The Los Angeles Times, Sacramento Bee, and the Associated press published articles on studies showing that Cannabis has therapeutic value. The studies were conducted through the Center for Medicinal Cannabis Research (CMCR) at the University of San Diego. The CMCR was created in 2000 to answer the question, “Does Marijuana have Therapeutic Value?”

 The CMCR have submitted their report to the legislature and Governor of California, in which the authors claim to “have found reasonable evidence that cannabis is a promising treatment.”

The CMCR report is a summary of the clinical trials on smoked or vaporized cannabis that were conducted by the organization. Basically, the organization spent 10 million dollars and completed 6 clinical trials. These trials demonstrate that cannabis is an effective pain medicine for MS and HIV/AIDS patients. Notably, one study showed that ”low potency” cannabis may be effective at reducing pain with out inducing a “high”.

The CMCR had to overcome numerous setbacks. At least 5 clinical trials were canceled for various reasons. In one instance a clinical trial on chemotherapy induced nausea and vomiting had to be cancelled because not enough cancer patients could be recruited. Additionally, the approval of a study by the government typically took 18 months.

The Full Report may be downloaded here: http://www.cmcr.ucsd.edu/CMCR_REPORT_FEB17.pdf

The Press Release can be viewed here:  http://health.ucsd.edu/news/2010/2-17-medical-marijuana.htm

Elsewhere, the Iowa Pharmacy Board is already expecting cannabis to available as a medicine soon. As the board has recommended to legislators that cannabis be rescheduled to allow medical use. Could Iowa potentially distribute cannabis through a pharmacy? Not unless cannabis is removed from schedule I.

A growing body of scientific research suggests that cannabinoid receptors or the endocannabinoid system may have a therapeutic role in major depression (MD) and/or bipolar disorder (BD). A paper published in “Pharmaceutic Research” demonstrated that certain variations or mutations associated with the Endocannabinoid system may make humans more susceptible to MD or BD. The current study found that specific mutations in both the CB1 receptor and FAAH enzyme, were found in human subjects suffering from MD and BP.  Interestingly, only the CB1 receptor mutations were linked to Major Depression, while both CB1 receptor and FAAH mutations were found patients suffering from bipolar disorders

What is the Endocannabinoid system (ECS)? And why is it linked to emotion?

The ECS is comprised of two receptors, the CB1 and CB2 receptor. The CB1 receptor is perhaps one of the most abundant receptors in the human brain. It is found in high amounts in many areas of the human brain, including parts of the brain important for emotion.  It is fairly common knowledge that THC, from the cannabis plant, can activate CB1 receptors. However, humans and many other animals also make a “natural THC” called Anandamide.  Anandamide is synthesized by cells in our body, and can impact a variety of natural processes such as eating, sleeping, memory, energy, and mood. Once Anandamide is synthesized it will be degraded or destroyed by another protein FAAH.  The enzyme activity or the rate at which FAAH destroys Anandamide will indirectly affect the level of CB1 activity.

So, if FAAH is over active there will be fewer signals in the brain telling you to eat and sleep, among other things.  If there is not enough FAAH, it will make a person hungry.

Mutations in FAAH or cannabinoid receptors may underlie many diseases; in fact a “Clinical Endocannabinoid Deficiency” has already been proposed to explain some chronic diseases such as “migraines, fibromyalgia, irritable bowel syndrome, and other functional conditions alleviated by clinical cannabis“. A previous study has also linked variations in FAAH and CB1 rceptors to anorexia nervosa and bulimia nervosa.

Acetaminophen and cannabinoid receptor interactions were the focus of a research article published in the journal of Neuropharmacology in late December 2009. The research demonstrates that the effects of Acetaminophen on pain are mediated through the CB1 receptor. Acetaminophen has previously been shown to elevate the levels of endocannabinoids in the body. Thus increasing the amount of activated cannabinoid receptors, leading to pain relief and anti-inflammatory effects.

Most prescription narcotics such as percocet and vicodin are cut with acetaminophen by pharmaceutical companies. This gives the pain killers more of a “kick.” Without acetaminophen, some pain killers are not nearly as effective. Researchers have been investigating the molecular mechanism for this interaction and the Endocannabinoid System appears to be a big player. Previous research has also shown that there is some “cross talk” between opiate receptors and cannabinoid receptors.

