Cannabinoids in Motor Control: From Receptor Distribution to Motor Disorders

Cannabinoid receptors occupy strategic control nodes within motor circuitry, making them potential targets for modulating different motor manifestations. They are positioned both within basal ganglia circuits that regulate movement and within spinal circuits that control skeletal muscle tone. Consequently, cannabinoids have been studied across diverse motor disorders, most notably in movement disorders and tone disorders, particularly those resulting in spasticity. Because motor control spans multiple anatomically and functionally distinct levels, relating cannabinoid signaling to effects on motor function is not straightforward. Limited understanding of cannabinoid receptor distribution has led to cannabinoids being tested even in disorders where receptor localization would predict little or no benefit. Mapping receptor distribution within individual motor circuits and integrating them with their pharmacological effects can help anticipate how cannabinoid signaling shapes motor output. Combined with characteristic motor manifestations, one can identify motor disorders in which cannabinoids may have therapeutic value. In this review, we integrate existing evidence to place cannabinoid receptors within key motor pathways, ranging from basal ganglia circuits controlling movement to peripheral mechanisms governing muscle tone. We consider both cannabinoid 1 receptor (CB1R) and cannabinoid 2 receptor (CB2R), with CB2R gaining attention only recently for its potential relevance within the central nervous system. Building on this framework, we infer how cannabinoids acting at these sites may modulate motor control, and consequently, influence motor manifestations across major motor disorders. Finally, we examine how these distribution-based expectations align with available clinical observations.