Cannabinoid-Induced Hyperemesis: A Conundrum-From Clinical Recognition to Basic Science Mechanisms

Area of Science:

• Pharmacology
• Gastroenterology
• Neuroscience

Background:

• Cannabinoids are clinically used as antiemetics, preventing chemotherapy-induced nausea and vomiting via CB₁ receptor stimulation.
• Cannabis-induced hyperemesis syndrome (CHS) is a recognized condition in chronic cannabis users, marked by cyclical vomiting and compulsive hot water bathing.
• Despite being considered rare, increasing case reports suggest CHS may be more prevalent.

Approach:

• This review critically examines proposed pathophysiological mechanisms for CHS.
• It explores both traditional hypotheses and current scientific explanations for cannabinoid-induced vomiting.
• The review synthesizes basic science findings relevant to the clinical presentation of CHS.

Key Points:

• Proposed mechanisms include pharmacokinetic factors (long half-life, accumulation of metabolites, withdrawal) and pharmacodynamic factors (altered receptor efficacy, signal transduction changes, receptor desensitization/downregulation).
• Other potential mechanisms involve changes in endocannabinoid levels, arachidonic acid metabolites, and differential effects on the brainstem versus enteric nervous system.
• Chronic cannabis exposure may be necessary for the intensity of emesis, but not necessarily for its initial induction.

Conclusions:

• The exact pathophysiological mechanisms underlying CHS remain largely unknown.
• Understanding these mechanisms is crucial for managing this paradoxical syndrome.
• Further research is needed to elucidate the complex interplay of factors contributing to CHS.