The neuroprotective effects of cannabinoids in preclinical disease models

The cannabinoid system regulates a broad spectrum of physiological and pathophysiological processes inside human body, particularly in central nervous system (CNS). Thus, it is not surprising that the cannabinoid system has been considered as a potential target for numerous CNS diseases. The bioactive compounds of Cannabis sativa and also the synthetic cannabinoids have shown antioxidant, anti-inflammatory and neuroprotective effects in preclinical models of CNS disease, including epilepsy, stroke, retinopathies, and neurodegenerative diseases of the motor neuron system such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). More than 100 phytocannabinoids have been isolated from cannabis sativa and their effects have been described in different preclinical models of CNS diseases. Amongst the phytocannabinoids, there is just one effective compound, delta-9 tetrahydrocannabinol (9-THC) that directly activates cannabinoid receptors to produce its therapeutic effects. However, the use of cannabinoid receptor agonists as therapeutic agents is limited because of their putative psychoactive properties and their potential of drug abuse. Interestingly, there are other phytocannabinoids, such as cannabidiol, with potential therapeutic and neuroprotective effects and lack of detrimental and psychoactive side effects. The recent reports of promising results for cannabidiol treatment in Phase III clinical trials in treatment-resistant epilepsies provides pivotal evidence of clinical efficacy for one plant cannabinoid. Even for 9-THC and other Cannabinoid receptor agonists, there are some therapeutic use with less side effects because of their local administration. For example, many studies support the local use of synthetic cannabinoids as new neuroprotective drugs to prevent and treat retinal diseases. The main biochemical and molecular mechanisms that have been associated with the therapeutic effects of cannabinoids will be discussed here, focusing on their relevance to brain function and neuroprotection.

Keywords:

Cannabidiol , Neuroprotective , Neurotoxicity