Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences
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Although psilocybin and dextromethorphan (DXM) are hallucinogens, they have different receptor mechanisms of action and have not been directly compared.
This study compared subjective, behavioral, and physiological effects of psilocybin and dextromethorphan under conditions that minimized expectancy effects.
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.
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.
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.
KeywordsPsilocybin Dextromethorphan Hallucinogen Psychedelic Subjective experience Mystical experience Insightful experience Humans
We thank Mary Cosimano, M.S.W, Taylor Marcus, Darrick May, M.D., and five other staff members for their roles as session monitors, Dr. Annie Umbricht for medical management, Frederick Barrett, Ph.D., for contributing to the study design, 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 and Michelle Rudek, Pharm.D., Ph.D., and Nichole Anders of the Analytical Pharmacology Core for analyzing dextromethorphan metabolism. The study was conducted in compliance with US laws.
Conduct of this research was supported by NIH R01DA03889 and T32 DA07209. Support for dextromethorphan metabolic analysis was supported by NIH grants P30CA006973 and UL1TR001079 and the Shared Instrument Grant S10OD020091 to the Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center.
Compliance with ethical standards
The study was approved by the Institutional Review Board of the Johns Hopkins University School of Medicine. Participants gave their written informed consent before beginning the study procedures and were paid for their participation.
Conflict of interest
Dr. Carbonaro is an employee of the U.S. Food and Drug Administration (FDA); however, the views presented in this article do not necessarily reflect those of the FDA and no official support or endorsement of this article by the FDA is intended or should be inferred. Roland Griffiths is on the Board of Directors of the Heffter Research Institute.
- Barrett FS, Griffiths RR (2017) Classic hallucinogens and mystical experiences: phenomenology and neural correlates. Curr Top Behav Neurosci. https://doi.org/10.1007/7854_2017_474
- Barrett FS, Robbins H, Smooke D, Brown JL, Griffiths RR (2017). Qualitative and quantitative features of music reported to support peak mystical experiences during psychedelic therapy sessions. Front Psychol 8:1238Google Scholar
- Brown RT, Nicholas CR, Cozzi NV, Gassman MC, Cooper KM, Muller D, Thomas CD, Hetzel SJ, Henriquez KM, Ribaudo AS, Hutson PR (2017) Pharmacokinetics of escalating doses of oral psilocybin in healthy adults. Clin Pharmacokinet. https://doi.org/10.1007/s40262-017-0540-6
- Carbonaro TM, Eshleman AJ, Forster MJ, Cheng K, Rice KC, Gatch MB (2015) The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice. Psychopharmacology 232(1):275–284CrossRefPubMedGoogle Scholar
- Fribourg M, Moreno JL, Holloway T, Provasi D, Baki L, Mahajan R, Park G, Adnewy SK, Hatcher C, Eltit JM, Ruta JD, Albizu L, Li Z, Umali A, Shim J, Fabiato A, MacKerell AD Jr, Brezina V, Sealfron SC, Filizola M, Gonzalez-Maeso J, Logothetis DE (2011) Decoding the signaling of a GPCR heteromeric complex reveals a unifying mechanism of action of antipsychotic drugs. Cell 147(5):1011–1023CrossRefPubMedPubMedCentralGoogle Scholar
- Gonzalez-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, Lopez-Gimenez JF, Zhou M, Okawa Y, Callado LF, Milligan G, Gingrich JA, Filizola M, Meana JJ, Sealfon SC (2008) Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 452:93–97CrossRefPubMedPubMedCentralGoogle Scholar
- Hood RW, Hill PC, Bernard S (2009) The psychology of religion: an empirical approach. Guilford Press, New YorkGoogle Scholar
- Jansen KLR (2004) Ketamine: dreams and realities. Multidisciplinary Association for Psychedelic Studies (MAPS), Sarasota, FLGoogle Scholar
- MacLean KA, Johnson MW, Griffiths RR (2015) Hallucinogens and club drugs. In: Galanter M, Kleber HD, Bradu L (eds) The American Psychiatric Press Textbook of Substance Abuse Treatment, Fifth ed. The American Psychiatric Press, Arlington, VA, pp 209–222Google Scholar
- Metzner R, Litwin G, Weil G (1965) The relation of expectation and mood to psilocybin reactions: a questionnaire study. Psychedelic Review 5:3–39Google Scholar
- Narby J (1999) The cosmic serpent DNA and the origins of knowledge. Jeremy P. Tarcher/Putnam, New York, NYGoogle Scholar
- Preller KH, Vollenweider FX (2016) Phenomenology, structure, and dynamic of psychedelic states. Curr Top Behav Neurosci. https://doi.org/10.1007/7854_2016_459
- SAMHSA (2015) 2014 National Survey on Drug Use and Health: detailed tables. Center for Behavioral Health Statistics and Quality. Substance Abuse and Mental Health Services Administration Rockville, MDGoogle Scholar
- SAMHSA (2016) 2015 National Survey on Drug Use and Health: detailed tables. Center for Behavioral Health Statistics and Quality. Substance Abuse and Mental Health Services Administration Rockville, MDGoogle Scholar
- Shulgin A, Shulgin A (1997) TiHKAL. Transform Press, Berkeley, CAGoogle Scholar
- Strassman R (2001) DMT: the spirit molecule. Park Street Press, Rochester, VAGoogle Scholar
- Strassman RJ, Qualls CR, Uhlenhuth EH, Kellner R (1994) Dose response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale. Arch Gen Psychiatry 51:98–108Google Scholar
- White W (2002) The DXM experience. https://www.erowid.org/chemicals/dxm/faq/dxm_experience.shtml#toc.5. Accessed 15 July 2017