Nearly 50 years ago, cannabinoids derived from medical cannabis - specifically THC, CBN and CBD - first showed anti-cancer activity in mice. Since then, many researchers have studied the ability of endogenous, plant-derived and synthetic cannabinoids to cause cancer cell death in vitro (in vivo) and to inhibit tumour growth in animals.

However, due in large part to the federal government's ban on cannabis, promising research on the anti-cancer effects of cannabinoids - anecdotal reports of cannabis oil extracts leading to cancer remission - has not yet been translated into clinical trials. Much work needs to be done to establish that medical cannabis and cannabinoids can fight human cancer, including as an adjunct to other therapies such as chemotherapy and radiotherapy, and to incorporate their use into treatment regimens.

With 1.9 million people diagnosed with cancer in the US each year, this apparent disconnect between labs and clinics is another troubling by-product of the war on drugs. While it is true that medical marijuana is becoming more widely accepted for its ability to treat cancer symptoms and the side effects of chemotherapy, it is unlikely that the field of research will change significantly until the federal government cancels/reschedules plans to grow the plant. In the meantime, pre-clinical work continues. Here are five other papers published in recent weeks, with encouraging overall results

CBD and Lung Cancer Stem Cells.

CBD dose-dependently reduces the viability of lung cancer cell populations and induces cell death. Cannabidiol (CBD) has previously been shown to fight several different types of cancer cells, but its effects on cancer stem cells - a small subpopulation of self-renewing cells that drive tumour initiation and progression - are less well known. In a paper published in November 2021 in the journal Pharmaceuticals, Danish researchers tested the effects of CBD on hard-to-treat lung cancer stem cells and cancer cells. The authors wrote: "We found that CBD reduced the viability of both cell populations in a dose-dependent manner and induced cell death." " However, the exact mechanism of CBD in cancer stem cells remains to be elucidated and appears to be related to the cellular environment."

CBD combined with chemotherapy

Three researchers from the Ontario Veterinary College in Canada conducted a study to examine the ability of CBD in treating canine uroepithelial carcinoma, the most common form of bladder cancer in dogs, both alone and in combination with in vitro chemotherapy. The authors write that in veterinary practice, treatment with chemotherapy alone causes most dogs to die of the disease within a year. In their findings, published in the journal Public Library of Science - General, CBD itself reduced cell viability and induced cell death in canine urinary tract epithelial cells, which was even more effective when combined with chemotherapy. "Further in vivo studies are warranted and clinical trials are necessary to investigate how best to implement CBD-chemotherapy combinations in a clinical setting," the authors conclude - a familiar refrain that could be equally applicable to human cancers.

Cannabinoids for chemotherapy-induced neuropathy.

Peripheral neuropathy is a side effect of chemotherapy drugs and is experienced by nearly 70% of patients within the first month of treatment. It is caused by nerve damage and manifests as weakness, numbness and pain in the hands and feet. In a comprehensive cancer treatment paper published in November 2021, a group of researchers at the Mayo Clinic in Minnesota and Sutter Health in California said that topical creams containing THC and/or CBD could help patients suffering from this disease. Their paper reviewed the cases of 26 cancer patients who tried topical cannabinoid treatments, 22 of whom reported remission of their flares. The data, the authors write, "provide a theoretical basis for a randomised placebo-controlled trial using a standardised product to determine the actual efficacy of such treatments."

The use of synthetic CBD analogues together with the chemotherapeutic drug paclitaxel provided long-term relief of neuropathic pain in mice.

Two weeks later, another paper in the journal Neurotherapeutics showed that using a synthetic CBD analogue called PECS-101 together with the chemotherapy drug paclitaxel provided long-term relief of mechanical and cold pain (a model of neuropathic pain) in mice. Further analysis by Brazilian researchers showed that this effect was mediated by the PPARy nuclear receptor, a known target of CBD.

Cannabinoids for cancer-related cachexia

In a review published in the Journal of Cachexia, Sarcopenia, and Muscle, a group of researchers at University College London evaluated the potential of cannabinoids to treat cancer-related cachexia, which is characterised by involuntary weight loss and anorexia. The authors wrote: "Previous research supports the use of cannabinoids for the treatment of cachexia in other chronic diseases, including HIV and multiple sclerosis." However, data on interventions in cancer populations are lacking. A literature search found 10 studies: four randomised controlled trials and six non-randomised studies. A meta-analysis of these limited studies did not show any statistically significant benefit from the use of cannabinoids, but patient-reported observations in the non-randomised studies did indicate an improvement in appetite.

Inhibition of endogenous cannabinoid degrading enzymes

If preclinical studies suggest that cannabinoids can inhibit tumour cell proliferation, invasion and metastasis (the spread of tumours to new sites) and support the death and degradation of cancer cells, could approaches aimed at increasing levels of self-cannabinoids or endogenous cannabinoids also be used as anti-cancer treatments? This was the central question explored in a recent review article in the journal Cancer. "In addition to the direct activation of cannabinoid receptors by exogenous application of the corresponding agonists, another strategy is to activate these receptors by increasing endogenous cannabinoid levels at the corresponding pathological hotspots," the German authors suggest. They went on to review the findings of previous studies showing that inhibition of FAAH and MAGL, the THC-like endogenous cannabinoid anandamide and 2-AG degrading enzymes, was associated with reduced tumour development and spread. Modulation of enzyme activity to improve endogenous cannabinoid tone has been the subject of research interest and topic of various therapeutic outcomes, but little progress has been made in clinical studies.