Cannabis-derived cannabinoids – specifically THC, CBN, and CBD – were first shown to exhibit anti-cancer activity in mice nearly 50 years ago.1 Since then, many researchers have investigated the ability of endogenous, plant-derived, and synthetic cannabinoids to cause cancer-cell death in vitro (outside a living organism) and inhibit tumor growth in animals.
However, due largely to federal prohibition of cannabis, promising research into the anti-carcinogenic effect of cannabinoids – backed by anecdotal accounts of cancer remission induced by cannabis oil extracts – have not yet been translated into clinical trials. Much work still needs to be done to establish that cannabis and cannabinoids can fight cancer in humans, including as an adjunct to other therapies like chemo and radiation, and to integrate their use into treatment protocols.
With 1.9 million Americans diagnosed with cancer every year, this glaring disconnect between the lab and the clinic is another troubling byproduct of the war on drugs. While it’s true that cannabis has been more widely accepted for its ability to treat cancer symptoms and the side effects of chemotherapy, until the plant is de/rescheduled federally, dramatic changes in the research landscape are unlikely. Meanwhile, preclinical work continues. Below are five more papers published in recent weeks, with generally encouraging results.
CBD & lung cancer stem cells
Cannabidiol (CBD) has previously been shown to fight several different types of cancer cells, but its effect on cancer stem cells2 – a small subpopulation of self-renewing cells that drive tumor initiation and progression – is less well known. A pair of Danish researchers sought to learn more. In a paper published in the journal Pharmaceuticals3 in November 2021, they describe a study in which they tested CBD’s effect on difficult-to-treat lung cancer stem cells and cancer cells. “We found that CBD decreased viability and induced cell death in both cell populations” in a dose-dependent manner, the authors write. “However, the exact mechanisms of CBD in cancer stem cells remain to be elucidated and seem to be cell context-dependent.”
CBD combined with chemotherapy
Three researchers based at Canada’s Ontario Veterinary College conducted a study of CBD’s ability to treat canine urothelial carcinoma, the most common form of canine bladder cancer, both alone and in combination with chemotherapy in vitro. In veterinary practice, treatment with chemo alone leads to most dogs succumbing to the disease within a year, the authors write. In their study, whose findings were published in the journal PLOS One4, CBD reduced cell viability and induced cell death in canine urothelial cells on its own – and worked even better when paired with chemotherapy. “Further studies in vivo are warranted, and clinical trials are necessary to investigate how best to implement CBD-chemotherapy combination treatments in a clinical setting,” the authors conclude – in a familiar refrain that could apply just as well to human cancers.
Cannabinoids for chemotherapy-induced neuropathy
Peripheral neuropathy is a side effect of chemotherapy drugs experienced by nearly 70 percent of patients within the first month of treatment. Caused by nerve damage, it manifests as weakness, numbness, and pain in the hands and feet. According to a group of authors with the Mayo Clinic in Minnesota and Sutter Health in California in a November 2021 Integrative Cancer Therapies paper5, topical creams containing THC and/or CBD could help patients experiencing this condition. Their paper reviews the cases of 26 cancer patients who tried topical cannabinoids to treat the condition, 22 of whom reported that they found relief. This data “provides the rationale for proceeding with a randomized placebo-controlled trial using a standardized product to determine the actual efficacy of such treatment,” the authors write.
Two weeks later, another paper in the journal Neurotherapeutics6 indicated that administering a synthetic analog of CBD named PECS-101 alongside the chemotherapy drug paclitaxel provided long-lasting relief of mechanical and cold allodynia (a model of neuropathic pain) in mice. Further analysis by the Brazil-based researchers suggested that this effect was mediated by PPARy nuclear receptors, a known target of CBD.
Cannabinoids for cancer-associated cachexia
In a review in the Journal of Cachexia, Sarcopenia, and Muscle7, a group of researchers with University College London assess the potential of cannabinoids to treat cancer-associated cachexia, a condition characterized by involuntary weight loss and anorexia. “Previous studies support the use of cannabinoids for cachexia in other chronic diseases including HIV and multiple sclerosis,” the authors write – but data is lacking on this intervention in cancer populations. A literature search turned up ten studies: four randomized controlled trials and six non-randomized studies. Meta-analyses of these limited studies did not reveal any statistically significant benefits of cannabinoid use, but anecdotal, patient-reported observations from the non-randomized studies did indicate improvements in appetite.
Inhibiting endocannabinoid-degrading enzymes
If preclinical research shows that cannabinoids can suppress tumor cell proliferation, tumor invasion, and metastasis (the spread of cancerous tumors to new sites), and support cancer cell death and degradation, then could approaches aimed at boosting levels of one’s own cannabinoids, or endocannabinoids, also serve as an anti-cancer therapy? That is the core question explored in a recent review article in the journal Cancers8. “In addition to the direct activation of cannabinoid receptors through the exogenous application of corresponding agonists, another strategy is to activate these receptors by increasing the endocannabinoid levels at the corresponding pathological hotspots,” the Germany-based authors suggest. They proceed to review findings from previous studies showing that inhibition of the enzymes FAAH and MAGL, which degrade the THC-like endocannabinoids anandamide and 2-AG, is associated with a reduction in tumor development and spread. Modulating enzymatic activity to improve endocannabinoid tone has been a subject of ongoing interest for a variety of therapeutic outcomes, but little headway has been made in terms of clinical advances.
Nate Seltenrich, an independent science journalist based in the San Francisco Bay Area, covers a wide range of subjects including environmental health, neuroscience, and pharmacology. Copyright, Project CBD. May not be reprinted without permission.
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