Traumatic brain injury (TBI) pathology remains mostly refractory to Young men are consistently over-represented as being at greatest risk for CB1 receptors mediate most of the psychomimetic effects of cannabis, its chief psychoactive . Sabra, CHI, severe, → Levels of weak antioxidants, Not evaluated. TBI and stroke are both acute and potentially lethal injuries, involving a . combination of CBD and hypothermia may produce the best results. the efficacy of whole plant, CBD-rich cannabis oil for traumatic brain injury. If you've suffered a concussion or traumatic brain injury, it might reassure you to Detailed below are 10 of the top CBD oils for the treatment of traumatic head . -CBD oil use provides natural pain relief, especially for those suffering chronic pain. -CBD oil can help ameliorate the mood-swings, anxiety, depression, and .
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However, exogenous 2-AG has also been shown to ameliorate TBI-induced transactivation of the nuclear factor NF-kB linked to cytokine production in wild type mice, but not in CB 1 knockout mice, suggesting that CB 1 receptors mediate the protective effects of exogenous 2-AG Panikashvili et al.
The blood vessels which carry oxygen rich blood to the brain are lined by endothelial cells as well as astrocytes. These cells, combined with specific transport proteins and enzymes, strictly regulate movement between the general circulation and CNS extracellular fluid, and are collectively known as the BBB. TBI has been well documented in producing cerebral blood flow pathology Kelly et al. Given that cannabinoids are known to exert vascular effects, producing vasodilation as well as hypotension reviewed in Hillard, b , their manipulation may hold promise as protectants against cerebrovascular damage.
Exogenous administration of 2-AG Panikashvili et al. However, Panikashvili et al. The mechanism by which 2-AG acts as a protectant of BBB integrity following traumatic insult is yet to be resolved. While the mechanism underlying the structural protection of the BBB was not explored following TBI, anandamide has been found to decrease BBB permeability in a model of ischaemic stroke by transient receptor potential cation channel, subfamily V, member 1 TRPV1 Hind et al.
The exploration of how anandamide may be exerting its protective effects of BBB integrity may yet yield further novel targets for the treatment of TBI. In cerebral circulation, CB 1 receptor activation produces vasodilation.
Indeed, the CB 1 receptor antagonist rimonabant inhibited hypotension induced by endotoxin shock and hemorrhagic shock, as well as increasing survival Varga et al. Though cannabinoids are yet to be explored in the context of TBI-induced changes in cerebral blood flow, CB 1 receptor antagonism may prove to be a potential target for the treatment of TBI-induced hypotension.
The key biological idea that structure dictates function also holds true for the neurophysiology of TBI. The use of cannabinoids has thus far been linked to protection against several of the CNS structural changes associated with TBI, with 2-AG being the most frequently studied eCB in this area. While a traumatic insult can result in the rapid onset of cerebral oedema, exogenously administered 2-AG protects against TBI-induced oedema Panikashvili et al.
Changes in protein physiology have also been found to occur following TBI. These proteins are thought to accumulate from damaged axons and as a result of a disturbed balance between genesis and catabolism Johnson et al.
MAGL inhibition also decreases astrocyte activation Mayeux et al. These consistent protective effects of 2-AG across varied TBI-related structural pathologies point to its important role in maintaining cell structure and promoting remodeling. Protective roles played by anandamide in injury-induced structural changes are yet to be ascertained. Furthermore, eCBs may not be working alone to offer protection from TBI-induced structural impairments.
These findings suggest that the regulatory activity of the eCB receptors in response to TBI may be mediated by endocrine as well as paracrine signaling mechanisms. Traumatic brain injury is well described to increase CB 1 and CB 2 receptor expression, which includes disruption of diurnal rhythms of CB 1 receptor expression Martinez-Vargas et al. Post-injury treatment with a CB 1 receptor antagonist reduces CB 1 receptor expression at 6 weeks following injury Wang et al.
The exact CNS circuits involved in NPE have yet to be identified, though a sudden rise in intracranial pressure, rapid sympathetic surge, increased systemic vascular resistance and increase in hydrostatic pressure in the pulmonary vasculature, as well as release of pro-inflammatory mediators may all contribute to interstitial pulmonary oedema formation Brambrink and Dick, While at the present time there are no studies evaluating the contributions of, or protection by, the eCB system to NPE following TBI, this may prove an interesting area of future investigation.
