Emerging Therapeutic Potential of Cannabidiol (CBD) in Neurological Disorders: A Comprehensive Review

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Δ9-Tetrahydrocannabinol (Δ9-THC) is a principal psychoactive extract of Cannabis sativa and has been traditionally used as palliative medicine for neuropathic pain. Cannabidiol (CBD), an extract of hemp species, has recently attracted increased attention as a cancer treatment, but Δ9-THC is also requiring explored pharmacological application. This study evaluated the pharmacological effects of Δ9-THC in two human colorectal cancer cell lines. We inves-tigated whether Δ9-THC treatment induces cell death in human colorectal cancer cells.

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Hippocampal differential expression underlying the neuroprotective effect of delta-9-tetrahydrocannabinol microdose on old mice

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Delta-9-tetrahydrocannabinol (THC) is the primary psychoactive compound of the cannabis plant and an exogenous ligand of the endocannabinoid system. In previous studies, we demonstrated that a single microdose of THC (0.002 mg/kg, 3–4 orders of magnitude lower than the standard dose for rodents) exerts distinct, long-term neuroprotection in model mice subjected to acute neurological insults. When administered to old, healthy mice, the THC microdose induced remarkable long-lasting (weeks) improvement in a wide range of cognitive functions, including significant morphological and biochemical brain alterations. To elucidate the mechanisms underlying these effects, we analyzed the gene expression of hippocampal samples from the model mice. Samples taken 5 days after THC treatment showed significant differential expression of genes associated with neurogenesis and brain development. In samples taken 5 weeks after treatment, the transcriptional signature was shifted to that of neuronal differentiation and survival. This study demonstrated the use of hippocampal transcriptome profiling in uncovering the molecular basis of the atypical, anti-aging effects of THC microdose treatment in old mice.

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Hippocampal differential expression underlying the neuroprotective effect of delta-9-tetrahydrocannabinol microdose on old mice

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Delta-9-tetrahydrocannabinol (THC) is the primary psychoactive compound of the cannabis plant and an exogenous ligand of the endocannabinoid system. In previous studies, we demonstrated that a single microdose of THC (0.002 mg/kg, 3–4 orders of magnitude lower than the standard dose for rodents) exerts distinct, long-term neuroprotection in model mice subjected to acute neurological insults. When administered to old, healthy mice, the THC microdose induced remarkable long-lasting (weeks) improvement in a wide range of cognitive functions, including significant morphological and biochemical brain alterations. To elucidate the mechanisms underlying these effects, we analyzed the gene expression of hippocampal samples from the model mice. Samples taken 5 days after THC treatment showed significant differential expression of genes associated with neurogenesis and brain development. In samples taken 5 weeks after treatment, the transcriptional signature was shifted to that of neuronal differentiation and survival. This study demonstrated the use of hippocampal transcriptome profiling in uncovering the molecular basis of the atypical, anti-aging effects of THC microdose treatment in old mice.

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The modulatory role of cannabis use in subconcussive neural injury

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Cannabis use has become popular among athletes, many of whom are exposed to repetitive subconcussive head impacts. We aimed to test whether chronic cannabis use would be neuroprotective or exacerbating against acute subconcussive head impacts. This trial included 43 adult soccer players (Cannabis group using cannabis at least once a week for the past 6 months, n = 24; non-cannabis control group, n = 19). Twenty soccer headings, induced by our controlled heading model, significantly impaired ocular-motor function, but the degrees of impairments were less in the cannabis group compared to controls. The control group significantly increased its serum S100B level after heading, whereas no change was observed in the cannabis group. There was no group difference in serum neurofilament light levels at any time point. Our data suggest that chronic cannabis use may be associated with an enhancement of oculomotor functional resiliency and suppression of the neuroinflammatory response following 20 soccer headings.

