Recently, a Doctor came out against using Cannabis for the treatment of HIV/AIDS. Among oncologists, his opinion is probably in the minority. This Doctor claims that no HIV patients he knows, would benefit from Cannabis. Unfortunately, the Doctor only discussed his opinion and did not site any current research from controlled studies to support his stance. Current research  in HIV/AIDS and cannabinoids has been promising– practically every clinical trial that has looked at HIV/AIDS and THC has shown that cannabinoids may help patients.

Some of the first patients that were infected with HIV were treated at San Francisco General Hospital.  It was probably there, that the medical staff first noticed patients who used Cannabis seemed to be doing better. Notably, cannabis became known as an effective treatment for HIV/AIDS wasting syndrome.  Among the medical staff, was Dr. Donald Abrams who recorded his observations and would later go on to conduct some of the most important clinical trials in the history of cannabinoid research. Dr. Abrams demonstrated that smoked Cannabis could effectively alleviate neuropathic pain in HIV/AIDS patients. Videos of Dr.Abrams presenting his results can be viewed here: Cannabis & Neuropathic Pain, Dr. Abrams, pt 1 and Cannabis & Neuropathic Pain, Dr. Abrams, pt 2

Later, other researchers would show, in a similar group of HIV patients, that smoked Cannabis can modulate pain where conventional opiates were ineffective. The beneficial effect of cannabis on HIV/AIDS symptoms in humans has inspired other researches to take a closer look at the mechanisms behind these effects.

A research team from Virginia Commonweatlh University showed that natural Delta9- THC and synthetic CP-55,940 could inhibit the HIV inflammatory response through the Cannabinoid Type II (CB2) Receptor. Once HIV invades a cell, the virus makes the cell secrete many proteins to attract other immune cells and this leads to the ongoing infection of other cells. One such protein called Tat is important for viral replication and gene expression; the effects of this protein on cell migration appear to be inhibited by both synthetic and natural cannabinoids. The main finding of these researchers is that cannabinoids can slow the migration of uninfected cells towards the Tat protein and thus could inhibit the HIV infection process and the associated inflammation.

Another research group also thought that the previous worked on HIV and cannabinoids was unbelievable. So, they sought to see if THC made the disease worse in monkeys. The researchers infected monkeys with SIV and studied them for 1 year. SIV is the equivalent of HIV in humans. Their research was published in September 2010 and the entire article can be found here:Molina Article on THC attenuates SIV.

Note that each monkey costs around $8,000.00 for the research study.

The researcher demonstrated that THC slows the progression of HIV in primates. See  Figure 4 below from the Article by Molina et al.

SIV THC Figure 4

In Figure 4, there are two groups of monkeys. The solid line is the THC group and the dotted line is the control group (no drug). Within 11 months, 80% of the control group died (dotted line). In the group that received the drug THC, no deaths were reported.

The authors conclude :”this study is the first to report in vivo experimental data demonstrating that chronic THC initiated prior to, and continued throughout the asymptomatic phase of SIV infection, does not impair the host’s ability to control viral load, and does not increase morbidity and mortality from the infection… THC treatment clearly did not increase disease progression, and indeed resulted in generalized attenuation of the classic markers of SIV disease (set point viral load/viral level in general)…based on our results and reports in the literature, we speculate that retention of body mass,attenuation of viral replication, and an overall immunosuppressant effect of cannabinoids may contribute to the amelioration of SIV disease progression seen in our study.”

However, THC is only part of the story. There are over 500 compounds on the Cannabis plant and some of these compounds may contain powerful medical properties which could treat a variety of diseases including Cancer and HIV/AIDS. For instance researchers have found that Cannabis extracts which contain Denbinobin can inhibit HIV replication in a petri dish. Denbinobin is found on the Cannabis and other plants as well.

The therapeutic promise of this plant remains high and some states have medical laws allowing the use of Cannabis for HIV. Furthermore, Marinol or synthetic THC in a capsule remains available by prescription in the U.S. GW pharmaceuticals has an extract available for the treatment of HIV symptoms but it is not allowed in the United States. It is available in Canada, UK, Spain, and soon to be available in South America.

Disclaimer: The information is not intended to treat and diagnose any illness. The views expressed are those of the author and do not reflect those of any University or its affiliates.

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Last month, Dr. Sean McAllister traveled from California to talk in Philadelphia on a potential new breast cancer treatment. Dr. McAllister has been studying the anti-cancer effects of cannabinoids for years and he has discovered that the cannabinoid, CBD (Cannabidiol) is a very potent inhibitor of breast cancer. Usually, his research draws a lot of media interest and then some.  His research sparks an interest in the general public, as CBD is also the second most abundant compound on the Cannabis plant.

Dr.McAllister shared his results of his recently published study on CBD and breast cancer. This is not the first paper on the anti-cancer activity of CBD, the McAllister lab also published other articles on cannabinoids and cancer: CBD and Breast Cancer and THC&CBD kill brain cancer cells.  The current study is an in depth look at how CBD kills breast cancer cells in an animal model. Specifically, CBD affects a protein called ID-1. ID-1 appears to be a major conductor of cancer cells and thus is an excellent target for a cancer treatment.

There are a variety of ways for a scientist to measure how effective an anticancer drug is. For instance in the image below is an experiment testing how CBD can stop the invasion of cancer cells. When cancer spreads it can eat through tissue, and CBD appears to be able to inhibit this aspect of breast cancer cells. The cancer cells are placed on a gel which contain small holes. The cells are dosed with a drug and after a few days you can count the number of cells that have made it through. This simulates what a tumor does as it eats its way through human tissues. The little black triangles are the cells, you can see that only a half-dozen or so made it through the gel when dosed with CBD (on the right). Without CBD, the control on the left, the cancer cells easily move through the gel.

Invasion assay pic control vs CBD

Dr.McAllister has previously demonstrated  that cannabinoids may have the unique ability to selectively kill cancer cells. The lab has also posted a youtube video showing this effect.

The therapeutic potential of CBD or a synthetic version thereof, is of interest to pharmaceutical companies. During his presentation, Dr. McAllister mentioned that work may soon start on a CBD and breast cancer clinical trial with STI pharmaceuticals.

However CBD is a scheduled drug in this country, but it doesn’t get you high and has virtually no toxicity! Furthermore, CBD also inhibits the negative effects of THC! Why is this safe and useful compound a scheduled drug of abuse!? Luckily, the government’s view on CBD hasn’t deterred researchers from developing this into a medicine.

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Articles like this and more are also available at www.examiner.com

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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.

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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 “Pharmacological 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.

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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.

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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.

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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.

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