Specifically, the lung possesses a basal tone of 2-AG Avraham et al. The heterogeneous clinical presentation of TBI pathology in populations of survivors is reminiscent of its cellular and molecular pathophysiology described above. Most frequently investigated measures in the pre-clinical TBI literature include neurological motor, and learning and memory impairments, leaving a wide breadth of TBI clinical effects yet to be studied.
Once again, components of the eCB system may become active to compensate for TBI symptomology given what is currently known of its regulatory effects within these areas, two examples being pain, and anxiety and depression Corcoran et al.
Learning and memory impairments are among the most frequently reported symptoms following TBI, and are slow to recover with deficiencies reported 10 years later Zec et al. The eCB system has been shown to play a well-documented role in memory regulation reviewed in Mechoulam and Parker, , and as such its manipulation holds considerable promise to address such a profound consequence of TBI.
The protective effects of 2-AG appear to be task specific, with ABHD6 inhibition showing learning and memory protection in a Y-maze task, but not a Morris water maze task. To date, only a Y-maze task has been used to evaluate the memory protective effects of FAAH inhibition, and this task-specific effect did not occur with a MAGL inhibitor. Mice are a well-used pre-clinical model organism to study the memory effects of TBI; however, they are known to perform behavioral tasks more readily, and with less error, when the task does not rely on aversive motivation Stranahan, This attribute of mice may, in some part, contribute to the task-related differences seen between the Y-maze task which uses exploratory behaviors associated with novelty and the aversively motivated escape behavior necessary in the Morris water maze.
Moving forward, the use of behavioral tasks able to selectively assess such frontal lobe-type memory impairments might improve the translational capacity of eCB TBI pre-clinical assessments one such example being the Morris water maze Reversal Task, which evaluates cognitive flexibility. Traumatic brain injury-induced neurological motor impairments currently represent the most frequently studied behavioral outcome measure in the TBI-cannabinoid literature.
In clinical populations, neurological motor impairments seen as a result of TBI show spontaneous improvement over time, but one third of patients continue to experience neuromotor abnormalities 2 years after injury Walker and Pickett, A variety of eCB system manipulations have thus far been found to be protective against the neurological motor deficits associated with murine models of TBI.
Both 2-AG and anandamide elevation provide protection against TBI-induced neurological motor deficits. MAGL inhibitors Zhang et al. FAAH inhibition has produced mixed findings in neurological motor tests, such as beam-walk deficit protection Tchantchou et al. In support of anandamide being protective against TBI-induced motor deficits, exogenous anandamide has also produced improved NSS performance Martinez-Vargas et al.
The involvement of the CB 2 receptor is further supported by rotarod deficit protection from a CB 2 receptor agonist Amenta et al. The role of entourage effects has also been evaluated in the area of TBI-induced neurological motor impairments. Co-release of endogenous fatty acid derivatives can potentiate 2-AG signaling, termed an entourage effect Ben-Shabat et al. Given FAAH is responsible for the degradation of various fatty acid amides in addition to anandamide Boger et al.
Thus any inferences drawn about anandamide through the use of FAAH inhibition needs to consider contributions of non-cannabinoid fatty acid amides. The signs of post-traumatic anxiety have been difficult to replicate in murine models of TBI Tucker et al. Also, as there is a limited number of studies evaluating eCBs in this area, no definitive conclusions can be made.
Thus far, only FAAH inhibition has been explored to address post-traumatic anxiety, and was found to protect against TBI-induced increases in anxiety-like behavior in mice Tchantchou et al. This protection in the zero maze was unaffected by either CB 1 or CB 2 receptor antagonists, suggesting that these receptors are dispensable. Modeling post-traumatic epilepsy is time consuming and faces other challenges such as a low percentage of animals that develop epilepsy Mazarati, , however, recent models that produce consistent replication of spontaneous seizure activity following a TBI are available Ping and Jin, Contrary to preclinical research demonstrating that the eCB system plays a protective roles against seizures Wallace et al.
This nascent body of data, suggests that eCB manipulations hold promise to treat injury-induced clinical symptoms outside of the more popular areas of learning and memory and neurological motor impairments.
Although currently well over one hundred phytocannabinoids have been elucidated from the Cannabis sativa plant Elsohly et al. The investigation of phytocannabinoids on TBI pathology not only holds topical relevance, but also but also holds promise as potential treatment for TBI and other disorders.
