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Report of Objective Clinical Responses of Cancer Patients to Pharmaceutical-grade Synthetic Cannabidiol

Authors:
Julian Kenyon
Julian Kenyon
WAI LIU
WAI LIU
WAI LIU
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Angus G Dalgleish at St George's, University of London
Angus G Dalgleish
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Abstract

Background/aim: Cannabinoids are widely used in the management of pain, nausea and cachexia in cancer patients. However, there has been no objective clinical evidence of any anticancer activity yet. The aim of this study was to assess the effects of pharmaceutical-grade synthetic cannabidiol on a range of cancer patients. Patients and methods: We analysed the data routinely collected, as part of our treatment program, in 119 cancer patients over a four-year period. Results: Clinical responses were seen in 92% of the 119 cases with solid tumours including a reduction in circulating tumour cells in many cases and in other cases, a reduction in tumour size, as shown by repeat scans. No side-effects of any kind were observed when using pharmaceutical grade synthetic cannabidiol. Conclusion: Pharmaceutical-grade synthetic cannabidiol is a candidate for treating breast cancer and glioma patients.
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Abstract. Background/Aim: Cannabinoids are widely used
in the management of pain, nausea and cachexia in cancer
patients. However, there has been no objective clinical
evidence of any anticancer activity yet. The aim of this study
was to assess the effects of pharmaceutical-grade synthetic
cannabidiol on a range of cancer patients. Patients and
Methods: We analysed the data routinely collected, as part
of our treatment program, in 119 cancer patients over a four-
year period. Results: Clinical responses were seen in 92% of
the 119 cases with solid tumours including a reduction in
circulating tumour cells in many cases and in other cases, a
reduction in tumour size, as shown by repeat scans. No side-
effects of any kind were observed when using pharmaceutical
grade synthetic cannabidiol. Conclusion: Pharmaceutical-
grade synthetic cannabidiol is a candidate for treating breast
cancer and glioma patients.
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 (1). 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 (2). 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 (3). Studies have shown that in
addition to being able to induce cell death directly, it is also
capable of interfering with intracellular signalling (4).
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 (5, 6). Furthermore, the sequence in which these
drugs are administered can also influence overall activity (5).
Studies have also indicated that in certain leukaemia cell
lines, CBD can increase the expression of the cyclin-
dependent kinase inhibitor p21waf1 (6). This increased level
appears to be maintained by CBD, which inadvertently
impedes cell death. Cytotoxicity can 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 (6).
The findings of a number of studies designed to examine
the role of cannabinoids in in the management of cancer
symptoms varied (7). 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 (8). 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
5831
This article is freely accessible online.
Correspondence to: Dr. Julian Kenyon, The Old Brewery, High
Street, Twyford, Winchester Hants SO21 1RG, UK. Tel: +44 01962
718000, Fax: +44 01962 717060, e-mail: jnkenyon@doveclinic.com
Key Words: Cancer, cannabinoids, ependymoma, prostate cancer,
breast cancer.
ANTICANCER RESEARCH 38: 5831-5835 (2018)
doi:10.21873/anticanres.12924
Report of Objective Clinical Responses of Cancer Patients
to Pharmaceutical-grade Synthetic Cannabidiol
JULIAN KENYON1, WAI LIU2and ANGUS DALGLEISH2
1The Old Brewery, Winchester Hants, U.K.;
2St George’s University of London, London, U.K.
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.
In order to assess its potential use, we focused on giving
patients with advanced cancer who requested CBD a
pharmaceutical-grade synthetic product at appropriate doses.
Activity of synthetic cannabinoid WIN on human cancer
cell lines has been reported (9). Every patient in this study
signed an informed consent allowing anonymous use of
their data.
Case Presentations
Patients were given synthetic, pharmaceutical-grade CBD (STI
Pharmaceuticals), registered under the Pharmaceutical Specials
scheme in oily drops at 5% (w/v) in 20 ml bottles. Each drop
contained 1 mg of synthetic CBD in neutral oil. This was
prescribed on an informed consent basis. 119 cancer patients
decided to have this treatment (Table I), and most of them had
metastatic cancers. Of the 119 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. This
is currently illegal, 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 (10).
