“Cannabinoids (CB) like ∆9-tetrahydrocannabinol (THC) can induce cancer cell apoptosis and inhibit angiogenesis.
Here we investigated the role of exogenous and endogenous cannabinoids in mouse skin cancer.
THC significantly inhibited tumor growth of transplanted HCmel12 melanomas in a CB receptor-dependent manner in vivo through antagonistic effects on its characteristic pro-inflammatory microenvironment.
Our results confirm the value of exogenous cannabinoids for the treatment of melanoma…”
“As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Δ9-tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor subtypes.
Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy.
During the last decade, however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers.
In addition to THC, there are many other cannabinoids found in CS, and a majority produces little to no psychoactivity due to the inability to activate cannabinoid receptors.
For example, the second most abundant cannabinoid in CS is the non-psychoactive cannabidiol (CBD). Using animal models, CBD has been shown to inhibit the progression of many types of cancer including glioblastoma (GBM), breast, lung, prostate and colon cancer.
This review will center on mechanisms by which CBD, and other plant-derived cannabinoids inefficient at activating cannabinoid receptors, inhibit tumor cell viability, invasion, metastasis, angiogenesis, and the stem-like potential of cancer cells.
We will also discuss the ability of non-psychoactive cannabinoids to induce autophagy and apoptotic-mediated cancer cell death, and enhance the activity of first-line agents commonly used in cancer treatment.”
“The use of Cannabis for medicinal purposes dates back to ancient times.” http://www.cancer.gov/cancertopics/pdq/cam/cannabis/patient/page1
“Cannabis has been used for medicinal purposes for thousands of years.” http://www.cancer.gov/cancertopics/pdq/cam/cannabis/healthprofessional/page1
“The use of Cannabis for medicinal purposes dates back at least 3,000 years. It came into use in Western medicine in the 19th century and was said to relieve pain, inflammation, spasms, and convulsions.” http://www.cancer.gov/cancertopics/pdq/cam/cannabis/patient/page2
“Cannabis has been shown to kill cancer cells in the laboratory” http://www.cancer.gov/cancertopics/pdq/cam/cannabis/patient/page1
“…cannabinoids may be able to kill cancer cells while protecting normal cells…
A laboratory study of delta-9-THC… showed that it damaged or killed the cancer cells…
A laboratory study of cannabidiol… showed that it caused cancer cell death…” http://www.cancer.gov/cancertopics/pdq/cam/cannabis/patient/page2
“Cannabinoids appear to kill tumor cells but do not effect their nontransformed counterparts and may even protect them from cell death.” http://www.cancer.gov/cancertopics/pdq/cam/cannabis/healthprofessional/page4
“Because cannabinoid receptors, unlike opioid receptors, are not located in the brainstem areas controlling respiration, lethal overdoses from Cannabis and cannabinoids do not occur.” http://www.cancer.gov/cancertopics/pdq/cam/cannabis/healthprofessional/page6
“Glioma stem-like cells (GSCs) correspond to a tumor cell subpopulation, involved in glioblastoma multiforme (GBM) tumor initiation and acquired chemoresistance. Currently, drug-induced differentiation is considered as a promising approach to eradicate this tumor-driving cell population.
Recently, the effect of cannabinoids (CBs) in promoting glial differentiation and inhibiting gliomagenesis has been evidenced. Herein, we demonstrated that cannabidiol (CBD) by activating Transient Receptor Potential Vanilloid-2 (TRPV2) triggers GSCs differentiation activating the autophagic process and inhibits GSCs proliferation and clonogenic capability.
Above all, CBD and carmustine (BCNU) in combination overcome the high resistance of GSCs to BCNU treatment, by inducing apoptotic cell death…
Altogether, these results support a novel mechanism by which CBD inducing TRPV2-dependent autophagic process stimulates Aml-1a-dependent GSCs differentiation, abrogating the BCNU chemoresistance in GSCs.”
“Cannabis has been used in medicine for thousands of years prior to achieving its current illicit substance status.
Cannabinoids, the active components of Cannabis sativa, mimic the effects of the endogenous cannabinoids (endocannabinoids), activating specific cannabinoid receptors, particularly CB1 found predominantly in the central nervous system and CB2 found predominantly in cells involved with immune function.
