The Therapeutic Role of CBD
Cannabis sativa is an herbaceous plant that is known to contain hundreds of chemical compounds with therapeutic effects. All the compounds are closely related and are known as cannabinoids. Among all these chemicals, CBD and THC have secured the most prominent position in medical research.
CBD research has lit up the world of medical research, and provided countless people with hope of new therapies. Let's examine the therapeutic role of CBD.
Therapeutic Potential of CBD
The pharmacological properties of CBD are varied. Through scientific research and clinical trials to date, CBD is known to have the following effects:
- Anti-rheumatoid arthritic
The reason behind the varied effects of CBD is believed to be due to its ability to interact across the body's signaling system.
CBD and the ECS
In human bodies, a natural system known as the endocannabinoid system exists. It is a communication system that plays an important role in many physiological functions. Researchers have shown that this system is implicated in the gastrointestinal tract functions, appetite, memory, pain, movement, and inflammation. The endocannabinoid system has two G-protein coupled receptors namely:
- Cannabinoid receptor 1
- Cannabinoid receptor 2
Receptor 1 is located in the central nervous system and is responsible for having a psychoactive potential. The other locations include the gastrointestinal system, adipocyte, liver, and skeletal muscles. CB2 receptors are more restricted in their locations. These are primarily found in the immune cells. These are also found in immune cells in tonsils, thymus, spleen and the enteric system of the GI tract. The activation of these receptors is based on 2-AG (arachidonoylglycerol). This 2-AG binds with the CB1 and initiate a resultant signaling cascade, by the release of neurotransmitters. These neurotransmitters affect the CNS and peripheral tissues. The most active components of cannabis are cannabinoid CBD and Δ-9-tetrahydrocannabinol (THC) both these compounds can mimic the action of 2-AG on the receptors and have the ability to initiate the signaling cascade. However, the non-psychoactive CBD binds to the CB2 receptor and these are mostly used for curing the neuropathic pain.
THC: CBD ratio
This ratio is the determining factor for the mode of action. For instance;
- Higher THC: CBD ratio is generally associated with prominent psychoactive symptoms.
- Lower THC: CBD ratio is comparably associated with the suppressed psychoactive symptoms, and it causes calmness and relief sensations.
Pharmacokinetics of CBD
- Research have assessed the oil-based capsule of CBD. Due to the hydrophobic nature, the absorption of the CBD from the gastrointestinal tract has been erratic.
- Aerosolized consumption of CBD generated the peak plasma concentration in just 5-10 minutes after the intake. The viability of drug, in this case, is also significantly high.
- CBD distributes in the tissue with a volume of distribution of 32L/kg. CBD accumulates preferentially in the adipose tissues due to the lipophilic behavior.
- The metabolism of CBD in the liver cells is complete. Firstly, it is hydroxylated to 7-OH-CBD. This primary product is further metabolized to several other products which are then eliminated through the body.
Routes of administration
Not only researches have been carried out to investigate the therapeutic potential of the cannabinoid, but also to investigate the dosage form and route of administration. Cannabinoids are lipophilic and require the heat of activation to work. The route of administration casts an impact on the metabolism and absorption of the drug. Scientists have come up with the following routes of administration and optimum dosage.
Inhalation or vaporization
This administrative route can be used for the quickest relief for a shorter period.
- The inhalation can also be carried out by the adaptive smoking behavior of the patient.
- In this adaptive behavior, the dosage is titrated and then consumed.
- The other method is vaporization, in which the drug is taken by the vaporizers. Vaporizers heat cannabis to the optimum temperature at which it decarboxylates.
- This method supplies the instant concentrated amount of drug to the brain and blood. This results in the immediate and short term relief.
- The viability of the drug consumed by this method is still high. this method is used to treat patients suffering from acute pain.
This administrative route may seem interesting but there are a few drawbacks associated with this:
- The amount of the cannabinoids received by the body is variable which depends on the amount of cannabis vaporized.
- The temperature and the duration of vaporization also affect the efficacy of the drug.
- These methods suit best for instant relief rather than a long term solution. The rate of decrease of cannabinoids in the plasma declines as fast as it increases.
- The oral route offers long term but slow-paced treatment.
- CBD can either be consumed as a pill or can be mixed with the food.
- The patients suffering from chronic pain, stress or arthritis can be relieved by the oral administration of the drug.
