Given the lack of FDA approved medications for the treatment of drug use, exercise may represent a form of behavioral modification suitable to treat different forms of drug dependence. Building up a “Runner’s High”  from intense exercise may overwrite  pathways in the brain by reinforcing the body’s natural reward system.

A group of subjects who smoked an average of 5.9 joints a day, reduced their daily intake of Cannabis to an average of 2.8 joints a day during the exercise portion of the experiment.

This data agrees with existing scientific evidence which demonstrates the positive effects of exercise on reducing drug craving. Given the low cost of exercise it could represent a treatment accessible to people who do not have access to health insurance or have failed to receive HMO approval for drug abuse medications. More studies are needed to confirm the benefits of exercise on drug dependence…[Read More]

Egypt is one of the great ancient civilizations with a notably advanced medical system. There is ample evidence to support the use of Cannabis as a medicine in ancient Egypt, as indications for use and instructions for preparation are written in some of the oldest medical texts in existence. Although, the extent of Cannabis use in ancient Egypt is debatable. Cannabis has been detected in mummies in Egypt, along with cocaine and nicotine by archeologists but these findings were subjected to intense debate.

The Papyrus Ramesseum III contains one of the oldest mentions of Cannabis. Instructions on preparing Cannabis and guidelines for treatment can also be found in the Chester-Beatty VI (Medical) Papyrus (1,300 BC), the Berlin papyus (1300 BC), the Hearst papyrus (1550 BC) , the Vienna papyrus (220 AD), and others. Below you find a few pictures of some of these prescriptions, along with an example or two of specific references to the plant. Many more examples exist than discussed here, for full review of all existing references please check out this article by Dr. Ethan Russo.

There is a hieroglyph regarded as “shemshemet” which means Cannabis. Many other ancient societies have left references to this plant found in ancient Sumerian, Chinese, Persian, Greek, and Hebrew texts. The image below provides depictions of shemshemet, bhang, kaneh bosem, and others.

Some remain unconvinced that Cannabis was widely used in Egypt during ancient times. As references to Cannabis appear and disappear throughout Egyptian records, a term referred to as ‘Cannabis Interuptus.’ This disappearing act is easy to understand as the papyrus is very delicate and hard to preserve given the human propensity for constant war, invasion, conflict, and the occasional overthrow of a dictatorial regime. Although, the disappearance or shortage of herbal products is something we can see today as Egypt suffered a “Hash Crisis”, a sort of hash famine swept the land.

Back to the ancient evidence, pollen has been been detected in ancient soil samples and mummies. Also, by the 9th and 10th century, Egyptian medicine became Islamic medicine. Despite Sharia law banning all intoxicants, the plant in “hashish form” continued to be used for its powerful medicinal qualities. The term for the plant and its products changed over time, adding another level of confusion, in Islamic medicine it was no longer referred to as “shemshemet” but instead was called “hashish, or shadanaj,the Royal grain.”

Research on Cannabis and the cannabinoids continues in Egypt. Recent publications discuss the metabolism of cannaflavins from the plant, toxicity & abuse potential, potential impact of use on lifestyle, and the synthesis of new cannabinoid drugs.

For additional images and notes on ancient Cannabis please visit http://antiquecannabisbook.com.

Over the last decade there have been numerous publications demonstrating the anti-cancer effects of plant and synthetic cannabinoids. Notably, the main ingredient of Cannabis, THC (tetrahydrocannabinol), has demonstrated the ability to kill multiple types of cancers in a variety of cancer research models. CBD (cannabidiol), another common plant component, has also shown the ability to kill cancer cells, recently it has been used to successfully treat breast cancer in a mouse research model of the disease.

Certain types of brain cancer appear to be vulnerable to cannabinoids such as THC and CBD. Scientific research has demonstrated that THC and other cannabinoids can kill extremely aggressive brain cancers known as glioblastoma multiforme (GBM) or grade IV astrocytomas. Researchers have also experimented with combining different cananbinoids for the treatment of aggressive brain cancers. So far, the results have been extremely promising. There is a need for new treatments for GBMs, as current  treatments for these cancers can extend life for up to 15 months, if you’re lucky.

