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Study: Is CBD the future of chronic bladder pain treatment?

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"Cannabinoids prevent the activation of your pain-sensing neurons"

A first-of-its-kind study using human donors is examining the potential of CBD for treating chronic bladder pain. Cannabis Health speaks to the scientist leading the research.

Chronic pain is an oppressive human health problem that affects millions worldwide. In 2011 alone, the direct and indirect costs of chronic pain were at $600 billion dollars in the USA. This outweighs the costs related to heart disease, cancer, and diabetes combined.

Among these patients are the nearly eight million women and four million men suffering from interstitial cystitis (IC), commonly referred to as chronic bladder pain.

The symptoms of this chronic disease include pelvic pain and urinary storage dysfunctions, which can severely impact quality of life.

There are currently no adequate treatments for people with chronic bladder pain and scientists say new therapeutic approaches are desperately needed to not only prevent pain but also address co-morbidities such as social isolation, depression and anxiety.

A growing body of evidence suggests that cannabinoids could be the answer for treating chronic pain and inflammation. And as the research effort increases, the formulation of novel cannabinoid formulations progresses alongside it.

One of these formulations, developed by Desert Harvest Inc., packages cannabidiol with aloe vera to increase the bioavailability of CBD by 25 per cent.

As with most areas of CBD research, evidence regarding its efficacy is limited, however, a new collaborative study between Desert Harvest and the McGill University Research Centre for Cannabis in Montreal hopes to change this.

The two-phase study aims to validate whether the CBD and aloe vera formulation could alleviate the pain symptoms in a preclinical model of IC.

Dr. Reza Sharif-Naeini

Dr. Reza Sharif-Naeini who leads the study said: “For the past 20 years or so, there hasn’t really been any development of new therapeutic drugs for patients with chronic pain.

“By partnering with industry colleagues, we’re trying to accelerate the speed to market for these analgesics so that the patients can benefit from them.”

The first phase of the study involved a rodent model in which mice were administered a compound that metabolises acrolein in the liver.

The compound then accumulated in the bladder causing tissue damage. The symptoms are similar to human IC, including bladder inflammation, pain and bladder overactivity.

Initial data from the study are encouraging. The researchers demonstrated treatment with the cannabidiol-aloe vera formulation significantly reduced pain symptoms.

“Although we only tested it for seven days, it was enough for us to see a significant reduction in bladder pain experienced by these animals,” Dr Sharif-Naeini said.

“It is a very important and exciting discovery.

“The next step for us is to start testing these compounds on human pain neurons to determine whether the effects can be translated to humans.”

The second phase of the study, expected to begin within the next month, will involve testing the effect of cannabidiol on neurons obtained from deceased human donors.

Dr Sharif-Naemi explained: “We’ve partnered with surgeons in local hospitals, so as soon as a donor dies the nervous tissue, including the pain-sensing neurons, can be harvested and kept alive in a small dish for about two weeks.

“[We] can assess the function of these pain neurons and see what happens when we apply these cannabinoid drugs to them.

“This way, we’ll be able to tell directly whether these compounds would have a beneficial effect on humans.”

The pain transmission pathway can be broken down into three steps. First are pain-sensing cells in the ‘periphery’, such as the skin or, in this case, the bladder. These nerve fibres detect the pain stimulus and transfer the information to the spinal cord.

At the spinal cord, pain transmitting neurons take information up the spine and into the brain where the third step takes place. This final step is referred to as pain interpretation.

“Cannabinoids can affect either one of these steps or all three of them together,” Dr Sharif-Naeini added.

“We think that in the periphery, cannabinoids prevent the activation of your pain-sensing neurons. This means that your nervous system doesn’t even detect the pain information; it is not allowed to enter into your central nervous system.

“This is what we’re going to test in the second phase of these studies.”

Sadly, current pharmacological treatments for chronic pain, mainly opioids, are burdened with severe side effects. A rise in opioid prescription over the past decade has led to what is referred to as the opioid epidemic.

Although not a primary factor, the treatment of chronic pain is thought to be linked to this crisis.

“The absence of proper pain management is one of the contributing factors that led us to the opioid epidemic in America, so there’s really a push to develop new treatments,” Dr Sharif Naeini said.

“There are people doing opioid research to come up with better ways of eliminating the side effects of opioids, but eventually we’re going to come to a place where maybe we have gotten all that we can out of opioids, and we need new alternatives.”

