Traumatic brain injury (TBI)

Traumatic brain injury (TBI)

What is Traumatic brain injury (TBI)?

An acquired brain injury (ABI) is an injury to the brain that is NOT related to birth (either genetically or caused by a birth trauma). There are two types of acquired brain injury: Traumatic brain injury (TBI) and non-traumatic brain injury (NTBI). 

Traumatic brain injury is caused by an external force to the head, followed by an altering in brain function. This external force can be many things, such as falls, assaults, vehicle accidents, sport injuries... 

In contrast, non-traumatic brain injury is caused by non-external forces, which can be a stroke, infectious diseases, seizures, meningitis, or lack of oxygen, etc…

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Understanding traumatic brain injury

TBI greatly varies in terms of mechanism, pathology and severity. Currently, there is currently no set criteria for the diagnosis of it. Its severity can be mild, moderate, or severe, based on criteria such as post-injury Glasgow Coma Score (GCS), which is a score for eye, verbal, and motor responses, with lower scores meaning more serious injury. Or, it can also be based on a duration of loss of consciousness, or other post-injury symptoms.

In terms of mechanisms, they are divided into primary and secondary injury. Primary injuries to the brain occur right at the time of impact. It can be diffuse axonal injury (the tearing and twisting of nerve fibres), cell death and neuron losses, abrupt changes in brain signals, or altered blood flow, etc. Secondary injuries can happen as soon as minutes, or as late as days or even months after the injury and leads to further destruction of the brain. It can be due to an increasing pressure inside the skull that affects the brain, or an increase in inflammation, or reactive oxygen species that damage the brain overtime.

In many cases, even thought people can seems to be alright after the initial injury, their condition may quickly get worse as time goes by. This may be due to the secondary injury.

Because of the nature of TBI being so complicated, there is currently no single pharmacological agent that can treat it effectively. TBI treatment will vary from person to person, depending on the different types of injury, mechanism, severity and symptoms. It can be a treatment for either short term or long term.

Combination of drugs for different purposes can be used, such as pain relievers, anticonvulsants, muscle relaxers, or even stimulants to help with deficits in cognitive functions. 

The Endocannabinoid system and Traumatic brain injury

As mentioned, there is currently no single pharmacological agent that can treat all types of traumatic brain injuries. However, research into the endocannabinoid system has been really promising, and can potentially bring us closer to such treatment.

This is because the endocannabinoid system plays a very important role in almost every aspects of a traumatic brain injury. Turns out, when the brain is injured, the body releases extra endocannabinoids as a self-protective response. Furthermore, the cannabinoid receptors can be targeted to control and inhibit some primary and secondary mechanisms of TBI. 

Some potential actions of the endocannabinoid systems and TBI are listed below:

Central Nervous System (CNS) cell death - Cannabinoids have shown effectiveness in reducing neurodegeneration and lesion volume.

Excitotoxicity - Excitatory neurotransmitters can cause toxic actions and kill brain cells. Research suggests that the endocannabinoid 2-AG can protect the integrity of glutamate receptor function, preventing excitotoxicity.

Reactive oxygen species (ROS) - Endo and phyto-cannabinoids are potent antioxidants to help reduce the damage of ROS.

Neuroinflammation - Manipulations of the endocannabinoid systems can help with both inflammation and also the pain caused by it. Cannabinoids can reduce inflammation by reducing the activation of inflammatory cells, or the cytokines released by pro-inflammation pathways.

Blood brain barrier - The brain has a barrier that separates itself and the rest of the circulatory system. It blocks unwanted things from entering the brain, such as bacteria or viruses, or many other toxic chemicals and substances. A traumatic injury to the brain can disrupt this barrier. Administering the endocannabinoid 2-AG, or inhibiting the enzyme that breaks down 2-AG, can inhibit the blood brain barrier breakdown. 

Cerebral circulation - activation of CB1 receptor is known for the vasodilator effect, which causes red eyes. Therefore, CB1 receptor antagonists can inhibit hypotension induced by endotoxin shock and hemorrhagic shock, leading to higher chance of survival after an injury. 

Cannabinoids in altering post traumatic brain injuries behaviours deficits

As you may already know, brain injuries can cause various behavioural deficits, such as learning and memory impairment, motor control impairment, inability to concentrate, decline in attention and processing speed, or having many seizures after a traumatic event.

Studies are still very limited, but still, the endocannabinoid system can be a promising target.

In terms of learning and memory, both the endocannabinoids 2-AG and anandamide have shown protective properties against TBI-induced neurological motor deficits in mouse models. And when it comes to seizures, preclinical research showed that the endocannabinoid system plays an important role as well. 

And lastly, some cannabinoids may have potential benefits in reducing any anxiety caused by a traumatic brain injury in some mice models.

How to use cannabinoids for Traumatic brain injury

Right after the injury

An early dose of CBD can help protect the nervous system and increase future recovery. So, CBD should be administered as soon as possible after a brain injury. An early dose of CBD can help protect the nervous system and increase future recovery.

However, the dosage range to be used has not been clearly agreed, because studies have been performed in laboratory rats and there are no clinical studies. Some people suggested that 400 - 600mg of CBD should be used, and should continue to do so every day thereafter. This is a relatively large dose of CBD, but what is special about CBD is that it is safe even in large doses and most people should have no problems using this dose.

Some other sources suggest that a moderate dose is sufficient, and that it is advisable to start with 10mg on the first day, then gradually increase the dose each day until improvement is seen. 

Long-term management

Even though both CBD and THC have some neuroprotective properties that can help with a brain injury, it is more advised to stick with CBD more. This is because the THC has more adverse effects that may overlap with the behaviour deficits of TBI, such as memory loss or motor control impairment. This can make it hard to monitor the progress of recovery. Some TBI patients already face challenges in everyday life when it comes to driving or doing their work. Adding another layer of impairment on top of that may not be a good idea. 

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However, THC may still be beneficial for pain management or to relieve stress and anxiety. So, you can still use THC if needed to, but just to be safe, always start low and increase the dose slowly to avoid any potential unwanted effects. Do not use THC while driving or operating machines. 

References

Hergert, D. C., Robertson-Benta, C., Sicard, V., Schwotzer, D., Hutchison, K., Covey, D. P., Quinn, D. K., Sadek, J. R., McDonald, J., & Mayer, A. R. (2021). Use of Medical Cannabis to Treat Traumatic Brain Injury. Journal of neurotrauma, 38(14), 1904–1917. https://doi.org/10.1089/neu.2020.7148

Schurman, L. D., & Lichtman, A. H. (2017). Endocannabinoids: A Promising Impact for Traumatic Brain Injury. Frontiers in pharmacology, 8, 69. https://doi.org/10.3389/fphar.2017.00069

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