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Cancer treatment is usually associated with several side effects. Of them, nausea and vomiting induced by chemotherapy are most commonly feared by the patients. Nausea and vomiting can occur within the first day after chemotherapy (acute), or up to 7 days post treatment (delayed), or even prior to treatment as a response to previous treatment cycles (anticipatory). The latter type of nausea is difficult to be treated by the classic anti-emetics.
In the 1970s, it has been demonstrated that smoked cannabis had the ability to attenuate chemotherapy-induced nausea and vomiting. However, its illegal aspects and psychotropic adverse effects (including paranoia, sleepiness, memory impairment, and anxiety) limited its use. Alternatively, medical cannabis compounds have been recommended to reduce the most apparent chemotherapy side effects. This study reviewed the potential of cannabinoid treatment (when given exogenously or by activation of the naturally-occurring cannabinoid system) for the treatment of nausea and vomiting induced by chemotherapy.
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Effects of cannabinoids on vomiting
The experimental studies have shown that the injected tetrahydrocannabinol (THC) caused a significant inhibition of vomiting induced by cisplatin, a common chemotherapeutic agent, by acting on its specific receptors (CB1) and this effect was reversed by the medications that block the action of THC receptors. Vomiting after the same chemotherapeutic medication is also suppressed by cannabidiol (CBD) and cannabidiolic acid (CBDA), where the antiemetic effect increases with increasing the dose.
It has been shown that anandamide, one of the endogenous cannabinoids which are produced in the body, reduced the incidence of vomiting following the administration of a specific chemotherapeutic agent (morphine-6-glucuronide) in animal models. Emesis induced by another medication for ovarian cancer, lithium chloride, can be inhibited by a commonly known endogenous cannabinoid 2-arachidonoylglycerol (2-AG) despite the contrary findings that have been reported elsewhere.
Effects of cannabinoids on nausea
Scientists usually use a recently recognized nausea-assessment tool called “conditioned gaping” in rats to detect its occurrence as a remarkable side effect of medication administration. Administration of a synthetic form of THC caused a marked inhibition of acute and anticipatory nausea-induced conditioned gaping in rats. Similarly, CBD and CBDA led to a significant reduction of conditioned gaping in both types of nausea, which would be further contrasted by their counteracting drugs.
Referring to the endogenously-produced cannabinoids, anandamide reduced the rate of nausea caused by lithium chloride, but the mechanism of action was not exerted through cannabinoids receptors in the body. It is worthy to note that nausea can be also prevented by inhibiting the specific enzyme that destroys anandamide. 2-AG was demonstrated to be a potent anti-emetic medication against conditioned gaping induced by acute or anticipatory nausea.
Most of cannabinoids, including synthetic THC, CBD, and CBDA showed potent actions against nausea and vomiting caused by chemotherapy treatment. Further, manipulation of endogenous cannabinoids compounds has also an effective role in relieving such symptoms. Future studies are needed to transform the preclinical experimental investigation into clinical trials on patients with acute and anticipatory nausea.