Oral Cannabidiol Prevents Allodynia and Neurological Dysfunctions in a Mouse Model of Mild Traumatic Brain Injury

Belardo, Carmela; Iannotta, Monica; Boccella, Serena; Rubino, Rosamaria Cristina; Ricciardi, Flavia; Infantino, Rosmara; Pieretti, Gorizio; Stella, L.; Paino, Salvatore; Marabese, Ida; Maisto, Rosa; Luongo, Livio; Maione, Sabatino; Guida, Francesca

doi:10.3389/fphar.2019.00352

Cited by 49 publications

(44 citation statements)

References 32 publications

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“…Similar to human studies, CBD did not produce complete analgesia in all models of chronic pain; in a cisplatin-induced mouse model of neuropathy, CBD attenuated but did not prevent hyperalgesia (Harris et al, 2016). Mechanical hyperalgesia was improved by CBD treatment following traumatic brain injury in mice, myofascial pain in rats, and 6-hydroxydopamine-induced mouse model of Parkinson's disease, however these studies require follow-up to inspect potential mechanisms of action (Belardo et al, 2019;Wong and Cairns, 2019;Crivelaro Do Nascimento et al, 2020). The preclinical work being done to disentangle the mechanisms of CBD in providing analgesic support in chronic pain is flourishing, but much remains in the wake of chronic disease and enhancing our understanding of the mechanisms at play.…”

Section: Mechanistic Insights For Cannabidiol Treatment Of Chronic Painmentioning

confidence: 78%

A Balanced Approach for Cannabidiol Use in Chronic Pain

et al. 2020

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Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa L., has gained traction as a potential treatment for intractable chronic pain in many conditions. Clinical evidence suggests that CBD provides therapeutic benefit in certain forms of epilepsy and imparts analgesia in certain conditions, and improves quality of life. CBD continues to be Schedule I or V on the list of controlled substances of the Drug Enforcement Agency of the United States. However, preparations labeled CBD are available publicly in stores and on the streets. However, use of CBD does not always resolve pain. CBD purchased freely entails the risk of adulteration by potentially hazardous chemicals. As well, CBD use by pregnant women is rising and poses a major healthhazard for future generations. In this mini-review, we present balanced and unbiased preclinical and clinical findings for the beneficial effects of CBD treatment on chronic pain and its deleterious effects on prenatal development.

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Section: Mechanistic Insights For Cannabidiol Treatment Of Chronic Painmentioning

confidence: 78%

A Balanced Approach for Cannabidiol Use in Chronic Pain

et al. 2020

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“…Specifically, CBD tended to normalise extracellular glutamate, D-aspartate, and γ-aminobutyric acid concentrations in the medial prefrontal cortex, suggesting a reduction in excitotoxicity. However, neuronal damage was not measured directly in this study [14].…”

Section: Neuroprotection-concussion and Subconcussionmentioning

confidence: 87%

“…While the primary injury may not be treatable, interventions that attenuate secondary sequelae are likely to be of benefit [203]. Only one study [14] has investigated the biochemical and neuropsychological effects of CBD in an animal model of TBI. Here, C57BL/6 mice were given chronic CBD treatment (3 μg•day −1 , oral) 1-14 and 50-60 days post-(weight drop) brain insult.…”

Section: Neuroprotection-concussion and Subconcussionmentioning

confidence: 99%

Cannabidiol and Sports Performance: a Narrative Review of Relevant Evidence and Recommendations for Future Research

et al. 2020

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Cannabidiol (CBD) is a non-intoxicating cannabinoid derived from Cannabis sativa. CBD initially drew scientific interest due to its anticonvulsant properties but increasing evidence of other therapeutic effects has attracted the attention of additional clinical and non-clinical populations, including athletes. Unlike the intoxicating cannabinoid, Δ 9-tetrahydrocannabinol (Δ 9-THC), CBD is no longer prohibited by the World Anti-Doping Agency and appears to be safe and well-tolerated in humans. It has also become readily available in many countries with the introduction of over-the-counter "nutraceutical" products. The aim of this narrative review was to explore various physiological and psychological effects of CBD that may be relevant to the sport and/ or exercise context and to identify key areas for future research. As direct studies of CBD and sports performance are is currently lacking, evidence for this narrative review was sourced from preclinical studies and a limited number of clinical trials in non-athlete populations. Preclinical studies have observed robust anti-inflammatory, neuroprotective and analgesic effects of CBD in animal models. Preliminary preclinical evidence also suggests that CBD may protect against gastrointestinal damage associated with inflammation and promote healing of traumatic skeletal injuries. However, further research is required to confirm these observations. Early stage clinical studies suggest that CBD may be anxiolytic in "stress-inducing" situations and in individuals with anxiety disorders. While some case reports indicate that CBD improves sleep, robust evidence is currently lacking. Cognitive function and thermoregulation appear to be unaffected by CBD while effects on food intake, metabolic function, cardiovascular function, and infection require further study. CBD may exert a number of physiological, biochemical, and psychological effects with the potential to benefit athletes. However, well controlled, studies in athlete populations are required before definitive conclusions can be reached regarding the utility of CBD in supporting athletic performance.

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“…Our behavioral experiments were carried a day after the exposure to pilocarpine and two days after mTBI induction. Previous reports indicated that mTBI mice develop long term neuropsychiatric condition of increased anxiety and later depression (Guida et al, 2017;Belardo et al, 2019). In this sense, could a bigger time lag from the seizures restore the hippocampal abilities of the mTBI treated animals?…”

Section: Discussionmentioning

confidence: 98%

Thrombin as Key Mediator of Seizure Development Following Traumatic Brain Injury

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Traumatic brain injury (TBI) commonly leads to development of seizures, accounting for approximately 20% of newly diagnosed epilepsy. Despite the high clinical significance, the mechanisms underlying the development of posttraumatic seizures (PTS) remain unclear, compromising appropriate management of these patients. Accumulating evidence suggest that thrombin, the main serine protease of the coagulation cascade, is involved in PTS genesis by mediating inflammation and hyperexcitability following blood brain barrier breakdown. In order to further understand the role of thrombin in PTS, we generated a combined mild TBI (mTBI) and status epilepticus mice model, by injecting pilocarpine to mice previously submitted to head injury. Interestingly, mTBI was able to reduce seizure onset in the pilocarpine animal model as well as increase the death rate in the treated animals. In turn, pilocarpine worsened spatial orientation of mTBI treated mice. Finally, thrombin activity as well as the expression of IL1-b and TNF-a was significantly increased in the mTBI-pilocarpine treated animals. In conclusion, these observations indicate a synergism between thrombin and mTBI in lowering seizure in the pilocarpine model and possibly aggravating inflammation. We believe that these results will improve the understanding of PTS pathophysiology and contribute to the development of more targeted therapies in the future.

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Oral Cannabidiol Prevents Allodynia and Neurological Dysfunctions in a Mouse Model of Mild Traumatic Brain Injury

Cited by 49 publications

References 32 publications

A Balanced Approach for Cannabidiol Use in Chronic Pain

A Balanced Approach for Cannabidiol Use in Chronic Pain

Cannabidiol and Sports Performance: a Narrative Review of Relevant Evidence and Recommendations for Future Research

Thrombin as Key Mediator of Seizure Development Following Traumatic Brain Injury

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