Cannabidiol MOA
With effects on more than 50 diverse receptors and enzymes, cannabidiol has broad-spectrum pharmacologic effects ranging from agonistic to inverse agonistic to antagonistic to allosteric interactions.1 With regard to neurologic disorders, cannabidiol acts as an agonist or partial agonists of serotonin, GABA-AR, A1–2AR, GlyR, PPARγ, dopamine D2, and GPR3/6 receptors.1,2 The neurologic effects of cannabidiol are also mediated through antagonism of a variety of enzymes (eg, CB1–2R, TRPM, VGSCs, AchE, and several others).1
Cannabidiol has the ability to cross the blood-brain barrier where it can reduce hyperexcitability, inflammation, pain perception, motor difficulties, and mood and behavioral disturbances.1,3 However, several challenges remain:
- Most of the data on cannabidiol’s mechanism of action are derived from preclinical models that do not account for genetic, metabolic, or other physiologic variations occurring within a patient population.4
- Clinical trials conducted in most therapeutic areas included a limited range of demographic factors, which could influence cannabidiol safety and pharmacokinetics in individual patients.3
- There is a lack of standardized dosing guidelines, studies on the therapeutic dose range, and cannabidiol formulation guidance needed to establish optimal treatment protocols.3,5
- The development of standardized cannabidiol formulations for specific neurologic conditions is needed.3
All this being said, there are planned or completed studies in epilepsy that may help better inform the potential for drug-drug interactions with antiseizure medications (NCT02607891, NCT02564952) and characterize the population pharmacokinetics of cannabidiol (NCT03196466).
References
- Castillo-Arellano J, Canseco-Alba A, Cutler SJ, et al. The polypharmacological effects of cannabidiol. Molecules. 2023;28:3271.
- Zavala-Tecuapetla C, Luna-Munguia H, López-Meraz ML, et al. Advances and challenges of cannabidiol as an anti-seizure strategy: preclinical evidence. Int J Mol Sci. 2022;23:16181.
- Singh K, Bhushan B, Chanchal DP, et al. Emerging therapeutic potential of cannabidiol (CBD) in neurological disorders: A comprehensive review. Behav Neurol. 2023;2023:8825358.
- Martinez Naya N, Kelly J, Corna G, et al. Molecular and cellular mechanisms of action of cannabidiol. Molecules. 2023;28:5980.
- O’Sullivan SE, Jensen SS, Nikolajsen NG, et al. The therapeutic potential of purified cannabidiol. J Cannabis Res. 2023;5:21.
