“Significant alterations of a balance in the cannabinoid system between the levels of endogenous ligands and their receptors occur during malignant transformation in various types of cancer, including gliomas. Cannabinoids exert anti-proliferative action in tumor cells. Induction of cell death by cannabinoid treatment…”
“Normal tissue toxicity limits the efficacy of current treatment modalities for glioblastoma multiforme (GBM).
We evaluated the influence of cannabinoids on cell proliferation, death, and morphology of human GBM cell lines and in primary human glial cultures, the normal cells from which GBM tumors arise. The influence of a plant derived cannabinoid agonist, Delta(9)-tetrahydrocannabinol Delta(9)-THC), and a potent synthetic cannabinoid agonist, WIN 55,212-2, were compared using time lapse microscopy.
We discovered that Delta(9)-THC decreases cell proliferation and increases cell death of human GBM cells more rapidly than WIN 55,212-2. Delta(9)-THC was also more potent at inhibiting the proliferation of GBM cells compared to WIN 55,212-2. The effects of Delta(9)-THC and WIN 55,212-2 on the GBM cells were partially the result of cannabinoid receptor activation.
The same concentration of Delta(9)-THC that significantly inhibits proliferation and increases death of human GBM cells has no significant impact on human primary glial cultures. Evidence of selective efficacy with WIN 55,212-2 was also observed but the selectivity was less profound, and the synthetic agonist produced a greater disruption of normal cell morphology compared to Delta(9)-THC.”
https://www.ncbi.nlm.nih.gov/pubmed/16078104
https://link.springer.com/article/10.1007%2Fs11060-004-5950-2
“Marijuana and its derivatives have been used in medicine for many centuries, and currently there is a renewed interest in the study of the therapeutic effects of cannabinoids…”
“Recently, cannabinoids (CBs) have been shown to possess antitumor properties. Because the psychoactivity of cannabinoid compounds limits their medicinal usage, we undertook the present study to evaluate the in vitro antiproliferative ability of cannabidiol (CBD), a nonpsychoactive cannabinoid compound, on U87 and U373 human glioma cell lines…”
“…the nonpsychoactive CBD was able to produce a significant antitumor activity both in vitro and in vivo, thus suggesting a possible application of CBD as an antineoplastic agent.”
“In conclusion, a cannabinoid-based therapeutic strategy for neural diseases devoid of undesired psychotropic side effects could find in CBD a valuable compound in cancer therapies along with the perspective of evaluating a synergistic effect with other cannabinoid molecules and/or with other chemotherapeutic agents as well as with radiotherapy. Whatever the precise mechanism underlying the CBD effects, the present results suggest a possible application of CBD as a promising, nonpsychoactive, antineoplastic agent.”
“Cannabinoids, the active components of Cannabis sativa L. (marijuana), and their derivatives exert a wide array of effects by activating their specific G protein-coupled receptors CB1 and CB2, which are normally engaged by a family of endogenous ligands–the endocannabinoids. Marijuana and its derivatives have been used in medicine for many centuries, and there is currently a renaissance in the study of the therapeutic effects of cannabinoids. Today, cannabinoids are approved to palliate the wasting and emesis associated with cancer and AIDS chemotherapy, and ongoing clinical trials are determining whether cannabinoids are effective agents in the treatment of pain, neurodegenerative disorders such as multiple sclerosis, and traumatic brain injury . In addition, cannabinoid administration to mice and/or rats induces the regression of lung adenocarcinomas, gliomas, thyroid epitheliomas, lymphomas, and skin carcinomas. These studies have also evidenced that cannabinoids display a fair drug safety profile and do not produce the generalized cytotoxic effects of conventional chemotherapies, making them potential antitumoral agents.”
“Gliomas are one of the most malignant forms of cancer, resulting in the death of affected patients within 1–2 two years after diagnosis. Current therapies for glioma treatment are usually ineffective or just palliative. Therefore, it is essential to develop new therapeutic strategies for the management of glioblastoma multiforme, which will most likely require a combination of therapies to obtain significant clinical results. In line with the idea that anti-VEGF treatments constitute one of the most promising antitumoral approaches currently available, the present laboratory and clinical findings provide a novel pharmacological target for cannabinoid-based therapies.”
