Complimentary and Alternative Medicine:

Cannabis and Cancer

Daniel Timpe
David Ruiz
Aurash Jason Soroosh
Jessica Wolf
Jovelle Dayola Delalamon

DFM 655: Nutrition Education and Communication

San Francisco State University
Fall 2015

The Cannabis plant is well-known throughout the world for its medical, recreational, and
industrial uses. Its leaves and flowers contain unique compounds known as cannabinoids, a
group of at least 105 bioactive lipids. Most of the psychoactive effects have been associated with
delta-9 tetrahydrocannabinol, or THC (Husni, et. al., 2014). More recently, non-psychoactive
cannabinoids have been studied for their medicinal viability, including their effect on.
cCancerous cellss responses to cannabinoids are actively being researched..
Cannabis has been used in Chinese and Ayurvedic medicine for thousands of years.
Cannabis was introduced as a Western medicine in the 1840s by Dr. W.B. OShaughnessy after a
trip to India. He witnessed Indian physicians treating a variety of ailments with cannabis and felt
it was a safe and effective medicine. At that time Cannabis was usually mixed in alcohol as a
tincture and administered orally primarily to treat inflammation, convulsions, spasms, and pain
(Bearman, 2014). Soon after,
iIn the early 1900s,s cannabis was associated with immigrants, criminals, and minorities
in the United States, resulting in it being demonizedits demonization. Cannabis was coined
marijuana in the 1930s. In 1937, the Mmarijuana Ttax Aact was established, which charged a
$1 tax per ounce for medical use, and a $100 tax per ounce for those who wanted to use it
recreationally. The American Medical Association opposed the act because of its obstructiveness
and extra cost to patients and farmers. In 1951, cannabis was listed in the Boggs Act along with
other narcotics that were believed to have no medical use. In 1970, the Ccontrolled substances
Substances act Act classified cannabis as a Sschedule I drug, meaning that it hasa classification
given to drugs with no medicinal use and a high potential for abuse (National Cancer Institute,
2015).

In 1980, Marinol, a synthetic form of THC, was tested on cancer patients and
successfully shown to control the side effects from common treatments and had positive results.
In 1985, the FDA approved Marinol to treat digestive issues in cancer patients and later approved
its use in HIV/AIDS patients to increase appetite and control wasting syndrome. In 1996,
California passed Pproposition 215, becoming the first state to legalize cannabis for medical
usess (medicalmarijuana.procon.org, 2013).
Whether for medical or recreational use, cCannabis is most commonly smoked or
vaporized after it is dried. Edible cannabis products are becoming more popular because of their
ability to efficiently deliver a wide array of cannabinoids without the irritating effects of
smoking. Fresh cannabis can be juiced and consumed, but has little to no psychoactivity. Topical
preparations of cannabis can be useful to treat localized issues. Specific dosages for treatment are
still unknown. This is complicated by the fact that cCannabinoid content varies significantly
between different strains of cannabis. Effects on an individual also vary, even between patients
treating the same disease (Malka, 2014).
Once they are introduced into the human body, cCannabinoids work by stimulating
membrane receptors in cells throughout the bodythe human body. The two most prominent
receptors are the cannabinoid 1(CB1) and cannabinoid 2(CB2) receptor. CB1 receptors are
generally found in the central nervous system, while CB2 receptors are mainly found in the
peripheral tissues. CB1 and CB2 receptors are both G-protein coupled receptors (Sulak, 2014).
In a recent study by Haustein et al. (2014), the role of psychoactive, non-psychoactive,
and endogenously synthesized cannabinoids in the human bodys immunological response to
cancer was examined. The goal was to explore cannabinoids ability to cause the upregulation of
intercellular adhesion molecule 1 (ICAM-1) in lung cancer cells, which may increase the cell's

susceptibility to the cytolytic activity of lymphokine-activated killer (LAK) cells which are
produced through stimulation by the human immune system. The in-vitro study found that the
non-psychoactive cannabinoid cannabidiol (CBD) induced ICAM-1 expression in two lung
cancer cell lines, as well as in metastatic cells directly from a lung cancer patient. This resulted in
a significant increase of tumor-cell lysis compared to the control. The same experiment was
performed with THC as well as the hydrolysis-stable anandamide analogue R(+)methanandamide (MA), which is resembles an endogenous cannabinoid receptor ligand. They
witnessed a similar increase in the upregulation of ICAM-1 by the lung cancer cells, resulting in
a significantly increased LAK cytotoxicity. To ensure it was actually cannabinoid receptor
stimulation that was the sole cause of these findings, CB1 and CB2 receptor antagonists were
used to block the activation of said receptors. It resulted in a significant decrease in the LAK
mediated lysis of the lung cancer cells. The final step was to ensure these cannabinoids are not
simply toxic to normal bronchial epithelial cells. Healthy lung cells were exposed to THC and
CBD, which marginally increased ICAM-1 upregulation. MA had no effect. None of the
cannabinoids significantly increased susceptibility of the healthy cells to lysis caused by LAK
cells (Haustein et al., 2014).
Cannabinoids also show promising potential to prevent angiogenesis in cancerous
tumors. Angiogenesis, also called neovascularization, is the growth of new blood vessels formed
initially from small sprouts or tubes via morphological changes in vascular endothelium.
Cancerous tumors secrete signaling molecules which lead to the formation of new blood vessels
that feed the tumor, support its growth, and facilitate metastases. For this reason, angiogenesis
has long been a target in cancer treatment. Numerous anti-angiogenic drugs have been approved
by the Food and Drug Administration, and more are undergoing clinical trials for treatment of a