Delta-9-tetrahydrocannabinol, the main bioactive cannabinoid in the plant, has been available as a prescription medication approved for treatment of cancer chemotherapy-induced nausea and vomiting and anorexia associated with the AIDS wasting syndrome.
Cannabinoids may be of benefit in the treatment of cancer-related pain, possibly synergistic with opioid analgesics.
Cannabinoids have been shown to be of benefit in the treatment of HIV-related peripheral neuropathy, suggesting that they may be worthy of study in patients with other neuropathic symptoms.
Cannabinoids have a favorable drug safety profile, but their medical use is predominantly limited by their psychoactive effects and their limited bioavailability.”
“After anecdotal reports of marijuana’s providing antiemetic activity in cancer chemotherapy patients refractory to standard agents, orally administereddelta 9-tetrahydrocannabinol (THC) was formally studied by a number of investigators.
In six of seven well-controlled studies, orally administered THC was a superior antiemetic agent compared with control agents.
Overall, the benefits of orally administered THC use represent a major advance in antiemetic therapy.”
“delta 9-Tetrahydrocannabinol (THC), prochlorperazine, and placebo were compared.
Nausea was absent in 40 of 55 patients receiving THC, in 8 of 55 patients receiving prochlorperazine, and in 5 of 55 in the placebo group.
THC appeared to be more efficacious in controlling the emesis associated with cyclophosphamide, 5-fluorouracil, and doxorubicin and less so for nitrogen mustard and the nitrosourea.
THC appears to offer significant control of nausea in most patients and exceeds by far that provided by prochlorperazine.”
“Fifty-three patients receiving antineoplastic chemotherapy who had experienced severe nausea and vomiting refractory to standard antiemetic agents were treated with delta 9-tetrahydrocannabinol (THC).
These patients were given THC 8 to 12 hours before, during, and for 24 hours after chemotherapy.
Ten patients (19%) had no further nausea and vomiting; 28 (53%) had at least a 50% reduction of nausea and vomiting compared to previous courses with the same agents.
We suggest that, since THC is a useful antimetic agent in patients having refractory chemotherapy-induced vomiting, existing restrictions prohibiting its therapeutic use should promptly be eased.”
“Hepatocellular carcinomas will emerge as a major form of malignancy in the coming decades.
When these tumors are in advanced stages, few therapeutic options are available.
Therefore, it is essential to search for new treatment modalities to fight this disease.
Evaluate the possible protective and therapeutic effects of Cannabis extract on dimethylnitrosamine (DMNA)-induced hepatocarcinogenicity in mice.
The protective effect of cannabis extract is more pronounced in group taking cannabis before DMNA.
Cannabinoids might exert their anti-tumor effects by the direct induction of apoptosis and can decrease telomerase activity by inhibiting the expression of the TERT gene…”
http://www.sciencedirect.com/science/article/pii/S209050681400027X
“While the global incidence of cutaneous melanoma is increasing, survival rates for patients with metastatic disease remain less than 10%. Novel treatment strategies are therefore urgently required, particularly for patients bearing BRAF/NRAS wildtype tumours.
Targeting autophagy is a novel means to promote cancer cell death in chemotherapy-resistant tumours and the aim of the present study was to test the hypothesis that cannabinoids promote autophagy-dependent apoptosis in melanoma.
Treatment with Δ9-Tetrahydrocannabinol (THC) resulted in the activation of autophagy, loss of cell viability and activation of apoptosis, while co-treatment with chloroquine or knockdown of Atg7, but not Beclin-1 or Ambra1, prevented THC-induced autophagy and cell death in vitro.
Administration of Sativex-like (a laboratory preparation comprising equal amounts of THC and cannabidiol (CBD)) to mice bearing BRAF wildtype melanoma xenografts substantially inhibited melanoma viability, proliferation and tumour growth paralleled by an increase in autophagy and apoptosis compared to standard single agent temozolomide.
Collectively our findings suggest THC activates non-canonical autophagy-mediated apoptosis of melanoma cells, suggesting cytotoxic autophagy induction with Sativex warrants clinical evaluation for metastatic disease.”