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

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.

• Authors: Chad J Reissig, Lawrence P Carter, Matthew W Johnson, Miriam Z Mintzer, Margaret A Klinedinst, Roland R Griffiths
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 223 Issue 1 Pg. 1-15 (Sep 2012) ISSN: 1432-2072 [Electronic] Germany
• PMID: 22526529 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Excitatory Amino Acid Antagonists
• GABA Modulators
• Hallucinogens
• Triazolam
• Psilocybin
• Dextromethorphan

Topics

• Adult
• Affect (drug effects)
• Attitude
• Dextromethorphan (administration & dosage, pharmacology)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Excitatory Amino Acid Antagonists (administration & dosage, pharmacology)
• Female
• Follow-Up Studies
• GABA Modulators (administration & dosage, pharmacology)
• Hallucinogens (pharmacology)
• Humans
• Male
• Psilocybin (pharmacology)
• Surveys and Questionnaires
• Triazolam (administration & dosage, pharmacology)
• Young Adult