Relative abuse liability of gamma-hydroxybutyric acid, flunitrazepam, and ethanol in club drug users.
OBJECTIVE
Despite the increasing concern about gamma-hydroxybutyric acid (GHB) toxicity, there are few studies examining the clinical pharmacology of GHB and its abuse potential. To evaluate GHB-induced subjective and physiological effects, its relative abuse liability and its impact on psychomotor performance in club drug users.


METHODS
Twelve healthy male recreational users of GHB participated in 5 experimental sessions in the framework of a clinical trial. The study was randomized, double-blind, double-dummy, and crossover. Drug conditions were a single oral dose of GHB (40 or 60 mg/kg), ethanol (0.7 g/kg), flunitrazepam (1.25 mg), and placebo. Study variables included vital signs (blood pressure, heart rate, oral temperature, pupil diameter), psychomotor performance (digit symbol substitution test, balance, Maddox-Wing), subjective effects (a set of 13 visual analogue scales, Addiction Research Center Inventory-49 items, and Evaluation of the Subjective Effects of Substances with Potential of Abuse questionnaires), and pharmacokinetics.


RESULTS
All active conditions induced positive effects related to their abuse potential. The administration of GHB produced euphoria and pleasurable effects with slightly higher ratings than those observed for flunitrazepam and ethanol. Gamma-hydroxybutyric acid induced a biphasic time profile with an initial stimulant-like effect related to the simultaneous rise of plasma concentrations and a latter sedative effect not related to GHB kinetics. Gamma-hydroxybutyric acid increased blood pressure and pupil diameter. Ethanol induced its prototypical effects, and flunitrazepam produced marked sedation. Gamma-hydroxybutyric acid and flunitrazepam impaired psychomotor performance, digit symbol substitution test, and balance task, whereas ethanol, at the dose tested, induced only mild effects exclusively affecting the balance task.


CONCLUSIONS
Our results suggest a high abuse liability of GHB and flunitrazepam in club drug users.
Abanades
Sergio
S
Pharmacology Research Unit, Human Pharmacology and Clinical Neurosciences Research Group, Institut Municipal d'Investigació Mèdica, c/Doctor Aiguader 80, Barcelona, Spain. sabanades@imim.es
Farré
Magi
M
Barral
Diego
D
Torrens
Marta
M
Closas
Neus
N
Langohr
Klaus
K
Pastor
Antoni
A
de la Torre
Rafael
R
D000284:Administration, Oral; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D005099:Exotropia / Q000139:chemically induced; D005445:Flunitrazepam / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006885:Hydroxybutyrates / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D008297:Male; D015877:Miosis / Q000139:chemically induced; D015878:Mydriasis / Q000139:chemically induced; D011569:Psychiatric Status Rating Scales; D011597:Psychomotor Performance / Q000187:drug effects; D019966:Substance-Related Disorders / Q000209:etiology / Q000523:psychology*; D011795:Surveys and Questionnaires; D013546:Sweating / Q000187:drug effects; D014839:Vomiting / Q000139:chemically induced
D014151:Anti-Anxiety Agents; D002492:Central Nervous System Depressants; D006885:Hydroxybutyrates; C111420:4-hydroxybutyric acid; D000431:Ethanol; D005445:Flunitrazepam