Cannabinoids and the immune system

This is a short review of the effect of cannabinoids on immune system and more specifically on the processes of inflammation and infection.

Cannabinoids are known to be able to modulate immune reaction, the brain; influence the T cells and cytokine expression (proteins involved in cell signaling and immune reactions).

How was discovered the endocannabinoid system? 

Back in 1992 was isolated the first endocannabinoid – anandamine – which was involved in the immune system processes. In 1994-1995 was discovered the second one – 2-arachidonoyl glycerol – which is involved in the nerve system. Since then there are several synthetic endocannabinoids that were synthetized.

It was discovered that endocannabinoids are released naturally in the body as a result of different types of brain injury. This led to the discovery of a novel system for intercellular signaling – the endocannabinoid system – which plays important role in the brain and in the periphery.

Which are the main receptors of the endocannabinoid system?

CB1 receptor, which is part of the endocannabinoid system, is localized in within the brain and regulates synaptic neurotransmission and medicates psychoactive effects. It is expressed mainly in the axons in the brain. In the periphery CB1 receptor is present in adipocytes, liver, pancreas and skeletal muscles. CB1 is also expressed in T lymphocytes and may be involved in cannabinoid-induced T helper cell biasing.

The other important receptor, CB2, was discovered in 1993 and is located within the periphery, especially in the immune cells (mainly B cells and macrophages) and also it seems to play important role in the central nervous system. CB2 receptor is more common for the immune system and the receptor is expressed in the thymus and in the spleen.

Some studies suggest there are more receptors involved in the endocannabinoid system.

What is the effect of cannabis derived cannabinoids on endocannabinoid system?

CBD is CB1/CB2 receptors agonist and induce anti-inflammartory effects. Similar effect is observed with THCV.

There is lots of controversy between different studies on the effect of cannabinoids on the immune system. Previous studies show inhibitory effect while recent studies suggest stimulation. This discrepancy could be explained with different concentrations – lower concentrations lead to stimulation while high concentrations – to inhibition.

The level of receptors expression also correlates to the level of activation and inhibition. For example, cannabis use increases the expression of the receptors CB1 and CB2.

What is the effect on smoking cannabis on the immune system?

T cells: Cannabinoids can influence T cell number and proliferation but they can also have effect on T helpers and cytokines secretion. Initial studies of blood of cannabis consumers show that T cells decrease in number or sensitivity, however other studies fail to confirm these results. These differences could be result of different THC concentrations, frequency of smoking, duration of inhale, etc. Other studies have shown stimulating effect in low doses of cannabinoids and inhibitory effect in high doses.

Natural killer cells (NK): It seems NK are not influenced by cannabinoids in humans.

Macrophages: CB1 receptor on the macrophages support their inhibition by cannabinoids, while CB2 receptor supports release of inflammation mediators. On the other hand macrophages can synthesize endocannabinoids.

Neutrophils: Cannabinoids have inhibitory effect on neutrophils.

B cells: Cannabinoids have inhibitory effect on B cells as well.

What are the therapeutic implications of the cannabinoids?

Multiple sclerosis: The ability of the cannabinoids to inhibit T cell responses makes them potential therapeutic agent for MS.

Parkinson’s disease: Cannabinoids could provide protection against progression of neuronal injury and influence local inflammatory events.

Atherosclerosis: CB2 receptor activation by THC inhibits atherosclerotic plaque progression in mice models.

Rheumatic disease: Cannabinoid receptors could become important therapeutic target for treatment of pain and inflammation associated with ostheoarthritis and rheumatoid arthritis. CBD has shows anti-arthritis effect in studies with patients with rheumatoid arthritis.

Diabetes and lipid metabolism: In diabetes cannabinoids may protect against pancreatic islets destruction and also in treatment of neuropathic pain.

Allergic asthma: Cannabinoids could modulate cytokines profiles, which could result in decreasing overproduction of mucus in the lungs.

Gut and liver disease: Cannabinoids may reduce gut inflammation via CB1 and CB2 receptor activation. They can also be used to treat immune-mediated liver inflammation, hepatic fibrosis and hepatic and intestinal neoplastic disease. [1]

Latest controversy on cannabinoid synthetic medications

A phase 1 clinical trial involving healthy volunteers in France with synthetic cannabinoid left one participant in comma with fatal outcome and 5 participants with irreversible damages. The study was for novel medication for pain relief. The news initially reported that the medication is cannabis derivate, however later on the pharmaceutical company and health authorities in France provided information that the medication is synthetic cannabinoid and not related to cannabis. [2]

Source 

  1. Cannabinoids and the immune system: An overview
  1. France clinical trial: 90 given drug, one man brain-dead 

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