Article History

Published: Sat 19, Sep 2020
Received: Tue 18, Aug 2020
Accepted: Mon 07, Sep 2020

View PDF

Download PDF

Abstract

This report is an observational study of objective responses of Breast Cancer patients to Pharmaceutical Grade Synthetic Cannabidiol. There were 29 total cases out of which 27 showed a clinical response.

1. Introduction

The use of a whole variety of cannabis oils of questionable quality, none of which were pharmaceutical grade, and all bought on the Internet has been a matter of routine by cancer patients, especially breast cancer patients. No anticancer effect of these oils has been noted [1-3]. Currently, it is illegal to buy cannabis oil on the internet as the Medicines and Health Regulatory Agency has defined CBD as a medicinal product, which can only be prescribed under the Pharmaceutical Specials scheme, as it is not currently a licensed medicinal product [4]. Cannabidiol targets CB1 and CB2 receptors, which have increased expression in breast cancer as compared to normal breast tissue [5], generally speaking, CB1 and CB2 receptors are upregulated in tumor tissue [6, 7]. Cannabidiol targets CB1 and CB2 cannabinoid receptors.

The phytocannabinoids are a group of chemicals extracted from the cannabis plant. A number of them are able to impede cancer cell growth, induce apoptosis and autophagy, and inhibit angiogenesis. The most widely known phytocannabinoid is Δ9-tetrahydrocannabinol (THC), and although it possesses these anticancer effects, it is also psychoactive, which has arguably hampered its clinical development. It is thought that these actions are mediated, in part, by binding to cannabinoid receptors that are expressed on a number of tissue types [8]. As one type of the receptor is found exclusively on brain cells, studies using THC have focused on this tissue type. In vitro data were promising and, in 2016, a pilot clinical study in patients with glioblastoma multiforme indicated THC was safe; however, no clear activity was reported [9]. The dosages were possibly on the conservative side, to minimise psychoactivity that would naturally restrict the use of THC as drug.

Of the 80+ phytocannabinoids, THC is possibly the only one to exhibit this psychoactivity. More recently, studies have diverted away from THC and focussed on other cannabinoids. The next most abundant compound is cannabidiol (CBD), which has a low affinity for the canonical cannabinoid receptors. In contrast to THC, in its pure state, according to the World Health Organisation, CBD did not have abuse potential and caused no harm [10]. Studies have shown that in addition to being able to induce cell death directly, it is also capable of interfering with intracellular signalling [11]. Alterations to pathways such as the PI3K/AKT/mTOR and the ERK suggests that CBD can modify the way certain cancer cells react to other treatments.

Indeed, studies have shown that combining CBD with conventional chemotherapy such as cytarabine and vincristine can lead to enhanced anticancer activity through modifications to these signalling pathways [12, 13]. Furthermore, the sequence in which these drugs are administered can also influence overall activity. Studies have also indicated that in certain leukaemia cell lines, CBD can increase the expression of the cyclin-dependent kinase inhibitor p21 [13]. This increased level appears to be maintained by CBD, which inadvertently impedes cell death. Cytotoxicity could be restored in these cells if the treatment regimen was altered to allow for a temporary cessation of exposure to CBD. Thus, the general efficacy of CBD may also be altered by adapting treatment protocols that include “drug-free” phases [13].

The findings from a number of studies designed to examine the role of cannabinoids in the management of cancer symptoms varied [14]. The most recent prospective analysis of nearly 3,000 patients using medical marijuana showed that a large proportion of patients reported improvement in their condition [15]. Patients often feel that conventional therapies are not working for them, and so they search the internet for alternative medicines. It is here that they find stories about cannabis working in patients with cancer, and understandably feel it is a route for them. The cannabis products they use vary and can be in the form of whole-plant extracts or purified oils; however, whatever the source, they self-prescribe dosages. A number of anecdotal positive responses have been reported, which sustains the interest in this type of medication.

We have previously reported on objective clinical responses in a variety of cancer patients using pharmaceutical grade synthetic cannabidiol [16]. Over five years ago, we decided to assess the potential use of pharmaceutical grade synthetic cannabidiol in breast cancer patients. Some of the cases reported here were presented in our previous paper [16].

2. Materials and Methods

Patients were given synthetic pharmaceutical grade synthetic cannabidiol (PGSC) (STI Pharmaceuticals), under the Pharmaceutical Specials scheme in oily drops at 5% (w/v) in 20ml bottles. Each drop contains 1mg of synthetic CBD in neutral oil. This was prescribed on an informed consent basis. Of the 32 patients described here in this observational study, every patient in this study signed an informed consent allowing anonymous use of their data. Medicinal use of synthetic cannabinoids has been extensively reviewed in a recent paper [17]. CBD was administered on a three days on and three days off basis, which clinically is found to be more effective than giving it as a continuous dose. The average dose was 10mg twice a day. For increased tumor mass, the dose was increased, in some cases up to 30 drops (30mg). We clearly demonstrated that there is a dose-response relationship in the treatment of cancer using pharmaceutical grade synthetic cannabidiol. In a number of cases where there was stable disease, the dose was reduced to 5 drops (5mg) twice a day. We assessed the majority of patients using circulating tumor cells tests [18, 19]; some decided not to have this.

TABLE 1: Outcomes-breast cancer.

3. Results

The results for our breast cancer cohort treated with PGSC is reported here in significantly more detail than in our previously published study [16]. This has been in response to many requests for more details on outcomes. The results are shown in (Tables 1 & 2). PGSC, as there was an absence of significant side effects. The only noted side effects were some degree of drowsiness in those patients who received a dose of 20mg twice a day or above. This side effect did not persist. The majority of cases showed a response either in circulating tumor cells [15, 16], in those who had this test done or in extended median survival.