wide variety of cancers. While most of those drugs are conventional pharmacological treatments,
more recent studies have introduced plant-based treatments, including cannabinoids (National
Cancer Institute, 2011).
The anti-angiogenic properties of cannabinoids are related to two cellular mechanisms.
One is the inhibition of both matrix metalloproteinases, which play a role in tumor invasion via
the destruction of the extracellular matrix (Aroui, et al., 2014). In a 2014 in vitroin vitro study of
lung cancer cells, cannabinoids increased the transcription of tissue inhibitor of matrix
metalloproteinasemetalloproteinase (TIMP-1), which was associated with decreased sprout
formation compared to the control, thus preventing the generation of new vessels. Aside from
that, metalloproteinases play a role in tumor invasion via the destruction of the extracellular
matrix. The increased TIMP-1 transcription also led to decreased tumor cell adhesion, which
signifies decreased possibility of metastasis (Ramer, Fischer, Haustein, Manda, & Hinz, 2014).
These results are not limited to in vitroin vitro models; in one 2011 study mice inoculated with
breast cancer were exposed to cannabinoids which resulted in a decrease in both angiogenesis
and metastasis.
The second anti-angiogenic mechanism of cannabinoids is due to the inhibition of the
vascular endothelial growth factor (VEGF) pathway. In cancerous tumors, VEGF leads to
morphological changes in the vascular endothelium that eventually grows into blood vessels
which feed the tumor, making VEGF a target for cancer therapy. In both in vitroin vitro and
animal models cannabinoids have been shown to inhibit VEGF-related vessel growth, thus
inhibiting angiogenesis (Solinas, et al., 2011).
There are several mechanisms in which cannabinoids can inhibit the proliferation and
migration of cancer cells, resulting in subsequent apoptosis and autophagy. For example, the

activation of CB1 or CB2 receptors promotes a down-regulation of gene transcription which

induces apoptosis by inhibiting adenyl cyclase activity. This can reduce both cyclic adenosine
monophosphate (cAMP) and protein kinase A activity (Hohmann & Guindon, 2011). The
activation of CB1 and CB2 receptors also induces apoptosis and autophagy by translocating
glyceraldehyde-3-phosphate (G3P) dehydrogenase into the nucleus, inhibiting glycolysis and
altering the cells AMP/ATP and ADP/ATP ratio. Furthermore, cannabinoid receptor activation
inhibits enzymatic activities in the citric acid cycle by increasing the levels of reduced cofactors
(NADH), which in turn inhibits the glycolytic pathway and eventually results in apoptosis
(Costanzo, et. al., 2013).
According to these studies and many others, cannabinoids have significant anti-cancer
properties. Pancreatic cancer, lung cancer, breast cancer, brain cancer, bone cancer, kidney
cancer, skin cancer, and almost every othermany other types of cancerous cells has have been
exposed to cannabinoids and the results documented. Although human cells lines are used, the
vast majority of the research has been done in vitroin vitro or in animal models. Chemical
reactions can occur in unpredictable ways within the human body. So far, cannabis in its natural
form has no known LD50, and has not resulted in any harmful drug interactions. There is almost
no evidence that suggests that human trials would bring harm to the subjects. The only barrier
seems to be the federal restrictions on research.
Although the psychoactivity of cannabis is apparent, the medicinal viability is too.
Conventional pain medication, muscle relaxantsers, anti-anxiety medications, and many other
commonly prescribed drugs have significant mind altering effects. Even worse, they can cause a
physical addiction to the drug. Cannabis has been proven to be safe and anecdotally effective in
treating a variety of ailments. In a patient diagnosed with cancer, there is no reason to exclude

cannabis as part of their treatment. Aside In addition tofrom the potential anti-cancer effects,
cannabinoids can help stimulate appetite and control side effects from conventional cancer
treatments.

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