Tag Archives: tetrahydrocannabinol

Phytocannabinoids

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“Phytocannabinoids, also called ”natural cannabinoids”, ”herbal cannabinoids”, and ”classical cannabinoids”, are only known to occur naturally in significant quantity in the cannabis plant, and are concentrated in a viscous resin that is produced in glandular structures known as trichomes.

In addition to cannabinoids, the resin is rich in terpenes, which are largely responsible for the odour of the cannabis plant.

Phytocannabinoids are nearly insoluble in water but are soluble in lipids, alcohols, and other non-polar organic solvents. However, as phenols, they form more water-soluble phenolate salts under strongly alkaline conditions.

All-natural cannabinoids are derived from their respective 2-carboxylic acids (2-COOH) by decarboxylation (catalyzed by heat, light, or alkaline conditions).

Types

At least 66 cannabinoids have been isolated from the cannabis plant. To the right the main classes of natural cannabinoids are shown. All classes derive from cannabigerol-type compounds and differ mainly in the way this precursor is cyclized.

Tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) are the most prevalent natural cannabinoids and have received the most study. Other common cannabinoids are listed below:

  • CBG Cannabigerol
  • CBC Cannabichromene
  • CBL Cannabicyclol
  • CBV Cannabivarin
  • THCV Tetrahydrocannabivarin
  • CBDV Cannabidivarin
  • CBCV Cannabichromevarin
  • CBGV Cannabigerovarin
  • CBGM Cannabigerol Monoethyl Ether

Tetrahydrocannabinol

Tetrahydrocannabinol (THC) is the primary psychoactive component of the plant. It appears to ease moderate pain (analgetic) and to be neuroprotective. THC has approximately equal affinity for the CB1 and CB2 receptors. Its effects are perceived to be more cerebral.

”Delta”-9-Tetrahydrocannabinol (Δ9-THC, THC) and ”delta”-8-tetrahydrocannabinol (Δ8-THC), mimic the action of anandamide, a neurotransmitter produced naturally in the body. The THCs produce the ”high” associated with cannabis by binding to the CB1 cannabinoid receptors in the brain.

Cannabidiol

Cannabidiol (CBD) is not psychoactive, and was thought not to affect the psychoactivity of THC. However, recent evidence shows that smokers of cannabis with a higher CBD/THC ratio were less likely to experience schizophrenia-like symptoms.

This is supported by psychological tests, in which participants experience less intense psychotic effects when intravenous THC was co-administered with CBD (as measured with a PANSS test).

It has been hypothesized that CBD acts as an allosteric antagonist at the CB1 receptor and thus alters the psychoactive effects of THC.

It appears to relieve convulsion, inflammation, anxiety, and nausea. CBD has a greater affinity for the CB2 receptor than for the CB1 receptor.

Cannabigerol

Cannabigerol (CBG) is non-psychotomimetic but still affects the overall effects of Cannabis. It acts as an α2-adrenergic receptor agonist, 5-HT1A receptor antagonist, and CB1 receptor antagonist. It also binds to the CB2 receptor.

Tetrahydrocannabivarin

Tetrahydrocannabivarin (THCV) is prevalent in certain South African and Southeast Asian strains of Cannabis. It is an antagonist of THC at CB1 receptors and attenuates the psychoactive effects of THC.

Cannabichromene

Cannabichromene (CBC) is non-psychoactive and does not affect the psychoactivity of THC It is found in nearly all tissues in a wide range of animals.

Two analogs of anandamide, 7,10,13,16-docosatetraenoylethanolamide and ”homo”-γ-linolenoylethanolamine, have similar pharmacology.

All of these are members of a family of signalling lipids called ”N”-acylethanolamides, which also includes the noncannabimimetic palmitoylethanolamide and oleoylethanolamine, which possess anti-inflammatory and orexigenic effects, respectively. Many ”N”-acylethanolamines have also been identified in plant seeds and in molluscs.

