“The organized tightly regulated signaling relays engaged by the cannabinoid receptors (CBs) and their ligands, G proteins and other effectors, together constitute the endocannabinoid system (ECS). This system governs many biological functions including cell proliferation, regulation of ion transport and neuronal messaging. This review will firstly examine the physiology of the ECS, briefly discussing some anomalies in the relay of the ECS signaling as these are consequently linked to maladies of global concern including neurological disorders, cardiovascular disease and cancer. While endogenous ligands are crucial for dispatching messages through the ECS, there are also commonalities in binding affinities with copious exogenous ligands, both natural and synthetic. Therefore, this review provides a comparative analysis of both types of exogenous ligands with emphasis on natural products given their putative safer efficacy and the role of Δ9-tetrahydrocannabinol (Δ9-THC) in uncovering the ECS. Efficacy is congruent to both types of compounds but noteworthy is the effect of a combination therapy to achieve efficacy without the unideal side-effects. An example is Sativex that displayed promise in treating Huntington’s disease (HD) in preclinical models allowing for its transition to current clinical investigation. Despite the in vitro and preclinical efficacy of Δ9-THC to treat neurodegenerative ailments, its psychotropic effects limit its clinical applicability to treating feeding disorders. We therefore propose further investigation of other compounds and their combinations such as the triterpene, α,β-amyrin that exhibited greater binding affinity to CB1 than CB2 and was more potent than Δ9-THC and the N-alkylamides that exhibited CB2 selective affinity, the latter can be explored towards peripherally exclusive ECS modulation. The synthetic CB1 antagonist, Rimonabant was pulled from market for the treatment of diabetes, however its analogue SR144528 maybe an ideal lead molecule towards this end and HU-210 and Org27569 are also promising synthetic small molecules.” https://www.ncbi.nlm.nih.gov/pubmed/28583800 http://www.sciencedirect.com/science/article/pii/S0163725817301511]]>
Category Archives: Cancer
Study shows non-hallucinogenic cannabinoids are effective anti-cancer drugs
“New research has shown that the non-hallucinogenic components of cannabis could act as effective anti-cancer agents. The anti-cancer properties of tetrahydrocannabinol (THC), the primary hallucinogenic component of cannabis, has been recognised for many years, but research into similar cannabis-derived compounds, known as cannabinoids, has been limited. The study was carried out by a team at St George’s, University of London. It has been published in the journal Anticancer Research. The team, led by Dr Wai Liu and colleagues carried out laboratory investigations using a number of cannabinoids, either alone or in combination with each other, to measure their anti-cancer actions in relation to leukaemia. Of six cannabinoids studied, each demonstrated anti-cancer properties as effective as those seen in THC. Importantly, they had an increased effect on cancer cells when combined with each other. Dr Liu said: “This study is a critical step in unpicking the mysteries of cannabis as a source of medicine. The cannabinoids examined have minimal, if any, hallucinogenic side effects, and their properties as anti-cancer agents are promising. “These agents are able to interfere with the development of cancerous cells, stopping them in their tracks and preventing them from growing. In some cases, by using specific dosage patterns, they can destroy cancer cells on their own. “Used in combination with existing treatment, we could discover some highly effective strategies for tackling cancer. Significantly, these compounds are inexpensive to produce and making better use of their unique properties could result in much more cost effective anti-cancer drugs in future.” The study examined two forms of cannabidiol (CBD), two forms of cannabigerol (CBG) and two forms of cannabigevarin (CBGV). These represent the most common cannabinoids found in the cannabis plant apart from THC.” https://www.sgul.ac.uk/alumni/magazine/study-shows-non-hallucinogenic-cannabinoids-are-effective-anti-cancer-drugs
“Enhancing the Activity of Cannabidiol and Other Cannabinoids In Vitro Through Modifications to Drug Combinations and Treatment Schedules” http://ar.iiarjournals.org/content/33/10/4373.abstract
“Non-hallucinogenic cannabinoids are effective anti-cancer drugs” https://www.sciencedaily.com/releases/2013/10/131014094105.htm“Cannabinoids used in sequence with chemotherapy are a more effective treatment for cancer. New research has confirmed that cannabinoids – the active chemicals in cannabis – are effective in killing leukaemia cells, particularly when used in combination with chemotherapy treatments.” https://www.sgul.ac.uk/news/news-archive/cannabinoids-used-in-sequence-with-chemotherapy-are-a-more-effective-treatment-for-cancer
“Anticancer effects of phytocannabinoids used with chemotherapy in leukaemia cells can be improved by altering the sequence of their administration.” https://www.ncbi.nlm.nih.gov/pubmed/28560402
Anticancer effects of phytocannabinoids used with chemotherapy in leukaemia cells can be improved by altering the sequence of their administration.
