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A recent study by a group of scientists in Bern, Switzerland, examining a cannabinoid extracted from a rare plant resembling moss – a member of the liverwort family – only growing in Japan, New Zealand and Costa Rica revealed properties potentially can be helpful for people suffering from inflammation and chronic pain.
What's even more interesting is that this moss is linked to a plant we know well – Cannabis Sativa –which has recently emerged as a potential approach for the treatment of seizures, multiple sclerosis, inflammation and many chronic health conditions.
Until now, researchers do not understand why this specific liver – which has a different way of life and reproduction than Cannabis – would harbor a compound as similar to tetrahydrocannabinol (THC), the psychoactive component found in marijuana. (It was previously believed that the only plant producing THC was Cannabis Sativa.)
What they realize is that cannabinoid isolated from this liver and THC present in cannabis are chemically similar , but also produce quite similar effects in the mammalian brain.
The study was recently published in the Journal, Progress of science.
The plant resembling moss of the genus Radula, Radula perrottetii, a member of the liverwort family, produces a compound called perrottetinene (PET) .
PET was first described in 1994 by Japanese phytochemist Yoshinori Asakawa. But it was only until Jürg Gertsch of the Institute of Biochemistry and Molecular Medicine at the University of Bern, evaluated the similarity of the structure and activity of this compound with THC in the brains of mammals.
Several years ago, Gertsch had noticed that hepatic drugs were promoted online as "legal highs", used by recreational and medicinal users in Switzerland, New Zealand and other parts of the world. But no research was done to evaluate the pharmacological properties of the cannabinoids contained in the plant. Gertsch is associated with his colleague Erick Carreira, from the ETH Chemistry Department of Zurich, and has made a comparison of THC and PET.
With the help of an animal model (mouse), the team demonstrated that PET reached the brain quite easily, but that it activated the cannabinoid receptors – CB1 and CB2 receptors – to a much lower degree than THC. Therefore, an essential difference between the two compounds is that PET is much less psychoactive than THC, making it more attractive for medicinal than recreational purposes. But the more potent anti-inflammatory effects of PET, compared to THC, based on initial studies, have certainly become an additional point of interest.
Gertsch thinks that the anti-inflammatory effect of PET on the brain, more powerful than that of THC, makes it remarkable, especially considering its potential medical applications.
"It's amazing that only two plant species, separated by 300 million years of evolution, produce psychoactive cannabinoids," Gertsch said in an interview. Press release.
And it turns out that the Maori people, originally from New Zealand, have been using the liver plant for centuries as a traditional medicine to treat liver abnormalities or digestive problems.
Physiology of cannabinoids
"The work of Jürg Gertsch and his colleagues is a significant step forward in understanding the role of plants beyond cannabis in the endocannabinoid system," said Ethan Russo MD, neurologist and director of research and development for the endocannabinoid system. 39; International Cannabis and Cannabinoid Institute (ICCI). "Perrottetinene of the hepatic, Radula marginata, has been shown to weakly stimulate the CB1 receptor, where THC and endocannabinoids, anandamide (ANA) and 2-arachidonylglycerol (2-AG) also bind.
"Although this activity has been proven by positive effects on hypothermia (lowered temperature), catalepsy (frozen behavior), hypolocomotion (decreased movement) and analgesia (reduced pain) on the tetrad of the mouse, and that it has been shown to enter the brain, it is unlikely to become a major target for recreational users because of its relatively low potency and especially since hepatic very slow growth and difficult to grow, "Russo added.
Russo also explained that "perrottetinene differs from THC in an essential way, which makes it potentially medically useful in that it reduces the levels of D2 and E2 prostaglandins in the brain without producing blood." inhibition of COX, and can therefore be an effective anti-inflammatory and analgesic. with a low risk of intoxication, ulcer formation or heart attacks or strokes.
Russo explained that this discovery should spur further biochemical prospecting in other hepatic species among this group of "primitive" plants often overlooked.