However, clinical and pre-clinical findings provide evidence suggesting that the primary psychoactive constituent of Cannabis sativa , THC, is neuroprotective when administered prior to a traumatic insult. In a 3 year retrospective study of patients who had sustained a TBI, urine toxicology screen results showed decreased mortality in individuals with a positive THC screen Nguyen et al. In two mouse models of CNS injury that yield cognitive deficits, pentylenetetrazole an excitotoxic agent and carbon monoxide induced hypoxic injury, prior administration of THC provided impairment protection Assaf et al.
Curiously, an extraordinarily a low dose of THC i. The authors explained this effect through the known biphasic effects of THC producing analgesia, acute hypothermia, and decreased locomotion at high doses 10 mg. Such low dose effects of THC have been found to potentiate calcium entry into cells in vitro Okada et al. Therefore, Assaf et al. Moreover, the molecular signaling cascades behind cardiac and cerebral ischaemia preconditioning include activation of ERK and Akt Dirnagl et al.
As such, individuals may experience very low plasma THC concentrations for prolonged periods after each application. This presumed prolonged exposure of THC due to its pharmacokinetics, as well as other potentially neuroprotective cannabinoids, such as CBD Perez et al.
A finding of increased clinical relevance, is that post-conditioning when the mildly noxious stimulus is applied after the insult with low dose THC also produced cognitive sparing effects in mice Assaf et al.
These findings, however, remain controversial, and are yet to be replicated in animal models of TBI. The phytocannabinoid CBD, currently being investigated in clinical trials for its seizure reduction potential in Tuberous Sclerosis Complex Gw Research Ltd, , has known anti-inflammatory properties.
As such CBD may be a promising future avenue of investigation in the study of neuroinflammation in response to brain injury. The eCB system, through release of its endogenous ligands or by changes in cannabinoid receptor constitutive activity, possesses promise in the treatment of diverse TBI pathology. An important step forward in understanding the role that the eCB system plays in TBI pathology includes not only the full characterization of ligands targeting cannabinoid receptors and eCB regulating enzymes, but also changes in cannabinoid receptors, eCB levels, and eCB regulating enzymes as a consequence of TBI.
So too do the plant-derived phytocannabinoids represent an understudied yet promising group of compounds given the neuroprotective results obtained from other types of CNS injury. In particular, CBD as well as other phytocannabinoids which do not bind cannabinoid receptors, represent promising molecules to treat TBI.
To date, the only reported cannabinoid to be specifically evaluated for the treatment of TBI in patient populations is Dexanabinol, also known as HU Although HU has been described as a cannabinoid by virtue that it is an enantiomer of the potent synthetic cannabinoid agonist HU, it does not bind or activate cannabinoid receptors.
This therefore brings to light an important consideration of the classification of cannabinoids. One consistently overlooked area across the study of TBI is the evaluation of the central penetration of systemically administered drugs. Pharmacological treatments will need to be assessed for their ability to cross the BBB. Furthermore, given the often biphasic nature of cannabinoid drugs, it is critical to move away from single dose pharmacology to full dose-response assessments, which may yield an increased understanding of the mechanism and potential of cannabinoids to treat TBI.
Overall, the abundant and growing pre-clinical research suggests that the eCB system possesses many promising targets for new and existing drugs that may ameliorate diverse TBI pathology.
LS performed the literature review and composed the article; AL contributed to the composition of the article. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
This research was funded by a Ruth L. National Center for Biotechnology Information , U. Journal List Front Pharmacol v. Published online Feb Schurman and Aron H. Author information Article notes Copyright and License information Disclaimer. This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology. Received Oct 15; Accepted Feb 2.
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Abstract The endogenous cannabinoid endocannabinoid system regulates a diverse array of physiological processes and unsurprisingly possesses considerable potential targets for the potential treatment of numerous disease states, including two receptors i. Open in a separate window. Traumatic Brain Injury Pathology Traumatic brain injuries are heterogeneous in their etiology, clinical presentation, severity, and pathology. Table 1 Effect of cannabinoids on TBI-induced cellular and molecular pathophysiology.
CNS Cell Death Traumatic brain injury-induced neuronal loss occurs almost immediately as necrotic cell death and continues for months following the initial insult via both necrotic and apoptotic cell death Raghupathi, Excitotoxicity Previous efforts to attenuate the effects of excitotoxicity following brain injury focused on NMDA receptor antagonists, presumably with the understanding that the induction of depressed NMDA receptor function would counteract TBI-induced excitotoxicity.