The majority of the patients were assessed using a
circulating tumour cell test before and after treatment (11),
since this is cheaper than carrying out repeated scans. A
number of patients however, as a matter of a normal
treatment course, had relevant scans. CBD was administered
on three days on and three days off basis, which clinically
was found to be more effective than giving it as a continuous
dose. The average dose was 10 mg twice a day. For increased
tumour 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 (12). A
fraction of the dose used for multiple sclerosis was used. Two
sprays of Sativex were given twice a day in three days on and
three days off pattern, as in the case of pharmaceutical-grade
synthetic CBD; patients on continuous dosing did not do as
well as those on this on-off repeating regimen. Some of our
patients reverted to cannabis oil bought on the Internet, and
following this, 80% of these cases relapsed.
We were unable to define a maximum tolerated dose for
CBD, as there was a complete absence of side effects. The
minimum duration of treatment required for CBD was six
months, but many continued for longer. Less than six months
appeared inadequate and had little effect, and therefore cases
in which CBD was used for less than six months have been
defined as un-assessable, and not included in the current
cohort of 119 cases.
We sought clear objective evidence of potential efficacy
where no other treatment option was available. The most
impressive case was a five-year-old male patient with an
anaplastic ependymoma, a very rare brain tumour. The
patient had had all standard treatments, surgery on two
occasions followed by chemotherapy and conformal photon
ANTICANCER RESEARCH 38: 5831-5835 (2018)
5832
Table I. Tabular presentation of our results on 119 cancer patients.
Cancer Tumour Stable Extended median Slowed No effect/ Died CBD as only Unknown Total
type free disease survival progression result treatment outcome cases
Anaplastic ependymoma 3 3 3
DIPG 1 1 1
Glioblastoma multiforme 4 3 3 4 7
Bladder 1 1 2
Breast 7 21 8 3 6 6 39
Head and Neck 1 1 2
Prostate 10 3 3 6 16
Neuroendocrine 1 1
Non-Hodgkin's lymphoma 1 6 1 3 8
Non-small cell lung 2 2 2 2
Colorectal 1 9 2 1 6 13
Pancreatic 2 2 2 4
Ovarian 5 1 3 1 6
Miscellaneous 2 6 5 1 1 1 1 15
Total 12 45 43 8 5 27 28 1 119
Kenyon et al: Clinical Responses to Pharmaceutical-grade Synthetic Cannabidiol
5833
Figure 1. Patient with ependymoma. A) A scan on the 6th of Jan 2016 showed enlargement of the posterior fossa mass. There were some, particularly
multimodal features of radionecrosis, but in the context of a previously rapidly progressive tumour, an element of disease progression was also
being considered. B) A subsequent scan on the 13th April 2016 showed further tumour progression and development of moderately severe
supratentorial hydrocephalus. C) On the 30 Sept 2016, scans showed substantial improvement/reduction in size of the residual disease. There had
been a substantial improvement in appearances, with marked reduction in size of the posterior fossa tumour from 3.4×3.2 cm in the sagittal plane
to 1.7×1.7 cm. D) Scans performed on the 14th Dec 2016, showed a slow improvement; with impressive resolution of left CPA recurrent ependymoma.
Figure 2. Patient with tanycytic ependymoma. A) A scan on the 13th Jan 2017 showed a reduction in the size and enhancement of the left periventricular
tumour. There was almost complete resolution of the parenchymal enhancement with a couple of small ependymal nodules remaining, but slightly
smaller. There was no significant change in the T2/FLAIR appearance with Wallarian degeneration extending into the corticospinal tracts. B) A follow-
up scan performed on the 21 Feb 2018 revealed evidence of disease progression with a near doubling of the enhancing soft tissue arising from the
ependymal surface of the left lateral ventricle and projecting into the body of the left lateral ventricle. There are new enhancing foci in the left putamen
and subthalamic region with further non-enhancing T2 hyperintense tumour expanding inferiorly into the left cerebral peduncle.
radiotherapy. No further treatment options were available to
him when treatment on CBD started in February 2016. A
scan carried out in December 2016 showed that tumour
volume had decreased by ~60%. Further scans, carried out
since December 2016, continued to show stable disease.