“Phytocannabinoids possess anticancer activity when used alone, and a number have also been shown to combine favourably with each other in vitro in leukaemia cells to generate improved activity.
We have investigated the effect of pairing cannabinoids and assessed their anticancer activity in cell line models. Those most effective were then used with the common anti-leukaemia drugs cytarabine and vincristine, and the effects of this combination therapy on cell death studied in vitro.
Results show a number of cannabinoids could be paired together to generate an effect superior to that achieved if the components were used individually.
For example, in HL60 cells, the IC50 values at 48 h for cannabidiol (CBD) and tetrahydrocannabinol (THC) when used alone were 8 and 13 µM, respectively; however, if used together, it was 4 µM. Median-effect analysis confirmed the benefit of using cannabinoids in pairs, with calculated combination indices being <1 in a number of cases.
The most efficacious cannabinoid-pairs subsequently synergised further when combined with the chemotherapy agents, and were also able to sensitise leukaemia cells to their cytotoxic effects.
The sequence of administration of these drugs was important though; using cannabinoids after chemotherapy resulted in greater induction of apoptosis, whilst this was the opposite when the schedule of administration was reversed.
Our results suggest that when certain cannabinoids are paired together, the resulting product can be combined synergistically with common anti-leukaemia drugs allowing the dose of the cytotoxic agents to be dramatically reduced yet still remain efficacious. Nevertheless, the sequence of drug administration is crucial to the success of these triple combinations and should be considered when planning such treatments.”
Single and combined effects of delta9 -tetrahydrocannabinol and cannabidiol in a mouse model of chemotherapy-induced neuropathic pain.
“It has been suggested that the non-psychoactive phytocannabinoid cannabidiol (CBD) can impact the pharmacological effects of delta-9-tetrahydrocannabinol (THC). We tested the hypothesis that CBD and THC would significantly mitigate mechanical sensitivity in a mouse model of paclitaxel-induced neuropathic pain, and that CBD+THC combinations would produce synergistic effects. We also tested the hypothesis that CBD would attenuate oxaliplatin- and vincristine- induced mechanical sensitivity.
KEY RESULTS:
Both CBD and THC alone attenuated mechanical allodynia in mice treated with paclitaxel. Very low ineffective doses of CBD and THC were synergistic when given in combination. CBD also attenuated oxaliplatin- but not vincristine-induced mechanical sensitivity, while THC significantly attenuated vincristine- but not oxaliplatin-induced mechanical sensitivity. The low dose combination significantly attenuated oxaliplatin- but not vincristine-induced mechanical sensitivity.CONCLUSIONS AND IMPLICATIONS:
CBD may be potent and effective at preventing the development of CIPN, and its clinical utility may be enhanced by co-administration of low doses of THC. These treatment strategies would increase the therapeutic window of Cannabis-based pharmacotherapies.” https://www.ncbi.nlm.nih.gov/pubmed/28548225 http://onlinelibrary.wiley.com/doi/10.1111/bph.13887/abstract]]>Systematic review of the potential role of cannabinoids as antiproliferative agents for urological cancers.