- This method is the choice of treatment when the patient needs a higher dosage of the cannabinoids more slowly.
- Viability of drug consumed orally varies a lot among individuals.
- Absorption is slower.
- Data from the few preclinical types of research carries through the derma patches have shown that the absorption of the drug is slow but long-lasting.
- The topical treatment has been used in the treatment of glaucoma. This method has a few limitations associated with this.
- As already mentioned that CBD is lipophilic so the transportation of the cannabinoid in the aqueous layer of the body proves to be the rate-limiting step. This problem can be overcome by the usage of the ∆9-THC prodrugs which can easily cross the aqueous layers and barriers. This achievement has directly assisted in reducing intraocular pressure of the anterior eye.
- The topical treatment including creams and ointments are rapidly increasing, but this area lacks research regarding the viability and distribution of the drug.
- This route offers a balanced treatment duration and the speed as compared to both the inhalation and oral medication.
- These medicines contain a blend of both CBD and ∆9-THC and are available in the spray form.
- These drugs are used to treat spasticity in patients suffering from multiple sclerosis.
- These CBD sprays are often used to treat neuropathic pain.
- Viability of drug consumed orally varies among individuals.
- Absorption is slower.
Pharmacokinetics of the cannabinoid through the rectal route has not been researched nor practiced in the clinical trials. So based on the scientific grounds, there is nothing to say about the efficacy of the drug. However, it is still in use by many people.
- This rectal administration has shown its efficacy in patients suffering from post-chemotherapy nausea.
- It can be used for the local treatment of the last parts of GIT (gastrointestinal tract).
- This method has the justification for the patients who cannot inhale or orally take the medication.
- Due to the hydrophobic nature of cannabinoid, the absorption rate is much lesser in the rectal tissues.
- The cannabinoids drugs commonly taken through this route are synthetic or pro-form of THC or CBD and is not natural. So risk factors may be associated with long term use.
CBD and Its Action Spectrum
CBD is widely acknowledged and celebrated medication due to its anti-epileptic effects. To date, several of the anti-epileptic drugs (AED) were of little practical benefit to a certain population of patients, but CBD has been very effective where many other drugs provided no benefit at all. It has now passed several linical and the research trials and is classified by the FDA as an anti-epileptic drug.
Dravet syndrome is also most commonly referred to as SMEI (severe myoclonic epilepsy of infancy). It is a complex epileptic disorder in children, mostly occurring in the first year of life. It is a rare genetic disorder and is marked with drug-resistant seizures. It is an early age encephalopathy epilepsy with a high mortality rate. Dravet syndrome is the result of the genetic mutation of the SCN1A gene, which is crucial for the proper functioning of the brain cells. The syndrome is often referred to as channelopathy because the mutation significantly affects the sodium channels of the brain, resulting in dysfunction. Children affected with Dravet syndrome suffer intellectual development deterioration around the age of 2. Difficulty in learning, language and hyperactivity are also observed.
The main focus of the treatment is to reduce the number of seizures. Convulsive seizures are often responsible for causing sudden epileptic deaths. The situation becomes more grave in the dravet syndrome because of the drug-resistant seizures. Till 2017 there was no clinically approved drug for the cure of Dravet syndrome. Anti-epileptic medications like valproic acid, clobazam, and zonisamide were used to treat seizures. The ketogenic diet is often used to treat drug-resistant seizures.
In 2018, the novel research was conducted on CBD as a powerful agent for controlling the frequency of the seizures. CBD as the anti-epileptic drug is now FDA approved the medicine for Dravet syndrome treatment.
The research has shown that CBD is an effective drug for controlling convulsive seizures. The subjects showed a remarkable decline in the frequency of these convulsive seizures than placebo medication.
CBD also does not affect the sleep cycle of the patient; this gives it a head start over the other neuropsychiatric medications. It is also approved that CBD treatment doesn’t cause any suicidal thoughts. Cannabis decreased the seizure frequency of the subjects from 12.4 to 5.9 is the treatment span.
CBD is known to cut the seizures by 50% if taken in the following dosages:
- 10mg/Kg per day.
- 20mg/Kg per day.
There are no significant side effects reported due to the long term usage of CBD as anti-seizures. However, some researchers have reported:
- Somnolence (drowsiness) in few subjects
- An elevated level of the liver enzymes.
