Cannabinoid receptors are a part of the body’s endocannabinoid system and have been linked to seizures. Learn here how CBD works on a molecular level.
The respected Epilepsy Foundation has several informational resources dedicated to medical marijuana. They have published studies detailing that CBD works for otherwise drug-resistant conditions.
There is now mounting evidence that cannabis can be helpful in controlling seizures. Unlike conventional drugs, cannabis products have few or no side effects.
The only exception is for interactions with drugs processed in the liver. CBD is a strong liver enzyme inhibitor.
A more recent study confirms the usefulness of CBD. It is useful for the treatment of Dravet Syndrome. Dravet Syndrome is a childhood seizure disorder that’s very difficult to treat. Other strong seizure medications are ineffective.
While the efficacy of the treatment is now studied and accepted, what are the mechanics? How does CBD work with cannabinoid receptors?
Read on to learn more.
The endocannabinoid (EC) system is part of the complex mechanism regulating the body. It balances the body’s immune response. It moderates appetite, and metabolism. It also affects the memory and other functions.
In spite of the vital role of this system, it remained unknown until the late 1960’s. Many of its processes and functions are still undiscovered.
Bias against EC system research goes back to the naming of the EC system itself. Named for the cannabis plant, research was against the law in the U.S.
The discovery and isolation of THC shut down research for decades. The “dangerous” psychoactive was off limits in the 1940’s. Understanding the EC system and the possible therapeutic properties stalled until the mid-1990’s.
Research of the EC system in the last few decades finally brought some understanding. Several integrated processes make up the EC system:
Together, these mechanisms regulate body processes and functions. CB1 and CB2 receptors respond to different cannabinoids. The density of the types of receptors varies in parts of the body.
Cannabinoid receptors accommodate different molecular structures. Like keys and locks, many different molecules may bind to a receptor. Certain molecules have preferential access. Other cannabinoids and terpenes may also bind to the receptor with different results.
CB2 receptors fight inflammation and tissue damage. They are a crucial part of immune system cells. CB2 receptors are also prevalent in the gastrointestinal system.
Some cells contain both types of cannabinoid receptors to control different functions. A single receptor recognizes many different compounds and produces varied distinct effects.
The role of cannabinoid receptors is cell to cell (or within the same cell) signaling. Cannabinoids themselves are fat-soluble. They are hydrophobic and do not move well in water.
Cannabinoids travel “backward” from postsynaptic to presynaptic cells. Cannabinoids are not stored by the body.
Fat cells synthesize them when needed. They have a short life and their degradation regulates bioactivity.
Disrupted endocannabinoid signaling is connected with many disorders. Researchers work to understand how to game the endocannabinoid system.
Some therapies seek to decrease pain, fight cancer and prevent diseases. Others delay aging-related brain function loss and promote health.
One theory says that the body does not generate enough endocannabinoids. This is the supposed root cause of many autoimmune disorders.
This “endocannabinoid deficiency syndrome,” is possibly the cause of many illnesses. Conditions like migraines, fibromyalgia, and epilepsy are examples.
This theory suggests treatment by phytocannabinoids (plant-based) or synthesized cannabinoids. These flood targeted cannabinoid receptors.
For some, the problem may not be a lack of endocannabinoids. It is a deficiency or misallocation of cannabinoid receptors.
Having more than an average number of a certain type of receptors is called overexpression. Excess cannabinoid receptors in the central nervous system accept more signals than expected.
CB1 receptor overexpression means a very high sensitivity to THC, which binds to CB1. As a result, certain strains and blends have a strong effect, even in small quantities.
Underexpressed receptors mean that there are fewer of a certain type than average. This might make delivering therapeutic doses more difficult.
Misallocation is having the receptors in the wrong place at the wrong time. This could also express itself in chronic disease.
The EC system regulates the release of neurotransmitters. Diseases such as Alzheimer’s disease and Parkinson’s disease may relate to endocannabinoid deficiency.
Surveyed literature finds that cannabinoid receptor activation produced anti-convulsant effects. The experiments used rodents as models of acute seizures. Blocked CB1 receptors were more likely to cause convulsions.
When examining the effects of cannabinoids, it reveals an interactive system. Endocannabinoids affect the development of epilepsy and neuroprotection.
Complex interactions between brain regions leads to a large variety of results. Contributions by endocannabinoid signaling change the effects. Timing, duration, different cannabinoid receptor sites and receptor interactions are all factors.
Research suggests that there is therapeutic potential in the regulation of endocannabinoid signaling. An equal amount of potential risk in the central nervous system also exists.
Factors such as receptor desensitization appear to play a role in the effects reported. The specific pharmacology of cannabinoids used makes a difference. (e.g. full vs partial agonists and neutral antagonists vs inverse agonists).
The effects of several plant cannabinoids are consistent with claimed benefits. Several studies of THC, CBD, and other compounds note their effects.
Cannabidiol (CBD) demonstrated beneficial therapeutic effects in clinical studies. It has an effect on seizures, epilepsy, development of epilepsy, and protection against nerve damage.
THC is a demonstrated anticonvulsant, with better results in combination with CBD. THC acts to activate the CB1 receptor. CBD acts as a weak antagonist (to deactivate the receptor) in balance.
The excessive excitation of neurons in the brain causes seizures and non-convulsive attacks. Cannabinoid receptors regulate the level of excitement within the neuron (Anandamide and 2-AG).
For a dysfunctional endocannabinoid system, treatment directly to cannabinoid receptors is possible. Tailored delivery of certain cannabinoids and terpenes is an avenue of research.
A condition known as “status epilepticus” occurs in the most severe forms of epilepsy. Status epilepticus involves both convulsive and nonconvulsive seizures. These last for a period of more than five minutes each or occur as more than one seizure every five minutes.
A patient requires immediate medical attention during an episode of status epilepticus. Loss of normal brain function causes brain damage or death. If provided prompt medical care, epileptic patients usually survive without major complications.
Status epilepticus is presently treated with benzodiazepines or barbiturates. Both classes of drugs are highly addictive.
They often produce physical weakness in the patient as a side effect. They are also ineffective for seizures in nearly half of all patients.
Evidence suggests cannabinoids that activate CB1 provide the greatest protection from epileptic seizures. In a 2006 study, a specific cannabinoid completely suppressed all attacks.
Also noted, the plant-based cannabinoid exceeded common drugs in control of prolonged attacks. (Phenytoin and phenobarbital for status epilepticus).
Studies show that agonists (activators) of cannabinoid receptors are critical to suppress seizures. Cannabinoid receptor agonists also prevent the onset of epileptic seizures.
By correcting the imbalance, the endocannabinoid system decreases the frequency and severity of seizures.
A 2007 article notes that neurons that were administered CB1 antagonist receptors convulsed. This was in the same manner as patients with status epilepticus. Neurons treated with CB1 agonist receptors ceased epileptic activity.
It is clear that both THC and CBD can play important roles in controlling epileptic seizures. Lesser cannabinoids may also contribute to controlling seizures or protecting against damage.
Research on the usefulness of cannabinoids in treatment is ongoing. A deeper understanding of the EC system is necessary. There is a lack of knowledge about the mechanisms and interactions.
The EC system is of vital importance to health, but the questions of why and how remain unanswered.
The focus of most current cannabinoid research is the treatment of illness. But an understanding of the EC system could point to specific therapies. Phyto-cannabinoids and synthetically derived cannabinoids can affect system balance and correct irregularities.
Proving the existence of endocannabinoid deficiency opens the door to therapies. Proof of cannabinoid receptors under or overexpression suggests methods to manage certain conditions. Rigorous, evidence-based studies to prove these theories are underway.