The proposed study will employ treatment-seeking AUD individuals who will be randomly assigned to receive either 15 mg of rapamycin (sirolimus) or placebo immediately after the first of two alcohol cue exposure sessions scheduled to occur on consecutive days. Subjective responses (i.e., craving) and physiological (heart rate & skin conductance) reactivity will be obtained before, during and after cue presentations in both sessions. The durability of any observed treatment effects will be assessed in a Follow-up session performed approximately 10 days following completion of the second session. Treatment effects on self-report measures of drinking behavior during the approximately 10 days preceding the Follow-up session will also be assessed.
We recently published results from a NIDA-funded study of a brief behavioral treatment that was designed to reduce the troublesome cravings that smokers encounter when they attempt to quit smoking. This intervention was based on a growing body of neuroscience studies showing that memories for prior learning can be retrieved by the presentation of cues involved in that learning. Once retrieved, the memories enter into a brief period of vulnerability, during which they can be modified, but after which they are reconsolidated (restabilized) back into long-term storage. The treatment potential of this phenomenon was initially demonstrated in a Science report in which inpatient heroin addicts were briefly exposed to cues associated with heroin use in order to prompt the heroin use memories into a vulnerable state. Once the memories were in this state, the heroin addicts received extinction training consisting of protracted exposure to heroin associated cues. It was argued that extinction would change the memories such that the cues would no longer be associated with heroin administration and reward. Remarkably, after just two sessions of retrieval-extinction training (RET), the investigators found that craving in response to heroin cues was substantially reduced for up to 6-months post-treatment. This effect was observed relative to a control group that received retrieval involving non-heroin cues, followed by extinction. These impressive initial findings led us to replicate and extend the study in cigarette smokers. In our study, one group of smokers received two sessions of RET with smoking cues whereas a control group received the same training except that retrieval consisted of brief exposure to neutral, smoking-unrelated cues. Craving and other reactions to familiar and novel smoking cues were assessed in test sessions performed 24-hrs, 2-weeks and 1-month after intervention; smoking behavior was also assessed over 1-month follow-up. Remarkably, at 1-month follow-up, craving to both familiar and novel smoking cues was significantly lower in the group receiving R-E training vs. control. Even more striking was the 25% reduction in the number of cigarettes smoked per day in the RET group vs. control. [Also of significance was suggestive evidence that, relative to control participants, more participants in the RET group achieved a 60% reduction in smoking (from pretreatment levels)]. The proposed project will replicate and extend these findings by 1) increasing the dose of intervention so as to bolster the observed treatment effects, 2) employing brain imaging methods to identify patterns of brain activity uniquely associated with the intervention and potentially predictive of treatment outcome, 3) adding a control group that will enhance understanding of the effects of RET, and 4) extending follow-up period to more completely document the long-term effects of RET. Positive findings from this study could lead to the development of a brief, effective behavioral intervention to reduce the burden levied against society by smoking. Importantly, this intervention could be easily adapted to treat other forms of addiction and co-occurring anxiety disorders, such as PTSD.
Our recently completed study has provided the first evidence that administration of the medication propranolol, following exposure to cocaine cues, can alter drug-associated memories and reduce craving and other drug cue-elicited responses in cocaine addicted persons. The proposed research will use two methods to increase the memory altering effects of propranolol observed in our recently completed study, and document lasting effects not only on craving and cue-elicited reactions, but also on cocaine use. Positive findings will set the stage for a formal clinical trial that could lead to significantly improved treatment outcomes for this treatment-resistant addiction.