These effects were observed when CBD was used along with other medications. More scientific relevance and pieces of evidence are required to provide the scientific basis of this phenomenon.
CBD is also a potential treatment of the few most common neuropsychiatric disorders.
Alzheimer's is one of the most common neurodegenerative disorders. It is marked with the loss of cognition in the patients. A larger proportion of about 35 million is currently affected by Alzheimer's. It is an irreversible brain disorder that grows progressively. Priory affects memory and the thinking, eventually, it results in the loss of ability to carry out even the simplest tasks. Alzheimer develops with age, often at the onset of the sixties. After cardiovascular disease and cancer, Alzheimer's can be ranked as third for being responsible for the casualties of elder people.
Alzheimer's is the result of dementia, which is referred to as the loss of ability to think or most commonly as the loss of memory. The medical world has already observed the complex changes that occur on the onset and during the progression of the disease.
Specifically talking about the symptoms, Alzheimer's is caused by unknown changes. There are many propositions regarding the cause of Alzheimer's. The early age of Alzheimer can be the outcome of any genetic mutation which affects brain faculties. The other reasons may include the progressive complex changes that the brain undergoes during decades.
Currently, the main goal of the treatment of Alzheimer's is to help the patient retain the mental functions, slowing down the memory loss and managing the behavioral symptoms.
The debate of the CBD effectiveness in the cure of the Alzheimer lasted for long. Recently research has been carried out to find the effectiveness of the CBD in the treatment of Alzheimer's. CBD has eliminated or reduced the oxygen buildup, inflammation and the decline in the brain cell. Alzheimer's is characterized by increased inflammation in the brain cells. This inflammation results when the immunity of the brain cannot filter the blockages. CBD is known to decrease inflammation. Mental faculties are suffered greatly in Alzheimer's because of a rapid decline in the brain cells. In 2011, according to the research held in Australia, CBD greatly increases the production and the development of brain cells thus curing the memory loss. In clinical trials, CBD has shown the ability to slow down or reverse the negative impacts of Alzheimer's.
The World Health Organization has assured that there are no risk factors associated with the use of pure cannabinoids. The best thing about CBD treatment is that it does not cause any dependence or abuse in the patients. A few cases were reported where the patient suffered from:
A few dementia patients have a complaint about the greater tremor rate on the elevated dosage level. So it is highly suggested to use the dosages according to your physician’s consent and prescription.
CBD is widely used to treat sleeping disorders and anxieties. The main reason behind the usage is that it does not alter the consciousness state and never triggers a psychoactive effect. The higher dosage of CBD is known to cause sedation.
Among the sleeping disorders, REM sleeping disorder or RBD is one of the most commonly observed. REM sleep behavior disorder is marked by the unusual movements in the rapid eye movement phase of the sleeping. Normally after 90 minutes of sleep, a person gets into the rapid eye movement phase of sleep. The muscles enter in a temporary phase of paralysis. In RBD muscles fail to develop this muscle atonia and remain active in their dreams. This causes physical agitation in the patient. Cause for RBD is still unknown to the medical world. RBD is treated either with medication or practicing healthier sleeping habits.
CBD has been used to cure the sleeping disorder particularly RBD. Research has shown that CBD treatment has lowered the frequency of RBD events significantly. CBD has known effects in reducing anxiety and promoting calmness. This improves the time and quality sleep of the patient.
A dosage of 10mg to 600 mg is safe to be used for curing the sleeping disorders.
The risk factors associated with the usage are:
- Dry mouth
- Low blood pressure
The past decade is marked by an exponential increase in the number of publications regarding the therapeutic effects of CBD. The future is predicted to be more promising for CBD. Although the evidence is limited till now hopes are high. Further areas where CBD is suspected to help are:
- Anxiety and Compulsion
- Post-traumatic Stress Disorder (PTSD)
- Traumatic brain injury
- Tourette’s syndrome
The experimental and clinical use of CBD has shown the anti-epileptic, antipsychotic and anxiolytic effects of the drug. The last decade is marked with significant research in the area of therapeutic effects of CBD on neuropsychiatric animal models. The quest for an even better understanding of the endocannabinoid system has not been quenched yet. However, there is a need for more precise safety considerations and the drug dosages for each disorder.