Dr Sharif-Naeini believes that cannabinoids could be a future alternative.

“Cannabinoids are an alternative with high potential. The more studies that are done, the more people can make informed decisions about what [medication] they take for their pain.

“Every time more research comes out it’s great because it allows us to better understand how the cannabinoid system functions.

“The hope is that we can develop better tools that will allow us to reduce pain in some of these intractable chronic pain syndromes, without necessarily affecting the patient’s functioning and cognitive capacity.”

Endometriosis

Does CBD affect endometriosis?

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Illustration of a female ulterus
Statistically one in 10 people with a fertile uterus suffer from endometriosis

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Always Pure Organics’ research assistant Alexandra Gkoutzidou explores the evidence behind the use of CBD to treat and manage the symptoms of endometriosis.

 

What is Endometriosis?

The endometrium is the lining of the uterus that hosts the zygote after fertilisation of the egg[3]. If the egg does not get fertilised, meaning does not embed itself to the endometrium, the endometrium sheds off, causing menstruation.

Then the endometrium will be reconstructed in expectation of the next zygote and shed off again if that does not happen. The endometrium, therefore, is destroyed and reconstructed every month.

When endometrium cells grow in different part of the uterus (other than the endometrium lining) or even the body, this is called endometriosis[2]. The endometrium cells will shed and regrow every month no matter their location in the body, causing lesions, painful periods (dysmenorrhea), pelvic pain, infertility, or subfertility.

Statistically one in 10 people with a fertile uterus suffer from endometriosis, but its cause is not clear yet.

The role of the endocannabinoid system

It appears that the endocannabinoid system (ECS) plays an important role in the normal processes of the female reproductive system[3, 9].

Studies show that proper regulation of the ECS is important to maintain a healthy regulated reproductive system. It has been observed that endocannabinoids’ and their degradative/oxidative enzymes’ expression fluctuate in the female reproductive organ in accordance with the stage of the menstrual cycle[5].

The levels of these endocannabinoids are raised to increase fertility during ovulation and then fall during the luteal phase of the menstrual cycle. Research has shown that this fluctuation of the ECS is not as well-regulated for people suffering from endometriosis.

The results have shown that people with endometriosis have low amount of CB1 receptors in the uterus and abnormal levels of endocannabinoids in their blood during their menstrual cycle.

Evidence shows that in the reproductive system, the use of cannabinoids operates in more than one way.

The way the cannabinoids operate in this system is related to both the amount of expressed cannabinoids and also in the phase of the menstrual cycle. The use of cannabinoids to treat endometriosis, is therefore a complicated case and in such cases it is important to consult a doctor instead of self-medicating, because high levels of the “wrong” cannabinoid, or even at the wrong time of the month could possibly affect ones fertility or cause other gynaecological issues.

What does the evidence say?

McHugh et al [4], researched the effect of THC and N-arachidonyl in the migration of endometrial cells in an animal cell culture. It was observed that while the above two cannabinoids induce migration of the endometrial cells, CBD prohibits it. While this research gives way to more in-depth research for the effect of CBD in human endometriosis, it does not provide sufficient data to claim that CBD is beneficial against endometriosis.

There are two clinical trials currently taking place, researching just that. The first is an open label phase II trial, studying an 1:1 ratio of THC and CBD administered to endometriosis patients to reduce hyperalgesia[6].

The second is a phase III double blind placebo study, where patients will receive norethindrone acetate, a type of hormonal treatment, in accompany with 10 or 20mg of CBD for the management of endometriosis pain[7].

Regardless, a lot of people are already using cannabis and/or CBD to treat the pain derived from endometriosis. Research that took place in Australia investigated the self-management strategies amongst Australian women with endometriosis [8]. This online research was published on social media and invited women to share their own methods of treating their endometriosis symptoms.

The authors suggested that the anonymity of an online research could increase engagement, due to the fact a lot of people use illegal substances to treat pain symptoms. The most common strategies used were self-care and lifestyle choices like heat, rest and meditation, but the most highly effective rated self-reported methods were cannabis, heat, hemp/CBD oil, and dietary changes.

