CBD Reverse Brain Damage

Introduction

Nowadays, marijuana has become an extremely common drug among youth. The scientific name of this plant is ‘Cannabis sativa’, and the chemical compounds obtained from the extract of this plant are known as cannabinoids and include cannabigerol, cannabidiol, cannabichromene, and tetrahydrocannabinol (THC) along with some other chemicals. Among these chemicals, tetrahydrocannabinol (THC) is the substance that gets you the characteristic ‘high’ when marijuana is consumed. 

Cannabis has been used for medical treatment for a long time now. The usefulness of using cannabis plant extracts to treat ailments related to the brain have particularly been so much highlighted in the past decade or so. Having found the sweet spot between the characteristic ‘high’ of the marijuana due to THC and the positive brain effects of marijuana due to the existence of cannabidiol (CBD), the therapeutic uses of marijuana are certainly increasing day by day.

At first, “Cannabinoid” was a collective term assigned to the set of naturally occurring aromatic hydrocarbon extracts obtained from the Cannabis plant. But, due to the increase in the acceptance of the medicinal use of marijuana, cannabinoids nowadays refer to a diverse set of therapeutic substances that have pharmacologic actions that closely resemble that of the plant-derived cannabinoids. 

How Cannabis extracts act on the Brain

The secret of the therapeutic use of marijuana lies behind the mechanism of action of marijuana on the brain. The most particular constituent of marijuana is the tetrahydrocannabinol (THC), which is the characteristic substance behind the drug abuse. The second major constituent is cannabidiol (CBD). CBD is not psychoactive and has an effect on the brain circuits that is a lot different from the THC effect. 

The cannabinoids (extracts of the Cannabis plant) act by binding to specific receptors in the brain tissue. These receptors are called cannabinoid receptors. These receptors are present on the cells throughout our central nervous system, and they are sometimes also called the CB1 and CB2 receptors. These receptors directly affect the function of the cell they are on, the psychic effects experienced after consuming marijuana have a rapid onset. Such receptors are found predominantly in the brain in the hippocampus and cerebellum. The psychoactive cannabinoids such as THC result in euphoria, enhancement of sensory perception, increased heart rate, decreased pain stimuli, and difficulties in concentrating on specific tasks. The high effect of THC is due to the rapid binding and action of THC on these receptors, which most commonly results in altered perception and sometimes hallucinations.

Cannabidiol (CBD) is however different in its effect on the human brain from THC. CBD, as explained earlier, is not psychoactive, and therefore prevents the brain from going into altered emotions and reality. It has been found that CBD may even counter the psychoactive effects of THC, canceling out the ‘high’ effect by giving a very controlled effect, that is therapeutic. Owing to its anti-psychotic effects, this compound has found itself being used for many pharmaceutical purposes.  These effects are possibly caused due to the opposite effects of THC and CBD on brain activity in regions such as the striatum, hippocampus, and prefrontal cortex. Many studies conducted by laboratories around the world, along with controlled clinical trials, have confirmed that CBD can be adopted as a well-tolerated, safe, and effective drug for antipsychotic purposes.

CBD as an anti-dote for Brain Damage

The therapeutic effects of CBD have carried it out to the field to be tested against various disorders related to the brain, and also against the congenital brain damage. However, the use of cannabinoids greatly needs to be cautious, as each and every illness the cannabis extracts are being used to treat requires a different combination of cannabinoids. If not used cautiously, the cannabinoids may even start showing negative effects. 

The endogenous cannabinoid system, or more commonly known as the endocannabinoid system, serves to regulate a wide array of physiological and psychological processes and possesses considerable potential targets for the potential treatment of numerous disease states. The endocannabinoid system is just another neurotransmitter system in our bodies just like the acetylcholine system or adrenaline system. The endocannabinoid system is composed of neurotransmitters known as endocannabinoids. Endocannabinoids are one of the most widely known, potent, and versatile signaling molecules known up to now. This is probably possible due to the two receptors (i.e., CB₁ and CB₂ receptors) and enzymes regulating their endogenous ligands. Cannabidiol, CBD, binds to these receptors and then alters the function of these receptors and the resulting actions of the body on which these receptors and their ligands affect.  CB₁ receptors are highly expressed on neurons in the central nervous system (CNS) in the inner brain areas such as the cerebral cortex and basal ganglia. CB₂ receptors are most commonly are expressed on immune cells, microglia in the CNS, and macrophages, monocytes, CD4+ and CD8+ T cells, and B cells in the periphery. Additionally, CB₂ receptors are also expressed on neurons, but to an extent that is almost as negligible as compared to the CB₁ receptors. The abundant distribution of CB₁ and CB₂ receptors throughout the brain and periphery accounts for their ability to impact a diverse variety of physiological and psychological processes and other emotions such as memory, anxiety, and pain perception. 