CBD was the only treatment. Four scans with the scan report
at the top of each scan are appended (Figure 1A-D).
Another impressive case was a 50-year-old patient with
progressive tanycytic ependymoma Grade 2 diagnosed in
June 2013, 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
from an oncology clinic in Central London.
In January 2017 a repeat scan showed tumour reduction. At
that point the patient stopped taking pharmaceutical-grade
synthetic CBD and switched to cannabis oil extract obtained
from an internet website. Further scans carried out in February
2018 showed doubling of tumour size and more growth down
the brain stem. He has since restarted pharmaceutical-grade
synthetic CBD and throughout continued to take the
metformin, atorvastatin, doxycycline and mebendazole. So, the
only change in November 2017 had been stopping the
pharmaceutical-grade synthetic CBD and switching to cannabis
oil extract obtained on the Internet (Figure 2A and B).
Other patients who clearly improved using pharmaceutical-
grade synthetic CBD had prostate cancer, breast cancer,
oesophageal cancer and a lymphoma, and these are
summarised in Table II.
Discussion
From our laboratory studies, we would not expect any
significant anti-cancer activity using continuous CBD alone,
as we have only observed cancer cell line apoptosis (cell
ANTICANCER RESEARCH 38: 5831-5835 (2018)
5834
Table II. Examples of patients who have been using pharmaceutical-grade synthetic CBD.
Age/Gender Diagnosis Comments
72/male Prostate cancer Patient has had cancer immunotherapy, sono and photodynamic therapy (14) which was successful.
On resumption of testosterone injections his prostate specific antigen (PSA) levels increased
to 16. We started him on CBD early in 2015 at a dose of 10 drops twice a day (10 mg),
three days on and three days off. There was a reduction in circulating tumour cells (CTCs) with
CBD alone from an initial 8.1 cells/7.5 ml to 5.9 cells/7.5 ml, then steady reduction over the
course of 12 months of 4.8, 4.2 then 3.2 cells/7.5 ml. He is still under treatment.
68/female Breast cancer with Patient was diagnosed in March 2014 with progressive disease.
bone metastases She started local radiotherapy. We started her on CBD in January 2015, all subsequent
scans showed stable disease. She has had no treatment other than CBD following radiotherapy.
65/female Oesophageal cancer Patient was diagnosed in May 2016. She had a stent put on place at that time and was given
an expected survival of three months. Since then, she has been on CBD as the only
treatment, and she has continued to refuse all standard treatments and investigations.
We last saw her in November 2016, when she was looking well and
had in fact regained weight. She died in January 2018.
65/female Breast cancer Patient was diagnosed in November 2009, and refused all conventional treatments
and investigations. On examination she had a large fungating lesion 15 cm in diameter in the
left breast, and also palpable left axillary nodes. She began treatment with CBD
in October 2014. We persuaded her to have radiotherapy in November 2014.
She only agreed to have half the recommended treatment course. She has continued
on CBD alone and on her last appointment the tumour in her left
breast was 2 cm in diameter, with no palpable axillary nodes.
62/female Breast cancer We first saw this patient in May 2014 and she has been on CBD,
as the only treatment, since October 2014. We carried out various CTC tests
in October 2014 which showed 10.6 cells per 7.5 ml. Subsequent tests in July and
October 2015, November 2016 and October 2017 showed CTCs to be 7.3, 6.8, 5.0
and 3.9 cells/7.5 ml, respectively. Patient is currently stable with no symptoms.
67/female Lobular breast Patient was diagnosed in November 2012. We first saw her in March 2014,
cancer we gave her CBD in October 2014, which is the only method of treatment. Initial CTCs in
October 2014 was 9.3 cells per 7.5ml. Follow-up measurements in September 2015, March 2016
and March 2017 have been 7.5, 6.8 and 3.0 cells/7.5 ml, respectively. All standard
clinical investigations and scans have been normal since the beginning of 2015.
death) when the agent is washed out of culture and
withdrawn (13). We have also observed a potential increased
cell killing ability when given after chemotherapy.
Cannabinoids have an accepted useful role in the
management of cancer symptoms, namely pain control,
nausea and cachexia, but not as part of primary treatment.
