Cannabinoids are in wide use for cancer pain, and for associated body-wasting and treatment nausea. For actual anti-oncogenic effects, research is still in its infancy. Pre-clinical laboratory work has shown strong enough grounds for optimism, though, that human trials are now beginning.
We report here on the first study of this kind, on Objective Clinical Responses of Cancer Patients to Pharmaceutical-grade Synthetic Cannabidiol (Enyon J, Liu W, Dalgleish A, Anticancer Research 38(10), 5831-5835, 2018). This was undertaken as a collation of routine data from 119 patients in treatment for a variety of solid-tumor cancersover a four-year period. Clinical responses were seen in 92% of the cases. These included reduction in tumor size and decrease in circulating tumor cells. No side-effects associated with cannabidiol were observed.
A number of cannabinoids are known to be able to impede cancer cell growth, induce apoptosis and autophagy, and inhibit angiogenesis, probably by binding to cannabinoid receptors, in a range of tissue types. Cannabidiol (CBD), which has a low affinity for the canonical cannabinoid receptors, is known to induce cell death directly, and be capable of interfering with intracellular signaling. Alterations to genetic pathways such as PI3K/AKT/mTOR and ERK suggest that CBD can modulate cancer cells’ response to non-CBD treatments. Combining CBD with conventional chemotherapy, for example, such as cytarabine and vincristine, can enhance efficacy. In certain leukemia cell lines, CBD can change the expression of the cyclin-dependent kinase inhibitor p21waf1. The sequence in which these drugs are administered can also influence overall activity.
In this study, patients were given synthetic, pharmaceutical-grade CBD, in oily drops at 5% (w/v) in 20 ml bottles. Each drop contained 1 mg of synthetic CBD in neutral oil. Of the 119 registered patients, 28 were given CBD as the only treatment. A third of these patients had already been taking cannabis oil extracted from the cannabis plant that had been bought on the Internet, with no beneficial response. The majority of the patients were assessed using a circulating tumor cell test before and after treatment; some patients, however, as a matter of normal treatment course, had relevant scans. CBD was administered on three days on and three days off basis. The average dose was 10 mg twice a day. For increased tumor mass, the dose was increased, in some cases up to 30 drops twice a day (30 mg). In a number of cases where stable disease was present, the dose was reduced to five drops twice a day (5 mg). In some cases, Sativex, which is licensed for use in multiple sclerosis, was used in conjunction with CBD as a source of THC, which synergises with CBD. A fraction of the dose used for multiple sclerosis was used. Two sprays of Sativex were given twice a day in a three days on and three days off pattern, as in the case of pharmaceutical-grade synthetic CBD. The minimum duration of treatment required for CBD was six months, but many continued for longer.
Results are tabulated below. There were clinical responses in 92% of the cases, ranging variously through tissue type and concomitant therapy.
Clear objective evidence of potential efficacy was sought where no other treatment option was available. The most impressive case was a five-year-old boy with an anaplastic ependymoma. He had undergone all standard treatments, with surgery, chemotherapy, and radiotherapy. CBD treatment started in February 2016. A scan carried out in December 2016 showed that tumor volume had decreased by ~60%. Further scans, carried out since December 2016, continue to show stable disease. CBD was the only treatment.
Another impressive case was a 50-year-old patient with progressive tanycytic ependymoma Grade 2, diagnosed in June 2013, and treated with biopsy and radical radiotherapy, which was completed on 3rd June 2015. He refused chemotherapy, and had no further treatment options. He started on pharmaceutical-grade synthetic CBD in July 2016 at a dose of 10 drops twice a day, three days on and three days off (10 mg). Prior to this he had been taking, for some time, metformin, mebendazole, doxycycline and atorvastatin. In January 2017 a repeat scan showed tumor reduction. At that point the patient stopped taking pharmaceutical-grade synthetic CBD and switched to cannabis oil extract obtained from an internet website, after which scans showed doubling of tumor size and more growth down the brain stem. Throughout, he continued to take the metformin, atorvastatin, doxycycline and mebendazole.
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The foregoing is a report on trends and developments in the cannabinoid industry. No product described herein is intended to diagnose, treat, cure or prevent any disease or syndrome.
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