High hopes for new marijuana drug

Marijuana

“Researchers have developed a synthetic compound which gives the benefits of marijuana without the high.

US researchers are developing a marijuana-derived synthetic compound to relieve pain and inflammation without the mood-altering side effects associated with other marijuana based drugs.

Professor Sumner Burstein, from the University of Massachusetts Medical School in Worcester, presented his team’s findings at last week’s national meeting of the American Chemical Society in Boston.

He is hopeful about the potential of the synthetic compound to treat a variety of conditions, including chronic pain, arthritis and Multiple Sclerosis.

The synthetic compound is called ajulemic acid, and has a formula based on that of THC. It has already produced encouraging results in animal studies of pain and inflammation, and is currently being tested on humans.

Exactly how ajulemic acid works is still under investigation but it appears to suppress chemical mediators, such as prostaglandins and cytokines, known to cause inflammation.

“We believe the compound will replace aspirin and similar drugs in most applications because of its lack of toxic side effects”, said Professor Burstein, referring to extensive animal studies, as well as a safety trial of the compound conducted in France last year among 15 healthy volunteers.

No clinically adverse effects were reported, including gastrointestinal ulcers, which have been associated with other non-steroidal anti-inflammatory compounds such as aspirin and ibuprofen.

But most significantly, no mood-altering side effects were reported. With an increasing number of medically beneficial compounds being found in marijuana, such as THC and CBD, researchers have been searching for years for ways to utilise these therapeutically without their associated “high”. They have had little success until now.

“Some people want the high,” admits Professor Burstein. “But the medical community wants efficacy without this effect.”

As well as animal studies of their own that show the compound is as potent a painkiller as morphine, Professor Burstein notes other promising animal studies that have been published. In rodent models of rheumatoid arthritis, the compound prevented joint damage. Tests of MS in rats showed the drug relieves muscle stiffness associated with the disease.

It is now undergoing tests in Germany in a group of 21 patients with chronic pain who take ajulemic acid orally twice daily, in capsule form.

Depending on these results, which will be available in about six weeks, the researchers predict the synthetic compound could be on offer by prescription within two years.

It could also be a promising alternative to current drugs used to treat arthritis, such as COX-2 inhibitors. These have been linked to adverse side effects, including heart attacks and stroke.”

http://www.abc.net.au/science/articles/2002/08/26/656786.htm?fb_action_ids=460011707368809&fb_action_types=og.likes&fb_source=aggregation&fb_aggregation_id=288381481237582

Cannabis drug ‘fights pain without high’

   “Scientists have developed a cannabis-based medicine which relieves chronic pain without any of the “high” normally associated with the drug.

They believe the discovery could pave the way for cannabis-based medication to become available by prescription within two years.

Much of the controversy surrounding the medicinal use of cannabis has centred on fears that it would be used solely for its mood-altering effects.

However, scientists at the University of Massachusetts in the United States say their discovery should help authorities to overcome these fears.

Dr Sumner Burstein and colleagues say early trials of the medication in animals and healthy patients have been promising.

The medication, called ajulemic acid or CT3, has been manufactured in laboratories.

It maximises the medicinal effects of tertrahydrocannabinol – the key ingredient of cannabis – without any of the mind-altering effects.

‘More effective’

In animal tests, this compound was found to be between 10 to 50 times more effective at reducing pain than tetrahydrocannabinol.

Those tests showed that ajulemic acid was very effective at preventing the joint damage associated with arthritis and relieving the muscle stiffness associated with multiple sclerosis.”

Read more: http://news.bbc.co.uk/2/hi/health/2207478.stm

Marijuana-Derived Compound Targets Pain, Inflammation

   “Researchers are developing a marijuana-derived synthetic compound to relieve pain and inflammation without the mood-altering side effects associated with other marijuana based drugs.

  They say the compound could improve treatment of a variety of conditions, including chronic pain, arthritis and multiple sclerosis. Their findings were presented at the 224th national meeting of the American Chemical Society, the world’s largest scientific society.

   The compound, called ajulemic acid, has produced encouraging results in animal studies of pain and inflammation. It is undergoing tests in a group of people with chronic pain and could be available by prescription within two to three years, the researchers say.