“The use of cannabinoids in medicine is limited by their psychoactive effects mediated by neuronal CB1 receptors. Although these adverse effects are within the range of those accepted for other medications, especially in cancer treatment, and tend to disappear with tolerance on continuous use, it is obvious that cannabinoid-based therapies devoid of side-effects would be desirable. As glioma cells express functional CB2 receptors, we used a selective CB2 ligand to target the VEGF pathway. Selective CB2 receptor activation in mice also inhibits the growth and angiogenesis of skin carcinomas.”
“Cannabinoids inhibit tumor angiogenesis…”
“Because blockade of the VEGF pathway constitutes one of the most promising antitumoral approaches currently available, the present findings provide a novel pharmacological target for cannabinoid-based therapies.”
“One of the most devastating forms of cancer is glioblastoma multiforme (grade IV astrocytoma), the most frequent class of malignant primary brain tumours. Current standard therapeutic strategies for the treatment of glioblastoma multiforme (surgical resection and focal radiotherapy) are only palliative…”
“The hemp plant Cannabis sativa L. produces approximately 60 unique compounds known as cannabinoids, of which Δ9-tetrahydrocannabinol (THC) is the most important owing to its high potency and abundance in cannabis. Δ9-Tetrahydrocannabinol exerts a wide variety of biological effects by mimicking endogenous substances – the so-called endocannabinoids – that bind to and activate specific cell surface receptors. cannabinoids have been proposed as potential antitumoral agents owing to their ability to inhibit the growth and angiogenesis of various types of tumour xenografts in animal models.”
“Here we report the first clinical study aimed at assessing cannabinoid antitumoral action, specifically a pilot phase I trial in which nine patients with recurrent glioblastoma multiforme were administered THC intratumoraly. The patients had previously failed standard therapy (surgery and radiotherapy) and had clear evidence of tumour progression. The primary end point of the study was to determine the safety of intracranial THC administration… Cannabinoid delivery was safe and could be achieved without overt psychoactive effects…. The fair safety profile of THC, together with its possible antiproliferative action on tumour cells reported here and in other studies, may set the basis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids.”
“Madrid, Spain: THC administration decreases recurrent glioblastoma multiforme (GBM) tumor growth in humans, according to the findings of the first-ever clinical trial assessing cannabinoids’ anti-tumor action.
Investigators at Complutense University in Spain administered THC intratumorally in nine patients diagnosed with recurrent GBM, an extremely rapid and lethal form of brain tumor. Patients in the study had previously failed standard therapy (surgery and radiotherapy) and had clear evidence of tumor progression. THC treatment was associated with reduced tumor cell proliferation in two subjects, authors reported.
Investigators did not determine whether THC positively impacted patients’ survival, though they did conclude that cannabinoid therapy does not facilitate cancer growth or decrease patients’ life expectancy. Median survival of the cohort from the beginning of cannabinoid administration was 24 weeks, and two patients survived for approximately one year. Survival for GBM patients following diagnosis is typically six to twelve months.
Researchers speculated that newly diagnosed glioma patients may respond more favorably to cannabinoid-based therapies.
Investigators also reported that THC demonstrated significant anti-proliferative activity on human GBM cells in culture.
“The fair safety profile of THC, together with its possible anti-proliferative action on tumor cells reported here and in other studies, may set the basis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids,” investigators concluded.
In 2005, investigators at the California Pacific Medical Center Research Institute in San Francisco reported that THC selectively decreases the proliferation of malignant cells and induces cell death in human GBM cell lines. Healthy cells in the study were unaffected by THC administration.
Separate preclinical studies indicate that cannabinoids and endocannabinoids can stave off tumor progression and trigger cell death in other cancer cell lines, including breast carcinoma, prostate carcinoma, colectoral carcinoma, skin carcinoma, and pancreatic adenocarcinoma.”
http://norml.org/news/2006/07/13/cannabinoids-curb-brain-tumor-growth-first-ever-patient-trial-shows
“Medical marijuana is gaining acceptance, but could it even help kids? Dr. William Courtney has seen it happen, and on Friday, told HuffPost Live host Alyona Minkovski about it. Saying he was “quite a skeptic 5 or 6 years ago”, Dr. Courtney continued that “my youngest patient is 8 months old, and had a very massive centrally located inoperable brain tumor.” The child’s father pushed for non-traditional treatment utilizing cannabis.
