Abuse liability and acute subjective and psychomotor effects of flunitrazep
am were assessed in ten methadone-maintained males with history of benzodia
zepine and alcohol use, who voluntarily participated in a double-blind, con
trolled, cross-over, randomized clinical trial. There were six experimental
sessions in which a single oral dose of flunitrazepam 1, 2, and 4 mg; tria
zolam 0.5 and 0.75 mg; and placebo was given. Evaluations included physiolo
gical measures; psychomotor performance tasks (simple reaction time, Digit
Symbol Substitution Test, balance task, Maddox-wing device); and self-admin
istered subjective effects questionnaires [Addiction Research Center Invent
ory (ARCI), Profile of Mood States (POMS), a series of visual analog scales
(VAS)]. All drugs but flunitrazepam 1 mg caused an impairment of psychomot
or tasks. Effects were more evident with the highest doses of both drugs. O
nly flunitrazepam 4 mg produced a significant decrease in balance time. Tri
azolam 0.75 mg induced increases in sedation measured by ARCI-PCAG, depress
ion in POMS, and VAS-drowsiness scores. Flunitrazepam 4 mg caused euphoria-
related effects as measured by increases in ARCI-MBG and "high" scores in t
he VAS. Our findings of flunitrazepam-induced euphoria in methadone-maintai
ned subjects together with epidemiological evidence of flunitrazepam abuse
by opioid dependents, suggest that it may be included in the group of benzo
diazepines with a relatively high abuse potential.