Agonist Therapy for Stimulant Addiction

Agonist therapy is the use of a (usually) long-acting medication that stimulates the same brain receptors as the drug of addiction. The most obvious example is opioid agonist therapy for opioid addiction using methadone or buprenorphine. Several medications potentially useful for alcohol addiction stimulate GABA receptors as does alcohol. One reason agonist therapy works is that it relieves drug hunger without inducing intoxication. Antagonist therapy, such as using naltrexone to treat opioid addiction can work, but it usually does not relieve drug hunger, so people stop them to seek intoxication. In this new study in Neuropsychopharmacology, a controlled-release form of amphetamine was studied as a treatment for cocaine addiction, with some intriguing results.

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Sustained Release d-Amphetamine Reduces Cocaine but not ‘Speedball’-Seeking in Buprenorphine-Maintained Volunteers: A Test of Dual-Agonist Pharmacotherapy for Cocaine/Heroin Polydrug Abusers

Mark K Greenwald1, Leslie H Lundahl1 and Caren L Steinmiller1,2

1. 1Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA
2. 2Department of Pharmacology and Toxicology, University of Toledo, Toledo, OH, USA

Correspondence: Dr M Greenwald, Department of Psychiatry and Behavioral Neurosciences, Substance Abuse Research Division, 2761 East Jefferson Ave., Detroit, MI 48207, USA. Tel: +1 313 993 3965; Fax: +1 313 993 1372; E-mail: mgreen@med.wayne.edu

Received 18 May 2010; Revised 27 August 2010; Accepted 28 August 2010; Published online 29 September 2010.
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Abstract

The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid/cocaine combination (‘speedball’-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8 mg/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8 mg/day maintenance and double-blind ascending SR-AMP weekly doses of 0, 30, and 60 mg/day, respectively. After 3 days (Saturday–Monday) stabilization at each SR-AMP weekly dose (0, 15, or 30 mg administered at 0700 and 1225 each day), on Tuesday–Friday mornings (0900–1200 hours), participants sampled four drug combinations in randomized, counterbalanced order under double-blind, double-dummy (intranasal cocaine and intramuscular hydromorphone) conditions: cocaine (COC 100 mg+saline); hydromorphone (COC 4 mg+HYD 24 mg); ‘speedball’ (COC 100 mg+HYD 24 mg); and placebo (COC 4 mg+saline). Subjective and physiological effects of these drug combinations were measured. From 1230 to 1530 hours, participants could respond on a choice, 12-trial progressive ratio schedule to earn drug units (1/12th of total morning dose) or money units (US$2). SR-AMP significantly reduced COC, but not HYD or speedball, choices and breakpoints. SR-AMP also significantly reduced COC subjective (eg, abuse-related) effects and did not potentiate COC-induced cardiovascular responses. This study shows the ability of SR-AMP to attenuate COC self-administration, as well as its selectivity, in cocaine/heroin polydrug abusers. Further research is warranted to ascertain whether SR-AMP combined with BUP could be a useful dual-agonist pharmacotherapy.