“The palliative effects of cannabis sativa (marijuana), which include appetite stimulation, attenuation of nausea and emesis, and pain relief, are well known. The active components of cannabis sativa (cannabinoids) and their derivatives have received growing interest due to their diverse pharmacological activities, such as cell growth inhibition and tumour regression. The aim of this review is to look at the current evidence on the antiproliferative effects of cannabinoids in urological malignancies, including renal, prostate, bladder, and testicular cancers.
The search yielded a total of 93 studies from Medline and PubMed, of which 23 studies were included in the final analysis. To date, there are various in vitro studies elucidating the potential mechanism of action of cannabinoids for urological cancers, along with population-based studies specifically for testicular malignancies. To date, no clinical trials have been conducted for urological cancer patients.
These results demonstrate that the role of endocannabinoids for urological malignancies is an area of active research. Further research is required not only to evaluate the crosstalk between cancer signaling pathways and cannabinoids, but also large randomized clinical studies with urological patients need to be conducted before cannabinoids can be introduced as potential therapeutic options for urological neoplasms.”
https://www.ncbi.nlm.nih.gov/pubmed/28515817 http://www.cuaj.ca/index.php/journal/article/view/4371]]>Compound found in cannabis helps 'shrink' four-year-old's brain tumour
“The family of a four-year-old boy from Nottinghamshire are backing new research into whether a non-psychoactive compound found in cannabis can reduce paediatric brain cancer cells. Experts from Nottingham’s Children’s Brain Tumour Research Centre, at The University of Nottingham, will test Cannabidiol (CBD) for its effects on paediatric brain tumours in youngsters. This research will form part of the pre-clinical phase of the evaluation of the potential use of cannabidiol in paediatric brain tumours” http://www.nottinghampost.com/compound-found-in-cannabis-helps-shrink-four-year-old-s-brain-tumour/story-30307458-detail/story.html
“Scientists plan study after Nottinghamshire boy’s tumour shrinks during cannabis compound treatment” https://nottstv.com/notts-scientists-treating-brain-tumours-with-cannabis-backed-by-four-year-old-boy-with-the-condition/
“Study looks at cannabis ingredient’s ability to help children’s tumours. UK research into cannabidiol (CBD) comes after surge in parents administering it to children without medical advice” https://www.theguardian.com/society/2017/may/02/study-cannabis-cannabidiol-cbd-ability-to-help-children-brain-tumours
“Little boy’s aggressive brain tumour shrinks thanks to CANNABIS compound, his parents claim” https://www.thesun.co.uk/living/3472080/little-boys-aggressive-brain-tumour-shrinks-thanks-to-cannabis-his-parents-claimed/
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“Little boy battling golf ball-sized brain tumour given new lease of life after being given a special OIL” http://www.mirror.co.uk/news/uk-news/little-boy-battling-golf-ball-10347423
“Four-year-old brain cancer patient sees tumour shrink – thanks to cannabis oil” http://metro.co.uk/2017/05/03/four-year-old-brain-cancer-patient-sees-tumour-shrink-thanks-to-cannabis-oil-6613034/
Compound found in cannabis helps ‘shrink’ four-year-old’s brain tumour
“The family of a four-year-old boy from Nottinghamshire are backing new research into whether a non-psychoactive compound found in cannabis can reduce paediatric brain cancer cells.
