Cannabinoids in addiction therapy - Focus on opioids

    September 27, 2022 2 min read

    Cannabinoids in addiction therapy - Focus on opioids

    It is known that cannabis use is common among opiate-dependent individuals, that this can interfere with treatment, and that its use drops significantly following opioid dose stabilization. Some sort of statistical relationship between use of the two substances should not be surprising. In parallel to the body’s endocannabinoid neural signaling network, there exists an endo-opioid system (the one responsible for runners’ high), and the two systems communicate. This suggests an expanded pharmacological strategy for treating opioid dependence. Current medications, such as methadone, buprenorphine, and naltrexone, tend to target only the endogenous opioid system. 

    Interaction between the two systems is complex. SA-57, an inhibitor of two different endocannabinoid catabolic enzymes, FAAH and MAGL, demonstrate an ability to reduce heroin-seeking behavior in a self-administration model in mice. A complicated interplay between chronic pain, analgesic tolerance, and morphine sensitivity has also been suggested by administration of cannabinoid receptor antagonist SR141716A in chronic opiate-exposed rodents. 

    Cannabinoid-induced reinstatement of heroin seeking in rats has also been significantly reduced, and even blocked, by low doses of naloxone and rimonabant together. Moreover, rats readily self-administerWIN 55,212-2, a potent experimental cannabinoid agonist,when access was given after of extinction from heroin, with a response rate that positively correlated with the extinction period. In these animals, cannabinoid intake was increased by naloxone and decreased by rimonabant. There appears therefore a differential effect of opioid and cannabinoid receptor blockade on heroin-seeking reinstatement and cannabinoid substitution in heroin-abstinent rats. Morphine exposure can actually change CB1 expression. It is possibly for this reason that regular use of synthetic cannabinoids significantly increased the duration of opioid-related withdrawal and craving symptoms in patients undergoing drug detoxification treatments. 

    Towards an interventional strategy

    Among cannabinoid agonists and antagonists, cannabidiol (CBD) could lead to a novel line of medication that indirectly regulates neural systems that modulate opioid-related behavior. CBD inhibits the reward-facilitating effect of morphine through activation of 5-HT1A receptors in the dorsal raphe nucleus. Morphine conditioning in mice has attenuated robustly by 10 mg/kg cannabidiol. When administered alone, this dose of cannabidiol was devoid of any effect at all. Cannabidiol appears then to inhibit cue-induced heroin seeking and normalize discrete mesolimbic neuronal disturbance. CBD does not exacerbate any of the adverse effects that are associated with fentanyl administration. Overall, co-administration of CBD and opioids appears safe and well tolerated. 

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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.