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Cannabis use disorder causes dopamine release deficits

The brain’s reward system consists of a group of structures that are activated by rewarding stimuli like food, sex and addictive drugs. Humans are naturally driven to do the things that make them feel good. In the presence of highly rewarding stimuli, such as cocaine, alcohol and other drugs, the brain’s reward system triggers the release of dopamine, a neurotransmitter (i.e., brain chemical) that is involved in the “high” the person experiences and motivates him or her to continue taking the drug.

Addictive drugs decrease dopamine release with repeated use

The results of position emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies have shown how the intravenous administration of stimulant drugs initially causes rapid firing of dopamine cells; at the same time, the repeated use of addictive drugs increases the threshold for dopamine to be activated and released. A 2008 paper by Nora D. Volkow, M.D., director of the National Institute on Drug Abuse (NIDA), and her colleagues reviewed the literature on dopamine release in people with drug addiction, and implicated decreased dopamine activity, as well as deregulation of the prefrontal cortex and striatum, in the loss of control and compulsive use of drugs seen in individuals with substance use disorders.

Volkow and her colleagues suggested that the repeated activation and release of dopamine by addictive drugs leads to marked decreases in both dopamine D2 receptors and in the release of dopamine in the striatum, which are related to deregulated activity in the dorsolateral prefrontal cortex (an area of the brain that plays a role in executive function), the orbitofrontal cortex (an area of the brain involved in decision-making and attributing salience to rewards) and cingulate gyrus (an area of the brain involved in inhibitory control); disrupted activity in these areas of the brain result in impaired regulation of intentional actions, compulsive behaviors and impulsivity, respectively.

Although people who abuse addictive substances initially experience a heightened release of dopamine, a number of studies co-authored by Volkow and her colleagues suggested that most drugs of abuse lead to reduced dopamine activity following their repeated use. For example, the authors have previously shown that alcoholics exhibit reductions in the availability of dopamine D2 receptors in the ventral striatum, which is associated with greater alcohol cravings. Notably, individuals who have attention-deficit hyperactivity disorder (ADHD) also demonstrate deficiencies in dopamine D2 receptors and dopamine release in the ventral striatum and caudate nucleus.

Do patients with marijuana dependence exhibit reduced dopamine?

A new study funded by the National Institute on Drug Abuse (NIDA) investigated whether these dopaminergic deficits were also present in individuals with cannabis use disorders without psychiatric comorbidity following the oral administration of d-amphetamine. The researchers examined the release of dopamine from inside and outside of the striatum in 11 participants with cannabis dependence and in 12 healthy controls. They completed PET scans before and after they orally administered d-amphetamine to participants.

Their results indicated that the participants with cannabis use disorders exhibited lower dopamine release in the associative striatum, which was related to inattention and negative symptoms in participants with cannabis dependence. The researchers suggested that a deficit in dopamine release in the striatum underlies cannabis use disorders in a similar way that it does with patients who abuse other addictive substances.

Sovereign Health of Texas provides comprehensive, individualized behavioral health treatment services for patients who have substance use disorders, including cannabis abuse and dependence, as well as co-occurring disorders. For more information on the treatment programs provided at Sovereign Health of Texas, please contact our 24/7 helpline to speak to a member of our team.

About the author

Amanda Habermann is a writer for the Sovereign Health Group. A graduate of California Lutheran University, she received her M.S. in clinical psychology with an emphasis in psychiatric rehabilitation. She brings to the team her background in research, testing and assessment, diagnosis and recovery techniques. For more information and other inquiries about this article, contact the author at


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