Abused drugs promote short- and long-term changes in how the endocannabinoid system, part of the body’s onboard cell-signaling network, regulates dopamine function in limbic functions. They commandeer neural systems related to the reward sensation in recreational drug use. The cannabinoid molecules in marijuana have preferential access to the CB1 neural receptor in particular, and should therefore modulate endocannabinoid-dependent processing of reward stimuli. In this lies the rationale for considering cannabinoid-based treatments for drug addiction, probably quite widely.
Animal studies have indeed shown the possible effects of cannabidiol (CBD) on opioid and psychostimulant addiction. Human studies as well have yielded data supporting use of CBD in cannabis and tobacco dependence. SLV330, an experimental CB1 receptor antagonist, has also been shown to attenuate ethanol and nicotine seeking in rats.
In precision studies, neutral CB1 antagonists appear more effective than orthosteric or inverse agonists, or negative allosteric modulators.
The inverse agonist SR14176 (rimonabant) has significantly inhibited cocaine, heroin, and nicotine self-administration in rats, though, unexpectedly, SR14176 by itself produces dysphoria. The neutral antagonists AM4113 and PIMSR1, administered together, have significantly attenuated cocaine, nicotine, and heroin self-administration in another rat model, though by themselves they did not have the same effect. The negative allosteric modulators GAT358 and GAT 369 had no effect when measured against nicotine-enhanced neural activity.
There is much to learn about the wider mechanisms of action in these agents and in addiction overall. In addiction to nicotine and cocaine, and possibly alcohol, there are epigenetic mechanisms at work, that include DNA methylation, histone modification, and alterations in microRNAs. It is known at least that the endocannabinoid system is pivotal in each of these.
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The foregoing is a report on trends and developments in the cannabinoid industry. No product described herein is intended to diagnose, treat, cure or prevent any disease or syndrome.
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