Abstract

Current pharmacotherapy of Parkinson’s disease (PD) is symptomatic and palliative, with levodopa/carbidopa therapy remaining the prime treatment, and nevertheless, being unable to modulate the progression of the neurodegeneration. No available treatment for PD can enhance the patient’s life-quality by regressing this diseased state. Various studies have encouraged the enrichment of treatment possibilities by discovering the association of the effects of the endocannabinoid system (ECS) in PD. These reviews delineate the reported evidence from the literature on the neuromodulatory role of the endocannabinoid system and expression of cannabinoid receptors in symptomatology, cause, and treatment of PD progression, wherein cannabinoid (CB) signalling experiences alterations of biphasic pattern during PD progression. Published papers to date were searched via MEDLINE, PubMed, etc., using specific key words in the topic of our manuscript. Endocannabinoids regulate the basal ganglia neuronal circuit pathways, synaptic plasticity, and motor functions via communication with dopaminergic, glutamatergic, and GABAergic signalling systems bidirectionally in PD. Further, gripping preclinical and clinical studies demonstrate the context regarding the cannabinoid compounds, which is supported by various evidence (neuroprotection, suppression of excitotoxicity, oxidative stress, glial activation, and additional benefits) provided by cannabinoid-like compounds (much research addresses the direct regulation of cannabinoids with dopamine transmission and other signalling pathways in PD). More data related to endocannabinoids efficacy, safety, and pharmacokinetic profiles need to be explored, providing better insights into their potential to ameliorate or even regress PD.

Highlights

  • Endocannabinoids, known as endogenous cannabinoids, are the endogenous lipid-based retrograde neurotransmitters that comprise of cannabinoid receptors and imitate the psychomotor effect of Cannabis sativa [1,2,3]

  • The observation that substantial regulation of the cannabinoid signalling mechanism exists in Parkinson’s disease (PD) has been supported by a large number of investigations

  • The studies reviewed above reveal that cannabinoids may affect LID and PD progression

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Summary

Introduction

Endocannabinoids, known as endogenous cannabinoids (eCBs), are the endogenous lipid-based retrograde neurotransmitters that comprise of cannabinoid receptors and imitate the psychomotor effect of Cannabis sativa [1,2,3]. Olfactory dysfunction, psychiatric symptoms, and autonomic dysfunction are common non-motor features Such motor functions are used to track the therapy response and assess improvement in PD patients [19,20,21]. The ongoing study aims at employing newer non-dopaminergic substances that can prevent LID and alleviate motor symptoms. The present review aims to lay out an overview of endocannabinoid and its probable influence for the treatment of parkinsonian symptoms, as well as for the expression of cannabinoid receptors in the symptomatology, cause, and treatment of PD progression (wherein cannabinoid signalling experiences alterations in the biphasic pattern and biochemical interactions between CBs, dopamine (DA), and ECS-targeted therapeutic interventions). Published literature data in the field were searched via the most well-known medical data bases (MEDLINE, PubMed, etc.), using specific key words in the topic of our manuscript, and resulting in 202 references mentioned at the final of this review type article

The Endocannabinoid System
Dopamine and Cannabinoid Interactions
Alterations Observed in ECS and Basal Ganglia in PD
Study Design
Therapeutic Implications of Cannabinoids in Oxidative Stress during PD
Antidepressant and Analgesic Effect of Cannabinoids in PD
Therapeutic Implications of Cannabinoids in Excitotoxicity in PD
Findings
Conclusions and Future Approach
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