Cannabinoids Counteract Prostate Cancer Growth

According to preclinical data to be published in the British Journal of Pharmacology, proliferation and selectively trigger cell suicide of prostate carcinoma is inhibited by the administration of non-psychotropic plant cannabinoids, in particular cannabidiol (CBD).

The anti-cancer properties of various non-psychoactive synthetic and botanical cannabinoids, including CBD, CBG (cannabigerol), CBN (cannabinol) and THCV (tetrahydrocannabivarin), in vivo and in vitro (in culture) were assessed by an international team of investigators from Italy and the United Kingdom.

Researchers reported, “The data presented here allow us to suggest that non-THC cannabinoids, and CBD in particular, retard proliferation and cause apoptosis (programmed cell death) of prostate carcinoma growth via a combination of cannabinoid receptor-independent cellular and molecular mechanisms. We suggest that non-THC cannabinoids might provide the basis for the development of novel therapeutic strategies for the treatment of prostate carcinoma.”

Authors of the study concluded, “The effects reported here, together with previously reported cannabinoid receptor-mediated effects of THC on PCCs (prostate carcinoma cells), might provide momentum to clinical studies on cannabinoids and cannabis extracts as a therapy for human prostate carcinoma, either in addition to currently used treatments, or as stand alones, as suggested also by our present in vivo data.”

A separate study of cannabinoids on prostate cancer that was published in the present edition of the Indian Journal of Neurology also concluded, “Prostate cancer cells possess increased expression of both cannabinoid 1 and 2 receptors, and stimulation of these results decrease in cell viability, increased apoptosis, and decreased androgen receptor expression and prostate-specific antigen excretion. It is our conclusion that it would be of interest to conduct clinical trials involving medicinal cannabis or other cannabinoid agonists, comparing clinical markers such as PSA with controls, especially in men with bone metastatic prostate cancer, whom would not only benefit from the possible anti-androgenic effects of cannabinoids but also from analgesia of bone pain, improving quality of life, while reducing narcotic consumption and preventing opioid dependence.”

The study “Non-THC cannabinoids counteract prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms,” appeared in the British Journal of Pharmacology.

Brain Cancer Cell Death Induced By Marijuana

Combined administration of the pharmaceutical agent temozolomide (TMZ) and THC exhibits strong anti-cancer activity in brain tumors resistant to conventional anti-cancer treatments, according to preclinical data published online in the journal Molecular Cancer Therapeutics.

The anti-tumor activity of the cannabinoids THC and CBD (cannabidiol) in glioma xenografts (tissue grafts) was assessed by investigators at Complutense University in Spain. It was reported by the authors that the administration of TMZ (the benchmark agent for the management of glioblastoma) in combination with THC “enhanced autophagy” (programmed cell death) in malignant tissue. The combined administration of THC, CBD, and TMZ “remarkably reduced the growth of glioma xenografts … [and] produced a strong antitumoral action in both TMZ-sensitive and TMZ-resistant tumors.”

They concluded, “Altogether, our findings support that the combined administration of TMZ and cannabinoids could be therapeutically exploited for the management of GBM (gliobastoma multiforme).”

A pilot study in 2006 that was published in the British Journal of Cancer reported that the intratumoral administration of THC was linked with minimized tumor cell proliferation in two of nine human subjects with GBM that is highly resistant to conventional anti-cancer treatments.

The study, “A Combined Preclinical Therapy of Cannabinoids and Temozolomide against Glioma,” appeared in the journal Molecular Cancer Therapeutics.

Cancer & Marijuana summary

Non-Psychotropic CBD Safe In Humans

According to clinical trial data published online by the journal Current Pharmaceutical Design, oral administration of the non-psychotropic cannabis plant constituent cannabidiol (CBD) is safe and well tolerated in humans.

The physiological and behavioral effects of CBD and THC versus placebo were assessed by investigators at Kings College in London in 16 healthy volunteers in a randomized, double-blind, crossover trial.

The study “Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers” appeared online in Current Pharmaceutical Design.

It was reported by the investigators that oral administration of THC (10 mg) was linked with different physiological and behavioral effects like increased heart rate and sedation whereas the oral administration of 600 mg of CBD was not. It was concluded, “There were no differences between CBD and placebo on any symptomatic, physiological variable. … In healthy volunteers, THC has marked acute behavioral and physiological effects, whereas CBD has proven to be safe and well tolerated.”

The non-psychotropic cannabis plant constituent cannabidiol (CBD) was termed safe, non-toxic, and well tolerated by a previous review of the use of CBD in human subjects, published in the scientific journal Current Drug Safety last year.

