Cannabinoids in Parkinson's Disease

Abstract

The endocannabinoid system plays a regulatory role in a number of physiological processes and has been found altered in different pathological conditions, including movement disorders. The interactions between cannabinoids and dopamine in the basal ganglia are remarkably complex and involve both the modulation of other neurotransmitters (γ-aminobutyric acid, glutamate, opioids, peptides) and the activation of different receptors subtypes (cannabinoid receptor type 1 and 2). In the last years, experimental studies contributed to enrich this scenario reporting interactions between cannabinoids and other receptor systems (transient receptor potential vanilloid type 1 cation channel, adenosine receptors, 5-hydroxytryptamine receptors). The improved knowledge, adding new interpretation on the biochemical interaction between cannabinoids and other signaling pathways, may contribute to develop new pharmacological strategies. A number of preclinical studies in different experimental Parkinson's disease (PD) models demonstrated that modulating the cannabinoid system may be useful to treat some motor symptoms. Despite new cannabinoid-based medicines have been proposed for motor and nonmotor symptoms of PD, so far, results from clinical studies are controversial and inconclusive. Further clinical studies involving larger samples of patients, appropriate molecular targets, and specific clinical outcome measures are needed to clarify the effectiveness of cannabinoid-based therapies.

Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science

“…These 2 synthetic forms of THC have also been shown to have analgesic benefit . ‐ There have been other benefits of THC reported also, including antioxidant and neuroprotective, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), MS, ‐ autism, Parkinson's, Tourette's syndrome, Huntington's disease/chorea, depression, posttraumatic stress disorder (PTSD), sickle cell disease pain, traumatic brain injury (TBI), hypothermia, duodenal ulcers, anorexia and cachexia, inflammatory bowel disease, spinal cord injury, antispasmodic, muscle relaxation, and spasticity, antibacterial effects against methicillin‐resistant Staphylococcus aureus (MRSA) strains, anti‐proliferative/pro‐apoptotic against tumor cell lines of multiple organ systems including brain, breast, colon, and blood, psoriasis,…”

“…There is medical evidence showing that CBD may be effective in treatment of a wide range of disorders including epilepsy (particularly medically‐refractory pediatric epilepsy syndromes), Alzheimer's disease, Parkinson's disease, MS, ‐ , Huntington's disease, ALS, anxiety disorders including PTSD, depression, dystonia, Meige's syndrome, schizophrenia and psychosis, stroke and hypoxic‐ischemic injury, antioxidant, TBI,…”

Phytocannabinoids in Neurological Diseases: Could They Restore a Physiological GABAergic Transmission?

“…Indeed, the stimulation of CBRs localized in the globus pallidus nucleus reduced the synaptic GABA re-uptake enhancing the GABAergic transmission in the circuit [69]. However, despite of the large number of studies performed on preclinical animal models of PD, clinical trials results using pCBs and ECs, are still not conclusive and often controversial, thus indicating the need of more accurate studies on large PD patient cohorts [70].…”

Distinctive Evidence Involved in the Role of Endocannabinoid Signalling in Parkinson’s Disease: A Perspective on Associated Therapeutic Interventions

“…Interaction between CB and DA appears to be much more complicated at the cellular level. In the striatum, the levels of eCBs are affected by the dopaminergic transmission initially as depicted by the higher levels of AEA following the stimulation of the D2 receptors as shown in Figure 1 [ 97 ]. Such phenomenon is based on either the suppression of its inhibition or the stimulation of its synthesis as proposed by the ability of the D2 receptor agonists to further modify the activity of the fatty acid amide hydrolase (FAAH) and N -acyl-phosphatidylethanolamine (NAPE) phospholipase D. Such activity of CBs stimulated by DA counteracts the action of D2 receptor in the striatum, indicating an inhibitory process focused at restricting the hyperkinetic effect of DA.…”