Work

Modulating the cognitive and subjective effects of THC in young adults with cannabis use disorder

Year: 2021

Type: article

Abstract: Young adults are particularly vulnerable to the negative effects of cannabis and the development of cannabis use disorder (CUD). CUD is largely defined by maladaptive decision-making, which often occurs while intoxicated in habitual cannabis users. This is problematic because cannabis and its major psychoactive chemical, THC, alter cognition and subjective experience. Pharmaco-TMS has informed mechanisms of movement; however no published research has examined the ability of TMS to modulate the acute effects of THC on decision-making dynamics, cognitive performance, and subjective effects in individuals with CUD. This ongoing double-blind, placebo and sham controlled study is enrolling young adults with CUD (n=6). On separate days, individuals receive randomized combinations of oral THC (0, 10, 30mg) and intermittent theta-burst stimulation (iTBS: sham, real). Decision-making and cognitive task performance and subjective effects are measured before dosing and directly following iTBS at the estimated THC concentration peak. Left dorsal lateral prefrontal cortex (DLPFC) stimulation targets are neuronavigated from individualized fMRI analyses isolating overlap between correct choice evaluation (decision-making task) and accurate high load working memory performance (N-Back). Primary measures are reinforcement learning modeled parameters from the decision-making task, accuracy from the N-Back task, and subjective drug effects on a visual analog scale. Preliminary analyses reveal trends in the ability of iTBS (real – sham) to modulate the effects of 30mg of THC on several outcomes (average±SEM). A modeled perseveration parameter during dynamic decision-making was lower (–0.48±0.21) and percent correct responding during high load working memory was greater (+7%±3.8), following iTBS. Several subjective measures also decreased following iTBS, including difficulty concentrating (–12%±14.5), feelings of high (–19.2%±17.2), and willingness to pay for drug (–12.5%±5.6). Together, these preliminary findings suggest that iTBS is a useful tool for studying the acute effects of THC on neurobehavioral outcomes relevant to understanding and treating CUD. Keywords: Cannabis, Learning, Neuronavigation, TMS

Source: Brain stimulation

DOI: 10.1016/j.brs.2021.10.233