  • 2-arachidonoyl glycerol (2-AG)

Another endocannabinoid, 2-arachidonoyl glycerol, binds to both the CB1 and CB2 receptors with similar affinity, acting as a full agonist at both, and there is some controversy over whether 2-AG rather than anandamide is chiefly responsible for endocannabinoid signalling ”in vivo”.

In particular, one ”in vitro” study suggests that 2-AG is capable of stimulating higher G-protein activation than anandamide, although the physiological implications of this finding are not yet known.

  • 2-arachidonyl glyceryl ether (noladin ether)

In 2001, a third, ether-type endocannabinoid, 2-arachidonyl glyceryl ether (noladin ether), was isolated from porcine brain.

Prior to this discovery, it had been synthesized as a stable analog of 2-AG; indeed, some controversy remains over its classification as an endocannabinoid, as another group failed to detect the substance at “any appreciable amount” in the brains of several different mammalian species.

It binds to the CB1 cannabinoid receptor (”K”i = 21.2 nmol/L) and causes sedation, hypothermia, intestinal immobility, and mild antinociception in mice. It binds primarily to the CB1 receptor, and only weakly to the CB2 receptor.

Like anandamide, NADA is also an agonist for the vanilloid receptor subtype 1 (TRPV1), a member of the vanilloid receptor family.

  • Virodhamine (OAE)

A fifth endocannabinoid, virodhamine, or ”O”-arachidonoyl-ethanolamine (OAE), was discovered in June 2002. Although it is a full agonist at CB2 and a partial agonist at CB1, it behaves as a CB1 antagonist ”in vivo”.

In rats, virodhamine was found to be present at comparable or slightly lower concentrations than anandamide in the brain, but 2- to 9-fold higher concentrations peripherally.

Function

Endocannabinoids serve as intercellular ‘lipid messengers’, signaling molecules that are released from one cell and activate the cannabinoid receptors present on other nearby cells.

Although in this intercellular signaling role they are similar to the well-known monoamine neurotransmitters, such as acetylcholine and dopamine, endocannabinoids differ in numerous ways from them. For instance, they use retrograde signaling.

Furthermore, endocannabinoids are lipophilic molecules that are not very soluble in water. They are not stored in vesicles, and exist as integral constituents of the membrane bilayers that make up cells. They are believed to be synthesized ‘on-demand’ rather than made and stored for later use.

The mechanisms and enzymes underlying the biosynthesis of endocannabinoids remain elusive and continue to be an area of active research.

The endocannabinoid 2-AG has been found in bovine and human maternal milk.

Retrograde signal

Conventional neurotransmitters are released from a ‘presynaptic’ cell and activate appropriate receptors on a ‘postsynaptic’ cell, where presynaptic and postsynaptic designate the sending and receiving sides of a synapse, respectively.

Endocannabinoids, on the other hand, are described as retrograde transmitters because they most commonly travel ‘backwards’ against the usual synaptic transmitter flow.

They are, in effect, released from the postsynaptic cell and act on the presynaptic cell, where the target receptors are densely concentrated on axonal terminals in the zones from which conventional neurotransmitters are released.

Activation of cannabinoid receptors temporarily reduces the amount of conventional neurotransmitter released.

This endocannabinoid mediated system permits the postsynaptic cell to control its own incoming synaptic traffic.

The ultimate effect on the endocannabinoid-releasing cell depends on the nature of the conventional transmitter being controlled.

For instance, when the release of the inhibitory transmitter GABA is reduced, the net effect is an increase in the excitability of the endocannabinoid-releasing cell.

On the converse, when release of the excitatory neurotransmitter glutamate is reduced, the net effect is a decrease in the excitability of the endocannabinoid-releasing cell.

Range

Endocannabinoids are hydrophobic molecules. They cannot travel unaided for long distances in the aqueous medium surrounding the cells from which they are released, and therefore act locally on nearby target cells. Hence, although emanating diffusely from their source cells, they have much more restricted spheres of influence than do hormones, which can affect cells throughout the body.

Other thoughts

Endocannabinoids constitute a versatile system for affecting neuronal network properties in the nervous system.

”Scientific American” published an article in December 2004, entitled “The Brain’s Own Marijuana” discussing the endogenous cannabinoid system.