Anecdotal evidence suggests that the use of CBD, THC and possibly other cannabinoids could help treat the pain related to endometriosis, but given the role the ECS has in the uterus there should be more in-depth research in order to realise the factual role CBD plays in endometriosis (if any). The pain sensory system is different to the reproductive system. The role of CBD in pain is well understood and the analgesic effect of CBD in endometriosis pain is probably related to it instead of an effect to the endometrial cells [5, 10, 11].

Nonetheless, CBD has been shown to have positive effects for patients with diseases related to ectopic movement of cells in the body, like cancer and psoriasis. Indeed, CBD has been shown not only to inhibit some cancer cells growth, but also to mediate these cell’s movement to other parts of the body (metastasis) [14, 15, 16].

Similarly, psoriasis is a disease which one of its symptoms is the over production of new skin cells too quickly, that causes the scales. In that case, CBD has been shown to positively affect the skin making it more elastic, better hydrated and reducing the amount of scales by promoting the balanced production of cells and minimising the ectopic production [12]. Similarly, CBD could possibly benefit the ectopic production of endometrial cells but it is yet to be researched.

The levels of cannabinoids in the uterus are strongly related to the phase of the menstrual cycle and they are formed so to increase fertility [9, 13]. Therefore, it is ill advised to use any cannabinoids if you are trying to get pregnant or have a related health problem without advising your doctor and testing whether the endocannabinoid levels are correct during your cycle. A well balanced ECS is the target so always follow the dosage directions.

 

References

[1] https://www.nhs.uk/conditions/endometriosis/

[2] doi: 10.1002/bies.201100099

[3] doi:10.1093/molehr/gas037

[4] DOI:10.1111/j.1476-5381.2011.01497.x

[5] DOI: 10.1089/can.2016.0035

[6] https://clinicaltrials.gov/ct2/show/NCT03875261

[7] https://clinicaltrials.gov/ct2/show/NCT04527003

[8] doi.org/10.1186/s12906-019-2431-x

[9] DOI: 10.1177/1933719114533730

[10] DOI: 10.11607/ofph.1274

[11] https://doi.org/10.1007/s40122-019-0114-4

[12] doi: 10.7417/CT.2019.2116

[13] DOI              10.1186/1471-2202-11-44

[14] DOI: 10.1007/s13105-018-0611-7

[15] doi: 10.17305/bjbms.2018.3532

[16] DOI: 10.3390/ijms2115540

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Case Studies

“CBD allows me to function” – biker ‘died’ three times after freak road accident

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Gary Brennan pictured with wife Shirley
Gary Brennan and wife, Shirley set up a trauma support service after the accident

After a serious motorbike accident, Gary Brennan almost lost his life, undergoing 54 operations to fix his broken body. Gary speaks to Cannabis Health about the “life-changing” accident and how CBD helps to manage the pain 11 years on.

On February 28th 2010, Gary Brennan collided with a car while riding his motorbike.

He broke both shoulder blades, tore his liver, crushed his kidney, shattered his pelvis fractured his spine and suffered from bleeding on the brain and a collapsed lung.

These are just some of the life-threatening injuries that he sustained in the accident.

So severe were his injuries that he was declared dead at the scene of the incident. Paramedics were able to resuscitate him before he was helicoptered to Leeds General Infirmary where he underwent emergency surgery.

During the operation, his heart stopped twice and his family were told that he may have just a few hours to live. He was put into an induced coma and relied on a life support machine to breathe.

Miraculously, Gary survived.

His condition stabilised enough to come out of the coma, but since then he has undergone a total of 54 operations.

When Gary’s condition stabilised enough to come out of the coma he was in excruciating pain. Having battled injuries that doctors deemed barely survivable, the 63-year-old was administered a plethora of drugs to keep the pain under control and has since undergone a total of 54 operations.

“The accident was life-changing to say the least,” Gary told Cannabis Health.

Gary Brennan underwent more than 50 operations

“I got through the operations and everything else, and then I got to the stage where I was lying in bed, zoomed out my head every day of my life with the drugs that I was taking.”

The cocktail of medications including morphine and ketamine kept the pain at bay but according to the father-of-four, it was “destroying” his brain.

Bed-bound, in pain and suffering from a relentless medication plan, Gary slipped into a period of depression and at one point considered suicide.

“I don’t say this lightly,” he said. “It brings tears to my eyes just thinking about it; that I actually even considered it having been a fit, active father-of-four and grandfather-of-six.

“But that was what the drugs were doing to me.”

Gary recalls waking up in the morning “groggy as hell” and in agonising pain until he took his medication.

