Cannabinoid modulation of drug reward and the implications of marijuana legalization.
Dan P Covey, Jennifer M Wenzel, Joseph Cheer
Brain Research December 2, 2015 DOI: 10.1016/j.brainres.2014.11.034 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Cannabis |
| Keywords | Dopamine Endocannabinoids Mesolimbic Nucleus accumbens Ventral tegmental area |
| Key findings | The authors argue that CB1 receptors are a central component of the endocannabinoid system that regulates mesolimbic dopamine function, controlling phasic dopamine release in the nucleus accumbens and shaping goal-directed behavior. They contend that abused drugs, including marijuana, cause short- and long-term adaptations in this system that hijack reward-related neural circuits to promote drug abuse, and suggest that legalization may increase marijuana's utility as a research tool for developing cannabinoid-based addiction treatments. |
Abstract
Marijuana is the most popular illegal drug worldwide. Recent trends indicate that this may soon change; not due to decreased marijuana use, but to an amendment in marijuana's illegal status. The cannabinoid type 1 (CB1) receptor mediates marijuana's psychoactive and reinforcing properties. CB1 receptors are also part of the brain endocannabinoid (eCB) system and support numerous forms of learning and memory, including the conditioned reinforcing properties of cues predicting reward or punishment. This is accomplished via eCB-dependent alterations in mesolimbic dopamine function, which plays an obligatory role in reward learning and motivation. Presynaptic CB1 receptors control midbrain dopamine neuron activity and thereby shape phasic dopamine release in target regions, particularly the nucleus accumbens (NAc). By also regulating synaptic input to the NAc, CB1 receptors modulate NAc output onto downstream neurons of the basal ganglia motor circuit, and thereby support goal-directed behaviors. Abused drugs promote short- and long-term adaptations in eCB-regulation of mesolimbic dopamine function, and thereby hijack neural systems related to the pursuit of rewards to promote drug abuse. By pharmacologically targeting the CB1 receptors, marijuana has preferential access to this neuronal system and can potently alter eCB-dependent processing of reward-related stimuli. As marijuana legalization progresses, greater access to this drug should increase the utility of marijuana as a research tool to better understand the eCB system, which has the potential to advance cannabinoid-based treatments for drug addiction.
Comparable studies
Other narrative reviews on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Causal association between cannabis and psychosis: examination of the evidence | 2004 | Review | |
| Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history. General (historical and pharmacological review) | 2018 | Review | |
| Psychiatric effects of cannabis | 2001 | Review | |
| Beyond THC: The New Generation of Cannabinoid Designer Drugs | 2011 | Review | |
| Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug | 2006 | Review |
Citations in the library
Cited by 6
- Impairment of Synaptic Plasticity by Cannabis, Δ9-THC, and Synthetic Cannabinoids. Cold Spring Harbor perspectives in medicine May 3, 2021
- Dark Classics in Chemical Neuroscience: Δ9-Tetrahydrocannabinol. ACS Chemical Neuroscience May 15, 2019
- Cannabinoids, interoception, and anxiety. Pharmacology, Biochemistry, and Behavior May 1, 2019
- Highway to hell or magic smoke? The dose-dependence of Δ9-THC in place conditioning paradigms. Learning & Memory September 2018
- Delta-9-tetrahydrocannabinol potentiates fear memory salience through functional modulation of mesolimbic dopaminergic activity states. European Journal of Neuroscience June 2018
and 1 more in the library
Cites 12
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- Cannabis use is quantitatively associated with nucleus accumbens and amygdala abnormalities in young adult recreational users. Journal of Neuroscience April 16, 2014
- Alterations of prefrontal cortex GABAergic transmission in the complex psychotic-like phenotype induced by adolescent delta-9-tetrahydrocannabinol exposure in rats. Neurobiology of Disease March 1, 2014
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