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New remarkable findings on cannabidiol in cancer therapy

Franjo Grotenhermen

Two studies on cannabidiol (CBD), one from basic research and one observation in people with glioblastoma, a very malignant brain tumour, particularly caught my attention this year. One study from October comes from Mexico. According to this study, CBD acts directly against the mitochondria of leukaemia cells (blood cancer), i.e. the power plants of cancer cells, by upsetting the calcium metabolism of the cells.

The second study comes from Austria. Glioblastoma multiforme grade IV is a fatal disease with an average survival of less than 1.5 years. Maximal resection followed by radiotherapy and chemotherapy has been the mainstay of treatment for many years, although survival is only extended by a few months. In recent years, more and more data from animal experiments with cannabinoids point to their potential role as tumour-inhibiting agents. In the Austrian study, a total of nine patients with brain tumours were described as a case series; all patients received CBD in a daily dose of 400 mg simultaneously with the standard treatment procedure of maximal resection followed by radiochemotherapy. At the time of submission of a recent scientific article, all but one patient were still alive with a median survival time of 22.3 months (range: 7 to 47 months). This is longer than expected.

But back to the basic research from Mexico. The anti-cancer properties of CBD have been demonstrated in tumours in different organs and tissues. Different molecular targets for CBD have been proposed, including cannabinoid receptors and some plasma membrane ion channels. With THC, it has always been relatively clear that the anti-cancer effect is due to activation of cannabinoid receptors. With CBD, however, this is apparently not the case. For example, Mexican scientists have shown that cell lines derived from T-cell acute lymphoblastic leukaemia, but not healthy T-cells, react very sensitively to CBD treatments.

The CBD effect does not depend on cannabinoid receptors or plasma membrane Ca2+-permeable channels. Instead, CBD directly targets mitochondria and alters their ability to deal with Ca2+. At lethal concentrations, CBD causes mitochondrial Ca2+ overload, stable mitochondrial transition pore formation and cell death. Our results suggest that CBD is an attractive candidate to be included in chemotherapeutic protocols for T-ALL treatment.

Study from Israel

Background: Cancer-related cachexia and anorexia syndrome (CACS) is a common phenomenon in cancer patients. Cannabis has been suggested to stimulate appetite, but research on this topic has yielded mixed results. The current study aimed to investigate the effect of dose-controlled cannabis capsules on CACS in advanced cancer patients. Methods: The cannabis capsules used in this study contained two fractions of oil-based compounds. The scheduled treatment was 2 × 10 mg per 24 hours for six months tetrahydrocannabinol (THC) 9.5 mg and cannabidiol (CBD) 0.5 mg. If patients suffered side effects, the dose was reduced to 5 mg × 2 per day (THC 4.75 mg, CBD 0.25 mg). Participants were weighed at each doctor's visit. The main objective of the study was a weight gain of ≥10% from baseline. Results: Of 24 patients who signed the informed consent form, 17 started cannabis capsule treatment, but only 11 received the capsules for more than two weeks. Three of six patients who completed the study period met the primary endpoint. The remaining three patients had stable weights. In the quality of life quaternaries, patients reported less loss of appetite after cannabis treatment (p=0.05). Tumour necrosis factor-α (TNF-α) decreased after cannabis treatment, but without statistical significance. According to patients' self-reports, an improvement in appetite and mood as well as a reduction in pain and fatigue was demonstrated. Conclusions: Despite several limitations, this preliminary study showed a weight gain of ≥10% in 3/17 (17.6%) patients with doses of 5mgx1 or 5mgx2 capsules daily, without significant side effects. The results warrant a larger trial of dose-controlled cannabis capsules in CACS.

DOI: 10.1177/1534735419881498 PMCID: PMC6785913 PMID: 3159579393

Study from Korea

Although oxaliplatin is an effective chemotherapeutic agent for the treatment of colorectal cancer (CRC), patients often develop resistance to it. Therefore, a new strategy for CRC treatment is needed. The purpose of this study was to determine the effect of cannabidiol (CBD), one of the constituents of the cannabis plant, in overcoming oxaliplatin resistance in CRC cells. We established oxaliplatin-resistant cell lines, DLD-1 R and colo205 R, in CRC DLD-1 and colo205 cells. Autophagic cell death was induced when oxaliplatin-resistant cells were treated with both oxaliplatin and CBD. In addition, nitric oxide synthase 3 (NOS3) phosphorylation was increased in oxaliplatin-resistant cells compared to parental cells. Combined treatment with oxaliplatin and CBD reduced phospho-NOS3 levels and nitric oxide (NO) production and led to the production of reactive oxygen species (ROS) by reducing superoxide dismutase 2, an antioxidant in mitochondria that causes mitochondrial dysfunction. Taken together, these results suggest that increased phosphorylation of NOS3 is essential for oxaliplatin resistance. The combination of oxaliplatin and CBD decreased NOS3 phosphorylation, resulting in autophagy by inducing the overproduction of ROS through mitochondrial dysfunction, thereby overcoming oxaliplatin resistance.

DOI: 10.3390/Cancer11060781 PMCID: PMC6627455 PMID: 31195721

Conflict of interest statement: The authors declare no conflict of interest.