CBD for Overactive Bladder
The sudden urge to go to the bathroom multiple times in a short period, or involuntary urine leaks at unfortunate times, is not only irritating and uncomfortable but could be embarrassing too. This condition where the bladder squeezes urine out at a wrong time is known as an overactive bladder.
Overactive bladder, or also called OAB, is challenging to control. One may feel the need to pee many times during day and night, and may also experience unintentional loss of urine (urgency incontinence) (1).
The first sign of OAB is the sudden urge to urinate that cannot be ignored. Also, the frequency of visits to the bathroom to leak is usually eight (8) or more times within 24 hours. Notably, individuals having OAB might experience nocturia or waking up more than two (2) times at night to urinate (2).
Often the cause is unknown. However, nerve problems, too much fluid intake, and drinking of caffeinated drinks such as coffee and tea could be factors for this disorder (3).
The bladder works in such a way that when it is filled up, the nerve sends signals to the brain that would trigger the need to urinate. These coordinated nerve signals would tell the muscles in the urethra and pelvic floor to either contract or relax. When the bladder muscles tighten, it will push our urine (4).
In most OAB cases, the bladder muscles start to contract involuntarily even when the bladder is not yet full. These involuntary tightening of the bladder muscle creates the urgency to urinate (5).
Having an overactive bladder could affect and disrupt a person’s social life. One might feel embarrassed and might limit work and social life.
A leaky bladder is not something you have to worry about forever. Researches revealed that cannabis could act on the brain and bladder signaling pathways.
The ECS or Endocannabinoid system is widely distributed in the urinary bladder. The cannabinoid receptors are present in the lower urinary tract as well as spinal and higher centers involved in lower urinary tract control (6).
The effect of cannabis on bladder activity is probably mediated through the mechanism that is dependent on the endocannabinoid receptors (7).
It is far from clear on how the mechanism of ECS and CBD affects one another. And the published data on the expression and functional sites of the cannabinoid receptors in the bladder are contradictory (8).
It is well established that the ECS binds to cannabinoid receptors CB1 and CB2. In the case of the urinary bladder, since CB1 is more present than CB2, the CB1 receptor binds to the ECS, resulting in the relaxation of the bladder during the filling up phase. (9)
The CB1 receptors are mainly found at the central and peripheral neuron terminals of the bladder, inhibiting neurotransmitter release (10).
In the study done by the University of Naples, Federico II, it showed that the contractions of the bladder were reduced in the bladders of both mice and humans (11).
Another study at University of Leicester indicated that cannabis could be used to treat overactive bladders. The patients with neurogenic hyperactivity of the detrusor muscle (the muscle responsible for draining the bladder) experienced relief from urinary incontinence after taking extract containing high levels of THC (12).
Despite the good results of THC, researchers are exploring more the use of CBDs as an alternative to the psychoactive effects of THC. CBD is the cannabis derivative that has more medicinal benefits and without the “high” after effect.
Medications used to treat overactive bladder are to calm the nerves. Similarly, cannabis can have a similar effect.
One study used the THC/CBD oromucosal spray to treat patients with multiple sclerosis (MS) overactive bladder. The result showed to be effective in improving overactive bladder symptoms in MS patients. It demonstrates a favorable impact on detrusor overactivity (13).
In a meta-analysis done in 2017 of scientific articles on human trials, there were three studies using THC or combination of THC and CBD on the efficacy of these compounds to the overactive bladder patients with MS (14).
On the same meta-analysis, researchers used the capsule or oromucosal spray. It was conclusive that cannabis treatment had decreased the incontinence episode in all three studies significantly (15).
Side-effects were noted, such as dizziness, headaches, vomiting, UTI, and dry mouth on patients that received treatment through a spray. However, there was no side-effect in tablet trials (16).
Moreover, these side-effects were mild compared to other conventional treatments. It is not known though if synthetic drugs or natural plant extracts were used (17).
With the spur of research on cannabis, it remains to be seen whether CBD will be as effective without having it combined with THC for OAB patients.
Overactive Bladder is socially disruptive because it could disrupt a person’s activity. The sudden and frequent back and forth to the comfort room, and unfortunate urine leak because of loss in bladder control is not only irritating but embarrassing.
The cause of such bladder dysfunction is not well established, but it may be due to lifestyle and nerve disorders.
Interestingly, ECS is widely distributed in the urinary system. And it is a known fact that cannabinoid receptors bind with the ECS. In this case, CB1 receptors are in the works.
