Overview of Traumatic Brain Injury
A traumatic brain injury (TBI) is a disruption of the normal function of the brain caused by a bump or blow to the head. A mild brain injury, or concussion, can cause temporary brain cell dysfunction, while a more serious injury can cause the brain tissue to bruise, tear or bleed and result in long-term complications or death.
In a TBI, the blow to the head causes damage to the brain cells. The damage can be isolated to the point of impact or can be more widespread if the impact causes the brain to moves back and forth within the skull. In addition, bleeding in the brain, or swelling, can cause greater damage to brain cells.
According to Mayo Clinic, additional complications can arise from TBI’s, including altered consciousness (coma, vegetative state, locked-in syndrome, brain death, etc…), seizures, fluid buildup, blood vessel damage, nerve damage, and intellectual, communication, sensory and behavioral problems.
The physical and psychological symptoms of a TBI can vary significantly and can arise immediately after the traumatic blow or even weeks later. Physical symptoms include a loss of consciousness or being dazed, headache, nausea or vomiting, fatigue, sleeping difficulties, sleeping more than usual and dizziness. It’s not uncommon for sensory problems, like blurred vision or ear ringing to occur. Also, memory and concentration problems, mood changes and a feeling of depression are cognitive symptoms of a TBI.
For mild brain injuries, rest and over-the-counter pain relievers for headaches are often adequate for recovery. More severe brain injuries require emergency care procedures to ensure oxygen, blood levels and blood pressure remain at adequate levels. Medications may be used to help limit secondary damage caused by fluid buildup. In some cases, surgery is required to repair skull fractures or to relief pressure by draining fluid.
Findings: Effects of Cannabis on Traumatic Brain Injury
Following the blow that leads to TBI’s, the body releases harmful mediators that lead to excitotoxicity, oxidative stress and inflammation and causes secondary, delayed neuronal death (Biegon, 2004). Cannabis, however, has been shown to offer protection to the neural system, thus reducing the amount of brain damage (Mechoulam, Spatz & Shohami, 2002) (Mechoulam & Shohami, 2007) (Mechoulam, Panikashvili & Shohami, 2002) (Biegon, 2004).
It’s cannabis’ two major cannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD) that are responsible for these beneficial effects following TBI’s. Cannabinoids have been shown to act on the CB1 and CB2 receptors of the endocannibinoid system, which in turn prevents the release of proinflammatory cytokines that are released after brain drama and cause damage (Panikashvili, et al., 2006). Activating of the CB1 and CB2 receptors also has been shown to stimulate the release of minocycline, which reduces brain swelling and neurological impairment, and diffuses further injuries to the brain’s axons (Lopez-Rodriguez, et al., 2015) (Biegon, 2004).
In one study, cannabinoid administered to mice with brain injuries caused a significant reduction of brain swelling, as well as better clinical recovery, reduced infarct volume, and reduced brain cell death compared to the control group (Panikashvili, et al., 2001). In another, CBD was found to reduce acute and apoptic brain damage (Castillo, et al., 2010). Piglets with brain injuries given CBD experienced less excitotoxicity, oxidative stress and inflammation (Pazos, et al., 2013). Mice that had suffered an impact brain injury showed marked recovery in object recognition and in performing a specific task after CB1 receptors were activated (Arain, Khan, Craig & Nakanishi, 2015). Cannabinoids have even shown to be effective at offering neuroprotection in newborn babies that have experienced a brain injury (Fernandez-Lopez, Lizasoain, Moro & Martinez-Orgado, 2013).
One study found that patients that had detectable levels of THC in their bodies were less likely to die as a result of a traumatic brain injury than those who didn’t (Nguyen, et al., 2014)
Arain, M., Khan, M., Craig, L., and Nakanishi, S.T. (2015, March). Cannabinoid agonist rescues learning and memory after a traumatic brain injury. Annals of Clinical and Translational Neurology, 2(3), 289-94. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369278/.
Biegon, A. (2004). Cannabinoids as neuroprotective agents in traumatic brain injury. Current Pharmaceutical Design, 10(18), 2177-83. Retrieved from http://www.eurekaselect.com/62903/article.
Castillo, A., Tolon, M.R., Fernandez-Ruiz, J., Romero, J., Martinez-Orgado, J. (2010, February). The neuroprotective effect of cannabidiol in an in vitro model of newborn hypoxic-ischemic brain damage in mice is mediated by CB(2) and adenosine receptors. Neurobiology of Disease, 37(2), 434-40. Retrieved from http://www.sciencedirect.com/science/article/pii/S096999610900309X.
Donat, C.K., Fischer, F., Walter, B., Deuther-Conrado, W., Brodhun, M., Bauer, R.., and Brust, P. (2014). Early increase of cannabinoid receptor density after experimental traumatic brain injury in the newborn piglet. Acta Neurobiologiae Experimentalis, 74,197-210. Retrieved from http://www.ane.pl/linkout.php?pii=7419.