The fact that we have been able to document improvement
in cancer in few patients strongly supports further studies of
CBD-based products in cancer patients who have exhausted
standard treatments. Our primary data in a murine glioma
model (14) showing enhanced sensitivity to radiotherapy
without any side-effects, suggests this would be an ideal
clinical trial to initiate in the first instance.
Conflicts of Interest
There are no conflicts of interest to disclose.
References
1 Pertwee RG: The pharmacology of cannabinoid receptors and
their ligands: an overview. Int J Obes 30: S13-18, 2006.
2 Guzmán M, Duarte MJ, Blázquez C, Ravina J, Rosa MC, Galve-
Roperh I, Sánchez C, Velasco G and González-Feria L: A pilot
clinical study of Delta9-tetrahydrocannabinol in patients with
recurrent glioblastoma multiforme. Br J Cancer 95: 197-203,
2006.
3 WHO Online Q&A. Cannabidiol (compound of cannabis)
December 2017. http://www.who.int/features/qa/cannabidiol/en/
(accessed March 2018)
4 Massi P, Solinas M, Cinquina V and Parolaro D: Cannabidiol as
potential anticancer drug. Br J Clin Pharmacol 75: 303-312,
2013.
5 Scott KA, Dalgleish AG and Liu WM: Anticancer effects of
phytocannabinoids used with chemotherapy in leukaemia cells
can be improved by altering the sequence of their administration.
Int J Oncol 51: 369-377, 2017.
6 Scott KA, Shah S, Dalgleish AG and Liu WM: Enhancing the
activity of cannabidiol and other cannabinoids in vitro through
modifications to drug combinations and treatment schedules.
Anticancer Res 33: 4373-4380, 2013.
7 Brown MRD and Farquhar-Smith WP: Cannabinoids and cancer
pain: A new hope or a false dawn? Eur J Intern Med 49: 30-36,
2018.
8 Bar-Lev Schleider L, Mechoulam R, Lederman V, Hilou M,
Lencovsky O, Betzalel O, Shbiro L and Novack V: Prospective
analysis of safety and efficacy of medical cannabis in large
unselected population of patients with cancer. Eur J Intern Med
49: 37-43, 2018.
9 Müller L, Radtke A, Decker J, Koch M and Belge G: The
Synthetic Cannabinoid WIN 55,212-2 Elicits Death in Human
Cancer Cell Lines. Anticancer Res 37: 6341-6345, 2017.
10 MHRA. Regulatory status of products containing CBD,
published 13th October 2016, updated 30th December 2016
http s: //w ww. go v.u k/g ov ernme nt /news /m hra-s ta temen t- on-
products-containing-cannabidiol-cbd
11 Papasotiriou I, Chatziioannou M, Pessiou K, Retsas I, Dafouli
G, Kyriazopoulou A, Toloudi M, Kaliara I, Vlachou I, Kourtidou
E, Kipourou V, Georgiou E, Ntanovasilis DA, Theodosiou C,
Pantopikou A and Apostolou P: 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 6: 543-553, 2015.
12 Scott KA, Dalgleish AG and Liu WM: The combination of
cannabidiol and Δ9-tetrahydrocannabinol enhances the
anticancer effects of radiation in an orthotopic murine glioma
model. Mol Cancer Ther 13: 2955-2967, 2014.
13 Scott KA, Shah S, Dalgleish AG and Liu WM: Enhancing the
activity of cannabidiol and other cannabinoids in vitro through
modifications to drug combinations and treatment schedules.
Anticancer Res 33: 4373-4380, 2013.
14 Kenyon JN, Fuller RJ and Lewis TJ: Activated cancer therapy
using light and ultrasound – a case series of sonodynamic
photodynamic therapy in 115 patients over a 4-year period. Curr
Drug Ther 4: 179-193, 2009.
