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someone's been dipping into the Blammy again

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Recent studies by Foltin, Fischman and colleagues and by Walsh and colleagues have evaluated the acute subjective and physiological effects of cocaine in combination with opioid mu agonists. The subjective effects of various dose combinations of mu agonists and cocaine were greater than those produced by either drug alone on measures such as "drug liking" and "high". The qualitative profile of subjective effects produced by the opioid/cocaine combination was roughly equivalent to the sum of effects produced by the two drugs singly, rather than producing novel or unique subjective effects. The cardiovascular effects of cocaine, including tachycardia and pressor action, were enhanced when cocaine was administered in the presence of the mu agonist. Other studies have compared the effects of cocaine in opioid-dependent subjects during chronic maintenance on mu opioid agonists. In studies of methodone-maintained patients, the subjective response to cocaine (e.g., "magnitude of drug effect", "good effect") was significantly greater compared to control subjects. Similarly, some studies in buprenorphine-maintained patients reported that the subjective response to cocaine was either enhanced or not appreciably altered compared to a control condition. Enhanced cardiovascular responses to cocaine were also observed under these chronic opioid dosing conditions. These and other findings suggest that administration of mu agonists generally enhances the effects of cocaine in humans, particularly the positive subjective responses to cocaine. This enhancement of subjective effects has been observed following pretreatment with opioids under both acute and chronic dosing procedures. Whether or not enhancement of physiological responses is observed appears to depend upon the specific opioid agonist chosen for testing as well as the range of test doses. The observed enhancement of subjective responses produced by speedball combinations may account for the high prevalence of speedball abuse as well as the persistent abuse of cocaine in patients enrolled in opioid maintenance therapy programs. Summary and Future Directions This symposium has provided a synthesis of recent research aimed at understanding the interactions between cocaine and abused opioids. Dr. Shippenberg described neurobiological evidence that both exogenous and endogenous opioids can modulate the actions of cocaine in the mesolimbic DA system. There is also evidence for a reciprocal influence of cocaine on the endogenous opioid peptide system. Understanding the interplay between these two systems continues to be a major challenge facing research in this area. The escalation of dual cocaine-opioid abuse has prompted renewed interest in the interactions between these drugs in relevant animal models of addiction. As discussed by Drs. Negus, Rowlett, and Mello, an important, though still elusive, goal of this research is to characterize the complex effects that combinations of cocaine and opioids can have in behavioral experiments. Growing evidence indicates that prominent individual differences exist in the DS effects of cocaine-opioid combinations, yet virtually nothing is known about their neurobiological correlates. Along similar lines, studies involving i.v. drug self-administration in monkeys suggest that low doses of cocaine and heroin, which fail to maintain self-administration when tested singly, do so if combined under a progressive-ratio schedule of drug injection. However, this appears not to be the case under other conditions, where self-administration of cocaine may be reduced by the addition of high doses of heroin. Human laboratory studies reviewed by Dr. Walsh have generally shown that opioids enhance the positive subjective effects of cocaine, although the findings do not fit easily within any simple model of drug interaction. Given the prevalence of cocaine use among untreated opioid abusers and methadone-maintained patients, there is a critical need to identify pharmacological mechanisms underlying speedball abuse in order to develop effective therapeutic strategies. By providing a state-of-the-field review of multidisciplinary research, this symposium has helped lay the groundwork for achieving this goal.