What is Bladder Cancer
The bladder is a hollow organ in the lower pelvis with flexible, muscular walls that can stretch to hold urine and squeeze to send it out of the body. The bladder's primary function is to store urine (the liquid waste made by the kidneys) which is then carried to the bladder through two tubes called the ureters. When urinating, the muscles of the bladder contract, and the urine is forced out of the bladder through a tube called the urethra.
The wall of the bladder has many several layers, each of which comprises different cells. Bladder cancer is when the cells that make up the urinary bladder growing out of control. And as more cancer cells develop, they can form a tumor. Sometimes, it can also spread to other parts of the body.
Most bladder cancers start in the innermost lining of the bladder which is called the urothelium or transitional epithelium. As the cancer grows into or through the other layers in the bladder wall, it becomes more advanced, and can be harder to treat. Over time, the cancer may grow outside the bladder, and into nearby structures. It can also spread to nearby lymph nodes, as well as other parts of the body including the bones, lungs, or liver.
Bladder cancer is now the 9th most commonly diagnosed cancer worldwide, with 614,298 new cases reported globally in 2022. In the United States, approximately 82,290 new cases were diagnosed in 2023, making it the sixth most commonly diagnosed cancer in the country.
Bladder Cancer Classification
Medical practitioners usually describe your bladder cancers based on how far it has spread into the bladder wall:
Non-invasive
Non-invasive bladder cancers (also called early or superficial) are only in the inner layer of cells (the transitional epithelium) and have not yet grown into the deeper muscle layers.
Papillary carcinomas: Most early non-invasive bladder cancer usually appears as small growths, shaped like mushrooms that grow out of the bladder lining. A surgeon can remove these growths and they may never come back.
Carcinoma in situ (CIS) is flat and does not grow out of the bladder wall. In CIS, the cancer cells look very abnormal and are likely to grow quickly. This is called high grade and is more likely to come back than other types of early bladder cancer.
High grade T1 tumors are early cancers that have grown from the bladder lining into a layer underneath, called the lamina propria. High grade T1 tumors are early cancers, but they can grow very quickly.
Invasive
Invasive bladder cancers have grown into deeper layers of the bladder wall, meaning the cancer has grown into a deeper (muscle) layer of the bladder, or beyond. Some people have invasive bladder cancer when they are first diagnosed.
However, sometimes transitional or urothelial cell bladder cancer can also become invasive. Invasive bladder cancer needs more intensive treatment than early (superficial) bladder cancer. This is because these cancers are more likely to spread and are tend to come back.
Symptoms of Bladder Cancer
Although common too many other conditions, early bladder cancer signs and symptoms may include:
- Blood in urine (hematuria), which may cause urine to appear bright red or cola colored, though sometimes the urine appears normal and blood is detected on a lab test
- Frequent urination
- Painful urination
- Back pain
Once bladder cancer spreads, the following symptoms may also present itself:
- Inability to urinate even when feeling urgent
- Unexplained weight loss
- A loss of appetite
- Swollen feet
- Bones hurting
- Extreme weakness and / or fatigue
Bladder Cancer Types
Urothelial carcinoma
Urothelial carcinoma, also known as transitional cell carcinoma (TCC), is by far the most common type of bladder cancer. As the name suggests, they start in the urothelial cells that line the inside of the bladder. Urothelial cells also line other parts of the urinary tract (incl., the renal pelvis, the ureters, and the urethra). People with bladder cancer sometimes have tumors in these places, too, so all the urinary tract needs to be checked for tumors.
Squamous cell carcinoma
Squamous cells are flat cells that make up the moist skin-like tissues lining your body organs. When squamous cells in the bladder form malignant neoplasms, they are called squamous cell carcinomas. Nearly all squamous cell carcinomas of the bladder are invasive.
Adenocarcinoma
All the moist skin-like tissues lining body organs, including the bladder, have some gland cells that produce mucus. Adenocarcinoma is an uncommon malignancy in the urinary bladder that develops from these cells in the lining of the bladder.
Small Cell Carcinoma
Small-cell carcinomas start in nerve-like cells called neuroendocrine cells. These cancers often grow quickly and is usually treated with the same chemotherapy used for small cell carcinoma of the lung.
Sarcoma
Very rarely, some people get a cancer of the bladder muscle or other structural tissues rather than the bladder lining. Cancers that start in the bladder muscle are called sarcomas and are usually treated differently to other bladder cancers.
Bladder Cancer Medications & Treatments
The oncologist and members of the care team may recommend a combination of treatment approaches.