The current understanding recognizes the role that endocannabinoids play in almost every major life function in the human body.

U.S. Patent # 6630507

In 2003 The U.S.A.’s Government as represented by the Department of Health and Human Services was awarded a patent on cannabinoids as antioxidants and neuroprotectants. U.S. Patent 6630507.”

http://www.news-medical.net/health/Phytocannabinoids.aspx

Cannabinoids – What are Cannabinoids?

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“Cannabinoids are a group of terpenophenolic compounds present in Cannabis (”Cannabis sativa”) and occur naturally in the nervous and immune systems of animals.

The broader definition of cannabinoids refers to a group of substances that are structurally related to tetrahydrocannabinol (THC) or that bind to cannabinoid receptors.

The chemical definition encompasses a variety of distinct chemical classes: the classical cannabinoids structurally related to THC, the nonclassical cannabinoids, the aminoalkylindoles, the eicosanoids related to the endocannabinoids, 1, quinolines and arylsulphonamides, and additional compounds that do not fall into these standard classes but bind to cannabinoid receptors.

The term ”cannabinoids” also refers to a unique group of secondary metabolites found in the cannabis plant, which are responsible for the plant’s peculiar pharmacological effects.

At the present time, there are three general types of cannabinoids: ”phytocannabinoids” occur uniquely in the cannabis plant; ”endogenous cannabinoids” are produced in the bodies of humans and other animals; and ”synthetic cannabinoids” are similar compounds produced in a laboratory.”

http://www.news-medical.net/health/Cannabinoids-What-are-Cannabinoids.aspx

Marijuana May Help Fight Brain Damage

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“Marijuana may actually help protect the brain against injury, a new study suggests.”

marijuana, cannabis, drug, addiction, weed

“While marijuana is most commonly known as a recreational drug, an increasingly number of studies show that the plant has many therapeutic qualities like relieving pain, insomnia, lack of appetite and other symptoms associated with conditions like cancer and PTSD.

Now a new study reveals that very low doses of Tetrahydrocannabinol (THC), the psychoactive ingredient in marijuana, may protect the brain from long-term cognitive damage in the wake of injury from hypoxia, seizures or toxic drugs.”

More: http://www.counselheal.com/articles/5586/20130530/marijuana-help-fight-brain-damage.htm

Medical marijuana ingredient prevents brain damage in mice

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“An Israeli researcher has found that tiny doses of the psychoactive chemical in marijuana helps the brain of mice combat injury.”

A medical marijuana plant grows in a dispensary in Seattle.

“The words “marijuana” and “brain damage” usually go in that order in medical literature. An Israeli researcher has flipped them around, finding that THC, the active ingredient in marijuana, may arrest some forms of brain damage in mice.

The loco weed already is favored by those who suffer from chronic diseases, not to mention fans of Cypress Hill, Bob Marley and the Grateful Dead.

But pharmacologist Josef Sarne of Tel Aviv University found that a minuscule amount of tetrahydrocannabinol may protect the brain after injuries from seizures, toxic drug exposure or a lack of oxygen.”

More: http://www.latimes.com/news/science/sciencenow/la-sci-medical-marijuana-brain-damage-20130530,0,1781822.story

Marijuana may help patients with Crohn’s disease, study says

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“New research published earlier this month might have more patients with Crohn’s disease turning to medical marijuana for relief.”
 
Crohn’s disease is an inflammatory bowel disease that affects around 500,000 people in North America.

 

In a first-of-its-kind clinical trial, an 8-week treatment regimen involving daily smoking of marijuana ‘cigarettes’ resulted in a reduction in overall disease severity in 10 of the 11 patients that were studied. 5 of these patients experienced complete remission of their disease.

 

The results were published online in the journal Clinical Gastroenterology and Hepatology and authored by scientists at the Meir Medical Clinical in Israel. Israel has one of the most fastest growing medical marijuana programs in the world, with over 11,000 registered patients as of today — up from just 400 in 2009.

