Affiliation:
1. Department of Pharmaceutical Sciences, Mercer University College of Pharmacy, Mercer University Health Sciences Center,United States
Abstract
:
Alcohol-use disorder (AUD) remains a major public health concern. In recent years,
there has been a heightened interest in components of the endocannabinoid system for the treatment
of AUD. Cannabinoid type 1 (CB1) receptors have been shown to modulate the rewarding effects
of alcohol, reduce the abuse-related effects of alcohol, improve cognition, exhibit anti-inflammatory,
and neuroprotective effects, which are all favorable properties of potential therapeutic candidates
for the treatment of AUD. However, CB1 agonists have not been investigated for the treatment
of AUD because they stimulate the motivational properties of alcohol, increase alcohol intake,
and have the tendency to be abused. Preclinical data suggest significant potential for the use
of CB1 antagonists to treat AUD; however, a clinical phase I/II trial with SR14716A (rimonabant),
a CB1 receptor antagonist/inverse agonist showed that it produced serious neuropsychiatric adverse
events such as anxiety, depression, and even suicidal ideation. This has redirected the field to
focus on alternative components of the endocannabinoid system, including cannabinoid type 2
(CB2) receptor agonists as a potential therapeutic target for AUD. CB2 receptor agonists are of particular
interest because they can modulate the reward pathway, reduce abuse-related effects of alcohol,
reverse neuroinflammation, improve cognition, and exhibit anti-inflammatory and neuroprotective
effects, without exhibiting the psychiatric side effects seen with CB1 antagonists. Accordingly,
this article presents an overview of the studies reported in the literature that have investigated CB2
receptor agonists with regards to AUD and provides commentary as to whether this receptor is a
worthy target for continued investigation.
Funder
National Institute of Neurological Disorders and Stroke
National Institute on Drug Abuse
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology,General Neuroscience
Cited by
5 articles.
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