Association of Marijuana Use With Blunted Nucleus Accumbens Response to Reward Anticipation

Abstract

Importance Marijuana use may alter ventral striatal response to reward, which may heighten susceptibility to substance use disorder (SUD). Cross-sectional studies have reported either increased ventral striatal response to reward or no difference in marijuana users compared with controls. Longitudinal research is needed to resolve the inconsistencies and disentangle preexisting susceptibility from the effects of marijuana use on neural function involved in reward responding. Objective To determine whether marijuana use among young adults prospectively impacts nucleus accumbens (NAcc) activation during reward anticipation. Design Longitudinal study of self-report marijuana use and brain function using functional magnetic resonance imaging (fMRI) at three consecutive time points. Setting Data were obtained from young adult participants in the Michigan Longitudinal Study, an ongoing, prospective study of youth at high risk for SUD and a contrast sample of control families. Participants The sample consisted of 108 young adults (36% female; 78% family history of SUD) who underwent three fMRI scans at approximately age 20 (time 1), 22 (time 2), and 24 (time 3). Main Outcome and Measures We investigated the impact of marijuana use on neural response in the NAcc to reward anticipation during a monetary incentive delay task (MIDT) using a cross-lagged model. Covariates for analyses included sex, age at first scan, family history of SUD, prior marijuana use, and binge drinking (prior and concurrent). This model was also tested separately with the inclusion of cigarette smoking. Results Greater marijuana use was associated with later blunted activation in the NAcc during reward anticipation (time 1 to time 2: β=−0.26, P=0.04; time 2 to time 3: β=−0.25, P=0.01). When we tested the cross-lagged model with the inclusion of prior and concurrent cigarette use, the impact of marijuana use from time 2 to time 3 remained significant and the effect of cigarette use was non-significant. Conclusions and Relevance Our findings indicate that marijuana use is associated with decreased neural response in the NAcc during the anticipation of non-drug rewards. Over time, marijuana use may alter anticipatory reward processing in the NAcc, which may increase risk for continued drug use and later addiction.

Associations between anhedonia and marijuana use escalation across mid‐adolescence

“…Given that anhedonia is a manifestation of deficient reward activity [11] this finding is discordant with preclinical evidence of THC-induced dampening of brain reward activity and prior adult observational data showing that heavy or problematic marijuana use is associated with subsequent anhedonia [6] and diminished brain reward region activity during reward anticipation [27]. Perhaps the typical level and chronicity of exposure to marijuana use in this general sample of high school students was insufficient for detecting cannabinoid-induced manifestations of reward deficiency.…”

“…Alternatively, repeated tetrahydrocannabinol (THC) exposure during adolescence produces enduring deficits in brain reward system function and anhedonia-like behavior in rodent models [26]. In observational studies of adults, heavy or problematic marijuana use is associated with subsequent anhedonia [6] and diminished brain reward region activity during reward anticipation [27]. Consequently, it is plausible that anhedonia may both increase risk of marijuana use and result from marijuana use.…”

Weeding Through Marijuana’s Effects on the Brain

“…However, it remains unclear whether these changes are the cause or the consequence of cannabis use. While Martz and colleagues 8 did not find that past use correlated with nucleus accumbens activation at time 1, age at onset of use showed a trend-level association, which propagates the widely accepted idea that early-onset cannabis use is associated with brain alterations. Thus, because some of the individuals from the study were already using cannabis at time 1, there was no baseline (ie, precannabis use) comparison where one's cannabis-naive brain response could be compared with their own cannabis-exposed brain response to determine the true effect.…”

“…This suggests the existence of predisposing factors, both genetic and environmental, that likely contribute to or interact with cannabis use. Indeed, Martz and colleagues 8 interpreted the inverse association between age at onset and time 1 nucleus accumbens response to a predisposing hypersensitivity of the reward system in the participants. In other words, these underlying factors not only increase the likelihood of cannabis use, but also increase the brain's susceptibility to the observed alterations.…”

Commentary on Lichenstein et al. (2017): Escalating cannabis use, weak corticostriatal connections and negative outcomes

“…Finally, although most studies have reported that reward anticipation is altered in cannabis users relative to non-users [9][10][11], Lichenstein et al did not find a significant difference between the trajectory groups during the anticipatory period for reward. Rather, they found that the effects of escalation of use were observable only during the receipt of reward.…”