The Use of CBD in Traumatic Brain Injury

Traumatic brain injury, as visible from the word itself, means a traumatic shock to the fragile areas of the brain within the skull due to abrupt force that is exerted on the skull due to an accident or a fall. The injury might cause internal bleeding due to a hemorrhage, which in result might cause permanent brain damage in the areas of the brain that are affected. The areas of the brain that are affected then result in various symptoms based on the area of the brain that is affected. The range of the severity of the symptoms may range from mere trembles to full disability of the area according to the brain region involved in the injury. The pathology of brain injuries includes two mechanisms. One of them is contact type brain injury, resulting due to laceration, contusion, or intracranial hemorrhage, resulting in direct damage to the brain areas that might come in the area of the injury. The range of physiological events that follow the application of an external brute force produce interacting acute and delayed traumas in the brain tissue, which are known as primary and secondary injuries. There may be necrotic cell death in the brain tissue, leading to permanent disabilities in the victims.

Traumatic brain injuries are heterogeneous in their clinical presentation. The signs and symptoms of a traumatic brain injury can be very vast. The onset of the symptoms may be as sudden as on the spot and time of the injury, or may not appear until weeks following the injury. The symptoms may not appear at all or maybe misleading as people may look fine even though they may act or feel differently. Headache and dizziness accompanied by confusion and fatigue may start immediately after an injury, but subsides over time. There might also be emotional symptoms, the victim might develop frustration and irritability in the general behavior later on after the injury. The severity of the symptoms involved in traumatic brain injury depends on the extent of injury to the head. Due to severe or repeated blows to the head, the injury might result in chronic traumatic encephalopathy. Chronic traumatic encephalopathy, also known as CTE disorder, may cause a wide range of problems in the victim, which may include motor disorders related to speech causing communication and cognition disabilities, irritation, and psychiatric disorders such as depression. The increased intracranial pressure resulting from fluid leakage into the brain tissue due to intracranial hemorrhage may lead to an overall reduction in cerebral blood flow which ultimately leads to necrosis in the tissue. The breakdown of the cerebrovascular endothelium due to the injury causes the dysfunction of the blood-brain barrier. Extracranial manifestations of traumatic brain injury can also result in TBI. Among them, pulmonary disabilities are the most common. 

Cannabidiol, due to its promising effects on the central nervous system of a person, has been extensively researched to judge its effects on reversing the brain damage caused due to traumatic brain injury. The endocannabinoid system of the central nervous system appears to be self-protective. There are some radical changes in the chemicals associated with the endocannabinoid system right after the injury. These changes, which include an increase in the levels of anandamide, are to eliminate the initial impacts of the injury, which most commonly include pain. After the traumatic brain injury (TBI), inflammation occurs almost every time. The inflammation spreads to both the secondary injury cascades and the repair of the CNS. Both of these systems are influenced by the endocannabinoid system to a great extent. A study was conducted and the results published on PubMed. This study determined the effects of recurring treatment with a cannabinoid type 2 receptor agonist (which enhances the receptor activity) on various weak points due to traumatic brain injury. These points included the blood-brain barrier integrity and neuronal degeneration in mice with TBI. The specific behavioral effects due to the traumatic injury were also studied.

The primary mechanism due to which CBD can be used to avert brain damage due to the traumatic brain injury lies in the vast anti-inflammatory properties of the CBD. CBD averts inflammation due to various ways. One of the factors through which CBD can avoid inflammation is the dysfunction of the cytokines (chemical substances in the body which serve to mediate inflammation through promoting it). Endocannabinoids, particularly nonpsychoactive agents such as CBD, affect the cytokine structure and biology of various cell systems. Antiproliferative effects of endocannabinoids on cancer cells have been studied well, and their effect on stopping the inflammation is large. As inflammation particularly spreads vastly after a tissue injury due to contusion or other contact causes, so the rate of inflammation surrounding the brain injury can be particularly dangerous, as it causes necrotic cell death in the tissue on a large scale. This cell death proves fatal to certain brain areas that are hit directly by the injury. So, in the case, if traumatic brain injury, stopping the inflammation gains prime importance, as it reduces the chance of the damage spread. The microglia, or the macrophages that exist in the brain tissue, have a very important role in inflammation. Moreover, there are cells in the brain tissue called astrocytes. The astrocytes serve to nourish the brain tissue under normal circumstances, providing vital nutrients to the neurons thus playing an important role in tissue growth. However, under traumatic brain injury where the brain tissue becomes necrotic, the astrocytes have been found secreting certain cytokines along with other chemicals such as nitric oxide that mediate inflammation. 

