Strouth, Liah Assessing the Efficacy of Fatty Acid Amide Hydrolase Inhibition on Cannabinoid Withdrawal-Induced Changes in Food Motivation in Long-Evans Rats. 2025. Radford University, Thesis. Radford University Scholars' Repository.
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Abstract
Cannabis use disorder (CUD) is becoming increasingly prevalent in the United States. While the behavioral withdrawal symptoms associated with CUD are aversive enough to prompt relapse, there is currently no Food and Drug Administration approved pharmacotherapy for CUD. Targeting the endogenous cannabinoid system via enzyme inhibition provides an attractive avenue for potential alleviation of the behavioral symptoms associated with cannabinoid withdrawal due to prior success alleviating somatic symptoms. This study evaluated the efficacy of inhibiting fatty acid amide hydrolase (FAAH), the primary enzyme responsible for breakdown of the endocannabinoid anandamide, in attenuating the motivational impairments observed during cannabinoid withdrawal in rodents. Thirty male and female Long-Evans rats were trained to lever press for sucrose pellets on a progressive ratio (PR) schedule of reinforcement allowing for assessment of motivation for a non-drug reinforcer (i.e., sucrose pellets) during cannabinoid withdrawal. To model cannabinoid dependence, rats received repeated administration of either the synthetic cannabinoid agonist CP55,940 (0.5 mg/kg, s.c., b.i.d.) or a vehicle solution over the span of seven days. Repeated administration produced both physiological and behavioral tolerance in the subjects as indicated by the normalization of PR performance and body temperature by day seven. On test day, rats received either a pretreatment of the FAAH inhibitor PF-3845 (10 mg/kg, i.e.) or vehicle before withdrawal was precipitated via administration of rimonabant (1 mg/kg, i.p.) in all subjects. Following rimonabant administration, decreased PR performance was observed across all treatment groups. PF-3845 was not successful in significantly attenuating cannabinoid withdrawal-induced motivational impairments. Rimonabant administration did not impact body temperature or marble burying performance, additional measures of withdrawal. This study did not include a positive control group that included a rescue dose of CP55,940, but this treatment is currently being investigated in ongoing research in the lab. Overall, the findings of the present study indicate that FAAH inhibition has a limited efficacy in reversing cannabinoid withdrawal-induced motivational deficits, highlighting the need for alternative pharmacotherapeutics for cannabinoid withdrawal to be investigated.
| Item Type: | Thesis |
|---|---|
| Subjects: | B Philosophy. Psychology. Religion > BF Psychology |
| Divisions: | Radford University > College of Humanities and Behavioral Sciences > Department of Psychology |
| Date Deposited: | 03 Dec 2025 06:28 |
| Last Modified: | 03 Dec 2025 06:28 |
| URI: | http://wagner.radford.edu/id/eprint/1279 |
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