“They were putting cannabinoid oil on the baby’s pacifier twice a day, increasing the dose… And within two months there was a dramatic reduction, enough that the pediatric oncologist allowed them to go ahead with not pursuing traditional therapy.”
The tumor was remarkably reduced after eight months of treatment. Dr. Courtney pointed out that the success of the cannabis approach means that “this child, because of that, is not going to have the long-term side effects that would come from a very high dose of chemotherapy or radiation… currently the child’s being called a miracle baby, and I would have to agree that this is the perfect response that we should be insisting is frontline therapy for all children before they launch off on all medications that have horrific long term side effects.””
http://www.huffingtonpost.com/2012/12/01/cannabis-for-infants-brai_n_2224898.html
“A detailed description of the endocannabinoid system is beyond the scope of this paper. Thus, in this section we briefly describe those components of the endocannabinoid system that act as targets for the pharmacological interventions aimed at determining the activity of the endocannabinoid system.”
“The term “endocannabinoid system” refers to the recently discovered neuromodulator system comprising cannabinoid receptors (which represent the receptors of Tetrahydrocannabinol (THC), the major active component of cannabis) and their endogenous ligands.”
“To date, two types of cannabinoid receptors have been identified: CB1 and CB2 receptors. These receptors belong to the superfamily of G protein coupled receptors, the CB1 receptor is widely distributed in the terminals of neurons, while the CB2 receptor is extensively expressed throughout the immune system. However, it has recently been reported that these receptors are present also in the brain.”
“No clinical trials carried out using cannabinoids in the treatment of affective disorders have been published to date, although anecdotal reports have described both antidepressant and antimanic properties of cannabis.”
“Indeed, pharmacological manipulations of the endocannabinoid system have elicited antidepressant-like effects in animal models of depression. Moreover, some animal models of depression seem to be associated to alterations in the endocannabinod system.”
“Although no clinical trials performed using cannabinoids in the treatment of affective disorders have been published to date, anecdotal reports have described both antidepressant and antimanic properties of cannabis”
“With advances in basic and clinical neuroscience, many gaps have appeared in the traditional monoamine theory of depression that have led to reformulation of the hypotheses concerning the neurobiology of depression. The more recent hypotheses suggest that melancholic depression is characterized by central glucocorticoid resistance that results in hypercortisolemia, which in turn leads to down-regulation of neurotrophins and subsequent neurodegeneration. Examining the neurobiology of depression from this perspective suggests that the endocannabinoid system may play a role in the etiology of melancholic depression. Specifically, pharmacological and genetic blockade of the cannabinoid CB1 receptor induces a phenotypic state that is analogous to melancholic depression, including symptoms such as reduced food intake, heightened anxiety, increased arousal and wakefulness, deficits in extinction of aversive memories and supersensitivity to stress. These similarities between melancholic depression and an endocannabinoid deficiency become more interesting in light of recent findings that endocannabinoid activity is down-regulated by chronic stress and possibly increased by some antidepressant regimens. We propose that an endocannabinoid deficiency may underlie some of the symptoms of melancholic depression, and that enhancement of this system may ultimately be a novel form of pharmacotherapy for treatment-resistant depression.”
“Pain has a negative impact on the quality of life in cancer patients…
…we hypothesized that a cannabinoid receptor agonist might be a novel therapy for cancer pain. Taking into consideration the side effects of a CB1 receptor agonist (which limits their clinical application), we chose a CB2 receptor agonist to investigate its effect in cancer pain…
Recent clinical trials have demonstrated that cannabinoids may have significant positive effects in refractory chronic and cancer pain. The cannabinoids are thought to exert most of their effects by binding to G protein–coupled cannabinoid receptors, which include 2 cloned metabotropic receptors: cannabinoid (CB)1 and CB2…
CONCLUSION: These data indicated that intrathecal administration of cannabinoid receptor agonists might relieve cancer pain… These results also suggested that cannabinoids might be a useful alternative or adjunct therapy for relieving cancer pain.
The use of a CB2 receptor agonist could be a novel option for treatment of cancer pain.”