Carbonaro, T.M., Johnson, M.W. & Griffiths, R.R. Subjective features of the psilocybin experience that may account for its self-administration by humans: a double-blind comparison of psilocybin and dextromethorphan. Psychopharmacology 237, 2293–2304 (2020).

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  • Psilocybin
  • Dextromethorphan
  • Hallucinogen
  • Psychedelic
  • Abuse liability
  • Reinforcing effects
  • Mood
  • Insight
  • Subjective experience
  • Mystical experience
  • Insightful experience
  • Humans