Moreso, studies have shown that THC, CBD, or a combination of these two has significantly influenced the contraction and relaxation of the bladder.
However, researchers are exploring more the use of CBD for AOB treatment because of its medicinal use, rather than THC mainly because of psychoactive effects.
Three studies show that the oromucosal spray has been effective in OAB patients with MS. There were notable side-effects, but it is mild compared to other treatments.
There is no established standard dosage for CBD use for OAB. Thus, it is encouraged to best consult a doctor expert on cannabis before administering CBD to patients with OAB.
UTI occurs when bacteria gets into the urinary system, which includes your kidneys, bladder, ureters, and urethra.
Females are more likely to acquire UTI than males. Infection in the bladder can be excruciating and upsetting. It can also have serious implications when it spreads to the kidneys. (1)
The lining of the bladder and urethra turns red and sore when one experiences a UTI. This causes pain in the pelvic part of the lower abdomen and lower back. The most common symptom is burning or pain while urinating.
There is a feeling of an intense need to urinate, but only a few drops are secreted. It is because the bladder is so distressed that it makes one feel like urinating, even though there is not much urine inside the bladder. The urine of a person with UTI also smells unpleasant.
This condition needs to be treated immediately because a kidney infection can spread to the bloodstream and cause a more severe health problem. (2)
CBD has wide-ranging activity in terms of reducing inflammation and the damaging effects of free radicals.
Here is how CBD works to lessen the inflammation we suffer during UTI. Once the urinary tract is infected, our body's protection mechanism starts to combat this infection. It directs a number of immune cells to the affected part to get rid of any pathogens that may damage the body. This results in inflammation and pain. CBD may have anti-inflammatory and analgesic properties that may reduce the effect of UTI by lessening the swelling and pain, and may help fight the bacteria that has infiltrated the body. (4)
CBD increases the endocannabinoid 2-ag, which reduces the number of immune cells being sent out. CBD not only helps with inflammation but can also help with treating pain. CBD also raises the endocannabinoid anandamide, which helps in reducing your pain sensitivity. (5)
CBD may also be a powerful antibacterial that can help destroy some of the most drug-resistant bacteria. It has been promoted for a wide range of health benefits and can be used as a treatment for people with UTI. A study reveals that CBD is remarkably effective in killing bacteria, including those responsible for many severe infections, such as staphylococci and streptococci. (6)
Urinary tract infections are quite common. However, this can be extremely painful and uncomfortable. Some cases lead to worse conditions. One must know how to spot UTI symptoms before they get too serious and get the right treatment that is needed.
CBD has emerged as a solution to a variety of medical conditions and CBD work continues to grow and validate its effectiveness across a wide variety of health concerns, including its impact on UTI.
As previously mentioned, the positive results suggest that CBD may have healing effects on UTI due to its anti-inflammatory, antibacterial, and pain-relieving properties.
Good hygiene and staying hydrated are some of the safe practices to prevent urinary tract infection. Most importantly, people who are experiencing aches, chills, or fever associated with kidney infections or symptoms that are indicative of a UTI must see the doctor immediately.
Summary for UKPID OXYBUTYNIN Helen Seymour, BPharm (Hons) National Poisons Information Service (Newcastle Centre) Regional Drug & Therapeutics Centre Wolfson Building Claremont Place Newcastle upon Tyne NE1 4LP UK This monograph has been produced by staff of a National Poisons Information Service Centre in the United Kingdom. The work was commissioned and funded by the UK Departments of Health, and was designed as a source of detailed information for use by poisons information centres. Peer review group: Directors of the UK National Poisons Information Service. SUMMARY Type of product For treatment of urinary incontinence Ingredients Oxybutynin hydrochloride 2.5mg, 5mg Tablets - 2.5mg, 3mg, 5mg Elixir - 2.5mg/5ml Toxicity Is mainly due to anticholinergic effects at autonomic nerve endings and in the brain. Common systemic features Systemic features of toxicity include flushing, dilated pupils, dry mouth and tongue, hot dry skin, sinus tachycardia, ataxia, nystagmus, drowsiness and delirium with confusion, agitation and visual hallucinations. Uncommon systemic features Coma, convulsions, cardiac conduction abnormalities and dysrhythmias, urinary retention. Management 1. Give oral activated charcoal if ingestion has occurred within 2 hours. 