Received August 22, 2018
Revised September 12, 2018
Accepted September 21, 2018
Kenyon et al: Clinical Responses to Pharmaceutical-grade Synthetic Cannabidiol
5835
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Full-text available
  • Feb 2024
This litrature review paper highlights the role of phytocannabinoids in controlling cervical cancer. Cervical cancer is one of the leading causes of cancer death among females worldwide. Cervical cancer (CC) is a malignant form of tumor which originates in the cervix. Cervical cancer, which develops in a woman's cervix, is the second-most common cancer among women in India The causative agent of cervical cancer is persistent infection with high-risk subtypes of the Human Papillomavirus (HPV) and the E5, E6 and E7 viral onco-proteins cooperate with host factors to induce and maintain the malignant phenotype. Human papillomavirus (HPV) is responsible for subclinical/clinical lesions in cervical cancer. HPV types 16 and 18 are the most common HPV types identified in invasive cervical cancer. Currently, the recommended therapeutic regimens include chemotherapy, radiation therapy either alone or in combination and surgical interventions. However, they present several limitations including side effects or ineffectiveness. Medicinal plants including Cannabis sativa have been used for decades for health benefits and to treat several different diseases including cervical cancer. Cannabis has been used for thousands of years for recreational, medicinal, or religious purposes. Phytocannabinoids are cannabinoids that occur naturally in the cannabis plant. The two phytocannabinoids the most well known for their therapeutic properties are, Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD). Cannabis and cannabinoids hold big promise for cancer therapy. However, there is a need to understand more about the role of Endocannabinoid system (ECS) in normal human physiology and malignant transformations. Molecular mechanisms of Endocannabinoid system (ECS) regulation and anticancer properties of cannabis also need to be clarified. The treatment durations in the existing trials are also of concern. Future epidemiological and clinical studies are required to further assess the benefits of herbal medicines for the prevention of cervical cancer. In addition, preclinical and human clinical trial evaluations of cannabis for cervical cancer treatment have not specifically been conducted, so further investigations related to this are warranted. Therefore, HPV immunization programme is the best ideal solution for the eradication of cervical cancer.
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Cannabis sativa: Cervical cancer treatment-Role of phytocannabinoids-A story of concern
Article
Full-text available
  • Feb 2024
This litrature review paper highlights the role of phytocannabinoids in controlling cervical cancer. Cervical cancer is one of the leading causes of cancer death among females worldwide. Cervical cancer (CC) is a malignant form of tumor which originates in the cervix. Cervical cancer, which develops in a woman's cervix, is the second-most common cancer among women in India The causative agent of cervical cancer is persistent infection with high-risk subtypes of the Human Papillomavirus (HPV) and the E5, E6 and E7 viral onco-proteins cooperate with host factors to induce and maintain the malignant phenotype. Human papillomavirus (HPV) is responsible for subclinical/clinical lesions in cervical cancer. HPV types 16 and 18 are the most common HPV types identified in invasive cervical cancer. Currently, the recommended therapeutic regimens include chemotherapy, radiation therapy either alone or in combination and surgical interventions. However, they present several limitations including side effects or ineffectiveness. Medicinal plants including Cannabis sativa have been used for decades for health benefits and to treat several different diseases including cervical cancer. Cannabis has been used for thousands of years for recreational, medicinal, or religious purposes. Phytocannabinoids are cannabinoids that occur naturally in the cannabis plant. The two phytocannabinoids the most well known for their therapeutic properties are, Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD). Cannabis and cannabinoids hold big promise for cancer therapy. However, there is a need to understand more about the role of Endocannabinoid system (ECS) in normal human physiology and malignant transformations. Molecular mechanisms of Endocannabinoid system (ECS) regulation and anticancer properties of cannabis also need to be clarified. The treatment durations in the existing trials are also of concern. Future epidemiological and clinical studies are required to further assess the benefits of herbal medicines for the prevention of cervical cancer. In addition, preclinical and human clinical trial evaluations of cannabis for cervical cancer treatment have not specifically been conducted, so further investigations related to this are warranted. Therefore, HPV immunization programme is the best ideal solution for the eradication of cervical cancer.
