Cannabis use disorders are an important public health problem in the United States, but no effective pharmacotherapies are available to treat these disorders. We intend to test a novel agonist pharmacotherapy, nabilone, for cannabis dependence and to study the relationship of this treatment with the brain using BOLD fMRI measures. The behavioral and physiological effects of nabilone and 9-THC overlap, suggesting that nabilone may ameliorate cannabis withdrawal symptoms while allowing treatment-seeking outpatients to benefit from medical management (MM) sessions when they are trying to stop using cannabis. We propose to assess the relationship of nabilone, when added to MM, on cannabis use patterns in cannabis-dependent patients. We also aim to determine the effects of nabilone on performance on neuropsychological tests and to assess the correlation of neuropsychological performance to brain changes using BOLD fMRI measures. For the K99 portion of this application, we will conduct Study 1, Pilot Study of Nabilone for Cannabis Dependence: Imaging and Neuropsychological Performance, in which subjects will receive either nabilone or placebo in addition to medical management (MM) over a 10-week treatment period. Subjects'responses to neuropsychological testing carried out while the subject is receiving fMRI scans at 3 time points: at baseline, 4 weeks, and 10 weeks. Following treatment completion, subjects will have a follow-up visit at 14 weeks. This pilot study will evaluate the feasibility of nabilone treatment for cannabis dependence and will establish effect sizes for the R00 portion of this application, Study 2, Nabilone for Cannabis Dependence: Imaging and Neuropsychological Performance, a larger trial in which subjects will receive high-dose nabilone, low-dose nabilone, or placebo in addition to MM. As in Study 1, subjects'responses to neuropsychological testing will be measured by 3 fMRI scans: at baseline, 4 weeks, and 10 weeks. In Study 2, subjects will undergo neuropsychological testing both inside and outside of the fMRI scanner, the techniques having been learned during Study 1 of the K99 phase. Cannabis use disorders are highly prevalent in the United States and rising among high school seniors, making the identification of efficacious treatments for cannabis dependence of critical clinical and public health significance. At the completion of these studies, we hope to have improved our understanding of the relationship of nabilone on cannabis use as well as have gained a better understanding of the relationship of medication, placebo, and medical management upon performance on neuropsychological testing and fMRI BOLD signaling in response to cognitive challenge paradigms administered while in the fMRI scanner.
We intend to test a novel agonist pharmacotherapy, nabilone, for cannabis dependence and to study the relationship of this treatment with the brain using BOLD fMRI measures. We hope to take steps toward developing a medication for cannabis dependence, an important public health problem.
|Hill, Kevin P; Palastro, Matthew D; Gruber, Staci A et al. (2017) Nabilone pharmacotherapy for cannabis dependence: A randomized, controlled pilot study. Am J Addict 26:795-801|
|Hill, Kevin P; Weiss, Roger D (2016) Minimal Physical Health Risk Associated With Long-term Cannabis Use--But Buyer Beware. JAMA 315:2338-9|
|DeVido, Jeffrey; Connery, Hilary; Hill, Kevin P (2015) Sleep-disordered breathing in patients with opioid use disorders in long-term maintenance on buprenorphine-naloxone: A case series. J Opioid Manag 11:363-6|
|Griffin, Margaret L; Bennett, Heather E; Fitzmaurice, Garrett M et al. (2015) Health-related quality of life among prescription opioid-dependent patients: Results from a multi-site study. Am J Addict 24:308-14|
|Hill, Kevin P (2014) Medical marijuana: more questions than answers. J Psychiatr Pract 20:389-91|
|Bracken, Bethany K; Rodolico, John; Hill, Kevin P (2013) Sex, age, and progression of drug use in adolescents admitted for substance use disorder treatment in the northeastern United States: comparison with a national survey. Subst Abus 34:263-72|
|Hill, Kevin P; Toto, Lindsay H; Lukas, Scott E et al. (2013) Cognitive behavioral therapy and the nicotine transdermal patch for dual nicotine and cannabis dependence: a pilot study. Am J Addict 22:233-8|
|Hill, Kevin P; Bennett, Heather E; Griffin, Margaret L et al. (2013) Association of cannabis use with opioid outcomes among opioid-dependent youth. Drug Alcohol Depend 132:342-5|
|Farren, Conor K; Hill, Kevin P; Weiss, Roger D (2012) Bipolar disorder and alcohol use disorder: a review. Curr Psychiatry Rep 14:659-66|