 

While the researchers say that their study was the first placebo-controlled trial — the “gold standard” when it comes to medical research — to investigate the effects of marijuana use on patients with Crohn’s disease, other studies have produced similar results.

 

Based on findings from both animal and human research, experts suggest that cannabis could play a role in the treatment of Crohn’s and other inflammatory bowel diseases by regulating intestinal hyperactivity, inflammation and pain.

 

Marijuana’s medical properties come directly from compounds known as cannabinoids, including the well-known tetrahydrocannabinol (THC) molecule. Interestingly, the cannabinoids found in the cannabis plant have been shown to mimic the activity of endocannabinoids – cannabinoids that are produced naturally by the human body.

 

Similarly, studies have identified a variety of digestive functions that can be modulated by cannabinoid activity, especially in inflammatory disease states.

 

Although the findings of the current study provide considerable support for the use of marijuana as a Crohn’s disease treatment, the authors call for more studies to “look into the role of cannabinoids in controlling inflammation and symptoms in inflammatory bowel disease.”

 

Indeed, larger studies may be able to provide stronger confirmation or perhaps refute the findings of the newest study, which failed to demonstrate complete remission of Crohn’s in the majority of the treatment group.

 

Still, the authors concluded their research by stating, “a short course of THC-rich cannabis produced significant clinical, steroid-free benefits to 11 patients with active Crohn’s disease, compared to placebo, without side effects.””

http://www.digitaljournal.com/article/350495

Could marijuana reduce diabetes risk? – Fox News

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“There’s an unexpected link between marijuana use and factors related to Type 2 diabetes that has medical researchers intrigued.”
Smoking marijuana_Reuters_Feb 6 2013.jpg

“Several studies have found that marijuana users take in more food calories than nonusers, but they still have lower rates of obesity and diabetes, and lower average body mass index (BMI) levels.

In a new study, researchers investigated what effects marijuana and its active ingredient tetrahydrocannabinol (THC) might have on people’s metabolism, especially insulin levels.

Insulin resistance an important risk factor for diabetes is a metabolic disorder that occurs when the body’s cells cannot properly intake insulin. The American Heart Association estimates 35 percent of U.S. adults have metabolic disorders that include insulin resistance.

To examine the link between THC and metabolism, researchers gathered the results of 4,657 adults from the National Health and Nutrition Examination Survey, a cross-sectional study administered annually by the Centers for Disease Control and Prevention.

Of the study’s participants, 579 were current marijuana users, 1,975 had used the drug in the past but not recently, and 2,103 had never tried marijuana. Researchers analyzed the participants’ fasting insulin levels, cholesterol levels, insulin resistance and waist sizes.

Multiple benefits seen”

Read more: http://www.foxnews.com/health/2013/05/16/could-marijuana-reduce-diabetes-risk/

Smoking cannabis could reduce the risk of diabetes by controlling blood sugar

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“People who regularly smoke cannabis may have a lower risk of developing diabetes, new research suggests.”
 
Marijuana users had significantly lower levels of the hormone insulin - indicating better blood sugar control“Marijuana users had significantly lower levels of the hormone insulin – indicating better blood sugar control… could pave the way for the development of treatments using the plant’s compound active ingredient, tetrahydrocannabinol, or THC.

Marijuana users had 16% lower fasting insulin levels than non-users.

They were also less likely to be insulin resistant and had smaller waists.

Previous research has found cannabis smokers are less likely to be obese.”

Read more: http://www.dailymail.co.uk/health/article-2324743/Smoking-cannabis-reduce-risk-diabetes-controlling-blood-sugar.html 

Regular Cannabis Users ‘Have Better Blood Sugar Control’

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“People who regularly use cannabis have better blood sugar control than those who do not, providing implications for use of the drug in diabetic control.”

Cannabis users have lower blood sugar levels than non-users (Reuters)

“Research published in the American Journal of Medicine found current marijuana users are less likely to be insulin resistant and have significantly lower fasting insulin levels, even after patients with diabetes were excluded from the study. 

