A wholesome endocannabinoid system is essential to the human physique’s immune capabilities. Jose Luis Pelaez Inc/Digital Vision through Getty Images
Over the previous 20 years, quite a lot of consideration has been given to marijuana – also called pot or weed. As of early 2023, marijuana has been legalized for leisure use in 21 states and Washington, D.C., and the usage of marijuana for medical functions has grown considerably over the last 20 or so years.
But few individuals know that the human physique naturally produces chemical compounds which can be similar to delta-9-tetrahydrocannabinol, or THC, the psychoactive compound in marijuana, which comes from the Cannabis sativa plant. These substances are referred to as endocannabinoids, they usually’re discovered throughout all vertebrate species.
Evolutionarily, the looks of endocannabinoids in vertebrate animals predates that of Cannabis sativa by about 575 million years.
It is as if the human physique has its personal model of a marijuana seedling inside, continually producing small quantities of endocannabinoids.
The similarity of endocannabinoids to THC, and their significance in sustaining human well being, have raised important curiosity amongst scientists to additional examine their position in well being and illness, and probably use them as therapeutic targets to deal with human ailments.
THC was first recognized in 1964, and is only one of greater than 100 compounds present in marijuana which can be referred to as cannabinoids.
Endocannabinoids weren’t found till 1992. Since then, analysis has revealed that they’re essential for a lot of necessary physiological capabilities that regulate human well being. An imbalance within the manufacturing of endocannabinoids, or within the physique’s responsiveness to them, can result in main medical problems, together with weight problems in addition to neurodegenerative, cardiovascular and inflammatory ailments.
We are immunologists who’ve been finding out the results of marijuana cannabinoids and vertebrate endocannabinoids on irritation and most cancers for greater than 20 years. Research in our laboratory has proven that endocannabinoids regulate irritation and different immune capabilities.
What is the endocannabinoid system?
A wide range of tissues within the physique, together with mind, muscle, fatty tissue and immune cells, produce small portions of endocannabinoids. There are two essential kinds of endocannabinoids: anandamide, or AEA, and 2-arachidonoyl glycerol, generally known as 2-AG. Both of them can activate the physique’s cannabinoid receptors, which obtain and course of chemical alerts in cells.
One of those receptors, referred to as CB1, is discovered predominantly within the mind. The different, referred to as CB2, is discovered primarily in immune cells. It is primarily by the activation of those two receptors that endocannabinoids management many bodily capabilities.
The receptors may be in comparison with a “lock” and the endocannabinoids a “key” that may open the lock and achieve entry into the cells. All these endocannabinoid receptors and molecules collectively are known as the endocannabinoid system.
The hashish plant comprises one other compound referred to as cannabidiol, or CBD, which has turn out to be fashionable for its medicinal properties. Unlike THC, CBD doesn’t have psychoactive properties as a result of it doesn’t activate CB1 receptors within the mind. Nor does it activate the CB2 receptors, which means that its motion on immune cells is unbiased of CB2 receptors.
Endocannabinoid receptors are discovered all through many of the human physique.
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Role of endocannabinoids within the physique
The euphoric “excessive” feeling that folks expertise when utilizing marijuana comes from THC activating the CB1 receptors within the mind.
But when endocannabinoids activate CB1 receptors, by comparability, they don’t trigger a marijuana excessive. One motive is that the physique produces them in smaller portions than the standard quantity of THC in marijuana. The different is that sure enzymes break them down quickly after they perform their mobile capabilities.
However, there may be rising proof that sure actions could launch mood-elevating endocannabinoids. Some analysis means that the relaxed, euphoric feeling you get after train, referred to as a “runner’s excessive,” outcomes from the discharge of endocannabinoids relatively than from endorphins, as beforehand thought.
The endocannabinoids regulate a number of bodily capabilities akin to sleep, temper, urge for food, studying, reminiscence, physique temperature, ache, immune capabilities and fertility. They management a few of these capabilities by regulating nerve cell signaling within the mind. Normally, nerve cells talk with each other at junctions referred to as synapses. The endocannabinoid system within the mind regulates this communication at synapses, which explains its skill to have an effect on a wide selection of bodily capabilities.
The elixir of endocannabinoids
Research in our laboratory has proven that sure cells of the immune system produce endocannabinoids that may regulate irritation and different immune capabilities by the activation of CB2 receptors.
In addition, we’ve proven that endocannabinoids are extremely efficient in lessening the debilitating results of autoimmune ailments. These are ailments through which the immune system goes haywire and begins destroying the physique’s organs and tissues. Examples embody a number of sclerosis, lupus, hepatitis and arthritis.
Recent analysis means that migraine, fibromyalgia, irritable bowel syndrome, post-traumatic stress dysfunction and bipolar illness are all linked to low ranges of endocannabinoids.
In a 2022 examine, researchers discovered {that a} defect in a gene that helps produce endocannabinoids causes early onset of Parkinson’s illness. Another 2022 examine linked the identical gene defect to different neurological problems, together with developmental delay, poor muscle management and imaginative and prescient issues.
Other analysis has proven that folks with a faulty type of CB1 receptors expertise elevated ache sensitivity akin to migraine complications and endure from sleep and reminiscence problems and anxiousness.
The endocannabinoid system – consisting of the endocannabinoids and the cannabinoid receptors – regulates nerve cell communication on the synapse, thereby taking part in a task in quite a lot of bodily capabilities.
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The likeness between marijuana and endocannabinoids
We consider that the medicinal properties of THC could also be linked to the molecule’s skill to compensate for a deficiency or defect within the manufacturing or capabilities of the endocannabinoids.
For instance, scientists have discovered that individuals who expertise sure kinds of continual ache could have decreased manufacturing of endocannabinoids. People who devour marijuana for medicinal functions report important reduction from ache. Because the THC in marijuana is the cannabinoid that reduces ache, it could be serving to to compensate for the decreased manufacturing or capabilities of endocannabinoids in such sufferers.
Deciphering the position of endocannabinoids remains to be an rising space of well being analysis. Certainly way more analysis is required to decipher their position in regulating completely different capabilities within the physique.
In our view, it should even be necessary to proceed to unravel the connection between defects within the endocannabinoid system and the event of varied ailments and medical problems. We assume that the solutions might maintain nice promise for the event of latest therapies utilizing the physique’s personal cannabinoids.
Prakash Nagarkatti receives funding from the National Institutes of Health and the National Science Foundation.
Mitzi Nagarkatti receives funding from National Institutes of Health.
