Evaluating Cannabis sativa L.’s neuroprotection potential: From bench to bedside

Background: Neurodegenerative diseases and dementia pose a global health challenge in an aging population, exemplified by the increasing incidence and prevalence of its most common form, Alzheimer’s disease. Although several approved treatments exist for Alzheimer’s disease, they only afford transient symptomatic improvements and are not considered disease-modifying. The psychoactive properties of Cannabis sativa L. have been recognized for thousands of years and now with burgeoning access to medicinal formulations globally, research has turned to re-evaluate cannabis and its myriad phytochemicals as a potential treatment and adjunctive agent for neurodegenerative diseases.

Purpose: This review evaluated the neuroprotective potential of C. sativa’s active constituents for potential therapeutic use in dementia and Alzheimer’s disease, based on published studies demonstrating efficacy in experimental preclinical settings associated with neurodegeneration.

Study design: Relevant information on the neuroprotective potential of the C. sativa’s phytoconstituents in preclinical studies (in vitro, in vivo) were included. The collated information on C. sativa’s component bioactivity was organized for therapeutic applications against neurodegenerative diseases.

Methods: The therapeutic use of C. sativa related to Alzheimer’s disease relative to known phytocannabinoids and other phytochemical constituents were derived from online databases, including PubMed, Elsevier, The Plant List (TPL, www.theplantlist.org), Science Direct, as well as relevant information on the known pharmacological actions of the listed phytochemicals.

Results: Numerous C. sativa -prevalent phytochemicals were evidenced in the body of literature as having efficacy in the treatment of neurodegenerative conditions exemplified by Alzheimer’s disease. Several phytocannabinoids, terpenes and select flavonoids demonstrated neuroprotection through a myriad of cellular and molecular pathways, including cannabinoid receptor-mediated, antioxidant and direct anti-aggregatory actions against the pathological toxic hallmark protein in Alzheimer’s disease, amyloid β.

Conclusions: These findings provide strong evidence for a role of cannabis constituents, individually or in combination, as potential neuroprotectants timely to the emergent use of medicinal cannabis as a novel treatment for neurodegenerative diseases. Future randomized and controlled clinical studies are required to substantiate the bioactivities of phytocannabinoids and terpenes and their likely synergies.