 “We believe that [the compound] will replace aspirin and similar drugs in most applications primarily because of a lack of toxic side effects,” says Sumner Burstein, Ph.D., lead investigator in the study and a professor in the department of biochemistry and molecular pharmacology at the University of Massachusetts Medical School in Worcester. “The indications so far are that it’s safe and effective,” he added.”

Read more: http://www.sciencedaily.com/releases/2002/08/020822071026.htm

The cannabinergic system as a target for anti-inflammatory therapies.

“Habitual cannabis use has been shown to affect the human immune system, and recent advances in endocannabinoid research provide a basis for understanding these immunomodulatory effects. Cell-based experiments or in vivo animal testing suggest that regulation of the endocannabinoid circuitry can impact almost every major function associated with the immune system.

 These studies were assisted by the development of numerous novel molecules that exert their biological effects through the endocannabinoid system. Several of these compounds were tested for their effects on immune function, and the results suggest therapeutic opportunities for a variety of inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, atherosclerosis, allergic asthma, and autoimmune diabetes through modulation of the endocannabinoid system.”

http://www.ncbi.nlm.nih.gov/pubmed/16918457

CNS immune surveillance and neuroinflammation: endocannabinoids keep control.

Abstract

“To avoid inflammatory escalation, the central nervous system (CNS) harbors an impressive arsenal of cellular and molecular mechanisms enabling strict control of immune reactions. We here summarize studies suggesting that the old paradigm of the “CNS immune privilege” is overly simplistic. The immune system is allowed to keep the CNS under surveillance, but in a strictly controlled, limited and well-regulated manner. The first line of defense lies outside the brain parenchyma to spare neuronal tissue from the detrimental effects of an inflammatory immune response. As a second line of defense neuroinflammation is unavoidable when pathogens infiltrate the brain or the CNS-immune-homeostasis fails. Inflammation in the CNS is often accompanied by divers brain pathologies. We here review recent strategies to maintain brain homeostasis and modulate neuroinflammation. We focus on Multiple Sclerosis as an example of a complex neuroinflammatory disease. In the past years, several in vitro, in vivo and clinical studies suggested that the endocannabinoid system participates crucially in the immune control and protection of the CNS. We discuss here the endocannabinoid system as a key regulator mechanism of the cross talk between brain and the immune system as well as its potential as a therapeutic target.”

http://www.ncbi.nlm.nih.gov/pubmed/18781977

Cannabinoid receptor stimulation is anti-inflammatory and improves memory in old rats

“The number of activated microglia increase during normal aging. Stimulation of endocannabinoid receptors can reduce the number of activated microglia, particularly in the hippocampus, of young rats infused chronically with lipopolysaccharide (LPS). In the current study we demonstrate that endocannabinoid receptor stimulation by administration of WIN-55212-2 (2 mg/kg/day) can reduce the number of activated microglia in hippocampus of aged rats and attenuate the spatial memory impairment in the water pool task. Our results suggest that the action of WIN-55212-2 does not depend upon a direct effect upon microglia or astrocytes but is dependent upon stimulation of neuronal cannabinoid receptors. Aging significantly reduced cannabinoid type 1 receptor binding but had no effect on cannabinoid receptor protein levels. Stimulation of cannabinoid receptors may provide clinical benefits in age-related diseases that are associated with brain inflammation, such as Alzheimer’s disease.”

“Our results are consistent with the hypothesis that CB receptors on hippocampal neurons modulate glutamatergic and GABAergic function and this leads to reduced microglia activation. This mechanism may underlie the neuroprotective effects of cannabinoids”.

“Importantly, the benefits of cannabinoid receptor stimulation occurred at a dose that did not impair performance in a spatial memory task, indeed the performance of aged rats was significantly improved. This finding is particularly relevant for elderly for patients suffering with diseases associated with brain inflammation, e.g. AD, Parkinson’s disease or multiple sclerosis. The current report is the first to our knowledge to demonstrate the anti-inflammatory actions of cannabinoid therapy in aged animals and strongly advocate an cannabinoid-based therapy for neuroinflammation-related diseases, as well as a potential tool to reduce the impairment in memory processes occurring during normal aging.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2586121/

[The endogenous cannabinoid system. Therapeutic implications for neurologic and psychiatric disorders].

