title: Abuse liability of flunitrazepam among methadone-maintained patients.
abstract: Abuse liability and acute subjective and psychomotor effects of flunitrazepam were assessed in ten methadone-maintained males with history of benzodiazepine and alcohol use, who voluntarily participated in a double-blind, controlled, cross-over, randomized clinical trial. There were six experimental sessions in which a single oral dose of flunitrazepam 1, 2, and 4 mg; triazolam 0.5 and 0.75 mg; and placebo was given. Evaluations included physiological measures; psychomotor performance tasks (simple reaction time, Digit Symbol Substitution Test, balance task, Maddox-wing device); and self-administered subjective effects questionnaires [Addiction Research Center Inventory (ARCI), Profile of Mood States (POMS), a series of visual analog scales (VAS)]. All drugs but flunitrazepam 1 mg caused an impairment of psychomotor tasks. Effects were more evident with the highest doses of both drugs. Only flunitrazepam 4 mg produced a significant decrease in balance time. Triazolam 0.75 mg induced increases in sedation measured by ARCI-PCAG, depression in POMS, and VAS-drowsiness scores. Flunitrazepam 4mg caused euphoria-related effects as measured by increases in ARCI-MBG and "high" scores in the VAS. Our findings of flunitrazepam-induced euphoria in methadone-maintained subjects together with epidemiological evidence of flunitrazepam abuse by opioid dependents, suggest that it may be included in the group of benzodiazepines with a relatively high abuse potential.
authors.affiliation: Pharmacology Research Unit, Institut Municipal d'Investigació Mèdica, and Universitat Autònoma de Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Farré
authors.forename: M T
authors.initials: MT
authors.lastname: Terán
authors.forename: P N
authors.initials: PN
authors.lastname: Roset
authors.forename: M
authors.initials: M
authors.lastname: Mas
authors.forename: M
authors.initials: M
authors.lastname: Torrens
authors.forename: J
authors.initials: J
authors.lastname: Camí
mesh_terms: D000328:Adult; D014151:Anti-Anxiety Agents; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D005445:Flunitrazepam; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008691:Methadone / Q000627:therapeutic use*; D009294:Narcotics / Q000627:therapeutic use*; D009293:Opioid-Related Disorders / Q000523:psychology* / Q000534:rehabilitation*; D011597:Psychomotor Performance / Q000187:drug effects; D019966:Substance-Related Disorders / Q000523:psychology*; D011795:Surveys and Questionnaires
chemical_list: D014151:Anti-Anxiety Agents; D009294:Narcotics; D005445:Flunitrazepam; D008691:Methadone