Effects of Baclofen on Cocaine Self-Administration: Opioid- and Nonopioid-Dependent Volunteers

Department of Psychiatry, College of Physicians and Surgeons of Columbia University and the Division on Substance Abuse, New York State Psychiatric Institute, New York, NY 10032, USA.
Neuropsychopharmacology (Impact Factor: 7.05). 09/2006; 31(8):1814-21. DOI: 10.1038/sj.npp.1300999
Source: PubMed


Preclinical and clinical studies suggest that GABAB receptor agonists selectively decrease cocaine use. The behavioral mechanism for the interaction between baclofen and cocaine in humans is not known, nor have its effects been characterized in individuals dependent on both cocaine and methadone. The objective of this study is to determine how maintenance on baclofen influences smoked cocaine's reinforcing and subjective effects, mood and cocaine craving prior to and after the initiation of cocaine use in cocaine-dependent volunteers with and without concurrent opioid dependence. Nontreatment-seeking volunteers (10 nonopioid dependent; seven methadone maintained), residing on an in-patient research unit for 21 days, were maintained on each baclofen dose (0, 30, 60 mg po) for 7 days. A smoked cocaine dose-response curve (0, 12, 25, 50 mg) was determined twice: on days 3-4 and days 6-7 of each baclofen maintenance condition. Cocaine sessions began with a sample trial, when participants smoked the cocaine dose available that session, and five choice trials, when participants chose between smoking the available cocaine dose or receiving one 5 dollars merchandise voucher. The results show that in the nonmethadone group, baclofen (60 mg) decreased self-administration of a low cocaine dose (12 mg). In the methadone group, baclofen decreased craving for cocaine. In both groups, baclofen decreased cocaine's effects on heart rate. Baclofen did not alter cocaine's robust subjective effects (eg 'High,' 'Stimulated') for either group. The results from this laboratory study appear consistent with clinical evidence showing that baclofen decreases cocaine use in nonopioid-dependent patients seeking treatment for cocaine dependence. The distinct pattern of effects in methadone-maintained participants suggests baclofen may not be effective in opioid-dependent cocaine users.

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    • "Abundant convincing evidences have revealed that the GABAB receptor agonist can suppress many behavior changes induced by opioid and non-opioid [17]. It has been reported that GABAB receptor agonist decreases the cocaine and nicotine self-administration [20,21], blocks expression and sensitization of anxiety-like behavior induced by ethanol withdrawal [22], and suppresses the development of sensitization to the locomotor of amphetamine [23]. In addition, GABAergic potentiation following chronic morphine treatment attenuates the rewarding effects of opioids in the ventral tegmental area [24]. "
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    ABSTRACT: Repeated morphine exposure can induce behavioral sensitization. There are evidences have shown that central gamma-aminobutyric acid (GABA) system is involved in morphine dependence. However, the effect of a GABAB receptor agonist baclofen on morphine-induced behavioral sensitization in rats is unclear. We used morphine-induced behavioral sensitization model in rat to investigate the effects of baclofen on behavioral sensitization. Moreover, dopamine release in the shell of the nucleus accumbens was evaluated using microdialysis assay in vivo. The present study demonstrated that morphine challenge (3 mg/kg, s.c.) obviously enhanced the locomotor activity following 4-day consecutive morphine administration and 3-day withdrawal period, which indicated the expression of morphine sensitization. In addition, chronic treatment with baclofen (2.5, 5 mg/kg) significantly inhibited the development of morphine sensitization. It was also found that morphine challenge 3 days after repeated morphine administration produced a significant increase of extracellular dopamine release in nucleus accumbens. Furthermore, chronic treatment with baclofen decreased the dopamine release induced by morphine challenge. Our results indicated that gamma-aminobutyric acid system plays an important role in the morphine sensitization in rat and suggested that behavioral sensitization is a promising model to study the mechanism underlying drug abuse.
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    • "Baclofen has also been investigated for its effects on relieving addiction to cocaine. In one study, users of freebase or crack cocaine who self-administered through inhalation of the drug (Haney et al., 2006). Users who were either treated with methadone or not were given varying doses of baclofen and subsequently were asked to choose to take either the available dose of cocaine or five dollar merchandise voucher. "

    Full-text · Chapter · Mar 2012
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    • "Baclofen has shown efficacy for reducing cocaine use among non-opioid dependent addicts in a laboratory study but it is not clear that baclofen can be effective outside of the laboratory. Interestingly, however, some aspects of the major study of baclofen suggests that it could be effective in combination with contingency management (Haney et al. 2006). "
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