Medical Marijuana Approved By Sweden

Medicinal cannabis would now be available as a prescription in Sweden after Sativex, a cannabis-based mouth spray, was approved by the Medical Products Agency for the treatment of multiple sclerosis (MS).

“This is great news for those who can’t get any relief from the most common drugs,” Jan Hillert, an MS researcher at Karolinska Institute and said the institute is planning to closely monitor prescriptions for Sativex to ensure against abuse.

The cannabis-based mouth spray does not result in a “high” as the cannabinoids included — a near 1:1 mix of tetrahydrocannabinol (THC) and cannabidiol (CBD) — are not administered in large enough doses, according to both the agency and Sativex manufacturer GW Pharmaceuticals, which grows medicinal cannabis and prepares the extract in Britain.

Sativex spray is used sublingually (under the tongue), has been shown by a series of medical studies to be successful for alleviating multiple sclerosis (MS) symptoms.
“Evidence generated from clinical trials shows that Sativex® has a positive impact on spasticity in multiple sclerosis, while alleviating associated symptoms including pain, bladder or sleep disturbance,” GW Pharmaceuticals said in a press release. “By relieving the symptoms of MS, Sativex® can improve patients’ quality of life and allow them greater independence in performing their daily activities.”

The cannabis spray is already available as a prescription medication in the United Kingdom, Germany, Spain, Denmark, Canada and New Zealand, according to GW.

Arthritis Pain Relieved By Cannabis Extracts

According to clinical trial data published in an issue of the journal Rheumatology, the use of cannabis extracts has the potential of suppressing pain and improving quality of sleep in patients suffering from rheumatoid arthritis. The study was titled, “Preliminary assessment of the efficacy, tolerability, and safety of a cannabis-based medicine in the treatment of pain caused by rheumatoid arthritis.”

In a randomized, double-blind, parallel group study, fifty-eight patients participated and thirty-one of them self-administered Sativex, a whole plant medicinal cannabis extract containing precise doses of the cannabinoids THC and cannabidiol (CBD), for five weeks while others received a placebo.

Patients using Sativex experienced statistically significant improvements in pain on movement, pain at rest, quality of sleep, inflammation, and intensity of pain compared to the placebo group, the study found.

This study is the first clinical trial for assessing the effects of either cannabis or cannabis extracts on patients with rheumatoid arthritis.

Survey data published in the International Journal of Clinical Practice in March 2005 reported that approximately one out of six medicinal marijuana patients in the UK use cannabis to alleviate symptoms of arthritis.

Previous clinical data on Sativex had revealed cannabis extracts to reduce neuropathic pain, spasticity, pain-related sleep disturbances, and urinary dysfunction in Multiple Sclerosis patients unresponsive to standard treatment.

HIV Progression Moderated By Cannabinoid Agonist

According to preclinical data published online in the journal PLoS ONE, progression of the human immunodeficiency virus (HIV) is moderated by the activation of specific endogenous cannabinoid receptors.

Investigators at the Mount Sinai School of Medicine in New York City evaluated whether administering a selective cannabinoid agonist could regulate HIV-1 infectivity and reported that HIV infection in culture is inhibited by activation of the CB2 receptor.

Authors concluded, “The clinical use of (selective CB2) agonists in the treatment of AIDS symptoms may also exert beneficial adjunctive antiviral effects … in late stages of HIV-1 infection.”

It was reported last year by investigators at the Louisiana State University Health Sciences Center that the long-term administration of delta-9-THC, the primary psychoactive compound in marijuana, is associated with reduced mortality in monkeys infected with the simian immunodeficiency virus (SIV), a primate model of HIV disease.

The authors concluded, while writing n the journal AIDS Research and Human Retroviruses: “Contrary to what we expected, … delta-9-THC treatment clearly did not increase disease progression, and indeed resulted in generalized attenuation of classic markers of SIV disease. … These results indicate that chronic delta-9-THC does not increase viral load or aggravate morbidity and may actually ameliorate SIV disease progression.”

Muscle Stiffness Mitigated By Cannabis Extracts

According to clinical trial data published in the Journal of Neurology, Neurosurgery & Psychiatry, administration of cannabis extracts in an oral form can significantly minimize muscle stiffness in patients with multiple sclerosis (MS).

