EFFECTS OF CANNABIDIOL ON VOCAL LEARNING AND RECOVERY FROM CNS DAMAGE

Cannabidiol (CBD) , a non-euphorigenic compound derived from Cannabis , shows promise for improving recovery following cerebral ischemia and was recently effective for the treatment of childhood seizures caused by Dravet and Lennox-Gastaut syndromes. This condition is associated with developmental delays , including language deficits. In addition to clinical evidence of anti-seizure efficacy , quality of life assessments indicates improved cognitive function that includes speech. These reports suggest that CBD may have efficacy to improve vocal learning. Based on clinical observations , we hypothesize that CBD has distinct efficacy to mitigate CNS damage and promote vocal learning. To test this hypothesis , we have employed a songbird , the male zebra finch , as a novel pre-clinical animal model. To assess the efficacy of CBD to mitigate CNS damage , we used adult birds , which received bilateral microlesions of HVC (used as a proper name) a pre-vocal motor cortical-like brain region that drives song learning. Moreover , to examine the efficacy of CBD to promote vocal learning , we used juvenile birds that received unilateral lesion of lMAN that plays a major role during the sensorimotor stage of vocal learning. Their songs were analyzed using Kullback-Leibler (KL) distance , syntax and production analysis to confirm the effects of CBD. Our results indicate that 10 and 100 mg/kg CBD effectively reduced the time required to recover vocal phonology and syntax. In the case of phonology , the magnitude of microlesion-related disruptions were also reduced. Also , our results demonstrated ability of CBD to improve vocal learning following damage to lMAN that plays a major role in vocal learning during sensorimotor stage. Treatment with 10mg/kg CBD for 10 days improved vocal learning in terms of phonology and measures of syntax. These results suggest CBD holds promise to improve functional recovery of complex learned behaviors following brain injury and therapeutic promise for treatment of speech- and/or language-related disorders. In addition to demonstrating CBD efficacy , the work represents establishment of an important new animal model to screen drugs for efficacy to improve vocal recovery and vocal learning