The study investigated the effects of acetaminophen in combination with different pain killers. The authors found that a combination of acetaminophen with gabapentin or morphine produced synergistic pain killing effects in rats.  The results may have clinical significance because the effect was observed in rats that are a model of spinal cord injury. Interestingly, this synergistic pain relief disappeared when the rats were given AM251. AM251 blocks the Cannabinoid Type 1 Receptor (CB1R) thus inhibiting CB1R activation.

Given the notable toxicity of acetaminophen,  cannabinoids might be a reasonable supplement to accompany current treatments for pain.

The Journal of Molecular Psychiatry recently published an LTE from a group of researchers who demonstrated that chronic low doses of the cannabinoid WIN55212, resulted in new brain cells or neurons in the hippocampus of old rats. As we age, our ability to make new cells decreases, this may be the cause of many age related disorders. A class of drugs that can restore neurons may be a potential cure for diseases such as Parkinson’s, depression, etc.

The data was simply amazing–3 weeks of treatment resulted in noticeable effects! So this blog includes the figures from the publication, see below.  On the left hand side, Figure A shows brain cells stained with red and green. Green, spindle like, staining indicates neuron growth. Pictures A and B show the typical neuron growth in developing brains. As you can see in pictures E and F, chronic administration of a non-psychotropic dose of WIN55212 restores neuron production in older rats, indicated by the green wisps. Note that this green stain is very low in old rats that did not receive the cannabinoid, pictures C and D.

The authors speculate, “Cannabinoid receptor stimulation therapy may thus provide clinical benefit for humans with age-associated memory impairment.”

Lots of molecules can activate cannabinoid receptors, so take your pick. More research is needed to determine which cannabinoids are the best option. None of the plant cannabinoids have not been explored for this effect. This not the first time cannabinoids have been linked to neurogenesis; HU-210 has also demonstrated similar effects.

On the first day of the ICRS meeting, Dr. Nagarkatti presented research which demonstrates that THC can reduce organ donor rejection by reducing “Graft vs. Host Diseases.”

Even in HLA matched organ donors, at least 50% experience a severe immune response to the donated tissue. When this happens, inflammation occurs and patients begin wasting away. THC prevents weight loss and suppresses the immune response against the tissue.

Many people have been removed from organ recipient lists for using cannabis, even for instances where it was approved by a physician.  How morbidly ironic that our medical care system will deny a medical marijuana user  an organ they need to live, when THC may improve your chances of a maintaining your organ transplant. As cannabinoids gain acceptance into the clinic,  THC (or synthetic versions thereof) could become mandatory for organ recipients.

Why are marijuana users kicked off of organ recipeint lists? well no one is really sure–probably something regarding the DEA and politics but definitely not science.

• Link article abstract of Dr. Nagarkatti’s paper

The full text is available for purchase through scientific literature websites.

A recent scientific publication from a lab in the UK has established a link between migraines and mutations in the Cannabinoid Type 1 receptor (CB1R aka The”Pot receptor”). Researchers extracted DNA from individuals who were surveyed and reported suffering from migraines. The researchers found the 1st direct evidence that an isoform or mutant form of CB1R can make you susceptible to migraines.

Previous studies have shown that the natural THC our body makes, anandamide, has migraine preventative actions (on the trigeminal nerve).

CB1R antagonists (things that block the receptor) reverse this protective effect. Thus, there is significant data suggesting that the CB1R is involved with migraines.

Interestingly, the International Headache Society has yet to classify or identify any migraine-related genes despite intense research into the subject.

GW Pharmaceuticals announced plans to expand their research agenda by investigating the therapeutic potential of new cannabis-ethanol sprays into the realm of metabolic diseases such as Obesity and Type II Diabetes.

For this project, GW is teaming up with Mike Cawthorne, the group director of the research team that “discovered the multi-billion dollar insulin sensitizer drug, Rosigilatzone.”

The new cannabis spray will be extracted from plants which contain high amounts of CBD and THCV. CBD has shown potential to treat fatty liver diseases and hpercholesterolaemia and also blocks the psychoactive effects of Delta9-THC. THCV, a natural antagonist or Cannabinoid receptor blocker, has notable effects on increasing energy expenditure. THCV, unlike Delta9-THC, is usually present only in small concentrations on the plant. However, GW may have developed a so called THCV-rich cannabis plant.

Developing a treatment for a complex illness, such as metabolic syndrome, can be explored using two cannabinoids in combination and can potentially “be addressed with a single medicine.”