A comparison of the acute behavioral effects of flunitrazepam and triazolam in healthy volunteers

Abstract

Flunitrazepam is an hypnotic benzodiazepine marketed in different European countries. Epidemiological studies have shown that it is frequently abused by opioid addicts. In a survey, "liking" scores for flunitrazepam in methadone maintenance patients were higher than ratings for other benzodiazepines. A double-blind, placebo controlled, crossover clinical trial was conducted to assess the acute behavioral effects of flunitrazepam (0.50 and 2 mg) and triazolam (0.25 and 0.50 mg) in healthy male volunteers. Drug effects on physiological measures, psychomotor performance, and subjective rating scales, including specific questionnaires to evaluate abuse liability (e.g., ARCI or "liking" scores), were assessed before and 6 h after drug administration. Flunitrazepam 2 mg produced the most intense disruptive effects on all the performance tasks, triazolam 0.50 impaired performance except balance. All study drugs at all doses produced sedation symptoms in all or part of the subjective effects questionnaires. Only flunitrazepam 2 mg induced significative increases in some of the scales ("liking", "good effects", "high") that could be related to a possible abuse potential. The results seem to indicate that flunitrazepam, when administered to healthy subjects, produces some pleasurable subjective feelings, that could indicate a higher abuse liability of this drug as compared with other benzodiazepines.

3,4-Methylenedioxymethamphetamine (Ecstasy) and Alcohol Interactions in Humans: Psychomotor Performance, Subjective Effects, and Pharmacokinetics

“…On the other hand, MDMA also reverted the effects of alcohol on the ARCI-BG, increasing the scores above those obtained after MDMA alone administration. This scale is a recognized measure of intellectual efficiency, and the administration of amphetamines or other stimulants increases the scores (Camí et al, 2000a), whereas the administration of sedatives as benzodiazepines or alcohol decrease the scores (Farré et al, 1996(Farré et al, , 1997Holdstock and de Wit, 1999).…”

“…This task is a direct measure of the extraocular musculature relaxation and indirect measure of central sedation. The administration of sedatives such as benzodiazepines or ethanol induced exophoria (Farré et al, 1993(Farré et al, , 1996, whereas the administration of stimulants as amphetamine or MDMA produced esophoria (Camí et al, 2000a). These findings suggest that MDMA can reduce the sedation associated to alcohol administration.…”

Abuse liability of flunitrazepam among methadone-maintained patients

“…The six drug conditions were as follows : ßunitrazepam 1, 2, and 4 mg (Rohipnol, Laboratorios Roche, S.A., Madrid, Spain), triazolam 0.5 and 0.75 mg (Halcion, Upjohn Farmoquímica, Madrid, Spain), and placebo (lactose). The doses of ßunitrazepam and triazolam were selected according to previous studies in healthy volunteers (Farré et al 1996). Drugs were supplied by the Pharmacy Department of Hospital del Mar as identically appearing opaque white soft-gelatin capsules.…”

“…In a study in healthy volunteers (Farré et al 1996), ßunitrazepam induced statistically signiÞcant increases in some pleasurablerelated subjective e¤ects (liking, good e¤ects, high) that may be related to its abuse potential. This study was designed to assess the acute subjective and psychomotor e¤ects of ßunitrazepam in methadonemaintained patients.…”

Modulation of human risky decision making by flunitrazepam

“…At 24 h after administration, abuse potential ratings for flunitrazepam were greater than placebo Griffiths 1998, 2005). Similarly, at doses ranging up to 2 mg, Farre et al (1996) found significantly increased rating scores on items related to abuse potential ("like drug", "good effects") compared to placebo. Furthermore, the 2-mg dose produced the greatest level of disruption in psychomotor performance (reaction time, balance, and digit symbol substitution).…”