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Prospective analysis of safety and efficacy of medical cannabis in large unselected population of patients with cancer
Article
Full-text available
  • Mar 2018
Background: Cancer is a major public health problem as the leading cause of death. Palliative treatment aimed to alleviate pain and nausea in patients with advanced disease is a cornerstone of oncology. In 2007, the Israeli Ministry of Health began providing approvals for medical cannabis for the palliation of cancer symptoms. The aim of this study is to characterize the epidemiology of cancer patients receiving medical cannabis treatment and describe the safety and efficacy of this therapy. Methods: We analyzed the data routinely collected as part of the treatment program of 2970 cancer patients treated with medical cannabis between 2015 and 2017. Results: The average age was 59.5 ± 16.3 years, 54.6% women and 26.7% of the patients reported previous experience with cannabis. The most frequent types of cancer were: breast (20.7%), lung (13.6%), pancreatic (8.1%) and colorectal (7.9%) with 51.2% being at stage 4. The main symptoms requiring therapy were: sleep problems (78.4%), pain (77.7%, median intensity 8/10), weakness (72.7%), nausea (64.6%) and lack of appetite (48.9%). After six months of follow up, 902 patients (24.9%) died and 682 (18.8%) stopped the treatment. Of the remaining, 1211 (60.6%) responded; 95.9% reported an improvement in their condition, 45 patients (3.7%) reported no change and four patients (0.3%) reported deterioration in their medical condition. Conclusions: Cannabis as a palliative treatment for cancer patients seems to be well tolerated, effective and safe option to help patients cope with the malignancy related symptoms.
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Cannabinoids and cancer pain: A new hope or a false dawn?
Article
Full-text available
  • Mar 2018
The endocannabinoid system is involved in many areas of physiological function and homeostasis. Cannabinoid receptors are expressed in the peripheral and central nervous system and on immune cells, all areas ideally suited to modulation of pain processing. There are a wealth of preclinical data in a number of acute, chronic, neuropathic and cancer pain models that have demonstrated a potent analgesic potential for cannabinoids, especially in patients with cancer. However, although there are some positive results in pain of cancer patients, the clinical evidence for cannabinoids as analgesics has not been convincing and their use can only be weakly recommended. The efficacy of cannabinoids seems to have been 'lost in translation' which may in part be related to using extracts of herbal cannabis rather than targeted selective full agonists at the cannabinoid CB1 and CB2 receptors.
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The Synthetic Cannabinoid WIN 55,212-2 Elicits Death in Human Cancer Cell Lines
Article
Full-text available
  • Nov 2017
Background: Studies have revealed that cancer might be treated with cannabinoids since they can influence cancer cell survival. These findings suggest an alternative treatment option to chemo- and radiotherapy, that are associated with numerous adverse side-effects for the patients. Materials and methods: Viability staining was conducted on lung cancer, testicular cancer and neuroblastoma cells treated with different concentrations of the synthetic cannabinoid WIN 55,212-2 and the percentage of dead cells was compared. Activity of apoptosis-related enzymes was investigated by the presence of DNA ladder in gel electrophoresis. Results: Treatment with different WIN 55,212-2 concentrations led to a significant dose-dependent reduction of cell viability. A DNA ladder was observed after WIN 55,212-2 treatment of testicular cancer and lung cancer cells. Conclusion: The application of WIN 55,212-2 was found to trigger cell death in the investigated cell lines. The decline in lung cancer and testicular cancer cell viability seems to have been caused by apoptosis. These findings may contribute to development of alternative cancer therapy strategies.
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Detection of Circulating Tumor Cells in Patients with Breast, Prostate, Pancreatic, Colon and Melanoma Cancer: A Blinded Comparative Study Using Healthy Donors
Article
Full-text available
  • Aug 2015
Cancer is a diverse disease characterized by abnormal cell growth and the ability to invade or spread to other parts of the body. Because the yearly cancer rate is increasing, an important area for cancer researchers is to improve the ability to detect and treat cancer early. The current study analyzes the potential of flow cytometry to be used to detect circulating tumor cells (CTCs) in patients with various cancer types and stages. CTCs are cells that have detached from the primary tumor and entered the blood stream in the process of metastasizing to other organs. To determine the accuracy of flow cytometry in detecting CTCs, a comparative study was performed on healthy donors. In this study, blood samples from patients with breast, prostate, pancreatic, colon and skin cancer were analyzed and compared with healthy donors. The data were collected and analyzed statistically with receiver operating characteristic curve analysis. The results indicate that CTCs can be detected in over 83% of the cancer patients and therefore may be a promising method for diagnosing cancer.
