Long-term Marijuana Use Associated with Dampened Nucleus Accumbens Reward Response

Alterations in reward processing may increase users' risk of continued drug use and subsequent addiction.

In a new study published in JAMA Psychiatry, researchers at the University of Michigan and Florida International University explored the connection between marijuana use and neural mechanisms involved in reward processing.

Marijuana use is especially prevalent in young adults, with 35% of individuals aged 21 and 22 reporting use within the past year. This pattern could be a result of users’ perceptions that marijuana carries low risks of harm, though studies have linked it with short-term negative consequences such as paranoia, altered perception, and impaired motor coordination. It is also associated with long-term negative consequences including academic problems, and impaired brain structure and function.

Marijuana use typically begins in adolescence, and previous findings show that “earlier onset of marijuana use leads to a faster transition to marijuana dependence and increases the risk of developing other substance use disorders (SUDs),” according to the new paper.

To a large extent, the psychoactive properties of the drug result from the binding of Δ9 –tetrahydrocannabinol (THC) to CB1 cannabinoid neural receptors. This stimulates dopamine transmission from the ventral tegmental area (VTA) to the nucleus accumbens (NAcc) in the ventral striatum, a region closely associated with reward-related behavior. A recent study using positron emission tomography (PET) found that long-term marijuana users had reduced reactivity of the ventral striatum during extracellular dopamine stimulation, and this effect was associated with increased addiction severity and craving.

Such findings suggest that marijuana use may impair the dopaminergic reward system, thus increasing SUD risk. Some research shows increased ventral striatum activation in marijuana users vs nonusers in response to monetary reward anticipation, while others found no such effect. In other research, increased “NAcc activation to reward anticipation has been linked to behavioral traits associated with substance use risk” and with later substance use problems, wrote the authors of the current study. “Thus, longitudinal studies that account for preexisting susceptibilities are needed to more clearly identify the cumulative effect of marijuana use on neural mechanisms underlying reward responsivity,” they stated.

To that end, the researchers used cross-lagged models to investigate prospective associations between marijuana use and activation of the NAcc in response to monetary reward anticipation in 108 young adults. They controlled for potential effects of sex, age, use of other substances, and family history of SUD. Participants were evaluated for psychosocial functioning every 3 years and for substance use each year starting at age 11 years. At the ages of 20, 22, and 24 years, participants underwent fMRI while performing a modified version of the monetary incentive delay task.

Consistent with their hypothesis and with previous findings, results show that greater “marijuana use was associated with later blunted activation in the NAcc during reward anticipation (time 1 to time 2: β = −0.26, P = .04; time 2 to time 3: β = −0.25, P = .01),” suggesting that such use is associated with reduced NAcc response to anticipation of nondrug rewards, the authors reported.

Such alterations in reward processing may increase users’ risk of continued drug use and subsequent addiction, and educating youth about these effects could help to improve prevention efforts.

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Martz ME, Trucco EM, Cope LM, Hardee JE, Jester JM, Zucker RA, Heitzeg MM. Association of Marijuana Use With Blunted Nucleus Accumbens Response to Reward Anticipation. JAMA Psychiatry. 2016; doi:10.1001/jamapsychiatry.2016.1161.