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BLOG: February 2020

Cannabis, the unwelcome healer: factsheet

Cannabis sativa, or cannabis, is kind of a herbal Dr. Jekyll and Mr. Hide. Originating from eastern Asia, it's been long used as industrial plant, primarily for its tough fiber (1938 Popular Mechanics article states that 30,000 products can be made from it). Also, its seed is edible, moreover, with plenty of fiber, proteins, and perfectly balanced essential fatty acids. Hemp is among the highest dollar value crops in the U.S.

At the same time, its flower and flower leafs potentially contain high concentrations of psychoactive substance THC (tetrahydrocannabinol), considered to belong to illicit drugs. However, its level can vary drastically: if it is no more than 0.3% by dry weight, plant is considered perfectly legal, and goes under the humble, but honorable name of hemp.

If it is more than that - and under controlled conditions THC level can be increased to as high as 30%, although is usually about 20% - it is marijuana, illegal substance with bad reputation (marijuana and cannabis are often seen to mean the same, but it is not so; both, hemp and marijuana are the same specie - cannabis).

For that reason, prompted by widespread marijuana use following large influx of refugees from Mexico during Mexican revolution 1910-1920, any private possession, sale and transportation of cannabis was practically banned from 1937 (Marihuana Tax Act), and illegal from 1970 (Controlled Substance Act), to be limited only to marijuana from 2018 (Agricultural Improvement Act).

Meanwhile, new research, most of it from this century, discovered that cannabis flower also contains other bioactive compounds, generally health-promoting, including anti-cancer compounds. All these compounds, including THC, are chemically closely related, and belong to cannabinoids.

Lastly, we've learned that our own bodies produce and use similar compounds as a part of their many regulative functions. It is known as endocannabinoid system, with endocannabinoids being the active compounds it uses. Does that makes us closer to cannabis than to other plants? You be the judge.

Looking back

The earliest archeological evidence of medicinal use of cannabis goes two thousands years back, to Han Dynasty in China, where it was considered helpful for various conditions, including rheumatic pain, constipation, and disorders of the female reproductive tract. Traditional Indian Ayurveda used it to treat neurological, respiratory, gastrointestinal, urogenital, and infectious diseases. [1]

Western medicine takes note of cannabis around mid-19th century, when Irish physician O’Shaughnessy and French psychiatrist Moro described its positive effects on pain, vomiting, convulsions, rheumatism, tetanus and mental wellness.

It was also listed as medicine in the U.S. Pharmacopoeia from 1851.

However, going into the 20th century, as the modern pharmaceutical industry developed and took over, cannabis use was, under various excuses, diminishing, to be finally removed from the Pharmacopoeia in 1941. Main reason was probably that it is a natural remedy that cannot be patented. Its potential psychoactive properties only made it easier.

Approved pharmacological uses

The first FDA-approved cannabis-derived drug, Epidiolex, is used to treat epileptic seizures. Also, oil or alcohol-based drops and capsules containing synthetic cannabinoids (Dronabinol and Nabilone, THC-based) are approved for suppressing nausea and vomiting in patients on chemotherapy, as well as to stimulate appetite in patients with acquired immune deficiency syndrome.

However, they are allowed only if the standard anti-emetics fail.

Another use for them is for the management of pain and cachexia related to cancer treatment, but they are not approved to be a part of primary cancer treatment, less so a sole cancer treatment.

What does cannabis do, and how?

The two most abundant active compounds of cannabis are tetrahydrocannabinol (THC) and cannabidiol (CBD). Their usual native concentration level in cannabis is up to 4% for the former, and about 1% for the latter. With controlled cultivation, either one, or both, can be significantly increased, or reduced to insignificant.

 As already mentioned, they belong to the large group of closely related compounds of the type found in cannabis, called cannabinoids; they are phytocannabinoids if plant-derived, synthetic cannabinoids if manmade, and endocannabinoids if produced by the body.

With the exception of THC, cannabinoids have generally similar action, although there are significant differences in their concentration level in the plant, their affinity for receptors and their potency.

While THC is psychoactive - probably the only cannabinoid with such effect - CBD is not. They both have antitumor effect. At the cellular level, the body uses endocannabinoids to regulate and control cellular life cycle. For that, our cells use so called cannabinoid, or CB-receptors
(CB-1 and CB-2), but it is established that cannabinoids can exert their actions through other receptors as well. [1]

Also, in some cases cannabinoids can exert cytotoxic effect on cancer cells through receptor-independent mechanisms. [2] Indeed, it is their ability to affect multiple cellular pathways that could be used to broaden and strengthen their effect.

