Effects of Cannabidiol and Tetrahydrocannabinol on Behavioral and Neurochemical Alterations in Experimental Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a progressive and debilitating neurodegenerative disorder that predominantly affects the substantia nigra (SN) and the locus coeruleus. In rodent models, administration of reserpine has been shown to induce motor dysfunction alongside impairments in memory, cognition, and emotional regulation. The study aims to investigate the modulatory effects of cannabidiol and tetrahydrocannabinol on neurobehavioral, neurochemical, and histoarchitectural changes in a reserpine-induced Parkinson’s disease mouse model. Forty-two adult mice (25–32 g and 8–10 weeks old) of either sex were randomly divided into seven groups (n = 6). Parkinsonian-like symptoms were induced through intraperitoneal administration of reserpine (0.5 mg/kg) once daily for ten days. Twenty-four hours after the last reserpine injection, mice received intraperitoneal treatments of cannabidiol (30 mg/kg or 60 mg/kg), tetrahydrocannabinol (4 mg/kg or 6 mg/kg), or a combination of CBD (60 mg/kg) and THC (6 mg/kg) for fourteen consecutive days. The data from each group were analysed using one-way analysis of variance (ANOVA), followed by Tukey’s post-hoc test for multiple comparisons. Treatment with CBD at 30 mg/kg and 60 mg/kg showed a significant reduction (P < 0.001) in open arm avoidance (71.75 ± 0.85 % and 68.50 ± 1.66 % respectively) compared to the reserpine-only group (96.25 ± 3.75 %). The study concludes that cannabidiol and tetrahydrocannabinol modulate neurobehavioral, neurochemical and histoarchitectural changes in reserpine-induced Parkinson’s disease in mice by reducing anxiety, improving cognition, increasing serotonin levels in the brain and reducing neuronal damage. Further molecular investigations are required to determine alterations in gene and protein expression related to monoamine neurotransmission, oxidative stress, and neuroinflammatory processes in Parkinson’s disease. Additionally, future research should explore the long-term effects of chronic administration of cannabidiol (CBD) and tetrahydrocannabinol (THC) in the management of non-motor symptoms associated with Parkinson’s disease.