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Lower urinary tract dysfunctions (LUTDs) are commonly reported in multiple sclerosis (MS) patients and are mainly related to neurogenic overactive bladder (OAB). The aim of this observational study was to assess the effect of a tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray on resistant … Do you have an urge to frequently urinate during the day and at night due to an overactive bladder? Cannabidiol (CBD) may help lessen constant urination.

THC/CBD oromucosal spray in patients with multiple sclerosis overactive bladder: a pilot prospective study

Lower urinary tract dysfunctions (LUTDs) are commonly reported in multiple sclerosis (MS) patients and are mainly related to neurogenic overactive bladder (OAB). The aim of this observational study was to assess the effect of a tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray on resistant OAB by means of clinical and instrumental tools. Twenty-one MS patients were screened, and 15 cases have been evaluated. They underwent a specific clinical assessment (overactive bladder symptom score, OABSS) and a urodynamic assessment evaluating the maximal cystometric capacity (CCmax), bladder compliance (Qmax), maximum detrusor pressure (Pdet max), detrusor pressure at the first desire (Pdet first), bladder volume at the first desire (BVFD), leakage volume (LV), and post-void residual volume (PVR), before and after 4 weeks of THC/CBD administration. A complete neurological evaluation, including the assessment of their spasticity using the Modified Ashworth Scale (MAS) and the spasticity 0-10 numerical rating scale (NRS), was performed at the same times. Mobility was evaluated through the 25-ft walking-time test (T25-WT). The THC/CBD treatment successfully reduced the OAB symptoms (p = 0.001). Regarding the urodynamic findings after the end of treatment, PVR was significantly reduced (p = 0.016). Regarding the urodynamic findings after the end of treatment, PVR was significantly reduced (p = 0.016), while BVFD and CCmax were increased although the difference was not statistically significant. THC/CBD oromucosal spray has shown to be effective in improving overactive bladder symptoms in MS patients demonstrating a favorable impact on detrusor overactivity.

Keywords: Cannabinoids; LUTDs; Multiple sclerosis; Nabiximols; Sativex; Spasticity.

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How CBD May Help With Overactive Bladder

The ECS ( endocannabinoid system) is present in almost all areas of the body (1) .

Evidence suggests that the components of the ECS, including anandamide and cannabinoid receptors, may be involved in bladder function regulation at several levels of the urination (micturition) pathway (2) .

Anandamide is an endogenous cannabinoid or endocannabinoid (3) . Research indicates that the body has receptors for the cannabinoids CB1 and CB2 in the brain, bladder, and other body parts (4) .

CB1, and to a lesser degree CB2, work at different levels on the detrusor muscles (5) . Studies suggest that CB1 receptors may affect urination, and their manipulation with cannabinoids from marijuana may help with overactive bladder (OAB) .

The detrusor muscle contracts during urination to push the urine out of the bladder and into the urethra (6) . When the detrusor muscle is relaxed, it allows the storage of urine in the urinary bladder .

Individuals with OAB may experience urinary symptoms like sudden and frequent urination urges that are hard to control (7) .

While no conclusive data can validate CBD’s benefits for OAB, recent results are promising.

A 2020 study hypothesized that a sudden strong need to urinate that is difficult to delay may result from damage to a descending pathway that starts with the excitatory neurons in the prefrontal cortex (8) .

Meanwhile, research shows that CBD may act on targets throughout the brain, including the prefrontal cortex (9) . Hence, CBD may help individuals with OAB.

CBD, unlike THC (tetrahydrocannabinol), has a very low affinity for cannabinoid receptors (10) . Still, the activation of the cannabinoid receptors can help the detrusor muscles function properly (11) .

Like CBD , THC is a cannabinoid found in the cannabis plant (12) . THC is the predominant psychoactive constituent of cannabis (sometimes called marijuana) (13) .

A 2018 observational study hypothesized that THC-CBD oromucosal spray may effectively improve OAB symptoms in multiple sclerosis patients, demonstrating a favorable impact on detrusor overactivity (14) .

Multiple sclerosis or MS is a disabling illness of the central nervous system consisting of the brain and the spinal cord ( 15) . Urinary tract infections are often experienced by MS patients (16) .

However, some researchers believe that CBD may reduce the efficacy and potency of THC ( 17) .

Benefits of Using CBD for Overactive Bladder

Overactive bladder affects approximately 33 million people in the United States (18) . The condition is not an expected part of aging, contrary to what many people assume. OAB is an actual medical condition that needs treatment.

A pilot prospective study suggested that THC – CBD oromucosal spray may help improve overactive bladder symptoms in MS ( multiple sclerosis ) patients (19) .

Common symptoms of MS are problems with bladder function and spasticity , which causes the muscles to feel heavy and stiff.

A 2020 mini-review article published in the journal Frontiers in Physiology indicated that neural circuits extending from the cerebral cortex to the bladder avoid urinary incontinence (20) .

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Urinary incontinence or leaking urine by accident is common among older people. Research suggests that one-fifth of individuals over 65 will lose some continence control (21) .