Having the power to control cell cycle and homeostasis, cannabinoids can control cancer cell growth, invasion (i.e. metastasis), and death. It includes not only activation of apoptotic (cell death) pathways, but also exerting anti-proliferative and anti-angiogenic (growing tumor's own blood vessels) effects. [3]

 In general, they tend to restore normal cell function, suppressing tumor growth. Numerous experimental studies, mainly those using cancer cell lines, but also those with cancer patients, confirmed that.

Since cancer does alter cellular function, and different cancers do it in different ways, the antitumor effect of cannabinoids varies more or less from one cancer form to another (that may apply to the same cancer location, such as ER-positive vs. ER-negative breast cancer).

But same can be said for any cancer treatment.

  Clinical results with cancer patients

While we only have a small number of actual cancer patients treated with cannabinoids, the results seem to be confirming their significant antitumor effect. Here are some examples from a recent U.K. study [4], using pharmaceutical-grade synthetic CBD:

- Prostate cancer, 72y male: in the course of 12 months on CBD, his PSA (prostate specific antigen) level dropped from 16 to 3.2 cells/7.5ml

- Esophageal cancer, 65y female: three month expected survival at the time of diagnosis, May 2015, CBD treatment alone, died January 2018 (no cause specified)

- Breast cancer, 65y female: on CBD, no other treatment except half the recommended radiation, went from 15cm tumor in the left breast and palpable left axillary nodes to 2cm tumor w/no palpable nodes

- Breast cancer, 62y female: started on CBD as the only treatment in May 2014; from October 2014 to October 2017 her CTC (Circulating Tumor Cell) tests steadily went down from 10.6 cells/7.5ml to 3.9 cells/7.5ml

- Anaplastic ependymoma (very rare brain tumor), 5y boy: after two surgeries, followed by chemotherapy and conformal photon radiotherapy, and no conventional treatment options left, CBD treatment started in February 2016 resulted in 60% tumor reduction by December the same year

- Progressive tanycytic ependymoma (spinal tumor) Grade 2, 50y male: after biopsy and radical radiotherapy treatment refused chemotherapy, went on CBD July 2016 and had tumor reduction in January 2017; after that he switched from the synthetic CBD to cannabis oil extract obtained on the Net, to have the tumor double in size by February 2018 (he was also on medications for unrelated conditions, metformin, mebendazole, doxycycline and atorvastatin)

The study recorded no side effect of any kind using CBD (standard dose 10mg/day every other day), and concluded that the results strongly support further investigations on the use of CBD as a part of primary cancer treatment where other options are exhausted, particularly in combination with radiotherapy.

The lest case illustrates the risk of using cannabis products of unknown quality, actual potency and purity. Since CBD itself, natural or synthetic, has identical molecular structure, its effects, including antitumor effect, are also very similar. Pharmaceutical grade CBD, however, is standardized to these important aspects and, as such, preferable.

* * *

In conclusion, there is a solid scientific and clinical evidence that cannabinoids do have significant antitumor effect, hence the treatment potential as well. That fact is not disputed by the National Cancer Institute [5] and the official medicine. Still, there is no rush to put in use, for the benefit of those who need it. At the moment, there's too much money to lose for the industry by switching to the nature-based medical preparations.

And that is a shame, since cannabinoids have much broader beneficial effect than for cancer treatment alone, including mood and anxiety disorders, movement disorders, neuropathic pain, multiple sclerosis, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity, and osteoporosis.[3]

Their sidelining, and sidelining or suppression of other valid alternative treatments in general, creates undesirable, dangerous situation where people who for any reason - and there are legitimate ones - prefer those treatments, are often left on their own. Official medicine's clam that it only promotes "proven" practices for patients' good is a monumental piece of hypocrisy of our days. Unfortunately, not the only one...

_________

[1] Cannabinoids in cancer treatment: Therapeutic potential
and legislation
, Dariš et al. 2019
[2] Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism, Fogli et al. 2006
[3] Cannabinoid pharmacology in cancer research: A new hope for cancer patients?, Javid et al 2016
[4] Report of Objective Clinical Responses of Cancer Patients to Pharmaceutical-grade Synthetic Cannabidiol, Kenyon et al. 2018
[5]
https://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq
 

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