The ream found cannabis users’ fasting insulin levels were 16% lower than non-users…

Cannabis in becoming increasingly used for medical purposes, with the active ingredient tetrahydrocannabinol (THC) approved in the US as a treatment for the side effect of chemotherapy. It is legal for recreational use in two states and 19 for medical use.

The researchers looked at data obtained through the National Health and Nutrition Survey between 2005 and 2010.

They looked at questionnaires from 4,657 people, of which 579 were regular cannabis users, 1,975 had used marijuana but not regularly and 2,103 had never used the drug.

Insulin and glucose were measured through blood samples after a nine hour fast and insulin resistance was calculated.

The team found that people who had used cannabis in the last month had lower levels of fasting insulin and insulin resistance and higher levels of high-density lipoprotein cholesterol (HDL-C), which is associated with better cardiovascular health…”

Read more: http://www.ibtimes.co.uk/articles/467817/20130515/cannabis-marijuana-lower-blood-sugar-levels-diabetes.htm

Smoking Marijuana May Lower Diabetes and Obesity Risk

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“Marijuana may lower the risk of diabetes, according to a new study that revealed people who regularly smoked marijuana had significantly better blood sugar control.”

marijuana, cannabis, drug, addiction, weed
 
“Researchers explained that regular marijuana users had significantly lower fasting insulin and were less likely to be insulin resistant, indicating they had better sugar control.

The study published in The American Journal of Medicine included data from 4,657 patients who had answered questions on drug use.  According to the study, 579 of the patients were current marijuana users, 1,975 had used marijuana in the past and 2,103 had never used.  Researchers measured all participants’ fasting insulin and glucose levels.

Researchers found that regular marijuana users had 16 percent lower fasting insulin levels than people who had never smoke marijuana.  Marijuana users were also more likely to have a smaller waist circumference.  Previous studies have linked a large waist circumference to diabetes risk.

The study also found that participants who reported using marijuana in the past had lower levels of fasting insulin and HOMA-IR and higher levels of high-density lipoprotein cholesterol (HDL-C).  However, these correlations were weaker in people who reported using marijuana at least once, but not in the past thirty days.  The findings suggest that the impact of marijuana use on insulin and insulin resistance exists during periods of recent use.

For centuries, marijuana has been used to relieve pain, boost mood and increase appetite.  Now, medical marijuana is often used by patients suffering cancer, multiple sclerosis and other painful conditions.

If the latest findings are confirmed, researchers said the study could lead to the development of new diabetes treatments using marijuana’s compound active ingredient, tetrahydrocannabinol, or THC.

Past epidemiologic studies revealed that marijuana users had lower rates of obesity and diabetes mellitus compared to people who have never used the drug.  Researchers said that previous findings suggest a link between cannabinoids and peripheral metabolic processes, but the latest study was the first to look at the relationship between marijuana use and fasting insulin, glucose, and insulin resistance.

“It is possible that the inverse association in fasting insulin levels and insulin resistance seen among current marijuana users could be in part due to changes in usage patterns among those with a diagnosis of diabetes (i.e., those with diabetes may have been told to cease smoking). However, after we excluded those subjects with a diagnosis of diabetes mellitus, the associations between marijuana use and insulin levels, HOMA-IR, waist circumference, and HDL-C were similar and remained statistically significant,” researcher Dr. Elizabeth Penner, said in a news release.

“These are indeed remarkable observations that are supported, as the authors note, by basic science experiments that came to similar conclusions,” American Journal of Medicine editor-in-chief Dr. Joseph Alpert wrote in an accompanying editorial.

“We desperately need a great deal more basic and clinical research into the short- and long-term effects of marijuana in a variety of clinical settings such as cancer, diabetes, and frailty of the elderly,” continues Alpert.” I would like to call on the NIH and the DEA to collaborate in developing policies to implement solid scientific investigations that would lead to information assisting physicians in the proper use and prescription of THC in its synthetic or herbal form,” he added.”

http://www.counselheal.com/articles/5381/20130515/smoking-marijuana-lower-diabetes-obesity-risk.htm

Marijuana Users Have Better Blood Sugar Control – ScienceDaily

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“May 15, 2013 — Regular marijuana use is associated with favorable indices related to diabetic control, say investigators. They found that current marijuana users had significantly lower fasting insulin and were less likely to be insulin resistant, even after excluding patients with a diagnosis of diabetes mellitus. Their findings are reported in the current issue of The American Journal of Medicine.

