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

Abstract

Rationale

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

Objective

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.

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.

Results

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.

Conclusions

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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References

  1. Adinoff B (2004) Neurobiologic processes in drug reward and addiction. Harv Rev Psychiatry 12(6):305–320. https://doi.org/10.1080/10673220490910844

    Article  PubMed  PubMed Central  Google Scholar 

  2. Barrett FS, Johnson MW, Griffiths RR (2015) Validation of the revised mystical experience questionnaire in experimental sessions with psilocybin. J Psychopharmacol 29(11):1182–1190

    CAS  Article  Google Scholar 

  3. Barrett FS, Carbonaro TM, Hurwitz E, Johnson MW, Griffiths RR (2018) Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: effects on cognition. Psychopharmacology 235(10):2915–2927. https://doi.org/10.1007/s00213-018-4981-x

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. Bershad AK, Schepers ST, Bremmer MP, Lee R, de Wit H (2019) Acute subjective and behavioral effects of microdoses of lysergic acid diethylamide in healthy human volunteers. Biol Psychiatry 86(10):792–800. https://doi.org/10.1016/j.biopsych.2019.05.019

    CAS  Article  PubMed  Google Scholar 

  5. Bouso JC, Pedrero-Pérez EJ, Gandy S, Alcázar-Córcoles MÁ (2016) Measuring the subjective: revisiting the psychometric properties of three rating scales that assess the acute effects of hallucinogens. Hum Psychopharmacol 31(5):356–372. https://doi.org/10.1002/hup.2545

    CAS  Article  PubMed  Google Scholar 

  6. Carbonaro TM, Johnson MW, Hurwitz E, Griffiths RR (2018) Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences. Psychopharmacology 235(2):521–534. https://doi.org/10.1007/s00213-017-4769-4

    CAS  Article  PubMed  Google Scholar 

  7. Church J (1990) Dextromethorphan, dysphoria and NMDA receptors. Neuromodulatory effects of dextromethorphan: role of NMDA receptors in responses. Trends Pharmacol Sci 11:146–147

    CAS  Article  Google Scholar 

  8. Church J, Sawyer D, McLarnon JG (1994) Interactions of dextromethorphan with the N-methyl-D-aspartate receptor-channel complex: single channel recordings. Brain Res 666:189–194

    CAS  Article  Google Scholar 

  9. Cohen AY (1971) The journey beyond trips: alternatives to drugs. J Psychedelic Drugs 3(2):16–21

    Article  Google Scholar 

  10. Dittrich A (1998) The standardized psychometric assessment of altered states of consciousness (ACSs) in humans. Pharmacopsychiatry 31(Suppl 2):80–84

    Article  Google Scholar 

  11. Fadiman J, Korb S (2019) Might microdosing psychedelics be safe and beneficial? An initial exploration. J Psychoactive Drugs 51(2):118–122. https://doi.org/10.1080/02791072.2019.1593561

    Article  PubMed  Google Scholar 

  12. Fantegrossi WE, Woods JH, Winger G (2004) Transient reinforcing effects of phenylisopropylamine and indolealkylamine hallucinogens in rhesus monkeys. Behav Pharmacol 15(2):149–157. https://doi.org/10.1097/00008877-200403000-00007

    CAS  Article  PubMed  Google Scholar 

  13. Griffiths RR, Richards WA, McCann U, Jesse R (2006) Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology 187(3):268–283 discussion 284–92

    CAS  Article  Google Scholar 

  14. Griffiths RR, Johnson MW, Richards WA, Richards BD, McCann U, Jesse R (2011) Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology 218(4):649–665

    CAS  Article  Google Scholar 

  15. Griffiths RR, Hurwitz ES, Davis AK, Johnson MW, Jesse R (2019) Survey of subjective “God encounter experiences”: comparisons among naturally occurring experiences and those occasioned by the classic psychedelics psilocybin, LSD, ayahuasca, or DMT. PLoS One 14(4):e0214377. https://doi.org/10.1371/journal.pone.0214377

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. Hutten NRPW, Mason NL, Dolder PC, Kuypers KPC (2019) Self-rated effectiveness of microdosing with psychedelics for mental and physical health problems among microdosers. Front Psychiatry 10:672. https://doi.org/10.3389/fpsyt.2019.00672