Interestingly, these astrocytes are found to express both the CB1 and CB2 receptors on their surfaces. The effect of the endocannabinoid neurotransmitters on these receptors has been well explained earlier. Various cannabinoids, such as nonpsychoactive CBD, can serve to have an inhibitory effect on the activity of the astrocytes spreading inflammation.

The endocannabinoid system of the central nervous system appears to be playing a promising role in averting the traumatic brain injury due to various causes. In particular, several cannabinoids, above all CBD, which do not bind cannabinoid receptors, appear to be the promising molecules to treat traumatic brain injury.  

CBD to Treat Alzheimer’s and Other Forms of Dementia

One of the most common neurodegenerative disorders of today is Alzheimer’s disease. It is a neurodegenerative disorder that causes gradual cell death in various areas of the brain occurs, thereby leading to a gradual loss of memories and disability to store new memories. It is the most common cause of dementia today all over the world. It’s a very common misconception that dementia almost always occurs due to Alzheimer’s, which is largely a misleading fact. There are many forms of dementia, including AD, Lewy body dementia, carbon monoxide induced dementia, paralytic dementia, memory loss due to traumatic brain injury, and loss of memory due to undersupply of blood to various areas of the brain. 

Alzheimer’s Disease is a disorder caused due to the gradual degeneration and the resultant death of cerebral cortical cells, and the effect of the death of these cells is visible in the form of dementia in the patient. The most common symptom of AD is memory loss, which may be so severe that personal neglect occurs in some of the patients. This disease may also lead to impaired cognitive abilities of a person. Acquired cognitive disabilities caused by this disease have a diverse effect on the social life, overall behavior, and day to day activity of the patients. 

Alzheimer's disease is neurodegenerative: it worsens over time and as the person ages. Although Alzheimer’s disease is not a normal part of aging in any person, the majority of the patients with this disease are 65 years or older. This does not mean that this disease cannot affect people of young age, almost every young person is at the same risk of having Alzheimer's like that of an old person. In the early stages of this disease, the memory loss is mild, but with late-stage Alzheimer's, the patient loses cognitive ability to carry on a conversation and respond to the specific stimuli in their surroundings. On average, a patient having Alzheimer's disease lives anywhere from 4 to 8 years after the initial diagnosis of the disease. But these numbers are not at all strict, and the patient lifespan can vary as long as 20 years depending on other factors such as nutrition and treatment of the disease. 

Alzheimer's disease is not curable at the present. But certain medications do exist for easing the symptoms and research is ongoing in every corner of the world to find its cure. Aside from Alzheimer’s being not curable at the present, unfortunately, there are no drugs that can temporarily slow the worsening of dementia symptoms and the neurodegeneration of the patient. 

However, the ability of cannabinoids such as CBD to fine-tune various vital brain circuits in the nervous system has found bright prospects in the treatment of various forms of dementia including Alzheimer’s. In this regard, a study was conducted and the results were published on PubMed. The study comprised a total of 21 cases in which cannabinoids particularly CBD obtained from Cannabis plants were used as a therapeutic measure against Alzheimer’s disease. 

The in vitro studies conducted to examine the effect of CBD on a patient with Alzheimer’s were carried out on the PC12 neuronal cells. The results emphasized that cannabidiol activated the Peroxisome Proliferator-Activated Receptor through an intrinsic pathway in the central nervous system. When this pathway was activated, it protected the neuronal PC12 cells from degradation due to oxidation and neurotoxicity. 

The in vivo studies pursued a more proactive approach toward the healing and anti-inflammatory properties of CBD. This included the administration of CBD to the right dorsal hippocampus of a mouse, supplemented with a component human alpha beta peptide, a chemical found in the human central nervous system. The studies showed that CBD actively inhibited the expression of glial fibrillary acidic protein due to its effect on the mRNA encoding GFAP. The CBD administered to the mouse also actively inhibited the expression of several inflammation-causing factors such as interleukin 1-beta protein. The healing properties of phytocannabinoids such as cannabidiol (CBD) for Alzheimer’s disease, and their effect in controlling and preventing further degeneration from happening in the central nervous system to prevent dementia were well pronounced.

