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Journal Article

Citation

Heal DJ, Gosden J, Smith SL. Front. Psychiatry 2024; 15: e1322434.

Copyright

(Copyright © 2024, Frontiers Media)

DOI

10.3389/fpsyt.2024.1322434

PMID

38915848

PMCID

PMC11194422

Abstract

Various countries and US States have legalized cannabis, and the use of the psychoactive(1) and non-psychoactive cannabinoids is steadily increasing. In this review, we have collated evidence from published non-clinical and clinical sources to evaluate the abuse, dependence and associated safety risks of the individual cannabinoids present in cannabis. As context, we also evaluated various synthetic cannabinoids. The evidence shows that delta-9 tetrahydrocannabinol (Δ(9)-THC) and other psychoactive cannabinoids in cannabis have moderate reinforcing effects. Although they rapidly induce pharmacological tolerance, the withdrawal syndrome produced by the psychoactive cannabinoids in cannabis is of moderate severity and lasts from 2 to 6 days. The evidence overwhelmingly shows that non-psychoactive cannabinoids do not produce intoxicating, cognitive or rewarding properties in humans. There has been much speculation whether cannabidiol (CBD) influences the psychoactive and potentially harmful effects of Δ(9)-THC. Although most non-clinical and clinical investigations have shown that CBD does not attenuate the CNS effects of Δ(9)-THC or synthetic psychoactive cannabinoids, there is sufficient uncertainty to warrant further research. Based on the analysis, our assessment is cannabis has moderate levels of abuse and dependence risk. While the risks and harms are substantially lower than those posed by many illegal and legal substances of abuse, including tobacco and alcohol, they are far from negligible. In contrast, potent synthetic cannabinoid (CB1/CB2) receptor agonists are more reinforcing and highly intoxicating and pose a substantial risk for abuse and harm. (1) "Psychoactive" is defined as a substance that when taken or administered affects mental processes, e.g., perception, consciousness, cognition or mood and emotions.


Language: en

Keywords

cannabis; abuse; cannabidiol (CBD); CB1 - CB2 cannabinoid receptors; delta 9 tetrahydrocannabinol; dependence; THC - tetrahydrocannabinol

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