Marijuana (Cannabis sativa) has been used for centuries to relieve pain, improve mood, and increase appetite. Outlawed in the United States in 1937, its social use continues to increase and public opinion is swinging in favor of the medicinal use of marijuana. There are an estimated 17.4 million current users of marijuana in the United States. Approximately 4.6 million of these users smoke marijuana daily or almost daily. A synthetic form of its active ingredient, tetrahydrocannabinol, commonly known as THC, has already been approved to treat side-effects of chemotherapy, AIDS-induced anorexia, nausea, and other medical conditions. With the recent legalization of recreational marijuana in two states and the legalization of medical marijuana in 19 states and the District of Columbia, physicians will increasingly encounter marijuana use among their patient populations.

A multicenter research team analyzed data obtained during the National Health and Nutrition Survey (NHANES) between 2005 and 2010. They studied data from 4,657 patients who completed a drug use questionnaire. Of these, 579 were current marijuana users, 1,975 had used marijuana in the past but were not current users, and 2,103 had never inhaled or ingested marijuana. Fasting insulin and glucose were measured via blood samples following a nine hour fast, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated to evaluate insulin resistance.

Participants who reported using marijuana in the past month had lower levels of fasting insulin and HOMA-IR and higher levels of high-density lipoprotein cholesterol (HDL-C). These associations were weaker among those who reported using marijuana at least once, but not in the past thirty days, suggesting that the impact of marijuana use on insulin and insulin resistance exists during periods of recent use. Current users had 16% lower fasting insulin levels than participants who reported never having used marijuana in their lifetimes.

Large waist circumference is linked to diabetes risk. In the current study there were also significant associations between marijuana use and smaller waist circumferences.

“Previous epidemiologic studies have found lower prevalence rates of obesity and diabetes mellitus in marijuana users compared to people who have never used marijuana, suggesting a relationship between cannabinoids and peripheral metabolic processes, but ours is the first study to investigate the relationship between marijuana use and fasting insulin, glucose, and insulin resistance,” says lead investigator Murray A. Mittleman, MD, DrPH, of the Cardiovascular Epidemiology Research Unit at the Beth Israel Deaconess Medical Center, Boston.

“It is possible that the inverse association in fasting insulin levels and insulin resistance seen among current marijuana users could be in part due to changes in usage patterns among those with a diagnosis of diabetes (i.e., those with diabetes may have been told to cease smoking). However, after we excluded those subjects with a diagnosis of diabetes mellitus, the associations between marijuana use and insulin levels, HOMA-IR, waist circumference, and HDL-C were similar and remained statistically significant,” states Elizabeth Penner, MD, MPH, an author of the study.

Although people who smoke marijuana have higher average caloric intake levels than non-users, marijuana use has been associated with lower body-mass index (BMI) in two previous surveys. “The mechanisms underlying this paradox have not been determined and the impact of regular marijuana use on insulin resistance and cardiometabolic risk factors remains unknown,” says coauthor Hannah Buettner.

The investigators acknowledge that data on marijuana use were self-reported and may be subject to underestimation or denial of illicit drug use. However, they point out, underestimation of drug use would likely yield results biased toward observing no association.

Editor-in-Chief Joseph S. Alpert, MD, Professor of Medicine at the University of Arizona College of Medicine, Tucson, comments, “These are indeed remarkable observations that are supported, as the authors note, by basic science experiments that came to similar conclusions.

“We desperately need a great deal more basic and clinical research into the short- and long-term effects of marijuana in a variety of clinical settings such as cancer, diabetes, and frailty of the elderly,” continues Alpert.” I would like to call on the NIH and the DEA to collaborate in developing policies to implement solid scientific investigations that would lead to information assisting physicians in the proper use and prescription of THC in its synthetic or herbal form.””