Abstracts

Rationale: Recently, we reported that a dual dispensary system of cannabidiol (CBD) extract applied directly to the injured region and with oil injection (IP) following traumatic brain injury (TBI) can reduce lesion volume and restore vestibulomotor and cognitive clinical functions. To determine whether CBD extract derived from cannabis sativa leaves containing THC has superior behavioral and neuroprotective effects than hemp derived CBD (CBDp), two CBD:THC extracts at different ratio concentrations of 300:1 and 10:1 were compared with CBDp in a pre-clinical TBI model.

Methods: The beam balance, alternating T-maze, and object recognition tests were used for vestibulomotor and cognitive functions. The forced swim test (FST) and elevated plus maze (EPM) were used to measure coping strategy. Brains were evaluated histologically with hematoxylin and eosin and immunohistochemically with NeuN, GFAP, and parvalbumin (PV).  

Results: Performance on all tests was restored to a greater degree with either of the CBD:THC extracts compared to CBDp, one being more efficacious than the other depending on the task. Vestibulomotor recovery was reached at 12 days with 300:1, 14 days with 10:1, and 21 days with CBDp. Only the TBI untreated group exhibited significant reduction in spontaneous alternation; the highest alternation rates were observed with both CBD:THC extract treatments. Time spent with novel objects was greatest with CBD:THC at 300:1, exhibiting a similar index ratio as sham controls. Although CBDp treated rats spent more time with objects than the TBI group, the amount of time spent with novel and familiar objects was equal thereby lacking recognition discrimination. In the EPM, sham animals spent the majority of time in open arms, TBI and CBDp groups spent most of the time in the closed arms, and the CBD:THC groups spent similar time in closed and open arms. In the FST, reduced floating was observed with CBD extract 300:1 than TBI alone. Both tests suggest reduced anxiety level was THC concentration dependent. Lesion volume and gliosis were reduced to a greater extent with preserved hippocampal neuronal labeling with CBD:THC extracts compared to CBDp. Concomitant reduction in parvalbumin interneuron labeling was observed not only within the hippocampus on the side of contusion following TBI, but also within the contralateral hippocampus. With CBDp and either of the CBD:THC extracts, PV cell counts were similar to controls on the contralateral side and partly restored ipsilaterally suggesting that CBD was responsible for their rescue.

Conclusions: The concentration ratio of CBD:THC is critical for optimal recovery of locomotor and cognitive functions. Ipsilateral and contralateral hippocampal sparing following TBI was correlated with preservation of neurons, glia, and fast spiking inhibitory PV interneurons which may contribute to their protection.

Funding: Private donation