Article History

Published: Mon 21, Sep 2020
Received: Tue 18, Aug 2020
Accepted: Mon 07, Sep 2020

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Abstract

This is an observational study of objective responses of Prostate Cancer patients to Pharmaceutical Grade Synthetic Cannabidiol. The total number of patients in the study was 12, 11 had a response of one kind or another.

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 prostate 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 prostate cancer as compared to normal prostatic tissue [5], and the overexpression of CB1 receptors has been associated with a higher Gleason Score and metastasis incidence, being a negative marker of disease outcome [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 (PGSC) [16]. Over five years ago, we decided to assess the potential use of PGSC in prostate cancer patients. Some of the cases reported here were presented in our previous paper [16].

2. Materials and Methods

Patients were given 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 12 patients described here in this observational study, every patient in this study signed an informed consent allowing anonymous use of their data. The 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 PGSC.

In a number of cases where there was stable disease, the dose was reduced to 5 drops (5mg) twice a day. In one case in this study, Sativex, which is licensed for use in multiple sclerosis, was used in conjunction with CBD as a source of THC, which synergises with CBD [18]. A fraction of the dose used for multiple sclerosis was used. Two sprays of Sativex were given twice a day on a three days on and three days off pattern, as in the case of the PGSC. Patients on continuous dosing did not do as well as those on an on/off repeating regimen. We assessed the majority of patients using circulating tumor cells tests [19, 20]; some decided not to have this.

3. Results

The results of our prostate cancer cohort previously 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). We were unable to define a maximum tolerated dose of CBD, 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. All cases showed a response either in circulating tumor cells [19, 20], in those who had this test done or in reducing PSA levels. All of those who stopped taking PGSC showed a subsequent increase in circulating tumor cells or in PSA. In patient P12, with a break in the supply of the PGSC, the circulating tumor cells went up from 1.2 cells per 7.5ml to 2.0 cells per 7.5ml, over a six-month period [19].

TABLE 1: Outcomes-prostate cancer.

TABLE 2: A detailed list of all of the patients in this observational study.

4. Discussion

PGSC 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 prostate cancer patients. To elucidate this further, then further studies addressing the weakness of this particular study are worth carrying out. This study was supported by a research grant from Alinova Biosciences.

Conflicts of Interest

None.

Funding

The writing of this study has been made possible by a grant from Alinova Biosciences.

Acknowledgements

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

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