Pain relief without the high
January 4, 2017
Science Daily/Leiden, Universiteit
Researchers at Leiden University led by Mario van der Stelt (Leiden Institute for Chemistry) have set ‘gold standards’ for developing new painkillers based on the medicinal effects of cannabis.
Medicinal marijuana
Medicinal marijuana is in frequent use as a painkiller, but its psycho-active side-effects are a major disadvantage. The pharmaceutical industry is desperately seeking a synthetic form of cannabis that inhibits inflammation and pain, but without the high. Leiden researchers have now brought the development of such drugs a step closer. In an article in Nature Communications they set out 'gold standards' for the use of reference substances, to improve trials with synthetic cannabis.
Many of the clinical trials carried out to date with with synthetic cannabis have failed, with no measurable effect being recorded in patients. One of the causes of these failures can be found in the pre-clinical lab, during testing with animals. Substances are often used in these tests whose biochemical and molecular-pharmaceutical effects have never been properly characterised. As a result, there have been a lot of contradictory publications on research findings, the results of which cannot be reproduced. This is having a major effect on the allocation of research funding, the use of animal testing and the exposure of patients to non-active substances.
International and public-private collaboration
Marjolein Soethoudt, a PhD candidate in Van der Stelt's research group, studied together with 12 international academic groups, the National Institute of Health (US) and pharmaceuticals concern Hoffman-LaRoche (Switzerland), the 18 most commonly used reference substances, including the psychoactive ingredient in marijuana, Δ9-THC. They carried out their studies under standardised conditions in 36 different tests, to analyse the molecular pharmacological characteristics of the substances. They hoped to be able to identify the most suitable reference sustances for the research on synthetic cannabis. The research led to three 'gold standards' that should make it possible to give an impetus to the development of new painkillers and anti-inflammatories.
Cannabinoid CB2 receptor
Δ9-THC binds to two types of proteins in the human body: the cannabinoid CB1 receptor in the brain and the cannabinoid CB2 receptor in the immune system. Activating the CB1 receptor in the brain makes you high, while activating the CB2 receptor has an anti-inflammatory effect. The three 'gold standards' are molecules that are highly selective in activating only the CB2 receptor and ignoring the CB1 receptor. These three gold standards also appeared to cause the fewest side-effects, nor did they give the mice a high. Earlier studies have shown that these substances do have an analgesic and anti-inflammatory effect. The researchers advise that these three gold standards should be used in future in research on new medicines that rely on the activation of the cannabinoid CB2 receptor for their effectiveness.
Omega-3 fatty acids fight inflammation via cannabinoids
July 18, 2017
Science Daily/University of Illinois at Urbana-Champaign
Chemical compounds called cannabinoids are found in marijuana and also are produced naturally in the body from omega-3 fatty acids. A well-known cannabinoid in marijuana, tetrahydrocannabinol, is responsible for some of its euphoric effects, but it also has anti-inflammatory benefits. A new study in animal tissue reveals the cascade of chemical reactions that convert omega-3 fatty acids into cannabinoids that have anti-inflammatory benefits -- but without the psychotropic high.
The findings are published in the Proceedings of the National Academy of Sciences.
Foods such as meat, eggs, fish and nuts contain omega-3 and omega-6 fatty acids, which the body converts into endocannabinoids -- cannabinoids that the body produces naturally, said Aditi Das, a University of Illinois professor of comparative biosciences and biochemistry, who led the study. Cannabinoids in marijuana and endocannabinoids produced in the body can support the body's immune system and therefore are attractive targets for the development of anti-inflammatory therapeutics, she said.
In 1964, the Israeli chemist Raphael Mechoulam was the first to discover and isolate THC from marijuana. To test whether he had found the compound that produces euphoria, he dosed cake slices with 10 milligrams of pure THC and gave them to willing friends at a party. Their reactions, from nonstop laughter, to lethargy, to talkativeness, confirmed that THC was a psychotropic cannabinoid.
It wasn't until 1992 that researchers discovered endocannabinoids produced naturally in the body. Since then, several other endocannabinoids have been identified, but not all have known functions.
Cannabinoids bind to two types of cannabinoid receptors in the body -- one that is found predominantly in the nervous system and one in the immune system, Das said.
"Some cannabinoids, such as THC in marijuana or endocannabinoids can bind to these receptors and elicit anti-inflammatory and anti-pain action," she said.
"Our team discovered an enzymatic pathway that converts omega-3-derived endocannabinoids into more potent anti-inflammatory molecules that predominantly bind to the receptors found in the immune system," Das said. "This finding demonstrates how omega-3 fatty acids can produce some of the same medicinal qualities as marijuana, but without a psychotropic effect."
https://www.sciencedaily.com/releases/2017/07/170718142909.htm