Abstract

“For about 5,000 years, cannabis has been used as a therapeutic agent. There has been growing interest in the medical use of cannabinoids. This is based on the discovery that cannabinoids act with specific receptors (CB1 and CB2). CB1 receptors are located in specific brain areas (e.g. cerebellum, basal ganglia, and hippocampus) and CB2 receptors on cells of the immune system. Endogenous ligands of the cannabinoid receptors were also discovered (e.g. anandamids). Many physiologic processes are modulated by the two subtypes of cannabinoid receptor: motor functions, memory, appetite, and pain. These innovative neurobiologic/pharmacologic findings could possibly lead to the use of synthetic and natural cannabinoids as therapeutic agents in various areas. Until now, cannabinoids were used as antiemetic agents in chemotherapy-induced emesis and in patients with HIV-wasting syndrome. Evidence suggests that cannabinoids may prove useful in some other diseases, e.g. movement disorders such as Gilles de la Tourette’s syndrome, multiple sclerosis, and pain. These new findings also explain the acute adverse effects following cannabis use.”

http://www.ncbi.nlm.nih.gov/pubmed/15776259

[Potential therapeutic usefulness of cannabis and cannabinoids].

Abstract

“Diseases in which Cannabis and cannabinoids have demonstrated some medicinal putative properties are: nausea and vomiting associated with cancer chemotherapy, muscle spasticity (multiple sclerosis, movement disorders), pain, anorexia, epilepsy, glaucoma, bronchial asthma, neuroegenerative diseases, cancer, etc. Although some of the current data comes from clinical controlled essays, the majority are based on anecdotic reports. Basic pharmacokinetic and pharmacodynamic studies and more extensive controlled clinical essays with higher number of patients and long term studies are necessary to consider these compounds useful since a therapeutical point of view.”

http://www.ncbi.nlm.nih.gov/pubmed/11205042

Therapeutic potential of cannabinoid receptor ligands: current status.

Abstract

“There are at least two types of cannabinoid receptors, CB1 also named CNR1 and CB2 also named CNR2, both coupled to G proteins. CB1 receptors exist primarily on central and peripheral neurons. CB2 receptors are present mainly on immune cells. Endogenous agonists for cannabinoid receptors (endocannabinoids) have also been discovered, the most important being arachidonoyl ethanolamide (anandamide), 2-arachidonoyl glycerol (2-AG), and 2-archidonyl glyceryl ether. Following their release, endocannabinoids are removed from the extracellular space and then degraded by intracellular enzymic hydrolysis. CB1/CB2 agonists are already used clinically as antiemetic or to stimulate appetite. Potential therapeutic uses of cannabinoid receptor agonists include the management of multiple sclerosis, spinal cord injury, pain, inflammatory disorders, glaucoma, bronchial asthma, vasodilatation that accompanies advanced cirrhosis, and cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/16810344

‘Cannabis’ receptor discovery may help understanding of obesity and pain

“Aberdeen scientists believe that the findings—published in the —might help our understanding of these conditions and also be a step towards the development of personalised therapies to help treat them.

The team from the University’s Kosterlitz Centre for Therapeutics studied around the gene CNR1. This gene produces what are known as cannabinoid receptors, which are found in the brain, and which activate parts of the brain involved in memory, mood, appetite and pain.

activate these areas of the brain when they are triggered by chemicals produced naturally in our bodies called .

Chemicals found in the drug cannabis mimic the action of these endocannabinoids and there is growing evidence that cannabis has pain relieving and anti-inflammatory properties which can help treat diseases such as and arthritis. 

In order to understand more about these side effects and the which determine how people respond, the scientists studied genetic differences around the CNR1 gene.

Dr Alasdair MacKenzie, who helped lead the team, said: “We chose to look at one specific genetic difference in CNR1 because we know it is linked to and addiction. What we found was a mutation that caused a change in the genetic switch for the gene itself—a switch that is very ancient and has remained relatively unchanged in overthree hundred million years of evolution, since before the time of the dinosaurs.”

http://phys.org/news/2012-08-cannabis-receptor-discovery-obesity-pain.html