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Cannabidiol’s neuroprotective properties and potential treatment of traumatic brain injuries

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Cannabidiol (CBD) has numerous pharmacological targets that initiate anti-inflammatory, antioxidative, and antiepileptic properties. These neuroprotective benefits have generated interest in CBD’s therapeutic potential against the secondary injury cascade from traumatic brain injury (TBI). There are currently no effective broad treatment strategies for combating the damaging mechanisms that follow the primary injury and lead to lasting neurological consequences or death. However, CBD’s effects on different neurotransmitter systems, the blood brain barrier, oxidative stress mechanisms, and the inflammatory response provides mechanistic support for CBD’s clinical utility in TBI. This review describes the cascades of damage caused by TBI and CBD’s neuroprotective mechanisms to counter them. We also present challenges in the clinical treatment of TBI and discuss important future clinical research directions for integrating CBD in treatment protocols. The mechanistic evidence provided by pre-clinical research shows great potential for CBD as a much-needed improvement in the clinical treatment of TBI. Upcoming clinical trials sponsored by major professional sport leagues are the first attempts to test the efficacy of CBD in head injury treatment protocols and highlight the need for further clinical research.

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A focused review on CB2 receptor-selective pharmacological properties and therapeutic potential of β-caryophyllene, a dietary cannabinoid

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The endocannabinoid system (ECS), a conserved physiological system emerged as a novel pharmacological target for its significant role and potential therapeutic benefits ranging from neurological diseases to cancer. Among both, CB1 and CB2R types, CB2R have received attention for its pharmacological effects as antioxidant, anti-inflammatory, immunomodulatory and antiapoptotic that can be achieved without causing psychotropic adverse effects through CB1R.

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Cannabis Therapeutics and the Future of Neurology

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Author: Ethan B. Russo Published in: Frontiers in Integrative Neuroscience  October 2018 Abstract Introduction: Cannabis burst across the Western medicine horizon after its introduction by William O’Shaughnessy in 1838 (O’Shaughnessy, 1838–1840;…

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Migraine Frequency Decrease Following Prolonged Medical Cannabis Treatment: A Cross-Sectional Study

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Authors: Joshua Aviram, Yelena Vysotski, Paula Berman, Gil M Lewitus, Elon Eisenberg, David Meiri Published in MDPI June 2020 Background Medical cannabis (MC) treatment for migraine is practically emerging, although…

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Acute and residual mood and cognitive performance of young adults following smoked cannabis

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Authors: Justin Matheson, Robert E. Mann, Beth Sproule, Marilyn A. Huestis, Christine M. Wickens, Gina Stoduto, Tony P. George, Jürgen Rehm, Bernard Le Foll, Bruna Brands Published in Science Direct…

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Novel interventions to reduce oxidative-stress related brain injury in neonatal asphyxia.

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Authors: A.L. Solevåga, G.M. Schmölzer, P.-Y.Cheung
Free Radical Biology and Medicine, October 2019
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Perinatal asphyxia-induced brain injury may present as hypoxic-ischemic encephalopathy in the neonatal period, and disability including cerebral palsy in the long term. The brain injury is secondary to both the hypoxic-ischemic event and the reoxygenation-reperfusion following…

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The endocannabinoid system and stroke: A focused review.

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Authors: Bradley Kolb, Hamidreza Saber, Hassan Fadel, Gary Rajah
Brain Circulation, January-March 2019
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Stroke is an important cause of morbidity and mortality worldwide. Development of novel neuroprotectants is of paramount importance. This review seeks to summarize the recent evidence for the role of the endocannabinoid signaling system in stroke pathophysiology, as well as th…

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Therapeutic potential of cannabinoids as neuroprotective agents for damaged cells conducing to movement disorders.

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Authors: Mario Antonazzo, María Botta, Harkaitz Bengoetxea, José Ángel Ruiz-Ortega, Teresa Morera-Herreras
International Review of Neurobiology, 2019
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The basal ganglia (BG), an organized network of nuclei that integrates cortical information, play a crucial role in controlling motor function. In fact, movement disorders such as Parkinson’s disease (PD) and Huntington’s disease (HD) are caused by the degeneration of specific…

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