The results of these studies, as a whole, provided strong evidence in the favour of CBD being an effective drug to check the progression of Alzheimer’s disease. CBD activated the peroxisome proliferator-activated receptor through the beta-catenin pathway to protect PC12 cells from neurotoxicity and oxidation stress that leads ultimately to cell death, thereby indirectly increasing the rate of cell survival along with reducing ROS production. CBD also indirectly reduced lipid peroxidation in the areas of the central nervous system. Lipid peroxidation is found to be the main culprit behind the uncontrolled tumor production through dangerous free radicals. Decreased lipid peroxidation, therefore, inhibited the hyperphosphorylation of the tau protein, which in turn inhibits acetylcholestrinase (the enzyme responsible for the breakdown of acetylcholine at neuromuscular junctions). All of this leads to an increased rate of neurogenesis in the hippocampus, which is a vital part of the brain involved in the formation of long-term memories. Discrepancies in this area of the brain mostly lead to various types of dementia. CBD indirectly promotes the health of the hippocampus, thereby reducing the risk of dementia in the later life of a person.

The Prospects of CBD in Reversing a Birth Brain Injury – Hypoxic Ischemic Encephalopathy (HIE)

Hypoxic Ischemic Encephalopathy (HIE) is the accidental asphyxiation of an infant during birth due to various causes. Hypoxic ischemic encephalopathy is also known as birth asphyxia, intrapartum asphyxia, or perinatal asphyxia. HIE is not a sparing disease usually, and it can mostly lead to cerebral palsy, along with the stunted growth of the nervous system translating to decreased learning and decreased cognitive abilities. 

HIE is a medical condition found in newborn babies, which usually occurs when the infant’s brain is accidentally subjected to reduced oxygen supply during birth. The mechanism of hypoxic-ischemic encephalopathy is visible from its name: Hypoxia is a term that explains the reduction in oxygen supply to a tissue due to various causes, ischemia stands for inadequate blood supply to an organ due to vasoconstriction or shock, and encephalopathy means a brain disease that alters the normal brain biology or its function due to abnormalities in its structure. Asphyxiation of the newborn due to any cause mostly results in hypoxic-ischemic encephalopathy, as it most commonly interferes with the supply of blood to the nervous tissue in the newborn. If the blood supply to the brain is altered during its developmental phases, it results in serious birth brain defects in the babies later on in their lives. HIE may also be caused due to strangulation of the umbilical cord around the neck of the baby, thereby causing dangerous strangulation. Or, it may also be caused due to the abnormal stretching of the mother’s pelvis to give birth to the baby. The short width of the pelvis does not give enough room to the baby’s head to come out, which results in compression of the vessels supplying blood to the brain, thereby causing ischemia and gradually leading to hypoxia. This hypoxia can affect different areas of the brain.

The particular area of the brain affected due to hypoxia will determine the types of symptoms that appear in the baby after birth. The length of time during which the baby experiences hypoxia also has a very important influence on the severity of this disease. In most cases, the disease is asymptomatic for the first three or four years of the baby’s life, and the doctors will not be able to diagnose the extent of damage to the baby’s brain until he or she is about three or four years of age. This makes HIE a particularly stealthy disease that remains hidden but is always there. Moreover, the early diagnosis of this disease and timely treatment prevents the disease from progressing and protects further areas of the brain to fall a victim to this degenerative disease.

Currently, hypothermia therapy is used over the world to treat babies suffering from hypoxic ischemia therapy. This process involves exposing the baby to a lower temperature of about 33 or 34 degrees Celsius so that the lower temperatures stop the rapidly spreading inflammation. 

We have explained how CBD helps reduce the inflammation in the nervous tissue through its pathways. The endocannabinoid system is naturally self-protective in the humans so that the system has protective measures in place. The anti-inflammatory effects of CBD are quite well understood. CBD serves to activate the Peroxisome Proliferator-Activated Receptor through a pathway in the central nervous system that is well understood. When this pathway is activated, the neuroprotective abilities of the endocannabinoid system are enhanced, and the neuronal PC12 cells are protected from neurotoxicity and oxidative stress. 