Jeffrey C. Raber, Ph.D., cannabinoids physiologist and CEO of The Werc Shop, an independent testing laboratory in southern California, also sees the potential benefits of perrottetinene from a clinical perspective but realizes that the and the extraction of the compound can be difficult, but can be overcome with creativity and ingenuity.
"The stereochemistry of this compound suggests that it may possess interesting clinical potential with a minimized psychoactive side effect," Raber explained. "Getting significant amounts of pure compound can be difficult at first, but viable pathways, natural or synthetic, could be developed if that proved interesting."
PET less psychoactive compared to THC
It is well known that low doses of THC may offer therapeutic potential in the treatment of various chronic diseases. But THC is limited from a therapeutic point of view because of a strong psychoactive effect at higher doses, other than illegal for the moment.
As previously mentioned, unlike THC, PET inhibits the production of inflammatory prostaglandins in the brain. As a result, PET probably has an effect on the cannabinoid receptors that interact with our endogenous endocannabinoids. More preclinical studies on various models of chronic and inflammatory pain will certainly be necessary to better understand its role in this context.
A group effort
To obtain adequate amounts of hepatic PET, Gertsch collaborated with his colleague, Erick Carreira, whose team developed a new way of synthesizing to preserve the 3D structure of the compound at the molecular level.
"This study is an excellent example of how new synthetic concepts can help enrich our pharmacological knowledge of biologically active natural substances," said Michael Schafroth, PhD, who studied and worked under Dr. Carreira's direction. Press release.
"Research on cannabinoids requires both solid basic research in the field of biochemical and pharmacological mechanisms and controlled clinical trials," added Gertsch.
The recent legalization of cannabis in Canada helps support continued support for research and the interest of patients in using combinations of CBD and THC to treat common conditions such as endometriosis, fibromyalgia and IBS makes it increasingly clear that the endocannabinoid system and its associated deficiencies may be the key to relieving pain and alleviating troublesome symptoms that are difficult to treat.
Use of CBD (Epidiolex, GW Pharmaceuticals) to treat persistent seizures associated with Dravet syndrome and Lennox Gastaut syndrome, as well as THC (2.7 mg) and CBD (2.5 mg) by spraying (nabiximols, Sativex, GW Pharmaceuticals) for the treatment of MS-associated spasticity is supported by published research and has proven to be a viable way to manage these difficult-to-treat conditions when they are available and as standard approaches provide only a minimal improvement.
Commercial aspects of cannabinoids
While clinicians are looking for less harmful treatments than opioids to treat chronic pain, PTSD, gastrointestinal and autoimmune disorders, liver liver and its derivatives could provide safer treatment . To achieve this, it will be necessary not only to refine the extraction and purification methods, but also to carry out a large number of preclinical studies on animal models, before even experimenting them in humans.
"By 2018, cannabis and hemp (CBD) have seen a phenomenal increase as an alternative treatment to relieve the symptoms of pain, epilepsy, PTSD, MS, fibromyalgia, endometriosis, gastrointestinal disorders and many other chronic conditions, "said Rich Able, a professional. medical device consultant based in Seattle.
"This is a very exciting time as major liquor companies and major pharmaceutical companies have invested billions of dollars in cannabis-related projects and clinical laboratories throughout the year," said Able. . "This trend will continue as clinicians potentially study safer alternative plant-based therapies such as the hepatic".
"Herbal compounds known as this one [PET] It can be difficult to protect by patents, which is one of the reasons the industry does not prioritize them, "said Greg Wesner, president of Lane Powell's IP litigation team, Seattle. "Nevertheless, even if the active pharmaceutical ingredient (API) itself is not patentable as a chemical entity, it may be possible to obtain patent protection for a drug candidate combining the API with an effective and patentable drug delivery technology. "
"In addition, the IPA could be the subject of a patent method of treatment if it turns out that the IPA is a new treatment for an indication of disease, "added Wesner.