“All it would do was numb my mind so that I didn’t feel the pain,” he added.

Knowing he had to find an alternative, he looked into CBD.

Although he was sceptical at first and questioned whether the benefits were merely a placebo effect, Gary found that CBD was helping reduce the pain while still allowing him to keep a “clear” head.

“Now I’ve got clarity, I’ve got a clear head, I can get out of bed in the morning. I still get the twinges but it’s not as severe pain,” he continued.

“The pain is always going to be there, but it’s handled in a different way. It doesn’t numb your brain, but the actual place that’s aching. It gives me relief and allows me to function.

“It changed my outlook on pharmaceutical drugs.”

Gary has now come off all prescription drugs apart from one, which he takes “now and then” to lower his blood pressure. Instead, he takes four capsules of CBD each day, equating to 720 milligrams.

Eleven years on from the crash, he has founded his own CBD brand, Brain Body Balance, and is working with US company, Ananda Scientific, to bring its patented Liquid Structure CBD formulation to the UK.

Ananda claims that the nano-sized technology makes its CBD formulation up to 20 times more bioavailable in the first 30 minutes than standard CBD. This is down to its “non-destructive” shell which contains the CBD and is able to pass through the gut and liver without being broken down. The shell only disintegrates when it reaches the small intestine, allowing for a greater amount of CBD to enter the bloodstream.

Ananda’s pharmaceutical-grade CBD is currently undergoing clinical trials to test its efficacy for treating pain, diabetes and mental health conditions including PTSD and anxiety.

Meanwhile, the nutraceutical arm of the company has launched over-the-counter products in the UK and the US through brands like Brain Body Balance.

Gary with one of his six grandchildren.

For Gary, producing a product with high bioavailability was a priority.

“I knew the product itself worked, but actually getting it into the bloodstream where it does its job is the hardest thing to do,” Gary said.

“You have to use stronger and stronger doses in order to get it into your bloodstream.”

Alongside his CBD venture, Gary set up the charity, Day One Major Trauma Support to limit the impact of trauma on patients and families in hospitals across Leeds and the wider Yorkshire area.

“When I was lying in hospital, the doctors would come around once a day and say, ‘how are you feeling, Gary?’, ‘can you feel your toes?’. Then they would say, ‘see you tomorrow’ and off they go,” he said.

“The nurse comes around, gives you your pills, then your family come in, pat you on the head and say it’ll be okay. Basically, that’s all you get.”

Aware of the lack of support, Gary set out to create a service that helped those like him who had suffered from major trauma. The charity provides financial assistance, legal advice and practical and emotional support.

Off the back of its success at Leeds General Infirmary, the charity will now be rolling out its services in all 27 major trauma centres in the UK.

Gary added: “Any help is there first-hand, no matter what, so nobody’s left in the lurch.”

 

 

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Pain

How cannabis medicines can help relieve back pain

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A new webinar will focus on how cannabis medicines can help relieve back pain

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A stand-alone webinar event will focus on the role that cannabis medicines can play in relieving back pain.

This new field of medicine can offer life-changing help to those patients who find that traditional pain medicines and clinical intervention are no longer helping or have unpleasant side effects.

The discussion will explore the potential benefits of the addition of cannabis medicines into a chronic pain management regime for this diverse patient group.

Dr Anthony Ordman

Including injury, wear and tear, musculoskeletal disorders such as scoliosis, axial spa or spina bifida or as a consequence of another underlying health condition such as multiple sclerosis, fibromyalgia, arthritis, Parkinson’s disease or cancer.

The healthcare professionals taking part have many years experience between them in complex pain management and expertise in the treatment of back pain for a variety of conditions.


The panel

Dr Anthony Ordman – consultant pain specialist at Integro Clinics and former president of the Pain Medicine Section of the Royal Society of Medicine

Dr Basil Almahdi – consultant pain specialist at Complex Spine Clinics London

Dr Brian Hammond, PhD – chiropractor & osteopath, CEO National Back Pain Association (BackCare)

Dr Basil Almahdi

The event, hosted by The National Back Pain Association (more commonly known as BackCare or BackPain UK) and Integro Medical Clinics will take place on Thursday 25 May from 7pm-8.30pm.

Click here to book your free place or email jessicasmith@integroclinics.com

For information and support visit Integro Medical Clinics and BackCare

 

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