TABLE 2 : Breast Cancer- a detailed list of patients included in this study.  

4. Discussion

PGSC in breast cancer is shown in this paper to have significant anticancer effects. This study is an observational study and prospective randomised control studies are worth doing using this approach, as it is free from side effects. The weakness of this study is that it is an observational study.

5. Conclusion

PGSC has an objective anticancer effect in breast cancer patients. To elucidate this further, then further studies addressing the weakness of this particular study are worth carrying out.

Funding

This study and writing of this study was supported by a research grant from Alinova Biosciences.

Conflicts of Interest

None.

Acknowledgements

Julian Kenyon would like to acknowledge the contributions made by Andrew Davies and Colin Stott to this paper.

REFERENCES

1. Radmila Pavlovic, Giorgio Nenna, Lorenzo Calvi, et al. “Quality Traits of “Cannabidiol Oils”: Cannabinoids Content, Terpene Fingerprint and Oxidation Stability of European Commercially Available Preparations.” Molecules, vol. 23, no. 5, pp. 1230, 2018. View at: Publisher Site | PubMed
2. Marcel O Bonn Miller, Mallory J E Loflin, Brian F Thomas, et al. “Labeling Accuracy of Cannabidiol Extracts Sold Online.” JAMA, vol. 318, no. 17, pp. 1708-1709, 2017. View at: Publisher Site | PubMed
3. Ryan Vandrey, Jeffrey C Raber, Mark E Raber, et al. “Cannabinoid Dose and Label Accuracy in Medical Cannabis Products.” JAMA, vol. 313, no. 24, pp. 2491-2493, 2015. View at: Publisher Site | PubMed
4. MHRA “Regulatory status of products containing CBD.” 2016.
5. Eduardo Pérez Gómez, Clara Andradas, Sandra Blasco Benito, et al. “Role of cannabinoid receptor CB2 in HER2 pro-oncogenic signalling in breast cancer.” J Natl Cancer Inst, vol. 107, no. 6, pp. djv077, 2015. View at: Publisher Site | PubMed
6. María M Caffarel, Clara Andradas, Emilia Mira, et al. “Cannabinoids reduce ErbB2-driven breast cancer progression through AKT inhibition.” Mol Cancer, vol. 9, pp. 196, 2010. View at: Publisher Site | PubMed
7. Cristina Vercelli, Raffaella Barbero, Barbara Cuniberti, et al. “Transient receptor potential vanilloid 1 expression and functionality in MCF-7 cells: A preliminary investigation.” J Breast Cancer, vol. 17, no. 4, pp. 332-338, 2014. View at: Publisher Site | PubMed
8. R G Pertwee “The pharmacology of cannabinoid receptors and their ligands: an overview.” Int J Obes, vol. 30, no. 1, pp. S13-S8, 2006. View at: Publisher Site | PubMed
9. M Guzmán, M J Duarte, C Blázquez, et al. “A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme.” Br J Cancer, vol. 95, no. 2, pp. 197-203, 2006. View at: Publisher Site | PubMed
10. “WHO Online Q&A.” Cannabidiol (compound of cannabis), 2017.
11. Paola Massi, Marta Solinas, Valentina Cinquina, et al. “Cannabidiol as potential anticancer drug.” Br J Clin Pharmacol, vol. 75, no. 2, pp. 303-312, 2013. View at: Publisher Site | PubMed
12. Katherine A Scott, Angus G Dalgleish, Wai M Liu “Anticancer effects of phytocannabinoids used with chemotherapy in leukaemia cells can be improved by altering the sequence of their administration.” Int J Oncol, vol. 51, no. 1, pp. 369-377, 2017. View at: Publisher Site | PubMed
13. Katherine Ann Scott, Sini Shah, Angus George Dalgleish, et al. “Enhancing the activity of cannabidiol and other cannabinoids in vitro through modifications to drug combinations and treatment schedules.” Anticancer Res, vol. 33, no. 10, pp. 4373-4380, 2013. View at: PubMed
14. Matthew R D Brown, W Paul Farquhar Smith “Cannabinoids and cancer pain: A new hope or a false dawn?” Eur J Intern Med, vol. 49, pp. 30-36, 2018. View at: Publisher Site | PubMed
15. Lihi Bar Lev Schleider, Raphael Mechoulam, Violeta Lederman, et al. “Prospective analysis of safety and efficacy of medical cannabis in large, unselected population of patients with cancer.” Eur J Intern Med, vol. 49, pp. 37-43, 2018. View at: Publisher Site | PubMed
16. Julian Kenyon, Wai Liu, Angus Dalgleish “Report of Objective Clinical responses of Cancer Patients to Pharmaceutical-grade Synthetic Cannabidiol.” Anticancer Res, vol. 38, no. 10, pp. 5831-5835, 2018. View at: Publisher Site | PubMed
17. Muralidhar Reddy P, Maurya N, Velmurugan B K “Medicinal Use of Synthetic Cannabinoids—a Mini Review.” Current Pharmacology Rep, vol. 5, pp. 1-13, 2019. View at: Publisher Site
18. Papasotiriou I, Chatziioannou M, Pessiou K, et al. “Detection of circulating tumor cells in patients with breast, prostate, pancreatic, colon and melanoma cancer: A blinded comparative study using healthy donors.” J Cancer Ther, vol. 6, pp. 543-553, 2015. View at: Publisher Site
19. Lei XU, Xueying Mao, Alistair Grey, et al. “Noninvasive Detection of Clinically Significant Prostate Cancer Using Circulating Tumour Cells.” J Urol, vol. 203, no. 1, 73-82, 2019. View at: Publisher Site | PubMed