2. Observation without other specific treatment will be sufficient for the majority of patients. In seriously poisoned patients the following measures may be required: 3. Ensure a clear airway. 4. Carry out arterial blood gas analysis in patients who are deeply unconscious. 5. Assisted ventilation is indicated if hypercapnia is present. 6. Correct hypoxia. 7. Correct hypotension by raising the legs above the level of the trunk. If this is ineffective, insert a central venous line and expand the intravascular volume. Dopamine may be necessary in addition in the most severe cases. 8. Rewarm slowly using conventional methods. 9. Treat skin blisters as burns. 10. Control convulsions with intravenous diazepam, 10mg. 11. Control delirium with oral diazepam (doses upto 20-30 mg every 2h may be required)/. 12. Resist the temptation to treat dysrhythmias with antiarrhythmic drugs. Correct hypoxia and acidosis and even in the absence of acidosis give 50mmol sodium bicarbonate intravenously. 13. Forced diuresis, haemodialysis and haemoperfusion are of no value. SUBSTANCE Oxybutynin Hydrochloride ORIGIN OF SUBSTANCE Synthetic NAME Brand Name Cystrin Ditropan Generic name Oxybutynin CHEMICAL GROUP Drugs for urinary frequency, enuresis and incontinence. BNF 7.4.2 SUBSTANCE IDENTITY REFERENCE NUMBER CAS 5633-20-5 (oxybutynin) 1508-65-2 (oxybutynin hydrochloride) Product licence number Cystrin 3mg 3433/0145 Cystrin 5mg 3433/0146 Ditropan elixir 13374/0003 Ditropan 2.5mg 13374/0001 Ditropan 5mg 13374/0002 MANUFACTURER Cystrin (+ generic oxybutynin) Pharmacia and Upjohn Davy Avenue Knowlhill Milton Keynes Bucks MK5 8PH Tel: 01908 661101 Fax: 01908 603051 Ditropan Smith and Nephew Healthcare Ltd. Healthcare House Goulton Street Hull HU3 4DJ Tel: 01482 222200 Fax: 01482 222211 PRESENTATION Form Tablets 2.5mg, 3mg, 5mg Liquid 2.5mg/5ml Pack sizes Cystrin 3mg 100 tablet pack Cystrin 5mg 100 tablet pack Ditropan 2.5mg 84 tablet pack Ditropan 5mg 84 tablet pack Ditropan elixir 150ml bottle PHYSIOCHEMICAL PROPERTIES Chemical structure C22H31NO3.HCl 4-Diethylaminobut-2-ynylalpha-cyclohexylmandelate hydrochloride Physical structure at room temperature Solid Colour White Odour Practically odourless Viscosity NA pH NA Solubility Freely soluble in water and alcohol Very soluble in methylalcohol and in chloroform Soluble in acetone Very slightly soluble in hexane USES Indications Urinary frequency and incontinence, neurogenic bladder instability and nocturnal enuresis Therapeutic dosage Adults 5mg 2-3 times a day, increased if necessary to a maximum of 5mg four times a day Elderly 2.5mg - 3mg twice daily initially, increased to 5mg twice daily according to response and tolerance Child (over 5 years): Neurogenic instability - 2.5mg - 3mg twice daily increased to 5mg twice daily (maximum 5mg 3 times a day) Nocturnal enuresis (preferably over 7 years) - 2.5mg - 3mg twice daily increased to 5mg 2 - 3 times daily Contraindications Intestinal obstruction or atony, severe ulcerative colitis or toxic megacolon; significant bladder outflow obstruction; glaucoma, myasthenia gravis Abuses NIF HAZARD/RISK CLASSIFICATION NIF PHARMACOKINETICS Absorption Oral - approx. 100% Distribution Throughout most of the body, with high concentrations in the stomach, intestines and liver, but only very small amounts are found in the central nervous system Metabolism approx. 94% undergoes first pass metabolism Elimination Very little unchanged drug is excreted in the urine Half-life Range 0.84h - 2.90h Mean 1.6h Breast milk Likely to be excreted TOXICOKINETICS NIF EPIDEMIOLOGY OF POISONING There is one report in the literature of oxybutynin overdose. ADVERSE EFFECTS Commonly reported adverse effects include dry mouth, constipation, blurred vision, nausea, abdominal discomfort, facial flushing and difficulty in micturition. Less frequently reported side effects include headache, urinary retention, dizziness, dry skin, diarrhoea and cardiac arrythmias. INTERACTIONS Other anticholinergic drugs Phenothiazines, amantadine, butyrophenones, levodopa, digitalis and tricyclic antidepressants MECHANISM OF ACTION Oxybutynin has anticholinergic and direct antispasmodic actions. The myorelaxant effects may reduce bladder