Last year, the journal of Molecular Cancer Therapeutics published research demonstrating that combination’s of THC and CBD, the two most abundant cannabinoids on the plant, can lead to a greater-than-additive or synergistic inhibition of cancer growth. Now, nearly a year to the date, the journal has published another article studying the anti-cancer effects of THC and CBD. The new article takes the next steps towards getting this therapy in to the clinic by testing THC and CBD in animals along side a common brain tumor drug TMZ (temozolomide).

The study was conducted in Spain, and the experiments analyzing the effects of cannabinoids were conducted with tumors or brain cancer cells from human samples and a tumor xenograft mouse model. A tumor xenograft model is basically a cancer that is induced into an animal that has a compromised immune system. This allows researchers to give a mouse a tumor consisting of human cells, thus a promising anti-cancer treatment can be tested on a human tumor in a more natural environment, than a petri dish.

The plant cannabinoids used for this study were “kindly provided by GW pharmaceuticals.”  THC and CBD were also provided as plant extracts or “botanical drug substances,” meaning they contained small amounts of other cannabinoids. Allowing these researchers to construct a custom anti-cancer, Sativex-like substance.  Other synthetic cannabinoids such as SR141716A and SR144528 were donated by Sonafi-Aventis.

The figure below shows that THC and TMZ can drastically inhibit the size of tumor.

In the following figure, the authors also examined combinations of THC,CBD, TMZ , and SAT-L (a “botonical drug substance” or extract containing a 1:1 ratio of THC and CBD, 7.5mg each). Interestingly their results also showed that TMZ resistant cells, can be killed by cannabinoids or in combination with cannabinoids.

The researchers conclude that:

“Taken together, our observations support that the administration of cannabinoids, and in particular of Sativex, which is currently used for palliative applications in patients with cancer and multiple sclerosis, alone or in combination with TMZ, could be of potential interest for the management of GBM.”

Cannabis-based medicines are most often prescribed to increase quality of life or treat symptoms of disease. As research continues on this ancient medicine, scientific data suggests that cannabinoids are not only promising treatments but represent potential cures.

Links to Cannabinoid & Cancer Studies:

Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition

Cannabidiol enhances the inhibitory effects of Delta⁹-tetrahydrocannabinol on human glioblastoma cell proliferation and survival

Cannabinoids for Cancer Treatments: Progress and Promise

Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum stress-related genes

Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines

Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma

Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation

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As early as 5,000 years ago Cannabis was noted for its effects on the central nervous system[1]. This often manifested in the form of pain relief, appetite stimulation, and sedation (Iverson 2000). Medicinal Cannabis preparations were widely used in western medicine during the 19^th century. At the time it was no secret that pharmaceutical preparations of Cannabis were variable. As the active ingredient was not known, quality control was virtually impossible, and this is in part why the plant fell out of use.

During the Victorian era, many plants were extracted for their unique properties, namely alkaloids. These plant chemists were successful because the alkaloids they were targeting are water soluble organic bases that form crystalline solids when combined with acids. Among the medicinal compounds isolated in the 19^th century were quinine, morphine, and cocaine. These were major advances in plant chemistry. The molecules on the cannabis plant, however, are almost completely insoluble in water. The chemical nature of cannabinoids prevented early Victorian scientists from making efficient extracts of these polar compounds. The active ingredient, THC, wasn’t isolated and identified until 1964.