Pharmaceutical Interventions
- Chemotherapy in the bladder (intravesical chemotherapy), to treat cancers that are confined to the lining of the bladder but have a high risk of recurrence or progression to a higher stage
- Chemotherapy for the entire body (systemic chemotherapy), to increase the chance for a cure in a person having surgery to remove the bladder, or as a primary treatment when surgery isn't an option
- Targeted therapy to treat advanced cancer when other treatments haven't helped
- Immunotherapy to trigger the body's immune system to fight cancer cells, either in the bladder or throughout the body
Non-Pharmaceutical Interventions
Surgery, to remove the cancer cells and include:
- Transurethral resection of bladder tumor (TURBT) remove cancers confined to the inner layers of the bladder
- Cystectomy surgery to remove all or part of the bladder
- Neobladder reconstruction, a urinary diversion in which the surgeon creates a sphere-shaped reservoir out of a piece of your intestine
- Ileal conduit, a urinary diversion in which the surgeon creates a tube (ileal conduit) using a piece of your intestine that runs from the kidneys to an urostomy bag worn on the abdomen
- Continent urinary reservoir, a type of urinary diversion procedure where the surgeon uses a section of intestine to create a small pouch (reservoir) to hold urine, located inside the body from where urine can be drained
Radiation therapy, a form of that uses beams of powerful energy, such as X-rays and protons, to destroy the cancer cells. Radiation therapy for bladder cancer usually is delivered from a machine that moves around the body, directing the energy beams to precise points. It is sometimes combined with chemotherapy to treat bladder cancer in certain situations, such as when surgery isn't an option or isn't desired.
CBD & Bladder Cancer
Research & Scientific Evidence
The clinical evidence for Cannabidiol (CBD) as a viable treatment option for Bladder Cancer is promising and has expanded significantly since 2021.
2021 In Vitro Study
In a comprehensive 2021 study, researchers demonstrated that CBD effectively promoted bladder cancer cell death in multiple cell lines (T24, 5637, and UM-UC-3). When T24 cells were treated with 12 µM CBD for 48 hours, flow cytometry analysis showed that early and late apoptotic cells accounted for 49.91%, indicating CBD's significant ability to enhance cell apoptosis.
To explore the molecular mechanisms, researchers established CBD-treated T24 cell transcriptome libraries. KEGG analysis revealed that significantly changed genes were enriched in the PI3K/Akt pathway. Through qRT-PCR and Western blot assays, they verified that CBD regulated bladder cancer cell growth and migration and induced apoptosis by inactivating the PI3K/Akt pathway.
This study also developed an innovative drug delivery system using chitosan to wrap CBD-loaded PLGA nanoparticles, which significantly enhanced adhesion to mouse bladder walls. The binding efficiency of mucin to chitosan-PLGA nanoparticles reached 97.04% ± 1.90%, demonstrating that this intravesical adhesion system could become a promising means for bladder cancer chemotherapy drug delivery.
2010 In vitro Study
Transient receptor potential (TRP) channels are calcium ion (Ca2+) permeable channels that are thought to contribute to calcium balance inside the cell. Evidence shows that these channels are implicated in the emergence and/or progression of certain epithelial cancers. Based on this, a 2010 study published in Urology, investigated the role of vanilloid 2 (TRPV2) channel proteins in the development of human urothelial carcinoma (UC) cells.
They did this by using CBD (a known selective TRPV2 agonist) to investigate the association between TRPV2 and UC cell death as well as determine whether Ca2+ influx into UC cells through TRPV2 is involved in apoptotic cell death. Focussing on Ca2+ permeable TRP channels expressed abundantly in human bladder cancer cells, they examined, using Ca2+ imaging analysis and biochemical approaches, whether the regulation of channel activity could lead to an inhibitory effect on the viability of UC cells.
They showed CBD induces an influx of Ca2+ into human UC cells, predominantly stimulating TRPV2 channels, and increases Ca2+ in UC cells, with continuous exposure to CBD-mediated apoptotic cell death via these channels. Therefore, although not directly investigating the effects of CBD on UC cells, they showed the mechanism by which CBD causes cancer cell death in UC cancer cells, making it a novel strategy for anti-tumor therapeutics.
2017 In vitro Study
In a later study from 2017 published in Scientific Reports, researchers investigated cannabinoid receptor (CB) expression on normal and human bladder cancer (BC) cells using immunohistochemistry. Again, although the effect of CBD in particular was not investigated, they did draw conclusions about the effectiveness of cannabinoid such as CBD on BC cell growth and motility.
They exposed human BC cells with CB agonists, and assessed for BC cell proliferation, apoptosis, and motility. Their results showed that CB2 receptors may selectively control some cellular functions in BC cells and that altogether supporting the specific use of CB2 as anti-tumor target. In addition, BC cells react to the cannabinoid-induced stress by activating autophagy as a defective survival signal that eventually leads up to apoptosis.
In conclusion, the data reiterates the well-known anti-metastatic properties of cannabinoids, showing a similar molecular mechanism involving CB2 for selective tumor cytotoxicity in BC cells.
2023 Published Study on Combination Therapy
Investigating the potential anti-tumor effects of cannabinoids in bladder cancer, and how cannabinoids could potentially synergize with chemotherapeutic agents, investigators published their results in a 2023 peer-reviewed study in Journal of Cannabis Research. Their study aimed to identify whether combining cannabinoids such as CBD and tetrahydrocannabinol (THC) with chemotherapeutic agents commonly used to treat bladder cancer (BC) are able to produce desirable synergistic effects.