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A recent study by a group of scientists in Bern, Switzerland, examining a cannabinoid extracted from a rare plant resembling moss – a member of the liverwort family – only growing in Japan, New Zealand and Costa Rica revealed properties potentially can be helpful for people suffering from inflammation and chronic pain.
Hepatic (Radula perrottetii)University of Bern / Stefan Fischer
What's even more interesting is that this moss is linked to a plant we know well – Cannabis Sativa –which has recently emerged as a potential approach for the treatment of seizures, multiple sclerosis, inflammation and many chronic health conditions.
Until now, researchers do not understand why this specific liver – which has a different way of life and reproduction than Cannabis – would harbor a compound as similar to tetrahydrocannabinol (THC), the psychoactive component found in marijuana. (It was previously believed that the only plant producing THC was Cannabis Sativa.)
What they realize is that cannabinoid isolated from this liver and THC present in cannabis are chemically similar , but also produce quite similar effects in the mammalian brain.
The study was recently published in the Journal, Progress of science.
The plant resembling moss of the genus Radula, Radula perrottetii, a member of the liverwort family, produces a compound called perrottetinene (PET) .
PET was first described in 1994 by Japanese phytochemist Yoshinori Asakawa. But it was only until Jürg Gertsch of the Institute of Biochemistry and Molecular Medicine at the University of Bern, evaluated the similarity of the structure and activity of this compound with THC in the brains of mammals.
Several years ago, Gertsch had noticed that hepatic drugs were promoted online as "legal highs", used by recreational and medicinal users in Switzerland, New Zealand and other parts of the world. But no research was done to evaluate the pharmacological properties of the cannabinoids contained in the plant. Gertsch is associated with his colleague Erick Carreira, from the ETH Chemistry Department of Zurich, and has made a comparison of THC and PET.
With the help of an animal model (mouse), the team demonstrated that PET reached the brain quite easily, but that it activated the cannabinoid receptors – CB1 and CB2 receptors – to a much lower degree than THC. Therefore, an essential difference between the two compounds is that PET is much less psychoactive than THC, making it more attractive for medicinal than recreational purposes. But the more potent anti-inflammatory effects of PET, compared to THC, based on initial studies, have certainly become an additional point of interest.
Gertsch thinks that the anti-inflammatory effect of PET on the brain, more powerful than that of THC, makes it remarkable, especially considering its potential medical applications.
"It's amazing that only two plant species, separated by 300 million years of evolution, produce psychoactive cannabinoids," Gertsch said in an interview. Press release.
And it turns out that the Maori people, originally from New Zealand, have been using the liver plant for centuries as a traditional medicine to treat liver abnormalities or digestive problems.
Physiology of cannabinoids
"The work of Jürg Gertsch and his colleagues is a significant step forward in understanding the role of plants beyond cannabis in the endocannabinoid system," said Ethan Russo MD, neurologist and director of research and development for the endocannabinoid system. 39; International Cannabis and Cannabinoid Institute (ICCI). "Perrottetinene of the hepatic, Radula marginata, has been shown to weakly stimulate the CB1 receptor, where THC and endocannabinoids, anandamide (ANA) and 2-arachidonylglycerol (2-AG) also bind.
"Although this activity has been proven by positive effects on hypothermia (lowered temperature), catalepsy (frozen behavior), hypolocomotion (decreased movement) and analgesia (reduced pain) on the tetrad of the mouse, and that it has been shown to enter the brain, it is unlikely to become a major target for recreational users because of its relatively low potency and especially since hepatic very slow growth and difficult to grow, "Russo added.
Russo also explained that "perrottetinene differs from THC in an essential way, which makes it potentially medically useful in that it reduces the levels of D2 and E2 prostaglandins in the brain without producing blood." inhibition of COX, and can therefore be an effective anti-inflammatory and analgesic. with a low risk of intoxication, ulcer formation or heart attacks or strokes.
Russo explained that this discovery should spur further biochemical prospecting in other hepatic species among this group of "primitive" plants often overlooked.
