Self-administration of gamma-hydroxybutyric acid (GHB) precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) in baboons
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Gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are gamma-hydroxybutyrate (GHB) pro-drugs and drugs of abuse.
Given the reports of abuse, and the ease at which GBL and 1,4-BD may be obtained, we investigated the reinforcing effects of GBL (n = 5) and 1,4-BD (n = 4) in baboons using IV self-administration procedures.
Sessions ran 24 h/day. Each injection was contingent upon completion of a fixed number (120 or 160) of lever responses. A 3-h timeout period followed each injection, limiting the total number of injections to eight per day. Self-administration was first established with cocaine (0.32 mg/kg/injection). GBL (10–130.0 mg/kg/injection), 1,4-BD (10–100 mg/kg/injection), or vehicle was substituted for cocaine for at least 15 days. Food pellets were available ad libitum 24 h/day and were contingent upon completion of ten lever responses.
GBL (32–100 mg/kg/injection) maintained significantly greater numbers of injections when compared to vehicle in four of five baboons, and the mean rates of injection were high (more than six per day) in three baboons and moderate in the fourth baboon (four to six per day). 1,4-BD (78–130 mg/kg/injection) maintained significantly greater numbers of injections when compared to vehicle in only two out of four baboons, and mean rates were moderate to high in both baboons. Self-injection of these doses of GBL and 1,4-BD generally inhibited food-maintained responding.
GBL and 1,4-BD have abuse liability. Given that GBL and 1,4-BD are self-administered, are easier to obtain than GHB, and are detected in seized samples, additional legal control measures of these GHB pro-drugs may be needed.
KeywordsGamma-hydroxybutyrate Self-administration Abuse liability Zolpidem Cocaine Reinforcement Operant behavior Drug abuse
- Andresen H, Aydin BE, Mueller A, Iwersen-Bergmann S (2011) An overview of gamma-hydroxybutyric acid: pharmacodynamics, pharmacokinetics, toxic effects, addiction, analytical methods, and interpretation of results. Drug Test Anal 3:560–8Google Scholar
- Beardsley P, Balster R, Harris L (1996) Evaluation of the discriminative stimulus and reinforcing effects of gammahydroxybutyrate (GHB). Psychopharmacology (Berl) 127:315–322Google Scholar
- CDC (1999) Adverse events associated with ingestion of gamma-butyrolactone: Minnesota, New Mexico, and Texas, 1998–1999. U.S. Government Printing Office, Atlanta, pp 137–140Google Scholar
- DEA (2000) Placement of gamma-butyrolactone in List I of the Controlled Substances Act (21 U.S.C. 802(34)). Drug Enforcement Administration, Justice. Final rule. Fed Regist 65:21645–21647Google Scholar
- ECDD WHO (2012) Gamma-hydroxybutyric acide (GHB) critical review report. In: World Health Organization (WHO), 35th Expert Committee on Drug Dependence (ECDD): Hammamet, TunisiaGoogle Scholar
- EMCDDA (2008) GHB and its precursor GBL: an emerging trend case study. European Monitoring Centre for Drugs and Drug Addiction thematic paper. EMCDDA, LisbonGoogle Scholar
- Irwin RD (1996) NTP Summary report on the mtabolism, disposition, and toxicity of 1,4-butanediol (CAS No 110-63-4). Natl Toxicol Prog Toxicity Rep Ser 54:1–28Google Scholar
- Karila L, Reynaud M (2010) GHB and synthetic cathinones: clinical effects and potential consequences. Drug Test Anal 3:552–9Google Scholar
- Vree TB, van Dalen R, Kleijn VD, Gimbrere JSF (1978) Pharmacokinetics of 1,4-butanediol and 4-hydroxybutyric acid in man, rhesus monkey, and dog. Anasthesiol Intensivmed Notfallmed Schmerzther 110:66–73Google Scholar
- Wojtowicz J, Yatema M, Wax P (2008) Withdrawal from gamma-hydroxybutyrate, 1,4-butanediol and gamma-butyrolactone: a case report and systematic review. Can J Emerg Med 10:69–74Google Scholar
- Wood DM, Brailsford AD, Dargan PI (2011) Acute toxicity and withdrawal syndromes related to gamma-hydroxybutyrate (GHB) and its analogues gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD). Drug Test Anal 3:417–25Google Scholar