Fernandez-Lopez, D., Lizasoain, I., Moro, M.A., and Martinez-Orgado, J. (2013). Cannabinoids: Well-suited candidates for the treatment of perinatal brain injury. Brain Sciences, 3, 1043-1059. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061885/.
Injury Prevention and Control: Traumatic Brain Injury. (2015, February 24). Centers for Disease Control and Prevention. Retrieved from http://www.cdc.gov/traumaticbraininjury/get_the_facts.html.
López Rodríguez, A.B., Mateos Vicente, B., Romero-Zerbo, S.Y., Rodriguez-Rodriguez, N., Bellini, M.J., Rodriguez de Fonseca, F., Bermudez-Silva, F.J., Azcoitia, I., Garcia-Segura, L.M., and Viveros, M.P. (2011, September). Estradiol decreases cortical reactive astrogliosis after brain injury by a mechanism involving cannabinoid receptors. Cerebral Cortex, 21(9), 2046-55. Retrieved from https://academic.oup.com/cercor/article-lookup/doi/10.1093/cercor/bhq277.
Lopez-Rodriguez, A.B., Siopi, E., Finn, D.P., Marchand-Leroux, C., Garcia-Segura, L.M., Jafarian-Tehrani, M., and Viveros, M.P. (2015, January). CB1 and CB2 cannabinoid receptor antagonists prevent minocycline-induced neuroprotection following traumatic brain injury in mice. Cerebral Cortex, 25(1), 35-45. Retrieved from https://academic.oup.com/cercor/article-lookup/doi/10.1093/cercor/bht202.
Mechoulam, R., and Shohami, E. (2007, August). Endocannabinoids and traumatic brain injury. Molecular Neurobiology, 36(1), 68-74. Retrieved from http://link.springer.com/article/10.1007/s12035-007-8008-6.
Mechoulam, R., Spatz, M., and Shohami, E. (2002, April 23). Endocannabinoids and neuroprotection. Science’s STKE, 2002(129). Retrieved from http://stke.sciencemag.org/content/2002/129/re5.full.
Mechoulam, R., Panikashvili, D., and Shohami, E. (2002, February). Cannabinoids and brain injury: therapeutic implications. Trends in Molecular Medicine, 8(2), 58-61. Retrieved from http://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(02)02276-1.
Nguyen, B.M., Kim, D., Bricker, S., Bongard, F., Neville, A., Putnam, B., Smith J., and Plurad, D. (2014, October). Effect of marijuana use on outcomes in traumatic brain injury. The American Surgeon, 80(10), 979-83. Retrieved from https://goo.gl/UU3g6s.
Panikashvili, D., Shein, N.A., Mechoulam, R., Trembovler, V., Kohen, R., Alexandrovich, A., and Shohami, E. (2006, May). The endocannabinoid 2-AG protects the blood-brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokines. Neurobiology of Disease, 22(2), 257-74. Retrieved from http://www.sciencedirect.com/science/article/pii/S0028390813001238.
Panikashvili, D., Simeonidou, C., Ben-Shabat, S., Hanus, L., Breuer, A., Mechoulam, R., Shohami, E. (2001, October). An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature, 413(6855), 527-31. Retrieved from https://goo.gl/FNFJPH.
Pazos, M.R., Mohammed, N., Lafuente, H., Santos, M., Martinez-Pinilla, E., Moreno, E., Valdizan, E., Romero, J., Pazos, A., Franco, R., Hillard, C.J., Alvarez, F.J., Martinez-Orgado, J. (2013, August). Mechanisms of cannabidiol neuroprotection in hyopoxic-ischemic newborn pigs: role of 5HT(1A) and CB2 receptors. Neuropharmacology, 71, 282-91. Retrieved from http://www.sciencedirect.com/science/article/pii/S0028390813001238.
Presley, C., Abidi, A., Suryawanshi, S., Mustafa, S., Meibohm, B., and Moore, B.M. (2015). Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist. Pharmacology Research & Perspectives, 3(4), e00159. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506688/.
Schurman, L. D., and Lichtman, A. H. (2017). Endocannabinoids: A Promising Impact for Traumatic Brain Injury. Frontiers in Pharmacology, 8, 69. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5314139/.
Shohami, E., Cohen-Yeshurun, A., Magid, L., Algali, M., and Mechoulam, R. (2011). Endocannabinoids and traumatic brain injury. British Journal of Pharmacology, 163(7), 1402–1410. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165950/.
Traumatic brain injury. (2014, May 15). Mayo Clinic. Retrieved from http://www.mayoclinic.org/diseases-conditions/traumatic-brain-injury/basics/definition/con-20029302.
Xu, Z., Lv, X.Q., Dai, Q. Ge, Y.Q. and Xu, J. Acute upregulation of neuronal mitochondrial type-1 cannabinoid receptor and it’s role in metabolic defects and neuronal apoptosis after TBI. Molecular Brain, 9,75. Retrieved from https://molecularbrain.biomedcentral.com/articles/10.1186/s13041-016-0257-8.