Jeffrey C. Raber, Ph.D., cannabinoids physiologist and CEO of The Werc Shop, an independent testing laboratory in southern California, also sees the potential benefits of perrottetinene from a clinical perspective but realizes that the and the extraction of the compound can be difficult, but can be overcome with creativity and ingenuity.
"The stereochemistry of this compound suggests that it may possess interesting clinical potential with a minimized psychoactive side effect," Raber explained. "Getting significant amounts of pure compound can be difficult at first, but viable pathways, natural or synthetic, could be developed if that proved interesting."
PET less psychoactive compared to THC
It is well known that low doses of THC may offer therapeutic potential in the treatment of various chronic diseases. But THC is limited from a therapeutic point of view because of a strong psychoactive effect at higher doses, other than illegal for the moment.
As previously mentioned, unlike THC, PET inhibits the production of inflammatory prostaglandins in the brain. As a result, PET probably has an effect on the cannabinoid receptors that interact with our endogenous endocannabinoids. More preclinical studies on various models of chronic and inflammatory pain will certainly be necessary to better understand its role in this context.
A group effort
To obtain adequate amounts of hepatic PET, Gertsch collaborated with his colleague, Erick Carreira, whose team developed a new way of synthesizing to preserve the 3D structure of the compound at the molecular level.
"This study is an excellent example of how new synthetic concepts can help enrich our pharmacological knowledge of biologically active natural substances," said Michael Schafroth, PhD, who studied and worked under Dr. Carreira's direction. Press release.
"Research on cannabinoids requires both solid basic research in the field of biochemical and pharmacological mechanisms and controlled clinical trials," added Gertsch.
The recent legalization of cannabis in Canada helps support continued support for research and the interest of patients in using combinations of CBD and THC to treat common conditions such as endometriosis, fibromyalgia and IBS makes it increasingly clear that the endocannabinoid system and its associated deficiencies may be the key to relieving pain and alleviating troublesome symptoms that are difficult to treat.
Use of CBD (Epidiolex, GW Pharmaceuticals) to treat persistent seizures associated with Dravet syndrome and Lennox Gastaut syndrome, as well as THC (2.7 mg) and CBD (2.5 mg) by spraying (nabiximols, Sativex, GW Pharmaceuticals) for the treatment of MS-associated spasticity is supported by published research and has proven to be a viable way to manage these difficult-to-treat conditions when they are available and as standard approaches provide only a minimal improvement.
Commercial aspects of cannabinoids
While clinicians are looking for less harmful treatments than opioids to treat chronic pain, PTSD, gastrointestinal and autoimmune disorders, liver liver and its derivatives could provide safer treatment . To achieve this, it will be necessary not only to refine the extraction and purification methods, but also to carry out a large number of preclinical studies on animal models, before even experimenting them in humans.
"By 2018, cannabis and hemp (CBD) have seen a phenomenal increase as an alternative treatment to relieve the symptoms of pain, epilepsy, PTSD, MS, fibromyalgia, endometriosis, gastrointestinal disorders and many other chronic conditions, "said Rich Able, a professional. medical device consultant based in Seattle.
"This is a very exciting time as major liquor companies and major pharmaceutical companies have invested billions of dollars in cannabis-related projects and clinical laboratories throughout the year," said Able. . "This trend will continue as clinicians potentially study safer alternative plant-based therapies such as the hepatic".
"Herbal compounds known as this one [PET] It can be difficult to protect by patents, which is one of the reasons the industry does not prioritize them, "said Greg Wesner, president of Lane Powell's IP litigation team, Seattle. "Nevertheless, even if the active pharmaceutical ingredient (API) itself is not patentable as a chemical entity, it may be possible to obtain patent protection for a drug candidate combining the API with an effective and patentable drug delivery technology. "
"In addition, the IPA could be the subject of a patent method of treatment if it turns out that the IPA is a new treatment for an indication of disease, "added Wesner.
