The endocannabinoid system is a complex biological system that is responsible for regulating a multitude of vital processes in the body was found by researchers in the 1990s who were exploring THC, a chemical is found in resin produced by the leaves and buds primarily of the female cannabis plant. The plant also contains more than 500 other chemicals, including more than 100 compounds that are chemically related to THC, called cannabinoids, and allowed us to discover a new system that, while extremely important in our day to day functions, little is known about it.

Cannabis Cannabis is a drug that is extracted from Indian Hemp plants such as Cannabis sativa and Cannabis indica. It can act as a depressant, stimulant, or a hallucinogen, which is the reason for experience of taking the drug is different for people. Depressant drugs are known for their ability to slow down the activity of the central nervous system (CNS) while stimulants are known for the exact opposite (raising levels of nervous activity in the body) and hallucinogens are know for containing psychoactive ingredients that cause anomalous changes in perception (in terms of thoughts, emotions, and consciousness).

Marijuana Marijuana, more commonly known as weed, is one cannabis drug that you may have heard of. It is a mixture of the dried flowers of Cannabis sativa. The main psychoactive (mind-altering) chemical in marijuana is delta-9-tetrahydrocannabinol (THC). When marijuana is smoked, THC (and other chemicals) diffuse from the lungs into the bloodstream, which carries them through the body to the brain. The effects are almost immediate. Many people experience a euphoria (a stimulant effect) or they might feel extremely relaxed (a depressant effect). The effects vary from person to person, but some usual effects include heightened sensory perception where colors are brighter and sounds are louder (a hallucinogenic effect), an altered perception of time, and an increased appetite.

THC and the Endocannabinoid System The endocannabinoid system promotes homeostasis and affects everything from sleep and appetite to pain, inflammation, and immunity, as well as memory, mood, reproduction, and more. It involves three main components: endocannabinoids, receptors, and enzymes. Current research has uncovered five types of cannabinoid receptors in our bodies, and though CB1 and CB2 are the two main receptors that have been researched the most, there are several receptors currently being reviewed. extracted from Indian Cannabis sativa and act as a depressant, hallucinogen, which experience of taking people. Depressant their ability to slow central nervous stimulants are known (raising levels of Cannabis Cannabis is a drug that is Hemp plants such as Cannabis indica. It can stimulant, or a is the reason for the drug is different for drugs are known for down the activity of the system (CNS) while for the exact opposite 8 Discovered in 1990, CB1 receptors were found to be mostly concentrated in the CNS. This part of the nervous system is responsible for appetite, memory, mood, motor regulation, pain, and sleep. The CB2 receptors are found mostly in the peripheral nervous system (PNS), particularly immune cells, which is why they play an important role in our immunity. Endocannabinoids, also called endogenous ligands because they are proteins that bind to receptors, are also part of the endocannabinoid system. The most studied of these endogenous endocannabinoids are anandamide, which has the acronym AEA, and 2-arachidonoylglycerol, which is denoted as 2-AG.

THC’s chemical structure is similar to the endocannabinoid anandamide. The similarity in their structures allows the body and the brain to recognize THC and to alter normal brain communication. Endogenous cannabinoids like anandamide send chemical messages between neurons in the nervous system and are known as neurotransmitters. These endogenous endocannabinoids affect many areas of the brain. THC’s similar structure to these neurotransmitters allows it to attach to cannabinoid receptors on neurons in these areas and activate them, disrupting regular functions and causing symptoms such as increased heart rate, coordination problems, dry mouth, red eyes, slower reaction times, memory loss and euphoria.

Neurotransmitters and Synaptic Transmission Neurotransmitters are a type of chemical messenger that transmits signals across a chemical synapse, such as a neuromuscular junction, from one neuron (nerve cell) to another “target” neuron, muscle cell, or gland cell in a process called synaptic transmission. The presynaptic neuron is the cell that sends the signal while the postsynaptic neuron receives it. Neurotransmitters are packaged into small sacs called vesicles in the presynaptic neuron and are released into the synaptic cleft (the microscopic space between the two neurons) when an action potential causes the vesicle to ‘fuse’ with the presynaptic membrane. These neurotransmitters bind to receptors on the post-synaptic membrane and cause a reaction or inhibit action.

In 1964, it was thought that neurotransmitters and neuromodulators could only be water-soluble molecules such as peptides, amino acids, or amines, but not lipids. THC is a lipid, so it was assumed that it could not act as a neurotransmitter. There is strong evidence that supports the theory that THC can bind to receptors. This hypothesis was confirmed in 1990 with the isolation and cloning of the first cannabinoid receptor, CB1, and later of CB2. Ordinary nerve cells send messages to other cells through the synaptic transmission process explained above, but what happens in the endocannabinoid system is different.

Endocannabinoids are synthesized and released from postsynaptic cells and travel backwards through a process scientifically called ‘retrograde signalling’ across the synapse, where they bind to the CB1s located in the presynaptic nerve terminals. They suppress excitatory and inhibitory neurotransmitter release, which essentially means they stop the neurons when they want to tell other neurons to do something, or not do something. There are new studies that now show us that non-retrograde signalling, which is when the postsynaptic endocannabinoid activates the postsynaptic receptor, also occurs, as well as neuron-astrocyte signalling.

CEDC The endocannabinoid system is just like any other system in the body, meaning it can, on occasion, have a few problems, whether because of a genetic mutation or an acquired disease. With this system, however, the danger is a lot greater because of just how prevalent and ubiquitous it is – it could affect any number of organs or organ systems. To the phenomenon when there are fewer or more endocannabinoids, endocannabinoid receptors and/or endocannabinoid enzymes, researchers have ascribed it the name clinical endocannabinoid deficiency – or CEDC. The primary reason researchers believe this exists is because when patients of some disorders (namely: migraines, fibromyalgia, depression, anxiety, multiple sclerosis, Huntington’s, Parkinson’s, and PTSD) have been treated using cannabis, the results have been positive. All in all, research into the relatively new field of the endocannabinoid system is still ongoing, and there is a lot we don’t know about how it works, and about its functions in our bodies. What we do know, is that the role it plays is an important one and understanding more about this biological system has the potential to change how we view certain disorders, and how much we understand them, resulting in medical breakthroughs that can lead to safer and more efficient treatments.

Tanisha Mehrotra
Tanisha Mehrotra

Student of NLCS Dubai
Member of NLCS Dubai Medical Society

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