Botanic Cannabinoids and the Endocannabinoid System: A Mechanistic Model for Motion Sickness Intervention

Motion sickness is a highly prevalent condition characterized by nausea, vomiting, and autonomic symptoms triggered by sensory conflict between the vestibular and visual systems. Current pharmacological treatments, including anticholinergics and antihistamines, often produce undesirable side effects such as sedation and dry mouth, and do not address the underlying neurophysiological dysregulation. The endocannabinoid system is a key neuromodulator of stress responses, emesis control, and homeostatic balance. Evidence from parabolic flight studies indicates that motion-susceptible individuals exhibit reduced circulating anandamide levels and downregulation of CB1 receptor expression, suggesting that hypoactivity of the endocannabinoid system contributes to symptom development. This theoretical paper proposes that targeted modulation of the ECS via botanic cannabinoids—such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD)—and selected terpenes may restore ECS tone, attenuate vestibular hyperactivation, normalize gastric rhythm, and reduce motion-induced nausea. We outline a mechanistic model for cannabinoid intervention, discuss key phytochemical candidates, and identify biomarker-driven endpoints for future clinical studies.