Experts from Nottingham’s Children’s Brain Tumour Research Centre, at The University of Nottingham, will test Cannabidiol (CBD) for its effects on paediatric brain tumours in youngsters. This research will form part of the pre-clinical phase of the evaluation of the potential use of cannabidiol in paediatric brain tumours” http://www.nottinghampost.com/compound-found-in-cannabis-helps-shrink-four-year-old-s-brain-tumour/story-30307458-detail/story.html
“Scientists plan study after Nottinghamshire boy’s tumour shrinks during cannabis compound treatment” https://nottstv.com/notts-scientists-treating-brain-tumours-with-cannabis-backed-by-four-year-old-boy-with-the-condition/
“Study looks at cannabis ingredient’s ability to help children’s tumours. UK research into cannabidiol (CBD) comes after surge in parents administering it to children without medical advice” https://www.theguardian.com/society/2017/may/02/study-cannabis-cannabidiol-cbd-ability-to-help-children-brain-tumours
“Little boy’s aggressive brain tumour shrinks thanks to CANNABIS compound, his parents claim” https://www.thesun.co.uk/living/3472080/little-boys-aggressive-brain-tumour-shrinks-thanks-to-cannabis-his-parents-claimed/
“Little boy battling golf ball-sized brain tumour given new lease of life after being given a special OIL” http://www.mirror.co.uk/news/uk-news/little-boy-battling-golf-ball-10347423
“Four-year-old brain cancer patient sees tumour shrink – thanks to cannabis oil” http://metro.co.uk/2017/05/03/four-year-old-brain-cancer-patient-sees-tumour-shrink-thanks-to-cannabis-oil-6613034/
Synthesis and antitumor activity of cannabigerol
“Cannabigerol was synthesized and evaluated for its inhibitory activity against mouse skin melanoma cells. Cannabigerol displayed significant antitumor activity.” https://link.springer.com/article/10.1007/BF02976895]]>
The Role of Cannabinoids in the Treatment of Cancer in Pediatric Patients.
“Cannabis has been used in folk medicine to alleviate pain, depression, amenorrhea, inflammation and numerous other medical conditions. In cancer patients specifically, cannabinoids are well known to exert palliative effects; their best-established use is the inhibition of chemotherapy-induced nausea and vomiting, but they are applied also to alleviate pain, stimulate appetite, and attenuate wasting. More recently, cannabinoids have gained special attention for their role in cancer cell proliferation and death. Anti-cancer efficacy of cannabinoids: The ability of cannabinoids to reduce tumor growth was reported for the first time by Munson et al. in 1975. They showed by in vitro and in vivo experiments that several phytocannabinoids, including THC, decreased Lewis lung adenocarcinoma proliferation in a dose-dependent manner. Nevertheless, it was not until the 2000s that the interest in these compounds as anti-cancer agents was renewed, predominantly due to the work of Guzman in gliomas, and the demonstration of cannabinoids’ anti-cancer effects on various types of tumors. The anti-tumorigenic effect of the endo- and phytocannabinoids was demonstrated in several in vitro and in vivo models of a wide variety of adult tumors including glioma, prostate, breast, leukemia, lymphoma, pancreas, melanoma, thyroid, colorectal and hepatocellular carcinoma tumors. Given our positive results, we suggest that non-THC cannabinoids such as CBD might provide a basis for the development of novel therapeutic strategies without the typical psychotropic effects of THC that limit its use in pediatric patients. Overall, the cannabinoids, and specifically the non-psychoactive CBD, may show future promise in the treatment of cancer” https://www.ima.org.il/FilesUpload/IMAJ/0/228/114216.pdf https://www.ima.org.il/imaj/ViewArticle.aspx?aId=4044 https://www.ncbi.nlm.nih.gov/pubmed/28457057]]>
Cannabis Use in Palliative Oncology: A Review of the Evidence for Popular Indications.
“A flowering plant of variegated ingredients and psychoactive qualities, cannabis has long been used for medicinal and recreational purposes. Currently, cannabis is approved in several countries for indications of symptomatic alleviation. However, limited knowledge on the benefits and risks precludes inclusion of cannabis in standard treatment guidelines. This review provides a summary of the available literature on the use of cannabis and cannabinoid-based medicines in palliative oncology. Favorable outcomes are demonstrated for chemotherapy-induced nausea and vomiting and cancer-related pain, with evidence of advantageous neurological interactions. Benefit in the treatment of anorexia, insomnia and anxiety is also suggested. Short- and long-term side effects appear to be manageable and to subside after discontinuation of the drug. Finally, cannabinoids have shown anti-neoplastic effects in preclinical studies in a wide range of cancer cells and some animal models. Further research is needed before cannabis can become a part of evidence-based oncology practice.”
https://www.ncbi.nlm.nih.gov/pubmed/28457056