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The pharmacology of cannabinoid receptors and their ligands: an overview
Article
Full-text available
  • May 2006
Mammalian tissues express at least two cannabinoid receptor types, CB1 and CB2, both G protein coupled. CB1 receptors are found predominantly at nerve terminals where they mediate inhibition of transmitter release. CB2 receptors occur mainly on immune cells, one of their roles being to modulate cytokine release. Endogenous agonists for cannabinoid receptors also exist, and are all eicosanoids. The first-discovered of these 'endocannabinoids' was arachidonoylethanolamide and there is convincing evidence that this ligand and some of its metabolites can activate vanilloid VRI (TRPV1) receptors. Certain cannabinoids also appear to have TRPV1-like and/or non-CB1, non-CB2, non-TRPV1 targets. Several CB1- and CB2-selective agonists and antagonists have been developed. Antagonists include the CB1-selective SR141716A, AM251, AM281 and LY320135, and the CB2-selective SR144528 and AM630. These all behave as inverse agonists, one indication that CB1 and CB2 receptors can exist in a constitutively active state. 'Neutral' cannabinoid receptor antagonists have also been developed. CB1 and/or CB2 receptor activation appears to ameliorate inflammatory and neuropathic pain and certain multiple sclerosis symptoms. This might be exploited clinically by using CB1, CB2 or CB1/CB2 agonists, or inhibitors of the membrane transport or catabolism of endocannabinoids that are released in increased amounts, at least in animal models of pain and multiple sclerosis. We have recently discovered the presence of an allosteric site on the CB1 receptor. Consequently, it may also prove possible to enhance 'autoprotective' effects of released endocannabinoids with CB1 allosteric enhancers or, indeed, to reduce proposed 'autoimpairing' effects of released endocannabinoids such as excessive food intake with CB1 allosteric antagonists.
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Anticancer effects of phytocannabinoids used with chemotherapy in leukaemia cells can be improved by altering the sequence of their administration
Article
  • May 2017
Phytocannabinoids possess anticancer activity when used alone, and a number have also been shown to combine favourably with each other in vitro in leukaemia cells to generate improved activity. We have investigated the effect of pairing cannabinoids and assessed their anticancer activity in cell line models. Those most effective were then used with the common anti-leukaemia drugs cytarabine and vincristine, and the effects of this combination therapy on cell death studied in vitro. Results show a number of cannabinoids could be paired together to generate an effect superior to that achieved if the components were used individually. For example, in HL60 cells, the IC50 values at 48 h for cannabidiol (CBD) and tetrahydrocannabinol (THC) when used alone were 8 and 13 µM, respectively; however, if used together, it was 4 µM. Median-effect analysis confirmed the benefit of using cannabinoids in pairs, with calculated combination indices being <1 in a number of cases. The most efficacious cannabinoid-pairs subsequently synergised further when combined with the chemotherapy agents, and were also able to sensitise leukaemia cells to their cytotoxic effects. The sequence of administration of these drugs was important though; using cannabinoids after chemotherapy resulted in greater induction of apoptosis, whilst this was the opposite when the schedule of administration was reversed. Our results suggest that when certain cannabinoids are paired together, the resulting product can be combined synergistically with common anti-leukaemia drugs allowing the dose of the cytotoxic agents to be dramatically reduced yet still remain efficacious. Nevertheless, the sequence of drug administration is crucial to the success of these triple combinations and should be considered when planning such treatments.