The effects of combining CBD oil along with hypothermia treatment to treat HIE appeared to be more promising than simply using CBD or hypothermia therapy to treat the congenital brain damage leading to hypoxic ischemic encephalopathy. Dr. Martinez Orgado, a Spanish associate professor of pediatrics, studied the effects of hypothermia therapy along with injecting CBD to the patients with congenital brain damage. The results of the study were very promising, and the use of CBD along with hypothermia therapy eliminated brain damage almost entirely. The treatment has started in Spain and the United Kingdom, involving babies suffering from brain damage getting hypothermia therapy alone, hypothermia along with CBD or hypothermia along with a placebo.

CBD for Curing Schizophrenia

Schizophrenia is a disorder characterized by a patient having a skewed perception of reality. Symptoms are usually psychic and involve frequent delusions accompanied by hallucinations, and disordered behavior that might result in disability. The onset of schizophrenia is upon late adolescence, but the disease also might appear in the people in their early twenties or thirties having no particular symptoms. It might also affect speech and thinking of the subject. People suffering from this disturbing mental disease experience an extremely disturbed lifestyle, that primarily causes major disturbances in the sleep patterns. 

Aripiprazole and risperidone are currently the drugs of choice in treating schizophrenia. The involvement of the endocannabinoid system in the neuronal circuits of the brain, and its ability to greatly affect the emotions of the person shows that cannabidiol has the potential ability to treat schizophrenia. CBD helps treat the cognitive impairments in the patients suffering from schizophrenia and thus helps in symptomatic treatment.

CBD for Parkinsonism

Parkinsonism is a neurodegenerative disorder characterized by involuntary tremors throughout the body, stiffness, and rigidity. The disease gradually progresses over time like Alzheimer’s, and the symptoms get greater over time. Parkinson’s disease is caused due to degeneration in the areas of the brain that produce dopamine: a neurotransmitter involved in executive functions of the brain such as coordinating the motor control of muscles, as well as lower-level functions including lactation, sexual function, and nausea. The exact cause of cell death in the areas that produce dopamine in the brain is still not understood to the scientists and continues to be the hotspot of Parkinsonism research.

Cannabis extracts, particularly CBD, has found to be useful in Parkinsonism. The pain-reducing properties of CBD help reduce pain. Research has also found that administering oral doses of CBD to patients having Parkinsonism helped relieved the tremors and muscle instability. The dose-related improvement due to the administration of CBD in dystonia was observed in all patients, and the collective effect of CBD ranged from relieving pain to getting rid of tremors throughout the body. Another complication that might occur in Parkinson’s disease is psychosis, and the symptoms of psychosis gradually aggravate over time. A small study conducted in 2009 found CBD to have particularly canceling effects on the symptoms of psychosis, thereby improving the sleep and general lifestyle of the patients having Parkinson’s disease. A study conducted at the University of Louisville, Kentucky shows that CBD acts as an inverse agonist on the CPR6 receptors that are found in the brainstem and are responsible for controlling movement, emotions, and learning - all of which are affected by Parkinsonism. This means that CBD responds to these receptors, and can act as a therapeutic agent in relieving the symptoms of this disease. Studies also show a promising effect of CBD in treating psychosis and resulting in insomnia due to Parkinsonism’s Disease Dementia (PDD).

Final Words

The extracts from Cannabis plant, in particular CBD, have highlighted the importance of using medical marijuana for the treatment of many diseases that were once considered incurable.  Particularly, the effects of cannabinoids on the endocannabinoid system of our nervous system which have neuroprotective effects are promising in degenerative diseases as mentioned above. Recently, FDA has approved the first cannabis containing medicine for clinical use, and CBD has been legalized in the majority of the states in the US, clearing its path in becoming a promising medication for not only disorders related to the brain, but also many other diseases such as rheumatoid arthritis and other inflammatory diseases due to its scientifically proven anti-inflammatory effects.  

REFERENCES

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2. "CBD Oil For Parkinson’S Disease: Possible Treatment And Prevention". Healthline, 2020, https://www.healthline.com/health/parkinsons-disease/cbd-oil-for-parkinsons#treating-parkinsons.
3. Zuardi, AW et al. "Cannabidiol For The Treatment Of Psychosis In Parkinson’S Disease". Journal Of Psychopharmacology, vol 23, no. 8, 2008, pp. 979-983. SAGE Publications, doi:10.1177/0269881108096519. Accessed 1 Sept 2020.
4. https://commons.wikimedia.org/wiki/File:Schizophrenia_(Brain).png