Neuroinflammation Hydrolytic enzymes of anandamide and 2-AG produce a shared metabolic product in the formation of free AA, the major substrate of the biosynthetic enzymes of pro-inflammatory eicosanoids Nomura et al.
Cerebrovascular Breakdown The blood vessels which carry oxygen rich blood to the brain are lined by endothelial cells as well as astrocytes. Treatment of Behavioral Deficits of TBI The heterogeneous clinical presentation of TBI pathology in populations of survivors is reminiscent of its cellular and molecular pathophysiology described above.
Table 2 Effect of cannabinoids on TBI-induced behavioral impairments. Learning and Memory Learning and memory impairments are among the most frequently reported symptoms following TBI, and are slow to recover with deficiencies reported 10 years later Zec et al. Neurological Motor Traumatic brain injury-induced neurological motor impairments currently represent the most frequently studied behavioral outcome measure in the TBI-cannabinoid literature.
Primary Phytocannabinoids and Traumatic Brain Injury Although currently well over one hundred phytocannabinoids have been elucidated from the Cannabis sativa plant Elsohly et al. Concluding Remarks and Future Directions The eCB system, through release of its endogenous ligands or by changes in cannabinoid receptor constitutive activity, possesses promise in the treatment of diverse TBI pathology. Author Contributions LS performed the literature review and composed the article; AL contributed to the composition of the article.
Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Diffuse axonal injury in head injury: Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain. Supply and demand for endocannabinoids. Pulmonary complications in patients with severe brain injury. A cannabinoid type 2 receptor agonist attenuates blood-brain barrier damage and neurodegeneration in a murine model of traumatic brain injury.
Experimental models for analysis of oligodendrocyte pathophysiology in stroke. The early critical phase of severe head injury: Fatty Acids 79 35— Late mortality after severe traumatic brain injury in New South Wales: The biphasic opening of the blood-brain barrier in the cortex and hippocampus after traumatic brain injury in rats. Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain.
Chemical probes of endocannabinoid metabolism. A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol. Fatty acid amide hydrolase substrate specificity. Guidelines for the management of severe traumatic brain injury. J Neurotrauma 24 Suppl. Pathogenesis, clinical picture and therapy. Guidelines for the surgical management of traumatic brain injury.
Factors affecting excitatory amino acid release following severe human head injury. CB2 receptors in the brain: Inhibition of an equilibrative nucleoside transporter by cannabidiol: Natural cannabinoids improve dopamine neurotransmission and tau and amyloid pathology in a mouse model of tauopathy. Blood-brain barrier pathophysiology in traumatic brain injury. N-oleoyldopamine, a novel endogenous capsaicin-like lipid that produces hyperalgesia.
The epidemiology of traumatic brain injury. The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: Monoacylglycerol lipase MAGL inhibition attenuates acute lung injury in mice. Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase.
Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor agonist.
Production and physiological actions of anandamide in the vasculature of the rat kidney. Determination and characterization of a cannabinoid receptor in rat brain. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Targeting the endocannabinoid system: To enhance or reduce?
Brain monoglyceride lipase participating in endocannabinoid inactivation. Ischemic tolerance and endogenous neuroprotection. A new perspective on cannabinoid signalling: Using a cost-benefit analysis to estimate outcomes of a clinical treatment guideline: Nonpsychotropic cannabinoid acts as a functional N-methyl-D-aspartate receptor blocker. The neurophysiology of brain injury.
Phytocannabinoids beyond the Cannabis plant — do they exist? Cerebral preconditioning and ischaemic tolerance. Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Segregation of two endocannabinoid-hydrolyzing enzymes into pre- and postsynaptic compartments in the rat hippocampus, cerebellum and amygdala.
Anandamide, but not 2-arachidonoylglycerol, accumulates during in vivo neurodegeneration. A2A receptors in inflammation and injury: Hemopressin is an inverse agonist of CB1 cannabinoid receptors. Characterization and localization of cannabinoid receptors in rat brain: Voltage-gated sodium NaV channel blockade by plant cannabinoids does not confer anticonvulsant effects per se.
