Can Cannabis sativa attenuate L-dopa-induced dyskinesias? Preliminary findings in a mouse model of Parkinson’s disease

L-DOPA-induced dyskinesias (LIDs) are a frequent and disabling complication of pharmacological treatment for Parkinson’s disease (PD), significantly affecting patients’ quality of life. The endocannabinoid system, particularly cannabidiol (CBD), has emerged as a promising therapeutic target due to its neuroprotective, anti-inflammatory, and modulatory effects on dopaminergic neurotransmission. This study aimed to evaluate the therapeutic effects of Cannabis sativa (CS) extract on LID development in an animal model of PD. First, HPLC was used to assess the presence of cannabinoids in plasma from C57BL/6 mice following acute oral administration of CS extract (60, 120, or 240 mg/kg). In an independent experiment, mice with severe nigrostriatal lesions induced by 6-OHDA received CS extract (60, 120, or 180 mg/kg, p.o.) or vehicle daily, 1 h before L-DOPA (12 mg/kg; dyskinesiogenic dose) or vehicle (i.p.) for 15 days. During treatment, LID severity was assessed using a previously validated scale. HPLC analysis detected cannabinoids in plasma following oral administration of CS extract. Preliminary results further suggest a reduction in LID severity in CS-treated animals compared with controls, with a similar trend across all three doses. Further studies are needed to confirm whether CS administration reduces LID severity and to determine whether this effect is associated with modulation of striatal synaptic microstructure.