The authors of the 2020 mini-review hypothesized that a sudden strong need to urinate that is difficult to delay may result from damage to a descending pathway that starts with the excitatory neurons in the prefrontal cortex (22) .

The prefrontal cortex is the part of the brain covering the front part of the frontal lobe.

Although CBD has multiple targets, it may influence the activity of excitatory and inhibitory signaling pathways. CBD may act on targets throughout the brain, including the prefrontal cortex (23) .

OAB occurs when the nerve signals between the brain and the bladder do not work correctly (24) . Hence, using CBD may be beneficial for people with overactive bladder .

A review article from the University of Leicester stated that dysregulation of the ECS in the human bladder may be responsible for developing OAB and detrusor overactivity ( 25) .

The detrusor muscle is a smooth muscle found in the bladder. Detrusor overactivity refers to a urodynamic observation marked by involuntary detrusor contraction during the filling phase that may be spontaneous or provoked (26) .

A randomized controlled trial involving multiple sclerosis and neurogenic detrusor overactivity patients explored the effect of cannabinoids on reducing urge incontinence episodes without affecting voiding (27) .

About 630 patients were randomized to receive oral administration of the cannabis extract, THC , or matched placebo .

Based on incontinence diaries, there was a 25% reduction in the cannabis extract group. THC indicated a 19% reduction in urinary incontinence episodes relative to placebo .

The results suggested that cannabis may modulate detrusor function (28) .

Any incontinence may affect a person’s overall quality of life. An individual with OAB may also experience emotional distress, anxiety, sleep disturbances, and issues with sexuality (29) .

A 2019 Permanente Journal study suggested that CBD may hold benefits for anxiety-related disorders (30) .

The study consisted of 72 adults with anxiety concerns and poor sleep. About 57 patients reported reduced anxiety scores within the first month and remained decreased during the study duration.

Meanwhile, 48 patients reported improved sleep scores within the first month, although their scores fluctuated over time. CBD was also well tolerated in most participants, excluding three patients.

The results suggested that CBD has a calming effect and may hold benefits for anxiety-related disorders (31) .

While the results of these studies are promising, they are still inconclusive. Hence, further longitudinal research and more clinical trials are warranted to determine the possible benefits of CBD for overactive bladder .

How Long Does CBD Take to Help Overactive Bladder ?

CBD ’s efficacy depends on various factors, including individuals’ body weight, metabolism, CBD potency, and route of administration.

A study hypothesized that THC – CBD oromucosal spray may help with OAB symptoms in patients with multiple sclerosis (32) .

An oromucosal spray may be administered via the sublingual (under the tongue) route. CBD administered sublingually usually takes effect within 15 to 30 minutes (33) .

How Long Will CBD Help With Overactive Bladder ?

CBD is being pursued as a treatment option for several medical conditions , usually by oral delivery (34) .

A systematic search was conducted to retrieve all articles reporting the pharmacokinetic data of cannabidiol in humans (35) .

Out of the 792 articles retrieved, about 24 articles included pharmacokinetics parameters in humans.

The half-life of CBD was reported between 1.4 and 10.9 hours following oromucosal spray, two to five days after chronic oral administration, 24 hours after intravenous therapy (delivery of substances into the veins), and 31 hours after smoking (36) .

The bioavailability of CBD after smoking was 31% (37) .

Half-life is the length of time needed for the concentration of a specific drug to decrease by 50% of its starting dose in the body (38) .

Meanwhile, bioavailability refers to the extent to which a drug or substance becomes entirely available to its intended biological destination (39) .

The Possible Side Effects and Risks of Using CBD for Overactive Bladder

The Food and Drug Administration ( FDA) does not recognize CBD as a medical treatment for overactive bladder .

In addition, like other pharmaceutical drugs, alternative treatments, and supplements, CBD may also carry some risks and side effects .

The most commonly known side effects of CBD include (40) :

  • Dry mouth
  • Diarrhea
  • Reduced appetite
  • Drowsiness
  • Fatigue

Another cause for concern is a possible drug interaction. CBD, when taken with other drugs, may inhibit cytochrome P450 enzyme production at high doses (41) .

Cytochrome P450 enzymes are a family of liver enzymes that metabolize nearly 60% of the pharmaceutical drugs people consume (42) .

Tolterodine is used to treat overactive bladder . It is included in a class of medications called antimuscarinics that relax the bladder muscles (43) .

Tolterodine is also metabolized by cytochromes P450 (44) . Therefore, CBD may interact with tolterodine.

Legality of CBD

The United States Congress ratified the 2018 Farm Bill, decriminalizing the commercial use of industrial hemp and products obtained from hemp plants (45) .

The bill indicates that Cannabis sativa L. and other derivatives of cannabis with no more than 0.3% THC content on a dry weight basis are considered federally legal (46) .

The Federal Comprehensive Drug Abuse Prevention and Control Act of 1970 created a drug schedule to classify substances into five categories based on the potential for drug abuse and possible medical use of various substances (47) .