spasm thus decreasing frequency of micturition. FEATURES OF POISONING Acute Ingestion: Common systemic features Systemic features of toxicity include flushing, dilated pupils, dry mouth and tongue, hot dry skin, sinus tachycardia, ataxia, nystagmus, drowsiness and delirium with confusion, agitation and visual hallucinations. Uncommon systemic features Coma, convulsions, cardiac conduction abnormalities and dysrhythmias, urinary retention. MANAGEMENT Prevention of absorption may be accomplished by giving activated charcoal/cathartic. Treatment is primarily supportive and includes monitoring for the development of seizures, hypertension, rhabdomyolysis, and arrhythmias. If the patient is deeply unconscious carry out arterial blood gases. Assisted ventilation is indicated if hypercapnia is present. Correct hypoxia. Correct hypotension by raising the legs above the level of the trunk. If this is ineffective, insert a central venous line and expand the intravascular volume. Dopamine may be necessary in addition in the most severe cases. Control convulsions with intravenous diazepam. Control delirium with oral diazepam (doses upto 20-30 mg every 2h may be required). Resist the temptation to treat dysrhythmias with antiarrhythmic drugs. Correct hypoxia and acidosis and even in the absence of acidosis give 50mmol sodium bicarbonate intravenously. Physostigmine is rarely used except in cases of otherwise refractory life-threatening emergencies and as a diagnostic challenge. Avoid when ingestion of tricyclic antidepressants is suspected. Bethanechol has been used to alleviate peripheral anticholinergic side effects. Alkaline diuresis and mannitol may be used to treat rhabdomyolysis. Peritoneal dialysis and hemodialysis are ineffective. Investigations Serum levels of anticholinergic drugs are not clinically useful. Monitor serum electrolytes, renal function and CPK levels in patients with prolonged seizures or coma. CASE DATA 1. Banerjee et al (1991) reported anticholinergic effects following ingestion of 100mg of oxybutynin in a 34 year old female. She had a sinus tachycardia which resolved 3 hours after admission, and in addition ventricular ectopics and bigeminy which continued for a further 30 hours. She recovered fully on symptomatic treatment alone.2 ANALYSIS NIF PREVENTION OF POISONING NIF OTHER TOXICOLOGICAL DATA Teratogenicity A small risk cannot be excluded, but a high risk of congenital anomalies in the children of women treated with oxybutynin during pregnancy is unlikely. No epidemiological studies of congenital anomalies among infants born to women who were treated with oxybutynin during pregnancy have been reported. An increased frequency of ventricular septal defects and decreased postnatal growth were observed among the offspring of pregnant rats treated with 250 times the usual human dose of oxybutynin in one study (Edwards et al., 1986). Such doses also produced maternal toxicity. No teratogenic effects were seen in rats after maternal treatment with 10-50 times the human therapeutic dose or in rabbits after maternal treatment with 8-120 times the human therapeutic dose of oxybutynin during pregnancy (Edwards et al., 1986). Author Helen Seymour, BPharm (Hons) National Poisons Information Service (Newcastle Centre) Regional Drug & Therapeutics Centre Wolfson Building Claremont Place Newcastle upon Tyne NE1 4LP UK This monograph was produced by the staff of the Newcastle Centre of the National Poisons Information Service in the United Kingdom. The work was commissioned and funded by the UK Departments of Health, and was designed as a source of detailed information for use by poisons information centres. Peer review was undertaken by the Directors of the UK National Poisons Information Service. Last updated November 1996 REFERENCES 1. Edwards JA, Reid YJ, Cozens DD: Reproductive toxicity studies with oxybutynin hydrochloride. Toxicology 40:31-44, 1986. 2. Banerjee S, Routledge PA, Pugh S and Smith PM. Poisoning with oxybutynin. Hum Exp Toxicol 1991; 10: 225 - 226. 3. Martindale: The Extra Pharmacopoeia. 31st Edition. Reynolds JEF (Ed.). Pharmaceutical Press 1996. 4. ABPI Compendium of Data Sheets and Summaries of Product Characteristics. Datapharm Publications Ltd. 1996-97 5. Therapeutic Drugs. Dollery C. (Ed.). Curchill Livingstone. 1991 6. British National Formulary. Number 32 (September 1996). British Medical Association and Royal Pharmaceutical Society 7. Poisindex System(R), Micromedex, inc., Denver Colorado, Edition Expires 31.12.96 8. Teratogen Information System (TERIS)(R), Micromedex, Inc., Denver Colorado, Edition Expires 31.12.96