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The Combination of Cannabidiol and Δ 9 -Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma Model
Article
  • Nov 2014
  • MOL CANCER THER
High-grade glioma is one of the most aggressive cancers in adult humans and long-term survival rates are very low as standard treatments for glioma remain largely unsuccessful. Cannabinoids have been shown to specifically inhibit glioma growth as well as neutralize oncogenic processes such as angiogenesis. In an attempt to improve treatment outcome, we have investigated the effect of Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) both alone and in combination with radiotherapy in a number of glioma cell lines (T98G, U87MG, and GL261). Cannabinoids were used in two forms, pure (P) and as a botanical drug substance (BDS). Results demonstrated a duration- and dose-dependent reduction in cell viability with each cannabinoid and suggested that THC-BDS was more efficacious than THC-P, whereas, conversely, CBD-P was more efficacious than CBD-BDS. Median effect analysis revealed all combinations to be hyperadditive [T98G 48-hour combination index (CI) at FU50, 0.77-1.09]. Similarly, pretreating cells with THC-P and CBD-P together for 4 hours before irradiation increased their radiosensitivity when compared with pretreating with either of the cannabinoids individually. The increase in radiosensitivity was associated with an increase in markers of autophagy and apoptosis. These in vitro results were recapitulated in an orthotopic murine model for glioma, which showed dramatic reductions in tumor volumes when both cannabinoids were used with irradiation (day 21: 5.5 ± 2.2 mm(3) vs. 48.7 ± 24.9 mm(3) in the control group; P < 0.01). Taken together, our data highlight the possibility that these cannabinoids can prime glioma cells to respond better to ionizing radiation, and suggest a potential clinical benefit for glioma patients by using these two treatment modalities. Mol Cancer Ther; 1-13. ©2014 AACR.
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Enhancing the Activity of Cannabidiol and Other Cannabinoids In Vitro Through Modifications to Drug Combinations and Treatment Schedules
Article
  • Oct 2013
  • ANTICANCER RES
Cannabinoids are the bioactive components of the Cannabis plant that display a diverse range of therapeutic qualities. We explored the activity of six cannabinoids, used both alone and in combination in leukaemic cells. Cannabinoids were cytostatic and caused a simultaneous arrest at all phases of the cell cycle. Re-culturing pre-treated cells in drug-free medium resulted in dramatic reductions in cell viability. Furthermore, combining cannabinoids was not antagonistic. We suggest that the activities of some cannabinoids are influenced by treatment schedules; therefore, it is important to carefully select the most appropriate strategy in order to maximise their efficacy.
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Activated Cancer Therapy Using Light and Ultrasound - A Case Series of Sonodynamic Photodynamic Therapy in 115 Patients Over a 4 Year Period
Article
  • Sep 2009
  • Curr Drug Ther
Activated Ca ncer Ther apy (ACT), al so know n a s Sonodyna mic Phot odynamic Ther apy (SPDT) i s a nove l therapeutic modality that utilises a non-toxic photosensitive agent with reported ultrasound-activated properties. SPDT has previously demonstrated significant tumour cell inhibition in animal studies. There has been much research into the effi-cacy of phot odynamic therapy and development in understanding of the underlying mechanism of tumour cytotoxicity. Synergistic ultrasound activation represents a promising development to activated sensitiser therapy, as photo-activation is limited by access and penetrance issues. Ultrasound has been demonstrated to activate a number of sono-sensitive agents allowing the possibility of non-invasive targeted treatment of deeper tumour sites than is currently achievable with pho-todynamic therapy. Thi s case se ries of 115 pa tients w ith a v ariety of ca ncer di agnoses reports on experiences of this treatment over a 4 year period using sublingual administration of a new dual activation agent, Sonnelux-1, followed by a protocol of LED light and low-intensity ultrasound exposure. Initial clinical observation suggests SPDT is worthy of fur-ther investigation a s an ef fective and w ell to lerated t reatment fo r a w ide v ariety o f p rimary an d m etastatic tumours, in-cluding those refractory to chemotherapy.
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Cannabidiol as potential anticancer drug
Article
Over the past years, several lines of evidence support an antitumorigenic effect of cannabinoids including Δ(9) -tetrahydrocannabinol (Δ(9) -THC), synthetic agonists, endocannabinoids and endocannabinoid transport or degradation inhibitors. Indeed, cannabinoids possess anti-proliferative and pro-apoptotic effects and they are known to interfere with tumour neovascularization, cancer cell migration, adhesion, invasion and metastasization. However, the clinical use of Δ(9) -THC and additional cannabinoid agonists is often limited by their unwanted psychoactive side effects, and for this reason interest in non-psychoactive cannabinoid compounds with structural affinity for Δ(9) -THC, such as cannabidiol (CBD), has substantially increased in recent years. The present review will focus on the efficacy of CBD in the modulation of different steps of tumourigenesis in several types of cancer and highlights the importance of exploring CBD/CBD analogues as alternative therapeutic agents. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.
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