Biochemistry and pharmacology of the endocannabinoids arachidonylethanolamide and 2-arachidonylglycerol. Prostaglandins Other Lipid Mediat. Endocannabinoids and vascular function 1. Endocannabinoids modulate human blood-brain barrier permeability in vitro. The development of acute lung injury is associated with worse neurologic outcome in patients with severe traumatic brain injury.
TRPV1 activation results in disruption of the blood-brain barrier in the rat. Endocannabinoid degradation inhibition improves neurobehavioral function, blood-brain barrier integrity, and neuroinflammation following mild traumatic brain injury.
Cerebral blood flow as a predictor of outcome following traumatic brain injury. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. Dexanabinol HU in the treatment of severe closed head injury: Cannabidiol-treated rats exhibited higher motor score after cryogenic spinal cord injury. The palmitoylethanolamide and oleamide enigmas: Are these two fatty acid amides cannabimimetic?
The epidemiology and impact of traumatic brain injury: Advertised as a natural dietary supplement for health and vitality, you may also receive benefits helpful for treating your brain injury or concussion. Aside from taste and effectiveness, you receive reassurances from the company that there are no pesticides, herbicides, solvents or chemical fertilizers used to grow the hemp used in this formulation, and all of these products are pet-safe, too. Trace amounts of THC are below 0. MCT fats can promote enhanced brain health, and when combined with the calming properties of CBD, your lifestyle may be improved as a direct result.
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According to the website ProjectCBD. He has beaten the bushes for evidence to prove that these concentrates are effective—even in the most extreme cases—like the chronic traumatic encephalopathy CTE diagnoses too many pro athletes have received of late as a result of repeated head injuries.
On what does Lee base his conclusions? Further, anecdotal evidence gathered from countless numbers of international studies give credit to this pairing of compounds for more than just brain repair.
When tested on mice, CBD normalized post-ischemic heart arrhythmia and lessened the amount of damage done to the brain. These results proved effective, whether administered before or after the rodents were injured.
CBD has been found to be so effective for head injuries that it is used as a first-line treatment by the Israel Defense Force IDF practitioners, who administer it to IDF soldiers who have just sustained brain trauma. Individuals with many different types of head injuries—especially those that cannot be cured because the damage is too profound—can still anticipate the following benefits and symptom relief after settling into a regimen of the right dose of CBD oil:.
Culinary nutritionist and holistic cannabis practitioner Janice Newell-Bissex has been keeping tabs on the state of cannabis-product acceptance by lawmakers for years, and while she reports that many of the brain-related disorders described in this article are being treated using CBD oils via physicians, she worries that lawmakers and health professionals still cling to myths that stand in the way of more acceptance.
Cannabis and derivatives continue to remain illegal and classified as Schedule 1 controlled substances, and prescriptive protocols undertaken by individual states are a jumble of confusion. Want to know where your state stands? At stake are a plethora of new formulations being introduced by manufacturers, not all of which are on the up and up.
Though some of the most reputable growers and distributors are happy to share their lab reports, these formulations still require due diligence by folks taking oil, so finding an authority on the subject makes a great first step in evaluating which products you should select. The products on our list have all been studied in-depth using a grading system that accounts for where the hemp is grown, what extraction methods are used in processing, whether the company utilizes an outside laboratory for testing, and more.
We can say with confidence that our list can provide you with a wonderful place to start when choosing which CBD product is right to help treat your symptoms related to head injuries or concussions. Lichtman Not thrilled about reading scientific jargon?
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Symptoms That May Be Alleviated By Taking CBD Oil Individuals with many different types of head injuries—especially those that cannot be cured because the damage is too profound—can still anticipate the following benefits and symptom relief after settling into a regimen of the right dose of CBD oil:
Cannabis: Optimal Treatment Method For Post-Concussion Syndrome Symptoms
Pot and CBD oil help my mood, depression, and anxiety/panic and pain. man I suffered a serious brain injury in high school and started using marijuana once I got home. . Best thing I did stopping that, but certain CBD oil messed me up. Cannabidiol (CBD) oil is a natural plant-based oil that contains phyto (plant) This oil is best taken with food. medications and/or if you have mental health symptoms that could be severe. Lewis M. CBD for Head Trauma. of Healing Depression: Integrated Naturopathic and Conventional Treatments. CBD is perhaps best known for treating epilepsy-related seizures and other similar In severe cases, head trauma can result in torn brain tissue, bleeding and other So, what role can CBD oil have in treating head injuries?.