Cannabinoid Hyperemesis Syndrome: Mechanisms Underlying Capsaicin Efficacy

A recent review published in Clinical Toxicology suggests that stimulation of the transient receptor potential vanilloid 1 (TRPV1) may explain the benefits of capsaicin and hot water hydrotherapy in patients experiencing cannabinoid hyperemesis syndrome.¹

To examine the mechanisms underlying the beneficial effects of capsaicin and hot water hydrotherapy previously observed in patients with cannabinoid hyperemesis syndrome, researchers reviewed 137 articles that discussed known and theoretical thermoregulatory mechanisms related to the endocannabinoid system.

The researchers noted that topical capsaicin, which has been successfully used for the treatment of approximately 20 cases of cannabinoid hyperemesis syndrome, binds and activates the TRPV1 receptor. Activation of this receptor causes the release of inflammatory neuropeptides, which are responsible for the characteristic burning, stinging, and itching associated with capsaicin exposure. A novel type of desensitization analgesia is triggered by this initial signaling cascade.

Heat (>43℃), acids (pH <6), pain, change in osmolarity, and endovanilloids also activate the TRPV1 receptor according to the study investigators.

Because cannabinoid hyperemesis syndrome may be caused by an imbalance in the endocannabinoid system from chronic exogenous stimulation, the researchers suggest that the endocannabinoid system and TRPV1 receptor interact. The investigators propose that the mechanism of this interaction and its resultant antiemetic effects involve the modulation of tachykinins, somatostatin, pituitary adenylate cyclase-activating polypeptide, and calcitonin gene-related peptide, in addition to downstream effects on histaminergic, cholinergic, and serotonergic transmission.

John R Richards, MD, professor in the department of emergency medicine at the University of California Davis Medical Center in Sacramento and lead study investigator, noted that this review led to surprising conclusions about “the complexity of the endovannilloid system as well as the endocannabinoid system, and their close association.” The results support the notion that, in patients experiencing cannabinoid hyperemesis, hot showers and “topical capsaicin applied to the abdomen may be worth trying, as well as haloperidol and benzodiazepines to mitigate the patient’s level of stress.”

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Reference

1. Richards JR, Lapoint JM, Burillo-Putze G. Cannabinoid hyperemesis syndrome: potential mechanisms for the benefit of capsaicin and hot water hydrotherapy in treatment [published online July 21, 2017]. Clin Toxicol (Phila). doi:10.1080/15563650.2017.1349910