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Brianna Hempel

hempel

bg0767a@student.american.edu

Curriculum Vitae

I am a fourth year doctoral student in the behavior, cognition and neuroscience program at American University. My research interests center around the motivational properties of marijuana and their neurobiological mediation, including how a number of environmental and experiential factors influence marijuana use and abuse. Our lab investigates the affective properties of abused drugs using animal models. Although the rewarding properties of a given compound are typically described as driving its abuse, we posit that both the rewarding and aversive effects of a drug impact drug-taking behavior and that assessing these stimulus properties can enable better predictions of abuse liability.

Marijuana abuse is particularly difficult to study in animals, as there is currently no reliable pre-clinical rodent model. The majority of my research has focused on developing a viable model by assessing factors that are known to enhance the rewarding properties of abused drugs, and more recently, attempting to bridge the gap between human recreational marijuana use (typically inhalation of the plant material) versus drug administration in animal research (intraperitoneal injections of Δ9-tetrahydrocannabinol or THC, the main psychoactive component of marijuana).


In my master's thesis, I sought to optimize the conditions under which THC's rewarding properties might be demonstrated by giving rats a history of THC prior to an assessment of its subjective effects (i.e. place and taste conditioning). My data showed that although a drug history of THC clearly weakened its aversive effects, there was no corresponding rise in reward. These findings indicate that even when the negative subjective effects of THC (likely anxiety, paranoia, etc.) are eliminated, rats do not find THC rewarding. However, the marijuana plant includes over 80 other phytocannabinoids besides THC that likely modulate its overall subjective effect. As such, I recently investigated whether cannabidiol (CBD), a prominent phytocannabinoid known for its therapeutic properties, is able to impact THC's affective profile. Overall, CBD had a transient and weak effect on THC induced place aversions, such that at one dose ratio (1:1 CBD:THC) the aversive properties of THC were attenuated. Based on these findings, it's likely that CBD alone is not shifting the abuse liability of marijuana. However, a full analysis of different phytocannabinoid combinations and their relative abuse potentials is much needed.

Currently, I am preparing to conduct a series of experiments that will constitute my doctoral dissertation. These studies will examine the role of the neurosteroid precursor, pregnenolone, in THC's subjective effects. Recent work has implicated pregnenolone as a negative allosteric modulator of the CB1 (cannabinoid) receptor and demonstrated that exogenous pregnenolone reduces self-administration of the synthetic cannabinoid WIN 55,212-2. I intend to examine whether aminoglutethimide, an inhibitor of pregnenolone synthesis, will alter THC's affective properties and potentially enable an assessment of THC reward and reinforcement.