Only a small percentage of marijuana treatment seekers are able to achieve abstinence. This proposal will investigate the interaction between marijuana and potential treatment medications, with the direct goal of using this information to improve marijuana treatment outcome. Our model for marijuana medication development is guided by the hypothesis that attenuating marijuana's positive or negative reinforcing effects will decrease relapse.
AIM #1 : To determine if the opioid antagonist, naltrexone, decreases marijuana's direct effects, and thus decreases the likelihood that marijuana smokers will relapse to marijuana use; relapse is defined as marijuana self-administration after a period of abstinence. Hypotheses: Naltrexone will decrease marijuana relapse by decreasing its direct effects.
AIM #2 : To determine if the alpha2-noradrenergic agonist, Iofexidine decreases marijuana withdrawal and thereby decreases relapse. Lofexidine will be compared to oral THC, which decreases marijuana withdrawal symptoms at doses that produce minimal intoxication. Thus, the effects of Iofexidine and oral THC alone and in combination will be determined. Hypotheses: 1) Lofexidine and oral THC alone will decrease a distinct subset of marijuana withdrawal symptoms, and will decrease marijuana relapse; 2) Lofexidine combined with oral THC will result in the largest decrease in marijuana withdrawal symptoms and relapse.
AIM #3 : To compare the effects of oral THC to THC administered using a newly developed oro-mucosal spray on marijuana withdrawal and relapse. Hypotheses: 1) Spray and oral THC alone will decrease marijuana withdrawal symptoms and relapse; 2) Spray THC will more consistently decrease marijuana withdrawal symptoms and relapse across individuals than oral THC.
AIM #4 : To determine if the GABAB agonist, baclofen decreases marijuana's direct effects and marijuana withdrawal, and thereby decreases relapse. Hypotheses: Baclofen will decrease marijuana relapse by decreasing both marijuana's direct effects and marijuana withdrawal. There are clear interactions between cannabinoid, opioid and GABA receptors in the CNS, yet the nature of these interactions remains unknown. The strength of this proposal lies in our utilization of a controlled laboratory setting to examine the interactive effects of potential treatment medications on marijuana's direct effects, marijuana withdrawal, and on marijuana relapse.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Special Emphasis Panel (ZDA1-KXA-N (14))
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Montoya, Ivan
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New York State Psychiatric Institute
New York
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Cooper, Ziva D; Bedi, Gillinder; Ramesh, Divya et al. (2018) Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability. Neuropsychopharmacology 43:2046-2055
Chao, Thomas; Radoncic, Vanya; Hien, Denise et al. (2018) Stress responding in cannabis smokers as a function of trauma exposure, sex, and relapse in the human laboratory. Drug Alcohol Depend 185:23-32
Vadhan, Nehal P; Corcoran, Cheryl M; Bedi, Gill et al. (2017) Acute effects of smoked marijuana in marijuana smokers at clinical high-risk for psychosis: A preliminary study. Psychiatry Res 257:372-374
Cooper, Ziva D; Haney, Margaret (2016) Sex-dependent effects of cannabis-induced analgesia. Drug Alcohol Depend 167:112-20
Haney, Margaret; Ramesh, Divya; Glass, Andrew et al. (2015) Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers. Neuropsychopharmacology 40:2489-98
Balter, Rebecca E; Cooper, Ziva D; Haney, Margaret (2014) Novel Pharmacologic Approaches to Treating Cannabis Use Disorder. Curr Addict Rep 1:137-143
Cooper, Ziva D; Haney, Margaret (2014) Investigation of sex-dependent effects of cannabis in daily cannabis smokers. Drug Alcohol Depend 136:85-91
Haney, Margaret; Bedi, Gillinder; Cooper, Ziva D et al. (2013) Predictors of marijuana relapse in the human laboratory: robust impact of tobacco cigarette smoking status. Biol Psychiatry 73:242-8
Cooper, Ziva D; Foltin, Richard W; Hart, Carl L et al. (2013) A human laboratory study investigating the effects of quetiapine on marijuana withdrawal and relapse in daily marijuana smokers. Addict Biol 18:993-1002
Cooper, Ziva D; Comer, Sandra D; Haney, Margaret (2013) Comparison of the analgesic effects of dronabinol and smoked marijuana in daily marijuana smokers. Neuropsychopharmacology 38:1984-92

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