Human Receptor Information

How Cannabis Helps the Body

Scientists have begun speculating that the root cause of disease conditions such as migraines and irritable bowel syndrome may be endocannabinoid deficiency.

For several years it has been postulated that marijuana is not, in the strict sense of the word, an intoxicant.

As written in the book Marijuana Is Safer: So Why Are We Driving People to Drink? (Chelsea Green, 2009), the word ‘intoxicant’ is derived from the Latin nountoxicum (poison). It’s an appropriate term for alcohol, as ethanol (the psychoactive ingredient in booze) in moderate to high doses is toxic (read: poisonous) to healthy cells and organs.

Of course, booze is hardly the only commonly ingested intoxicant. Take the over-the-counter painkiller acetaminophen (Tylenol). According to the Merck online medical library, acetaminophen poisoning and overdose is “common,” and can result in gastroenteritis (inflammation of the gastrointestinal tract) “within hours” and hepatotoxicity (liver damage) “within one to three days after ingestion.” In fact, less than one year ago the U.S. Food and Drug Administration called for tougher standards and warnings governing the drug’s use because “recent studies indicate that unintentional and intentional overdoses leading to severe hepatotoxicity continue to occur.”

By contrast, the therapeutically active components in cannabis — the cannabinoids — appear to be remarkably non-toxic to healthy cells and organs.This notable lack of toxicity is arguably because cannabinoids mimic compounds our bodies naturally produce — so-called endocannabinoids — that are pivotal for maintaining proper health and homeostasis.

In fact, in recent years scientists have discovered that the production of endocannabinoids (and their interaction with the cannabinoid receptors located throughout the body) play a key role in the regulation of proper appetite, anxiety control, blood pressure, bone mass, reproduction, and motor coordination, among other biological functions.

Just how important is this system in maintaining our health? Here’s a clue: In studies of mice genetically bred to lack a proper endocannabinoid system the most common result is premature death.

Armed with these findings, a handful of scientists have speculated that the root cause of certain disease conditions — including migraine, fibromyalgia, irritable bowel syndrome, and other functional conditions alleviated by clinical cannabis — may be an underlying endocannabinoid deficiency.

Now, much to my pleasant surprise, Fox News Health columnist Chris Kilham has weighed in on this important theory.

Are You Cannabis Deficient? via Fox News

If the idea of having a cannabis deficiency sounds laughable to you, a growing body of science points at exactly such a possibility.

… [Endocannabinoids] also play a role in proper appetite, feelings of pleasure and well-being, and memory. Interestingly, cannabis also affects these same functions. Cannabis has been used successfully to treat migraine, fibromyalgia, irritable bowel syndrome and glaucoma. So here is the seventy-four thousand dollar question. Does cannabis simply relieve these diseases to varying degrees, or is cannabis actually a medical replacement in cases of deficient [endocannabinoids]?

… The idea of clinical cannabinoid deficiency opens the door to cannabis consumption as an effective medical approach to relief of various types of pain, restoration of appetite in cases in which appetite is compromised, improved visual health in cases of glaucoma, and improved sense of well being among patients suffering from a broad variety of mood disorders. As state and local laws mutate and change in favor of greater tolerance, perhaps cannabis will find it’s proper place in the home medicine chest.

Perhaps. Or maybe at the very least society will cease classifying cannabis as a ‘toxic’ substance when its more appropriate role would appear to be more like that of a supplement.

Cannabinoid Receptor Type 1

  • CB1 receptors are found primarily in the brain, to be specific in the basal ganglia and in the limbic system, including the hippocampus.
  • They are also found in the cerebellum and in both male and female reproductive systems. CB1 receptors are absent in the medulla oblongata, the part of the brain stem responsible for respiratory and cardiovascular functions. Thus, there is not a risk of respiratory or cardiovascular failure as there is with many other drugs. CB1 receptors appear to be responsible for the euphoric and anticonvulsive effects of cannabis.

Cannabinoid Receptor Type 2

  • CB2 receptors are almost exclusively found in the immune system, with the greatest density in the spleen.
  • While found only in the peripheral nervous system, a report does indicate that CB2 is expressed by a subpopulation of microglia in the human cerebellum.
  • CB2 receptors appear to be responsible for the anti-inflammatory and possibly other therapeutic effects of cannabis.

Harnessing the Cannabinoid system

  • Exogenous compounds
  • Phytocannabinoids
  • THC, CBD, combinations
  • Synthetic cannabinoids
  • Nabilone
  • Endogenous manipulation
  1. – FAAH inhibitors
  2. -MAGL, DAGL inhibitors
Receptor targets
  1.  -CB1
  2. -CB2
  3. -TRPV1
  4. -PPAR
  5. -5-HT
Endocannabinoid system regulates activity in a wide variety of systems

The endocannabinoid system refers to a group of neuromodulatory lipids and their receptors that are involved in a variety of physiological processes including appetite, pain-sensation, mood, memory and it mediates the psychoactive effects of cannabis.

CB1 Receptors

The CB1 receptor is expressed mainly in the brain central nervous system but also in the lungs, liver and kidneys.

Distribution of CB1 Receptors

CB1 cannabinoid receptors appear to mediate most, if not all of the psychoactive effects of delta-9-tetrahydrocannabinol and related compounds. This G protein-coupled receptor has a characteristic distribution in the nervous system: It is particularly enriched in cortex, hippocampus, amygdala, basal ganglia outflow tracts and cerebelluma distribution that corresponds to the most prominent behavioral effects of cannabis.

Cannabinoid Synaptic Circuit Breakers

Cannabinoid receptors and endocannabinoid signaling are distributed throughout the rostrocaudal neuraxis. Retrograde signaling via endocannabinoid mediates synaptic plasticity in many regions in the central nervous system.

Enteric Nervous System

The nervous system exerts a profound influence on all digestive processes, namely motility, ion transport associated with secretion and absorption and gastrointestinal blood flow. Some of this control emanates from connections between the digestive system and central nervous system, but just as importantly, the digestive system is endowed with its own, local nervous system referred to as the enteric or intrinsic nervous system. The magnitude and complexity of the enteric nervous system is immense it contains as many neurons as the spinal cord.

Cannabinoids as Immune Modulators

Cannabinoid receptors are G protein-coupled receptors and they have been linked to signaling pathways and gene activities in common with this receptor family. In addition, cannabinoids have been shown to modulate a variety of immune cell functions in humans and animals and more recently, have been shown to modulate T helper cell development, chemotaxis, and tumor development. Many of these drug effects occur through cannabinoid receptor signaling mechanisms and the modulation of cytokines and other gene products.