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

Although reports of dextromethorphan (DXM) abuse have increased recently, few studies have examined the effects of high doses of DXM. This study in humans evaluated the effects of supratherapeutic doses of DXM and triazolam. 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. 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. High doses of DXM produced effects distinct from triazolam and had characteristics that were similar to the classic hallucinogen psilocybin.