Marijuana Blunts Reward Response in Young Adult Brains

Pam Harrison

July 07, 2016

Long-term use of marijuana is associated with alterations in neural circuits involved in reward processing that may, in turn, contribute to substance abuse later on, new research shows.

Investigators at the University of Michigan, in Ann Arbor, found that greater use of marijuana was associated with blunted activation of the nucleus accumbens (NAcc) during performance of a monetary incentive task by young adults aged 20 to 24 years. The NAcc is a key region within the brain's reward circuitry.

The effect of marijuana remained significant over several years, as reflected in performance of the same task.

"Our findings support the view that continued consumption [of marijuana] produces long-term alterations in neural circuits involved in reward processing, which may in turn contribute to drug- seeking behavior and compulsive use," the authors, led by Meghan Martz, write.

"Finding a prospective association between marijuana use and decreased NAcc activation to monetary reward supports a mechanism through which marijuana use may lead to enhanced vulnerability to SUD [substance use disorder]," they add.

The study was published online July 6 in JAMA Psychiatry.

Robust Evidence

A total of 108 young adults from the Michigan Longitudinal Study and a control sample underwent three functional MRI (fMRI) scans at about the age of 20 years (time 1), 22 years (time 2), and 24 years (time 3).

The Michigan Longitudinal Study is a prospective study of youth who come from families with high levels of SUD. Of the 84 participants from the Michigan Longitudinal Study included in the study, more than three quarters had a family history of SUD.

The contrast sample of youths came from families with no history of substance abuse.

"Participants performed a modified version of the monetary incentive delay task," the investigators write.

During the task, participants could win or lose small to large amounts of money. Their neural response to their anticipation of gaining the reward was imaged using fMRI.

Self-reports on the use of marijuana and other drugs had been collected during a long-term follow-up period.

On the first imaging study (time 1 to time 2), use of marijuana in the past year was significantly and negatively associated with NAcc activation, at an effect size of β = -.26 (P = .04).

On the second fMRI study (time 2 to time 3), use of marijuana in the past year was again negatively associated with NAcc activation, with about the same effect size of β= -.25 (P = .01).

After controlling for smoking, marijuana still had a significant effect on NAcc activation between the second and the third fMRIs, at an effect size of β= -.29 (P = .005).

"Our findings indicate that continued marijuana use may result in a blunted NAcc response to nondrug rewards, even when controlling for previous and concurrent substance use.... This work provides robust evidence that marijuana use has long-term associations with anticipatory reward processing," the researchers note.

Negative Consequences

These findings add to a growing body of evidence that marijuana has both short- and long-term negative effects on the brain.

There is evidence, for example, that individuals who start smoking marijuana early transition to dependence on cannabis more quickly and are more likely to develop other SUDs.

The active ingredient in cannabis, delta-9-tetrahydrocannabinol, binds to cannabinoid neural receptors, stimulating transmission of dopamine from the ventral tegmental area to the NAcc in the ventral striatum.

"The ventral striatum is a region involved in reward-driven behavior, including substance use," the researchers write.

It is therefore possible that the effect that marijuana has on neural systems leads to a "general blunting" of the usual reward response over time.

"This blunting may lead to further drug use in an attempt to counteract insufficient reward responsivity," they add.

Alternatively, a blunted reward response might be associated with general anhedonia, which could serve to perpetuate substance abuse.

Does Cannabis Cause Brain Changes?

In an accompanying editorial, Francesca Filbey, PhD, University of Texas at Dallas, notes that because the blunted response in the NAcc was only present as cannabis use escalated, "one interpretation is that cannabis use triggered these changes."

If this proves to be the case, it could be argued that marijuana causes a sort of "hypersensitivity" in the brain's reward circuitry to marijuana that trumps reactions to other types of rewards, such as those associated with food and sex.

"However, it remains unclear whether these changes are the cause or the consequence of cannabis use," Dr Filbey writes.

In the current study, some of participants had been using cannabis prior to undergoing their first fMRI, so there was no baseline "precannabis use" image to compare a person's cannabis-naive brain response to the monetary incentive task with their cannabis-exposed brain response.

In his editorial, Dr Filbey cites the Dunedin Study (Proc Natl Acad Sci. 2012;109:E2657-E2664), a prospective study conducted in New Zealand of a cohort of 1037 individuals who were followed from birth to age 38 years. In that study, the investigators found that by the age of 38 years, the IQ scores of those participants who had started using cannabis in early adolescence had dropped by 8 points.

"Together these 2 prospective studies suggest that changes in the brain are a consequence of cannabis use," Dr Filbey writes.

It will take a large study, such as the Adolescent Brain Cognitive Development Study that was recently initiated by the National Institutes of Health, to more robustly answer this "chicken and egg" question.

The study was funded by grants from the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism. Neither the authors nor Dr Filbey have disclosed any relevant financial relationships.

JAMA Psychiatry. Published online July 6, 2016. Abstract, Editorial


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