Cannabinoids and pain

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The most common medical use of cannabis today and throughout human history is for the treatment of chronic pain, which is usually accompanied by some other disability or mood disorder. Estimates indicate that approximately 20% of the world's population suffers from chronic pain.

Chronic pain is defined as pain that persists for more than three months. Current pharmacotherapies for chronic pain are ineffective in many patients. The latest research shows that approximately 40 percent of patients with chronic pain are not satisfied with their treatment. In the past twenty years, the effectiveness of cannabis in reducing chronic pain has provided increasing evidence that the endocannabinoid system regulates the processing of pain.

 

Pre-Clinical Evidence of Analgesic Effects

There is a very good pre-clinical evidence that cannabinoids are highly effective in reducing pain in animal models. The simplest tests measure the effect of drugs on acute pain.

The especially imperative need for new treatments for chronic pain requires the use of pre-clinical models of inflammatory and neuropathic pain to evaluate the potential effectiveness of cannabinoids in relieving distress. Models of chronic pain include models of inflammatory pain and models of neuropathic pain.

THC is effective when administered orally, systemically, or directly into the brain or the spinal cord (Costa and Comelli 2014). However, the psychoactive side effects of THC limit its usefulness in treating pain. One approach to overcoming that obstacle is the addition of CBD to THC. CBD has anti-nociceptive effects. Since THC is a mixed CB1/CB2-receptor agonist, another approach is the development of CB2 agonists that only act on the non-psychoactive CB2 receptors that are primarily located in the peripheral nervous system. Evaluation of THC in pathological pain (such as chronic inflammatory pain, in which the CB2 receptor plays a pivotal role) has shown it to be an effective anti-nociceptive agent. For instance, in a rat model of chronic arthritic pain, THC was equally potent and effective in non-arthritic rats and arthritic ones. However, in arthritic rats the anti-nociceptive effects of THC were produced via activation of both the CB1 receptor and the CB2 receptor, when in non-arthritic rats the anti-nociceptive effect was mediated only by its action on the CB1 receptors (Cox et al. 2007). Data suggest that chronic pain experienced by arthritics involves both peripheral CB2 receptors and central CB1 receptors. Therefore, treatments aimed at stimulating peripheral CB2 receptors may reduce chronic arthritic pain. Another way to reduce the psychoactive side effects of central stimulation of CB1 receptors is to develop peripherally restricted cannabinoid-receptor agonists that do not cross the blood-brain barrier. Ajulemic acid, a peripherally restrictive analogue of a metabolite of THC, binds to CB1 receptors and to CB2 receptors and reduces pain in chronic neuropathic and inflammatory animal models mediated by action at CB1 receptors only (Dyson et al. 2005; Costa and Comelli 2014).

Because of interactions between the endocannabinoid system and the opiate system, synergistic effects have been reported between THC and opiates in the regulation of pain.

Low doses of THC have been found significantly enhance morphine-induced analgesia when THC and opiates are co-administered systemically into the spinal cord or dire into the ventricles of the brain in animal models. Therefore, pre-clinical findings suggest that combined treatment with cannabinoids and opioids could be able to produce long-term anti-nociceptive effects at doses that do not produce side effects, without tolerance to each effect.

 

CBD

CBD was subsequently found to be effective in a model of chronic pain when given orally. The results are suggesting that CBD was not effective against acute pain but was effective against chronic pain. In addition, CBD has been shown to be effective in relieving neuropathic chemotherapy-induced pain in rats, and in diabetic mice (Ward et al. 2014), without the development of tolerance. An additional benefit of CBD is that it has been shown to block the progression of arthritis in a mouse model of collagen-type-II-induced arthritis.  

Because CBD is not psychotropic, it is a strong candidate for treatment of chronic inflammatory and neuropathic pain.

 

Cannabinoids are naturally occurring compounds found in the Cannabis sativa plant. Of over 450 different compounds present in the plant, only around 60 are termed cannabinoids.

The most known among these compounds is the delta-9-tetrahydrocannabinol (Δ9-THC), which is the main psychoactive ingredient in cannabis.

Cannabidiol (CBD) is another important component, which makes up about 40% of the plant resin extract and it’s a part of many products that you can find on the market today. Including our only Delta 8 Store where you can find all the products available on the market.

Cannabinoids groups

Cannabinoids are the group of chemical compounds found in the cannabis plant that have physical and mental affects when they interact with cannabinoid receptors in your cells.

Cannabinol (CBN) is a mildly psychoactive cannabinoid found only in trace amounts in Cannabis, and is mostly found in aged Cannabis. Pharmacologically relevant quantities are formed as a metabolite of tetrahydrocannabinol (THC).

The cannabinoids are separated into the following groups:

  • Cannabigerols (CBG)
  • Cannabichromenes (CBC)
  • Cannabidiol (CBD)
  • Tetrahydrocannabinol (THC)
  • Cannabinol (CBN)
  • Cannabinodiol (CBDL)
  • Other cannabinoids including cannabicyclol (CBL), cannabielsoin (CBE) and cannabitriol (CBT)

 

EFFECTS OF CANNABINOIDS

Cannabinoids exert their effects by interacting with specific cannabinoid receptors present on the surface of cells.

These receptors are found in different parts of the central nervous system and the two main types of cannabinoid receptors in the body are CB1 and CB2.

In 1992, a naturally occurring substance in the brain that binds to CB1 was discovered, called anandamide. This cannabinoid-like chemical and others that were later discovered are referred to as endocannabinoids.

The effects of cannabinoids depends on the brain area involved. Effects on the limbic system may alter the memory, cognition and psychomotor performance; effects on the mesolimbic pathway may affect the reward and pleasure responses and pain perception may also be altered.

DIFFERENCES BETWEEN CANNABINOIDS

The main way in which the cannabinoids are differentiated is based on their degree of psychoactivity.

For example, CBG, CBC and CBD are not known to be psycholgically active agents whereas THC, CBN and CBDL along with some other cannabinoids are known to have varying degrees of psychoactivity.

The most abundant of the cannabinoids is CBD, which is thought to have anti-anxiety effects, possibly counteracting the psychoactive effects of THC.

When THC is exposed to the air, it becomes oxidized and forms CBN which also interacts with THC to lessen its impact.

This is why cannabis that has been left out unused will has less potent effects when smoked, due to the increased CBN to THC ratio.

The Human Endocannabinoid System

The endocannabinoid system is a nerve signaling system throughout the human body that helps maintain physiological, emotional and cognitive stability. They’re similar to cannabinoids, but they’re produced by your body. Once in your body, THC interacts with your ECS by binding to receptors, just like endocannabinoids. It’s powerful partly because it can bind to both CB1 and CB2 receptors. This allows it to have a range of effects on your body and mind. For example, THC may help to reduce pain and stimulate your appetite.

Experts are currently looking into ways to produce synthetic THC cannabinoids that interact with the ECS in only beneficial ways.

 

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(Source: Cannabinoids and the brain by Linda A. Parker)