An optimal ratio of cannabidiol (CBD) to tetrahydrocanabinol (THC) was hypothesized to protect against neuropathological consequences following traumatic brain injury (TBI). Varied CBD:THC extract concentrations were compared with hemp CBD lacking THC (CBD 0 ). Neurons, glia, and parvalbumin interneurons (PV-INs) were evaluated. Weight loss was observed following high doses of THC dominant cannabis, THC 100:1 . Neuroscores and vestibulomotor performance were restored most with CBD:THC 300:1–10:1 . However, THC dominant treatments resulted in early onset to spontaneous seizures post-TBI. The alternating T-maze showed the CBD 10:1 group had the highest spontaneous alternation rates whereas TBI + vehicle, CBD 0 , CBD 1:1 , and THC 100:1 groups had the lowest. The novel object recognition memory task showed CBD 300:1 treated animals had the best performance, while TBI or THC 100:1 treated groups had the worst. The forced swim test (FST) revealed immobility time was highest after TBI and lowest after THC 20:1 or THC 100:1 treatment post-TBI. The elevated plus maze (EPM) revealed the CBD 0 group spent the most time in closed arms. Both tests indicate that reduced anxiety was THC dependent. In the absence of TBI, THC 20:1 treatment resulted in the highest mobility. All combinations resulted in reduced injury post-TBI but CBD 10:1 and THC 20:1 afforded the most protection and THC 100:1 the least. Reduced GFAP labeling was highest with CBD dominant cannabis supporting its neuroprotective role against inflammation. Rescue of diminished bilateral PV-INs was observed within the hippocampus and medial prefrontal cortex (mPFC) with CBD dominant treatment (CBD 300 , CBD 0 ) supporting their anticonvulsant effect. Loss of PV-INs with THC dominant treatment supports their proconvulsant effect. Thus, CBD and THC have different beneficial therapeutic effects indicating an optimal concentration ratio is critical for neuropathological therapeutics. There is currently no optimal treatment that can prevent behavioral and cellular pathology as well as onset of spontaneous seizures associated with traumatic brain injury (TBI). We hypothesized that an optimal ratio of CBD:THC is required to protect against neuropathological consequences following TBI. Six extracts with varied CBD:THC ratio concentrations were compared with hemp CBD lacking THC. CBD dominant cannabis with critical THC dosing afforded the most neuroprotection and behavioral recovery, whereas THC dominant cannabis stimulated spontaneous seizure onset. CBD and THC had different beneficial therapeutic effects indicating an optimal concentration ratio is critical for neuropathological therapeutics. Absorbable medical carriers will offer delivery treatment options to optimize both short- and long-term drug efficacy relating to neuropathological disorders. • Restored Neuroscores and vestibulomotor performance post-TBI was superior with dose ratios of CBD:THC300:1–10:1. • THC dominant treatments resulted in early onset to spontaneous seizures post-TBI. • Both CBD and THC were required for restored learning and memory and afford bilateral neuroprotection. • Rescue of bilateral PV-INs with CBD dominant treatment supports their anticonvulsant effect. • Loss of PV-INs with THC dominant treatment supports their proconvulsant effect
Friedman et al. (Wed,) studied this question.
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