Therapeutic applicability of cannabidiol and other phytocannabinoids in epilepsy, multiple sclerosis and Parkinson's disease and in comorbidity with psychiatric disorders

Abstract

Studies have demonstrated the neuroprotective effect of cannabidiol (CBD) and other Cannabis sativa L. derivatives on diseases of the central nervous system caused by their direct or indirect interaction with endocannabinoid system‐related receptors and other molecular targets, such as the 5‐HT1A receptor, which is a potential pharmacological target of CBD. Interestingly, CBD binding with the 5‐HT1A receptor may be suitable for the treatment of epilepsies, parkinsonian syndromes and amyotrophic lateral sclerosis, in which the 5‐HT1A serotonergic receptor plays a key role. The aim of this review was to provide an overview of cannabinoid effects on neurological disorders, such as epilepsy, multiple sclerosis and Parkinson's diseases, and discuss their possible mechanism of action, highlighting interactions with molecular targets and the potential neuroprotective effects of phytocannabinoids. CBD has been shown to have significant therapeutic effects on epilepsy and Parkinson's disease, while nabiximols contribute to a reduction in spasticity and are a frequent option for the treatment of multiple sclerosis. Although there are multiple theories on the therapeutic potential of cannabinoids for neurological disorders, substantially greater progress in the search for strong scientific evidence of their pharmacological effectiveness is needed.

Endocannabinoid System Changes throughout Life: Implications and Therapeutic Potential for Autism, ADHD, and Alzheimer’s Disease

“…Although CBD is a non-competitive negative allosteric modulator of CB1R and a low-affinity agonist of CB2R, other pharmacological targets seem to mediate the therapeutic effects of CBD. In this context, the beneficial effects of CBD for ASD children could be related to its inhibitory action on FAAH activity, resulting in increased AEA levels, and agonism in relation to TRPV1 and 5-HT1A receptors that mediate anti-convulsant and behavioral functions [ 1 , 3 ]. However, large, randomized, placebo-controlled clinical trials are necessary to fully understand the benefits and risks of CBD-rich extract use by different age groups, mainly children and adults.…”

“…Cannabinoids are compounds that act on cannabinoid receptors and can be categorized into three types: phytocannabinoids, which are derived from plants like cannabidiol (CBD); endocannabinoids, which are endogenous compounds, namely anandamide (AEA) and 2-arachidonoylglycerol (2-AG); and synthetic cannabinoids, such as dronabinol and nabilone [ 1 ].…”

“…THC is a CBR agonist with desirable effects, but also has addictive potential. On the other hand, CBD appears to have distinct properties, including opposite effects to THC [ 1 ]. CBD is a non-intoxicating ingredient, with preclinical evidence suggesting several biological proprieties, such as anti-inflammatory, neuroprotective, antipsychotic, analgesic, anticonvulsant, antiemetic, and antioxidant properties [ 3 , 4 ].…”

“…CBD acts in regard to several receptors and molecular targets, showing therapeutic properties throughout neuropsychiatric disorders, stemming from diverse central nervous system actions, including the agonist effect on the serotonin receptor (5-HT1A) associated with its anxiolytic and antidepressant properties [ 3 ]. In addition to this, adequate levels of both THC and CBD seem to have protective effects against neurological diseases [ 1 ].…”

“…Neurological disorders are a significant global public health issue due to their high prevalence, associated chronic disability, and severe impact on patients’ quality of life. Although the pathophysiology of these diseases is complex and not entirely understood, genetic, biological, and environmental factors are relevant to their appearance and progression [ 1 , 5 ]. There is increasing evidence of cannabinoids’ therapeutic potential on the behavioral impairments exhibited in neurodevelopmental and neurodegenerative disorders [ 5 ].…”