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Body's own 'cannabis' helps pain June 22, 2005 - BBC News
A cannabis like chemical produced naturally in the brain aids pain relief, researchers have found.
The US scientists said the finding may lead to new drugs which can stimulate this natural response.
Research has so far concentrated on developing compounds in cannabis itself into medications.
But, writing in Nature, the team said their new understanding of how the brain chemical works could lead to drugs with fewer side-effects.
When the body experiences pain under stressful circumstances, such as a injury during sport or even after a gunshot wound, the body is protected for a period of time - a response called stress-induced analgesia.
A study in rats by the researchers from the University of California, Irvine, and the University of Georgia found, for the first time, how chemicals called endocannabinoids play a part in this process.
Production of one cannabinoid compound, 2-AG, was found to be triggered by stress-related pain.
The researchers then looked at ways of boosting this natural response.
Normally, an enzyme called monoacylglycerol lipase brings the production of 2-AG to a halt.
The team, including Professor Danielle Piomelli, director of the Center for Drug Discovery at the University of California, Irvine, developed a chemical which was able to block the enzyme's action, meaning the body could theoretically continue to keep producing 2-AG.
Professor Piomelli said: "This study shows for the first time that natural marijuana-like chemicals in the brain have a link to pain suppression.
"Aside from identifying an important function of these compounds, it provides a template for a new class of pain medications that can possibly replace others shown to have acute side effects.
"If we design chemicals that can tweak the levels of these cannabinoid compounds in the brain, we might be able to boost their normal effects," Professor Piomelli said.
Dr Andrea Hohmann, a neuroscientist at the University of Georgia, who also worked on the research, added: "There is no prescription or over-the-counter drug that allows us to manipulate the level of the brain's compounds.
"This is the first time anyone has shown that one of the body's natural occurring cannabinoids, 2-AG, has anything to do with pain regulation under natural conditions."
Dr Anita Holdcroft, a reader in anaesthesia at Imperial College, told the BBC News website said the paper added to knowledge about how the body dealt with pain.
"This 2-AG cannabinoid doesn't have a receptor in the brain.
"So while it was known it played a role in the body's response to pain, people did not know how."
The state of euphoria induced by prolonged exercise was known first as 'second wind' and more recently as 'runner's high'. Scientists originally attempted to explain the experience in terms of the effects of the 'stress hormones' adrenaline and noradrenaline. Then came the 'endorphin hypothesis'. And now we have the 'endocannabinoid hypothesis': a suggestion that the physical and psychological wellbeing experienced by many endurance athletes is due to the exercise-induced activation of endogenous cannabinoids - lipids whose actions in the body resemble those of the active constitutent of cannabis.
This theory, supported by scientific evidence that exercise boosts blood concentrations of endocannabinoids, is given a thorough airing in a review by US researchers published in the British Journal of Sports Medicine.
Their first point is that the endorphin hypothesis - that the runner's high is induced by the release of endogenous opioids in response to exercise - doesn't hold water because, among other lesser reasons, these chemicals are simply too large to cross the blood-brain barrier and exert the central effects that are claimed for them.
The endocannabinoid hypothesis, on the other hand, is supported by the following observations:
*Unlike opioids, endocannabinoids can suppress pain at peripheral sites as well as centrally;
*Unlike opioids, they do not produce such side effects as severe respiratory depression, pinpoint pupils and constipation;
*Endocannabinoids inhibit swelling and inflammation and reduce pain caused by the release of chemicals (such as lactic acid);
*The intense psychological experiences reported by users of cannabis - sedation, reduced anxiety, distortions of time estimation, euphoria, enhanced sensory perception and feelings of wellbeing - are strikingly similar to the experience of runner's high;
*Research on animals has suggested that one of the principal roles of the endocannabinoid system may be the refinement of movements needed for coordinated locomotion;
*Activation of endogenous cannabinoids through exercise could account for the phenomenon of exercise addiction;
*Endocannabinoids act as vasodilators and bronchodilators, which should make exercise feel easier.
As the authors of the review point out: 'Further research is necessary to characterise the precise nature of this endocannabinoid response to exercise, specifically the relative importance of factors such as the nature of the activity, exercise duration, exercise intensity, sex and age.'
But in the meantime they suggest that the endocannabinoid hypothesis is a feasible alternative to the endorphin theory and should be investigated as such.
I had gangreen on my gullbladder when I was 15 and didn't know it. The pain kept me up for hours usually 3 days a week. The pain was the worst I've ever felt it must have been simalar to pain from a gunshot wound. Unbelievably I found after about a year of dealing with this that the one thing that made the pain go away was marijuana. Shortly afterwards I had it removed in surgery. I don't smoke pot anymore but I believe everyone should have the oppurtunity to use a harmless drug such as pot if it could help them with they're pain.