Phytocannabinoids and Cannabis-Based Products as Alternative Pharmacotherapy in Neurodegenerative Diseases: From Hypothesis to Clinical Practice

Abstract

Historically, Cannabis is one of the first plants to be domesticated and used in medicine, though only in the last years the amount of Cannabis-based products or medicines has increased worldwide. Previous preclinical studies and few published clinical trials have demonstrated the efficacy and safety of Cannabis-based medicines in humans. Indeed, Cannabis-related medicines are used to treat multiple pathological conditions, including neurodegenerative disorders. In clinical practice, Cannabis products have already been introduced to treatment regimens of Alzheimer’s disease, Parkinson’s disease and Multiple Sclerosis’s patients, and the mechanisms of action behind the reported improvement in the clinical outcome and disease progression are associated with their anti-inflammatory, immunosuppressive, antioxidant, and neuroprotective properties, due to the modulation of the endocannabinoid system. In this review, we describe the role played by the endocannabinoid system in the physiopathology of Alzheimer, Parkinson, and Multiple Sclerosis, mainly at the neuroimmunological level. We also discuss the evidence for the correlation between phytocannabinoids and their therapeutic effects in these disorders, thus describing the main clinical studies carried out so far on the therapeutic performance of Cannabis-based medicines.

Intracellular Molecular Targets and Signaling Pathways Involved in Antioxidative and Neuroprotective Effects of Cannabinoids in Neurodegenerative Conditions

“…Cannabis-based products have been introduced into clinical studies for AD and PD, and they have demonstrated small improvements in some secondary symptoms and quality of life. Positive results have mostly been assigned to their anti-inflammatory, immunosuppressive and antioxidant effects, as well as the ability of these products to modulate the ECS [ 228 ]. Similarly, in patients with ALS, cannabis was found to be moderately effective against some symptoms (appetite loss, depression, and spasticity) but did not improve speech and swallowing deficits [ 227 ].…”

The Role of Cannabinoid Type 2 Receptors in Parkinson’s Disease

“…As regards the clinical studies, only a few data are currently available. Although there are different trials analyzing cannabis-based medicines in PD patients, no clinical trials specifically investigating the role of CB2 receptors or the effects of specific CB2 receptor agonists in PD patients are currently present [ 11 , 82 , 83 ].…”

“…The pathological hallmarks of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta and the presence of Lewy bodies, which are intra-cytoplasmic inclusions consisting mainly of α-synuclein aggregations [ 6 ]. Most of the motor deficits present in PD patients are due to the progressive death of dopaminergic neurons in the substantia nigra pars compacta and to the subsequent loss of projections to the striatum [ 11 ]. Indeed, this neurodegeneration leads to dopamine depletion, facilitating the impairment of critical pathways linked with the regulation of voluntary movements, involving the basal ganglia, brainstem, cerebral cortex, and thalamus [ 11 ].…”

“…Most of the motor deficits present in PD patients are due to the progressive death of dopaminergic neurons in the substantia nigra pars compacta and to the subsequent loss of projections to the striatum [ 11 ]. Indeed, this neurodegeneration leads to dopamine depletion, facilitating the impairment of critical pathways linked with the regulation of voluntary movements, involving the basal ganglia, brainstem, cerebral cortex, and thalamus [ 11 ].…”

“…However, there are different trials investigating cannabis-based medicines in PD patients [ 11 , 82 , 83 ]. Although clinical studies investigating cannabis-based medicine or isolated phytocannabinoids in PD show only a few conclusive data, the use of cannabis-based medicine appears promising [ 11 ].…”