Using concentration curves of the different agents, they identified:
- The range at which each exert anti-tumor effects
- Evaluated the activation of the apoptotic cascade
- Whether cannabinoids have the ability to reduce invasion
They found that both CBD and THC reduce cell viability of BC cell lines. However, cannabinoids in combination with chemotherapeutic agents induced differential responses, ranging from antagonistic to additive synergistic effects.
They concluded that their results indicate that cannabinoids such as CBD can reduce human bladder transitional cell carcinoma cell viability, and that they can potentially exert synergistic effects when combined with other chemotherapeutic agents depending on the concentrations used.
Advanced Delivery Systems
Recent advances in nanotechnology have revolutionized drug delivery approaches for bladder cancer treatment. Nanoparticle-based systems offer significant advantages including targeted delivery, controlled release, and reduced systemic toxicity.
Polymeric Nanoparticles: Polysaccharide-based nanoparticles made with chitosan, either alone or combined with polylactic acid or poly(ε-caprolactone), have shown superior drug delivery capabilities. These systems demonstrate at least similar efficacy to pure drug delivery while providing enhanced targeting and reduced side effects.
Multifunctional Systems: Superparamagnetic iron oxide nanoparticles (SPIONs) combined with polymeric carriers can deliver therapeutic agents while simultaneously serving as MRI contrast agents, enabling both treatment and diagnostic imaging in a single platform.
Enhanced Targeting: Surface functionalization of nanoparticles with targeting ligands and incorporation into in situ gelling systems facilitates controlled drug release for extended periods, significantly improving treatment outcomes for bladder cancer patients.
Cannabis Compounds Beyond CBD
Recent research has expanded beyond traditional cannabinoids to explore other cannabis-derived compounds. Cannflavin A, a flavonoid unique to cannabis, has shown the ability to produce synergistic effects with cannabinoids, gemcitabine, and/or cisplatin in bladder cancer cells, suggesting that multiple cannabis compounds may work together to enhance anti-cancer effects.
Epidemiological Evidence
Interestingly, epidemiological research provides compelling evidence regarding cannabis use and bladder cancer risk. A study following men over an 11-year period found that while tobacco consumption was associated with increased bladder cancer risk, cannabis use alone was associated with a 45% reduction in bladder cancer incidence. This suggests that chronic cannabis use leads to accumulation of several cannabis components in the urine, which may reduce the potential for tumor development in the bladder.
Anecdotal Evidence
The internet is full of stories from people who have effectively treated their bladder cancer with cannabis oil. However, when it comes to CBD and bladder cancer, the anecdotal evidence centres more around CBD being used as a complementary therapy.
CBD as a Complementary Treatment
Most of the available evidence indicates that CBD may complement cancer treatment, and that CBD may help people with cancer by helping reduce pain and inflammation. In addition, many people suffering from cancer also report having other side effects from chemotherapy treatment, including sleep problems, feelings of anxiety and depression.
In one large case series study investigating the effects of CBD on anxiety and sleep, the results show CBD helps improve sleep and/or anxiety in clinical populations. Similarly, CBD can further support cancer patients by reducing stress, anxiety, depression while also helping to promote REM sleep that is thought to help improve overall mood.
Current Clinical Landscape
The bladder cancer treatment landscape has evolved significantly, with numerous immunotherapy trials currently underway. Recent FDA approvals include:
- Pembrolizumab (Keytruda) for BCG-unresponsive non-muscle-invasive bladder cancer
- Combination therapies like Anktiva with BCG showing promising results in clinical trials
The development of biomarkers and circulating tumor DNA (ctDNA) testing is also advancing personalized treatment approaches.
Future Directions
The combination of CBD's demonstrated anti-cancer mechanisms with advanced nanoparticle delivery systems represents a promising avenue for future bladder cancer treatment. The ability to target specific pathways like PI3K/Akt while achieving enhanced tissue penetration through nanotechnology could significantly improve therapeutic outcomes.
Research into cannabis-derived compounds beyond CBD, including cannflavin A and other cannabinoids, suggests that whole-plant extracts or carefully formulated combinations may provide synergistic benefits that surpass individual compounds alone.
Bottom Line
Scientific evidence strongly suggests that CBD can support bladder cancer patients through multiple mechanisms. The recent identification of the PI3K/Akt pathway as a key target, combined with advanced nanoparticle delivery systems achieving over 97% binding efficiency, represents significant progress in translating laboratory findings toward clinical applications.
CBD demonstrates particular promise for reducing chemotherapy-induced neuropathic pain, inflammation, nausea and vomiting, while also supporting overall quality of life through improved sleep and reduced anxiety. The epidemiological evidence suggesting a protective effect of cannabis use adds further support to its potential therapeutic value.
If you or a loved one are suffering from bladder cancer and want to try CBD, talk to your medical practitioner first. He or she can help put together a comprehensive plan that includes CBD along with other treatment options to help manage symptoms safely and effectively. The emerging combination of CBD with advanced delivery systems and conventional therapies may offer new hope for improved outcomes in bladder cancer treatment.
