The Neurotherapeutic Arsenal in Cannabis sativa: Insights into Anti-Neuroinflammatory and Neuroprotective Activity and Potential Entourage Effects

Abstract

Cannabis, renowned for its historical medicinal use, harbours various bioactive compounds—cannabinoids, terpenes, and flavonoids. While major cannabinoids like delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have received extensive scrutiny for their pharmacological properties, emerging evidence underscores the collaborative interactions among these constituents, suggesting a collective therapeutic potential. This comprehensive review explores the intricate relationships and synergies between cannabinoids, terpenes, and flavonoids in cannabis. Cannabinoids, pivotal in cannabis’s bioactivity, exhibit well-documented analgesic, anti-inflammatory, and neuroprotective effects. Terpenes, aromatic compounds imbuing distinct flavours, not only contribute to cannabis’s sensory profile but also modulate cannabinoid effects through diverse molecular mechanisms. Flavonoids, another cannabis component, demonstrate anti-inflammatory, antioxidant, and neuroprotective properties, particularly relevant to neuroinflammation. The entourage hypothesis posits that combined cannabinoid, terpene, and flavonoid action yields synergistic or additive effects, surpassing individual compound efficacy. Recognizing the nuanced interactions is crucial for unravelling cannabis’s complete therapeutic potential. Tailoring treatments based on the holistic composition of cannabis strains allows optimization of therapeutic outcomes while minimizing potential side effects. This review underscores the imperative to delve into the intricate roles of cannabinoids, terpenes, and flavonoids, offering promising prospects for innovative therapeutic interventions and advocating continued research to unlock cannabis’s full therapeutic potential within the realm of natural plant-based medicine.

The Use of Compounds Derived from Cannabis sativa in the Treatment of Epilepsy, Painful Conditions, and Neuropsychiatric and Neurodegenerative Disorders

“…It is renowned for its complex chemical composition, diverse physiological effects, and significant implications for pharmacology and medicine. Cannabis sativa possesses anticonvulsive, analgesic, anti-inflammatory, and neuroprotective effects [ 40 , 41 ]. Moreover, it has been reported to possess antioxidant, antibacterial, antifungal, anti-inflammatory, and anticancer properties [ 42 ].…”

Antimicrobial, Probiotic, and Immunomodulatory Potential of Cannabis sativa Extract and Delivery Systems

“…Cannabinoids are unique chemical compounds found in cannabis that interact with the endocannabinoid system in humans and other animals. The most well-known cannabinoid is ∆ 9 -tetrahydrocannabinol (THC), which has analgesic, anticonvulsant, antiepileptic, sleep-improving, appetite-stimulating, and antiemetic effects through partial agonism on CB 1 and CB 2 receptors and agonism on G protein-coupled receptor 55 (GPR55) and GPR18, while also displaying antinociceptive and antiemetic actions via antagonism on 5-hydroxytryptamine (5-HT3A) receptors [3,4]. The other most known cannabinoid is cannabidiol (CBD), which has various therapeutic effects, including anti-inflammatory, anxiolytic, and antiepileptic properties, without inducing psychotropic effects like THC [5].…”