In the 1990s, researchers made discoveries essential for the establishment of the cannabinoid research field. By the end of the decade scientists discovered two distinct cannabinoid receptors (i.e., CB1 and CB2), isolated endogenous cannabinoids (e.g.,Anandamide and 2-Arachidonylglycerol), synthesized a cadre of ligands, and generated cannabinoid receptor knockout mice (Matsuda 1990, Gerard 1990, Zimmer 1999). Efforts to identify and clone the CB1 receptor also demonstrate that the CB1 receptor is one of the most abundant proteins in the brain. Thus, cannabinoid receptors became an attractive target for drug development. The availability of synthetic THC and novel analogs has allowed researchers to begin characterizing the role of this neuronal G-protein coupled receptor. The sum of all knowledge on how cannabinoid receptors and their ligands work together in mammals is referred to as the endocannabinoid system.

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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There are numerous references in popular Cannabis literature which claim that Cannabis strains can smell like mango, melon, and even grapes. Well, it might not be their imagination. The odor of cannabis comes from over 120 terpenes (a.k.a. terpenoids fragrance molecules) that are made by the plant(1).

The main ingredients in Cannabis Fragrance

Terpenes have some interesting effects on humans, including modulating the effects of THC (2) and decreasing memory loss(3). Terpenes are non-toxic and other types of plants have a unique mixture as well. One terpene is unique to Cannabis (m-mentha-1,8(9)-dien-5-ol). All others occur in fruits, vegetables, and flowers. Many of the beneficial terpenes on Cannabis also occur in tropical fruits. So, maybe it isn’t your imagination when something smells like mango, melon, or even grapes.

Cannabis’ odor molecules may offer benefits to patients, as these molecules have medical applications of their own. At a recent cannabinoid science meeting Ethan Russo M.D. highlighted some of the most interesting aspects of terpenes; the fragrant component of Cannabis(4):

• Linolool has anti-anxiety and sedative properties (also in lavender).

• Beta-Caryophyllene is a potent activator of CB2 Receptors and is found in nearly all plants.

• Myrcene has analgesic, anti-inflammatory, and muscle relaxing properties (also in Mangos).

• Nerolidol has sedative and anti-malarial properties (Also in citrus rind). Limonene is also found in citrus rinds and is very abundant in Cannabis.
  

Limonene is available through retailers by the bottle or barrel

Terpenoids can also alter the effects of THC and other cannabinoids. It’s probably best to think of these skunky molecules as enhancing the positive effects of cannabis and reducing the negative effects of cannabis. For instance, terpenes are also wonderful antioxidants. ‘Skunky’ molecules should not be confused with ‘funky’ odors, from contamination such as fungus or, bacteria, a smell that resembles musk or moldy bread.

Unfortunately and ironically, the smell of this plant causes a lot of trouble. Since THC does not have a smell, drug dogs are trained to find one, very smelly molecule called -caryophyllene-epoxide. It’s an unfortunate catch 22 for Cannabis patients; that the odor molecules in Cannabis are probable cause for police. Yet, smell does not necessarily have anything to do with potency. Even the smelliest Cannabis could, in theory, not have THC in its trichomes.

Non-cannabinoid parts, such as terpenes, are of medical importance and possibly central to understanding the diverse benefits and varieties of Cannabis reported by patients-over 700 varieties of cannabis have been reported.

GW pharmaceutical’s Cannabis extract, Sativex maintains a strict ratio of THC and CBD but also maintains a strict ratio of certain terpenes. The data on the cannabinoid content is widely available on the web and in cannabis scientific literature, yet the company doesn’t mentions what the actual concentrations of terpenoids might be.

You could try to sniff out the culprits but even the most well trained perfumist may not be able to pick out an individual terpene from Cannabis.

Attempting to sniff out the terpene content of Sativex or Cannabis is tempting and it’s hard not to speculate: is it linalool? Is it eugenol? Or is it 1,8-cineole? Only time (and our perhaps our noses) will tell.

1) Grotenhermen, Russo. Cannabis and Cannabinoids. Page 34 (2002)
2) Agarwal et al. Research communication in substance abuse 1989;10:155-168.
3) Carta et al. Brain Research 1998; 809 (1);1-4.
4) O’Shannauesy’s Winter/Spring 2008. Russo Previews What’s in The Organic Pipeline.

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