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.

Modulation of human risky decision making by flunitrazepam

“…Furthermore, the 2-mg dose produced the greatest level of disruption in psychomotor performance (reaction time, balance, and digit symbol substitution). These results were replicated at 4 mg flunitrazepam vs placebo in methadone maintenance patients (Farre et al 1998). McKay and Dundee (1980) observed significant memory impairment with 1 mg flunitrazepam, whereas Jackson et al (1993) observed impaired reaction time but did not find significant effects on memory with 2 mg flunitrazepam.…”

Human Pharmacology of Ayahuasca: Subjective and Cardiovascular Effects, Monoamine Metabolite Excretion, and Pharmacokinetics

“…Oral administration of the freeze-dried material induced feelings of increased activation (ARCI-A, VAS-stimulated), euphoria and well being (ARCI-MBG, VAS-high, VAS-liking, VAS-good effects), and somatic effects (ARCI-LSD), in addition to perceptual modifications (HRS-Perception, VAS-visions) and changes in thought content (HRS-Cognition) and increased emotional lability (HRS-Affect). Increases in VAShigh have been observed after a great variety of drugs including MDMA , cocaine (Farré et al, 1993), and the sedative flunitrazepam (Farré et al, 1998). The VAS-stimulated item reflects more specifically the effects of psychostimulants such as amphetamine and MDMA .…”

“…The VAS-stimulated item reflects more specifically the effects of psychostimulants such as amphetamine and MDMA . Increases in VAS-drunken, which was the least modified VAS item by ayahuasca, have been observed mainly after sedatives, such as flunitrazepam (Farré et al, 1998), and alcohol (Farré et al, 1993), but also after 125 mg of MDMA . Regarding the HRS, our findings are in line with results by other researchers who have demonstrated statistically significant increases in all HRS jpet.aspetjournals.org scales after the administration of various psychedelics, such as i.v.…”

“…VAS were 100-mm horizontal lines with the following labels: "any effect," indicating any effect, either physical or psychological, that the volunteer attributed to the administered drug; "good effects," indicating any effect the volunteer valued as good; "liking," reflecting that the volunteer liked the effects of the administered substance; "drunken," indicating any dizziness or lightheadedness; "stimulated," indicating any increases in thought speed and/or content, or any increases in associations and/or insights; "visions," indicating modifications in visual perception, including any variations in object shape, brightness, or color and any illusion, abstract or elaborate, seen with either eyes closed or open; and "high," which reflected any positive psychological effect the volunteer attributed to the drug. Except for the "visions" item, the other VAS items administered had been used in human studies by other researchers assessing the subjective effects of a variety of psychoactive drugs (Farré et al, 1993(Farré et al, , 1998Camí et al, 2000). The volunteers were requested to answer the VAS immediately before administration (baseline) and at 15, 30, 45, 60, and 75 min, and 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 h after administration.…”

Office-Based Treatment in Opioid Dependence: A Critical Survey of Prescription Practices for Opioid Maintenance Medications and Concomitant Benzodiazepines in Vienna, Austria

“…Benzodiazepine use is strongly linked to a range of negative consequences, including poorer adherence to maintenance programs [24,25] , greater psychological distress, more HIV risk-taking behaviors, poorer health and social functioning, and an increased incidence of overdosing and mortality [26,27] . Several studies have highlighted the potential for these drugs to have additive effects when taken together, including increased sedation and respiratory depression, even at therapeutic doses of each drug [28][29][30] . The risks posed by concomitant benzodiazepine use may vary according to the maintenance drug used.…”