“Preclinical models provided ample evidence that cannabinoids are cytotoxic against cancer cells. Among the best studied phytocannabinoids, cannabidiol (CBD) is most promising for the treatment of cancer as it lacks the psychotomimetic properties of delta-9-tetrahydrocannabinol (THC). In vitro studies and animal experiments point to a concentration- (dose-)dependent anticancer effect. The effectiveness of pure compounds versus extracts is the subject of an ongoing debate. Actual results demonstrate that CBD-rich hemp extracts must be distinguished from THC-rich cannabis preparations. Whereas pure CBD was superior to CBD-rich extracts in most in vitro experiments, the opposite was observed for pure THC and THC-rich extracts, although exceptions were noted. The cytotoxic effects of CBD, THC and extracts seem to depend not only on the nature of cannabinoids and the presence of other phytochemicals but also largely on the nature of cell lines and test conditions. Neither CBD nor THC are universally efficacious in reducing cancer cell viability. The combination of pure cannabinoids may have advantages over single agents, although the optimal ratio seems to depend on the nature of cancer cells; the existence of a ‘one size fits all’ ratio is very unlikely. As cannabinoids interfere with the endocannabinoid system (ECS), a better understanding of the circadian rhythmicity of the ECS, particularly endocannabinoids and receptors, as well as of the rhythmicity of biological processes related to the growth of cancer cells, could enhance the efficacy of a therapy with cannabinoids by optimization of the timing of the administration, as has already been reported for some of the canonical chemotherapeutics. Theoretically, a CBD dose administered at noon could increase the peak of anandamide and therefore the effects triggered by this agent. Despite the abundance of preclinical articles published over the last 2 decades, well-designed controlled clinical trials on CBD in cancer are still missing. The number of observations in cancer patients, paired with the anticancer activity repeatedly reported in preclinical in vitro and in vivo studies warrants serious scientific exploration moving forward.”
Category Archives: Bladder Cancer
Cannabis as a potential compound against various malignancies, legal aspects, advancement by exploiting nanotechnology and clinical trials
“Various preclinical and clinical studies exhibited the potential of cannabis against various diseases, including cancer and related pain. Subsequently, many efforts have been made to establish and develop cannabis-related products and make them available as prescription products. Moreover, FDA has already approved some cannabis-related products, and more advancement in this aspect is still going on. However, the approved product of cannabis is in oral dosage form, which exerts various limitations to achieve maximum therapeutic effects. A considerable translation is on a hike to improve bioavailability, and ultimately, the therapeutic efficacy of cannabis by the employment of nanotechnology. Besides the well-known psychotropic effects of cannabis upon the use at high doses, literature has also shown the importance of cannabis and its constituents in minimising the lethality of cancer in the preclinical models. This review discusses the history of cannabis, its legal aspect, safety profile, the mechanism by which cannabis combats with cancer, and the advancement of clinical therapy by exploiting nanotechnology. A brief discussion related to the role of cannabinoid in various cancers has also been incorporated. Lastly, the information regarding completed and ongoing trials have also been elaborated.”
Cannabidiol Effectively Promoted Cell Death in Bladder Cancer and the Improved Intravesical Adhesion Drugs Delivery Strategy Could Be Better Used for Treatment
“Cannabidiol (CBD), a primary bioactive phytocannabinoid extracted from hemp, is reported to possess potent anti-tumorigenic activity in multiple cancers.
However, the effects of CBD on bladder cancer (BC) and the underlying molecular mechanisms are rarely reported.
Here, several experiments proved that CBD promoted BC cells (T24, 5637, and UM-UC-3) death.
In summary, this work demonstrates that CBD may become a novel reliable anticancer drug and the developed intravesical adhesion system is expected to turn into a potential means of BC chemotherapy drug delivery.
We believe that our study makes a significant contribution to the field because these results can be developed as a promising strategy for a safer and more efficient anticancer therapy.”
The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases
“The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems.
In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development.
The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development.
The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases.
This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.”
https://www.mdpi.com/1422-0067/22/17/9472
“Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment”
Cannabis-Derived Compounds Cannabichromene and Δ9-Tetrahydrocannabinol Interact and Exhibit Cytotoxic Activity against Urothelial Cell Carcinoma Correlated with Inhibition of Cell Migration and Cytoskeleton Organization
“Cannabis sativa contains more than 500 constituents, yet the anticancer properties of the vast majority of cannabis compounds remains unknown. We aimed to identify cannabis compounds and their combinations presenting cytotoxicity against bladder urothelial carcinoma (UC), the most common urinary system cancer.
An XTT assay was used to determine cytotoxic activity of C. sativa extracts on T24 and HBT-9 cell lines. Extract chemical content was identified by high-performance liquid chromatography (HPLC). Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and cell cycle, using stained F-actin and nuclei. Scratch and transwell assays were used to determine cell migration and invasion, respectively. Gene expression was determined by quantitative Polymerase chain reaction (PCR).
The most active decarboxylated extract fraction (F7) of high-cannabidiol (CBD) C. sativa was found to contain cannabichromene (CBC) and Δ9-tetrahydrocannabinol (THC). Synergistic interaction was demonstrated between CBC + THC whereas cannabinoid receptor (CB) type 1 and type 2 inverse agonists reduced cytotoxic activity.
Treatments with CBC + THC or CBD led to cell cycle arrest and cell apoptosis. CBC + THC or CBD treatments inhibited cell migration and affected F-actin integrity. Identification of active plant ingredients (API) from cannabis that induce apoptosis and affect cell migration in UC cell lines forms a basis for pre-clinical trials for UC treatment.”