Some states have passed laws permitting recreational and medical marijuana . However, these state laws do not change the fact that, under federal law, marijuana is still listed as a Schedule I drug (48) .

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Substances listed in the Schedule I drugs have a high abuse potential with no acceptable medical use (49) . Thus, medications under this category may not be dispensed, prescribed, or administered under federal law.

Rules and regulations regarding medical cannabis may be confusing. Therefore, consumers should familiarize themselves with various state laws.

Colorado is one of the states that legalized recreational and medical marijuana (50) .

Under HB 21-1317, Colorado limits the daily purchase of marijuana to two ounces of flower and eight grams of concentrates, like shatter and wax, for medical marijuana patients (51) .

The concentrate limit for medical patients between 18 and 20 is two grams per day (52) .

Exceptions to the limits apply to patients whose physicians confirm in writing that the patients have a physical hardship that should allow them to exceed their daily purchase limits (53) .

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How can CBD help with overactive bladder?

A study suggested that THC – CBD oromucosal spray may help improve overactive bladder symptoms in MS ( multiple sclerosis ) patients (54) .

Another research indicated that the components of the endocannabinoid system may be involved in bladder function regulation at several levels of the urination pathway (55) .

CBD interacts with the endocannabinoid system, consisting of cannabinoid receptors (CB1 and CB2), enzymes, and cannabinoids (56) . The CB1 receptor is widely expressed throughout various peripheral tissues, including the urinary bladder (57) .

CBD may interact with cannabinoid receptors like CB1 at reasonably low concentrations (58) . CB1 plays a role in the pathophysiology of detrusor overactivity associated with bladder outlet obstruction (59) .

What evidence or research exists to say that CBD helps with overactive bladder?

There is limited evidence that suggests CBD helps with OAB ( overactive bladder ).

OAB causes frequent and sudden urination urges that may be hard to control. It occurs when the nerve signals between the brain and the bladder do not work correctly (60) .

A 2020 study hypothesized that a sudden strong need to urinate that is difficult to delay may result from damage to a descending pathway that starts with the excitatory neurons in the prefrontal cortex (61) .

CBD may act on targets throughout the brain, including the prefrontal cortex (62) . Hence, CBD may help people with overactive bladder .

Is there any evidence that CBD can make overactive bladder worse?

There is no evidence suggesting that CBD can make overactive bladder worse.

CBD is relatively safe and is generally well tolerated (63) . However, the compound may still carry risks and side effects such as dry mouth and fatigue (64) .

For this reason, ensure to consult your healthcare provider, especially if you are using CBD products like CBD oil for the first time to help with leakage or bladder control problems.

Will CBD interact with any current medication I may be taking for overactive bladder?

Yes, CBD may interact with any current medications you are taking for OAB .

The non-psychoactive compound may inhibit cytochrome P450 enzyme production at high doses (65) . The cytochrome P450 enzymes are vital for the metabolism of various medications.

Tolterodine, a medication used to treat OAB , is metabolized by cytochrome P450 enzymes (66) . Thus, CBD may interact with tolterodine.

Are there other treatments I should consider alongside CBD to help with overactive bladder?

Ensure to consult your physician first if you are considering other treatments or supplements alongside CBD .

They can advise you regarding risks, possible drug-to-drug interactions, and the best medication for OAB.

Medications for OA include tolterodine, which helps relax the bladder (67) .

In addition, your clinician may suggest behavioral therapies to manage an overactive bladder . Behavioral interventions often work and carry no side effects (68) .

Kegel exercise is a behavioral therapy that may help strengthen your pelvic floor muscles and urinary sphincter.

Meanwhile, bladder training involves training oneself to delay voiding once the urge to urinate is felt.

An individual with OAB may begin with slight delays like 30 minutes and then gradually work their way up to urinating every three to four hours (69) .

Meanwhile, studies show that gosha-jinki-gan (GJG), a traditional Chinese herbal medicine, may help with OAB (70) . However, most clinical trials were done on animal models.

Can I fail a drug test if I use CBD for an overactive bladder?

CBD is non-psychoactive (71) . Hence, it does not cause a euphoric high (72) .

Still, some CBD products like full-spectrum CBD oil have small amounts of THC . This psychoactive compound may build up in the body when taken regularly over as little as four to six days (73) .

An increased THC level in one’s bloodstream may result in a positive drug test.

What is the dosage for an overactive bladder?

The FDA does not recognize CBD as a medical treatment for overactive bladder . Therefore, there is no standard CBD dosage for OAB .

A study from Current Drug Safety stated that chronic use and high doses of CBD up to 1,500mg per day are well tolerated in humans (74) .

Meanwhile, mid-range doses of CBD between 10mg and 100mg per day have been shown to possibly help with pain management , anxiety, and multiple sclerosis (75) .

An individual with OAB may also experience anxiety (76) . Meanwhile, multiple sclerosis patients often experience overactive bladder symptoms (77 ) .

It is crucial to talk with your healthcare provider first if you are considering using CBD to manage OAB symptoms. They can recommend a proper CBD dosage for your condition.

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