The use of cannabinoids versus placebo in 279 subjects with multiple sclerosis was assessed by investigators at the University of Plymouth, Clinical Neurology Research Group, in the United Kingdom over a period of twelve weeks. The study involved cannabis extracts including standardized doses of THC and cannabidiol (CBD), a non-psychoactive constituent in cannabis, in a soft gelatin capsule.

It was reported by the investigators that oral cannabis extracts were better than placebo for treating muscle stiffness and pain associated with multiple sclerosis.

Authors concluded: “Treatment with standardized oral extract of cannabis sativa relieved muscle stiffness. The proportion of participants experiencing relief was almost twice as large in the cannabis extract group as in the placebo group. … Effective pain relief is also achieved by cannabis extracts, especially in patients with a high baseline pain score. Our findings suggest that standardized cannabis extracts can be clinically useful in treating the highly complex phenomenon of spasticity in MS.”

Separate clinical trials assessing cannabis extract administration on patients with multiple sclerosis have indicated that cannabinoids may alleviate symptoms of the disease long-term and could also act in ways for mitigating the disease progression. An oral spray containing plant cannabis extracts, Sativex, is presently legal in over a dozen countries, including Canada, Germany, Great Britain, New Zealand, and Spain by prescription to treat MS-related symptoms.

Cannabinoid Receptor Agonists May Be Effective Anti-Lymphoma Agents

According to researchers at Virginia Commonwealth University in Richmond, Delta-9-tetrahydrocannibinol (THC), the major component of marijuana, and other cannabinoids induce apoptosis in murine tumors of immune origin.

Dr. Mitzi Nagarkatti explained in an interview with Reuters Health that cancers of the immune system like other cells express a cannabinoid receptor known as CB2. Compounds that bind CB2 receptors selectively induce apoptosis in these cancer cells, Nagarkatti said. Moreover, “compounds that interact with CB2 will not exhibit psychotropic effects.”

Dr. Nagarkatti and her colleagues in a series of in vitro experiments exposed murine lymphoma and mastocytoma cells to four cannabinoid receptor agonists. THC and two of the others significantly minimized cell viability and increased apoptosis. The effect of THC was confirmed by in vivo experiments. Cells collected from animals treated with the highest dose of THC showed 77.3% apoptosis ten days after mice were injected with lymphoma cells and two weeks of THC-treatment cured 25% of lymphoma-bearing mice.
“It is possible that the immunosuppressive effects of THC may have interfered with the host’s antitumor immunity, which may account for a lower percentage of cures,” the researchers commented. The research team is conducting murine dose-ranging studies. It was also demonstrated by the research group that three human leukemia and lymphoma cell lines expressed CB2 and not CB1. Three cannabinoids, including THC, induced apoptosis in these cell lines in vitro, and THC demonstrated the same effect when cultured with cells from patients diagnosed with acute lymphoblastic leukemia.

“Recently, however, we identified a human cell line that was resistant,” Dr. Nagarkatti’s team reports. “Further studies are in progress to address whether this cell line lacks physical or functional cannabinoid receptors and/or signaling molecules that trigger apoptosis.” In addition, the research team is “screening a large number of CB2 analogs to identify compounds that are highly efficacious in killing the cancer cells,” Dr. Nagarkatti said. “We are also investigating whether endogenous cannabinoids can exert antitumor activity.”

Physiological Effects Of Marijuana

The U.S. federal government has widely claimed that the potency levels of marijuana have risen anywhere from 10 to 25 times since the 1960s though these claims lack substance.

While testifying in front of the U.S. House Subcommittee on Crime, Director of the National Institute on Drug Abuse Alan Leshner said in 1999, “There’s no question that marijuana, today, is more potent than the marijuana in the 1960s. However, if you were to look at the average marijuana potency which is about 3.5 percent, it’s been relatively stable for the last 20 years. Having said that, it’s very important that what we have now is a wider range of potencies available than we had in the 1970s, in particular.”

However, those supporting legalization of marijuana are of the view that the data is skewed as testing was only conducted on marijuana of specific geographic origins in the 1960s and 1970s and it cannot be believed to be a representative of marijuana potency overall.
It is worthwhile to note that a type of Mexican marijuana contains low levels of THC — 0.4 to 1 percent while typical THC levels range from 0.3 to 4 percent though THC levels are as high as 15 percent in some plants. The potency of marijuana is dependent on many factors, including growing climate and conditions, plant genetics, harvesting and processing. Moreover, female plant varieties of marijuana tend to have higher levels of THC than male varieties.

In order to determine the average potency levels of marijuana, researchers need to evaluate a cross section of cannabis plants that was not done in the 1960s and 1970s.