    Article  PubMed  PubMed Central  Google Scholar 

  17. Johnson MW, Griffiths RR (2013) Comparative abuse liability of GHB and ethanol in humans [published correction appears in Exp Clin Psychopharmacol 21(5):374] Exp Clin Psychopharmacol 21(2):112–123 https://doi.org/10.1037/a0031692

  18. Johnson MW, Griffiths RR, Hendricks PS, Henningfield JE (2018) The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act. Neuropharmacology 142:143–166. https://doi.org/10.1016/j.neuropharm.2018.05.012

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Kuypers KP, Ng L, Erritzoe D et al (2019) Microdosing psychedelics: more questions than answers? An overview and suggestions for future research. J Psychopharmacol 33(9):1039–1057. https://doi.org/10.1177/0269881119857204

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. Labate BC, Cavnar C, Rodrigues T (2016) Drug policies and the politics of drugs in the Americas. Springer International Publishing, Switzerland

    Book  Google Scholar 

  21. Lea T, Amada N, Jungaberle H, Schecke H, Klein M (2019) Microdosing psychedelics: motivations, subjective effects and harm reduction [published online ahead of print, 2019 Nov 25]. Int J Drug Policy 75:102600 https://doi.org/10.1016/j.drugpo.2019.11.008

  22. MacLean KA, Leoutsakos JM, Johnson MW, Griffiths RR (2012) Factor analysis of the mystical experience questionnaire: a study of experiences occasioned by the hallucinogen psilocybin. J Sci Study Relig 51(4):721–737

    Article  Google Scholar 

  23. Martin WR (1973) Assessment of the abuse-potentiality of amphetamines and LSD-like hallucinogens in man and its relationship to basic animal assessment programs. In: Goldberg L, Hoffmeister F (eds) Bayer-Symposium IV, psychic dependence. Springer-Verlag, New York, pp 146–155

    Google Scholar 

  24. Metzner R (2004) Teonanacatl: sacred mushroom of visions. Four Tree, El Verano

    Google Scholar 

  25. Müller CP, Schumann G (2011) Drugs as instruments: a new framework for non-addictive psychoactive drug use. Behav Brain Sci 34(6):293–310

    Article  Google Scholar 

  26. Nichols DE (2016) Psychedelics. Pharmacol Rev 68:264–355

    CAS  Article  Google Scholar 

  27. NIDA, National Institute on Drug Abuse (2019) https://www.drugabuse.gov/publications/drugfacts/hallucinogens (accessed online July 2019)

  28. Passie T (2019) Science of microdosing psychedelics. Psychedelic Press, London

    Google Scholar 

  29. Pollan M (2018) How to change your mind: what the new science of psychedelics teaches us about consciousness, dying, addiction, depression, and transcendence. Penguin Press, New York

    Google Scholar 

  30. Reissig CJ, Carter LP, Johnson MW, Mintzer MZ, Klinedinst MA, Griffiths RR (2012) High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens. Psychopharmacology 223(1):1–15

    CAS  Article  Google Scholar 

  31. Schuster CR, Thompson T (1969) Self administration of and behavioral dependence on drugs. Ann Rev Pharmacol 9:483–502

    CAS  Article  Google Scholar 

  32. 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 51:98–108

  33. Studerus E, Gamma A, Vollenweider FX (2010) Psychometric evaluation of the altered states of consciousness rating scale (OAV). PLoS One 5(8):e12412

    Article  Google Scholar 

  34. U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration (SAMHSA), Center for Behavioral Health Statistics and Quality (2019) National survey on drug use and health 2002–2018 (NSDUH-2002-2018). Retrieved from https://datafiles.samhsa.gov/ (last accessed online August 2019)

  35. Volkow ND, Michaelides M, Baler R (2019) The neuroscience of drug reward and addiction. Physiol Rev 99(4):2115–2140. https://doi.org/10.1152/physrev.00014.2018

    CAS  Article  PubMed  Google Scholar 

  36. Wasson RG (1980) The wondrous mushroom: mycolatry in Meso-america. McGraw-Hill, New York

    Google Scholar 

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Acknowledgments

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.

Funding

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.

Conflict of interest

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). https://doi.org/10.1007/s00213-020-05533-9

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Keywords

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