Education and communication are critical to effectively incorporating cannabis into cancer treatment
“Providers need to be better equipped to discuss medical cannabis with patients even if they are not willing to prescribe it. The oncology community would be well served to ensure that providers are aware of existing cannabis research and are able to incorporate it into their communications with patients instead of leaving patients to figure out medical cannabis on their own.”
https://pubmed.ncbi.nlm.nih.gov/32986251/
https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.33204
Cancer patients’ experiences with medicinal cannabis-related care
“Background: Little is known about medical cannabis (MC)-related care for patients with cancer using MC.
Methods: Semistructured telephone interviews were conducted in a convenience sample of individuals (n = 24) with physician-confirmed oncologic diagnoses and state/district authorization to use MC (Arizona, California, Florida, Illinois, Massachusetts, Oregon, New York, and Washington, DC) from April 2017 to March 2019. Standard qualitative techniques were used to assess the degree of MC-related health care oversight, MC practices, and key information sources.
Results: Among 24 participants (median age, 57 years; range, 30-71 years; 16 women [67%]), MC certifications were typically issued by a professional new to a patient’s care after a brief, perfunctory consultation. Patients disclosed MCuse to their established medical teams but received little medical advice about whether and how to use MC. Patients with cancer used MC products as multipurpose symptom management and as cancer-directed therapy, sometimes in lieu of standard-of-care treatments. Personal experimentation, including methodical self-monitoring, was an important source of MC know-how. Absent formal advice from medical professionals, patients relied on nonmedical sources for MC information.
Conclusions: Patients with cancer used MC with minimal medical oversight. Most received MC certifications through brief meetings with unfamiliar professionals. Participants desired but were often unable to access high-quality clinical information about MC from their established medical teams. Because many patients are committed to using MC, a product sustained by a growing industry, medical providers should familiarize themselves with the existing data for MM and its limitations to address a poorly met clinical need.”
https://pubmed.ncbi.nlm.nih.gov/32986266/
“Notably, oncology patients reported using medical cannabis (MC) for symptom management and as cancer‐directed therapy, sometimes instead of traditional treatments.”
https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.33202
Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis
“In recent years, and even more since its legalization in several jurisdictions, cannabis and the endocannabinoid system have received an increasing amount of interest related to their potential exploitation in clinical settings. Cannabinoids have been suggested and shown to be effective in the treatment of various conditions. In cancer, the endocannabinoid system is altered in numerous types of tumours and can relate to cancer prognosis and disease outcome. Additionally, cannabinoids display anticancer effects in several models by suppressing the proliferation, migration and/or invasion of cancer cells, as well as tumour angiogenesis. However, the therapeutic use of cannabinoids is currently limited to the treatment of symptoms and pain associated with chemotherapy, while their potential use as cytotoxic drugs in chemotherapy still requires validation in patients. Along with cannabinoids, cannabis contains several other compounds that have also been shown to exert anti-tumorigenic actions. The potential anti-cancer effects of cannabinoids, terpenes and flavonoids, present in cannabis, are explored in this literature review.”
https://pubmed.ncbi.nlm.nih.gov/32708138/
https://www.mdpi.com/2072-6694/12/7/1985
Cannabinoids as anticancer therapeutic agents.
“The recent announcement of marijuana legalization in Canada spiked many discussions about potential health benefits of Cannabis sativa. Cannabinoids are active chemical compounds produced by cannabis, and their numerous effects on the human body are primarily exerted through interactions with cannabinoid receptor types 1 (CB1) and 2 (CB2). Cannabinoids are broadly classified as endo-, phyto-, and synthetic cannabinoids. In this review, we will describe the activity of cannabinoids on the cellular level, comprehensively summarize the activity of all groups of cannabinoids on various cancers and propose several potential mechanisms of action of cannabinoids on cancer cells.”
https://www.ncbi.nlm.nih.gov/pubmed/32249682
“Endocannabinoids and phytocannabinoids can be used for cancer therapy. Cannabis extracts have stronger anti-tumor capacity than single cannabinoids. Combination of several cannabinoids may have more potent effect on cancer.”
https://www.tandfonline.com/doi/abs/10.1080/15384101.2020.1742952?journalCode=kccy20
The Endocannabinoid System: A Target for Cancer Treatment.
“In recent years, the endocannabinoid system has received great interest as a potential therapeutic target in numerous pathological conditions.
Cannabinoids have shown an anticancer potential by modulating several pathways involved in cell growth, differentiation, migration, and angiogenesis.
However, the therapeutic efficacy of cannabinoids is limited to the treatment of chemotherapy-induced symptoms or cancer pain, but their use as anticancer drugs in chemotherapeutic protocols requires further investigation.
In this paper, we reviewed the role of cannabinoids in the modulation of signaling mechanisms implicated in tumor progression.”
https://www.ncbi.nlm.nih.gov/pubmed/31979368
https://www.mdpi.com/1422-0067/21/3/747
“In addition to the symptomatic therapy of cancer patients, the antitumor effects of cannabinoids (whether in monotherapy or in combination with other cancer therapies) have promising potential in the treatment of cancer patients.” https://www.ncbi.nlm.nih.gov/pubmed/31950844
“In addition to the well-known palliative effects of cannabinoids on some cancer-associated symptoms, a large body of evidence shows that these molecules can decrease tumour growth in animal models of cancer. In addition, cannabinoids inhibit angiogenesis and decrease metastasis in various tumour types in laboratory animals. Thus, numerous studies have provided evidence that thc and other cannabinoids exhibit antitumour effects in a wide array of animal models of cancer.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791144/
“Antitumour actions of cannabinoids.” https://www.ncbi.nlm.nih.gov/pubmed/30019449
“The endocannabinoid system as a target for the development of new drugs for cancer therapy” https://www.ncbi.nlm.nih.gov/pubmed/12723496
“Cannabinoids as Anticancer Drugs.” https://www.ncbi.nlm.nih.gov/pubmed/28826542