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High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens

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An Erratum to this article was published on 19 June 2013

Abstract

Rationale

Although reports of dextromethorphan (DXM) abuse have increased recently, few studies have examined the effects of high doses of DXM.

Objective

This study in humans evaluated the effects of supratherapeutic doses of DXM and triazolam.

Methods

Single, acute oral doses of DXM (100, 200, 300, 400, 500, 600, 700, and 800 mg/70 kg), triazolam (0.25 and 0.5 mg/70 kg), and placebo were administered to 12 healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Subjective, behavioral, and physiological effects were assessed repeatedly after drug administration for 6 h.

Results

Triazolam produced dose-related increases in subject-rated sedation, observer-rated sedation, and behavioral impairment. DXM produced a profile of dose-related physiological and subjective effects differing from triazolam. DXM effects included increases in blood pressure, heart rate, and emesis; increases in observer-rated effects typical of classic hallucinogens (e.g., distance from reality, visual effects with eyes open and closed, joy, anxiety); and participant ratings of stimulation (e.g., jittery, nervous), somatic effects (e.g., tingling, headache), perceptual changes, end-of-session drug liking, and mystical-type experience. After 400 mg/70 kg DXM, 11 of 12 participants indicated on a pharmacological class questionnaire that they thought they had received a classic hallucinogen (e.g., psilocybin). Drug effects resolved without significant adverse effects by the end of the session. In a 1-month follow-up, volunteers attributed increased spirituality and positive changes in attitudes, moods, and behavior to the session experiences.

Conclusions

High doses of DXM produced effects distinct from triazolam and had characteristics that were similar to the classic hallucinogen psilocybin.

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Acknowledgments

This research was supported by NIDA grant DA003889. We would like to thank Mary Cosimano, M.S.W., Lilian Salinas, and Jenna Cohen for serving as assistant session monitors. We thank John Yingling for technical assistance, Barine Duman Majewska, J.D. for database programming, and Linda Felch for statistical assistance. The study was conducted in compliance with United States laws.

Disclosures

Lawrence Carter is a current employee of Jazz Pharmaceuticals and owns stock and stock options in the company.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD, 21224-6823, USA

    Chad J. Reissig, Matthew W. Johnson, Miriam Z. Mintzer, Margaret A. Klinedinst & Roland R. Griffiths

  2. Department of Neuroscience, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD, 21224-6823, USA

    Roland R. Griffiths

  3. Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA

    Lawrence P. Carter

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  1. Chad J. Reissig
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Correspondence to Roland R. Griffiths.

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Reissig, C.J., Carter, L.P., Johnson, M.W. et al. High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens. Psychopharmacology 223, 1–15 (2012). https://doi.org/10.1007/s00213-012-2680-6

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  • DOI: https://doi.org/10.1007/s00213-012-2680-6

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