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The new type of painkiller that could treat side effects of chemotherapy



Researchers are exploring treatments that could reduce pain amongst chemotherapy patients

Drugs targeting the endocannabinoid system hold promise as a novel painkiller, say researchers.

Researchers in the US are exploring treatments that could reduce pain amongst chemotherapy patients, without producing the psychoactive effects associated with THC.

The endocannabinoid system was discovered in the 1990s by researchers in Israel who were looking at the effects of cannabis on the brain. Named after the plant, the system is thought to act as a regulator, keeping the body’s internal functions in equilibrium.

The system consists primarily of endocannabinoids (cannabinoids produced by the body), receptors and enzymes. The two main receptors which endocannabinoids bind to are known as CB1 and CB2.

The stimulation of CB1 receptors is responsible for the medical effects of cannabis as well as its intoxicating effects caused by THC. Meanwhile, CB2 receptors are expressed on cells in the immune system meaning they can produce anti-inflammatory effects without the psychoactive effects associated with CB1 stimulation.

The therapeutic uses of cannabis are not a new discovery.

Ancient texts from China, Iran and India have been found to include information about the medicinal properties of the plant. In 19th century Europe, William O’Shaughnessy introduced cannabis to western countries, leading to the use of cannabis extracts for treating pain and seizure disorders.

Speaking at a New York Academy of Sciences webinar in January, Dr Aron Lichtman, of Virginia Commonwealth University said: “Everything that we think cannabinoids do for the treatment of pain and other disease states, much of this has already been thought through thousands of years ago.

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“Much of the research today and what is thought to be its clinical uses, has really long been known from ancient research on botanicals.”

Lichtman believes there is a “great need” for the development of non-opioid medications to treat pain associated with various diseases and injuries.

According to the scientist, a potential solution could be drugs targeting the endocannabinoid system.

The endogenous cannabinoid system is known to moderate neuronal and immune cell function; two key factors associated with pain.

Chemotherapeutic agents such as Taxanes can have severe dose-limiting side effects, preventing an increase in the level of the treatment.

Sensory neuropathy is a common side effect that can in occur in half of patients. The condition, caused by the damage of the body’s sensory nerves, can be experienced for as long as three years after treatment particularly affecting the hands, fingers, feet and toes.

The condition, known as chemo-induced peripheral neuropathy (CIPN), is resistant to traditional analgesics making treatment difficult.

There have been a number of preclinical studies looking at potential CIPN treatments which have found that CB1 and CB2 agonists can be effective in treating the condition in rodent models.

Much of the current research involves flooding the endocannabinoid system with THC, stimulating the receptors in an effort to reduce pain. Although initial findings have been positive, Lichtman’s research takes a different approach.

He and his team focused on the endocannabinoid regulating enzymes, or inhibitors, which he says also show analgesic effects in rodent models. Specifically, Lichtman’s research looks at the enzyme, monoacylglycerol lipase (MAG lipase) which is expressed widely thoughout the nervous system.

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Its inhibition leads to elevated levels of 2-Arachidonoylglycerol (2-AG), an endocannabinoid that binds to the CB1 receptor. According to a number of animal models, this produces both antinociceptive effects (blocking the detection of pain) and anti-inflammatory effects.

“[This] means that when you inhibit MAG lipase, you’re going to get some stimulation of CB1 and CB2 receptors. This is quite different from what we heard previously about THC where you stimulate receptors everywhere,” Lichtman said.

“In the case of these endocannabinoid regulating enzymes, it’s a lot more localised. These endocannabinoids are believed to be produced and released on demand. So when you block an enzyme such as MAG lipase and raise 2-AG levels, you don’t get the widespread psychotropic effects that you see with cannabis or THC.”

Lichtman’s research involved giving mice an injection of the chemotherapy agent, Pacitaxel. Hypersensitive to heat, the mice were exposed to a filament to create a scenario similar to patients who are treated with chemo agents.

The mice who had been administered Paclitaxel experienced pain, whereas the others did not. When the mice were given a drug that inhibited MAG lipase, the mice appeared to experience less pain.

The research found that repeated administration of the drug led to full tolerance, however, if used at low doses, Lichtman believes MAG lipase inhibitors could be a “promising strategy” to treat CIPN.

Despite these promising results, he stressed that more work is needed to clarify the research findings.

“Preclinical studies are used or completed to show that cannabinoids can be a good treatment for many different indications,” he added.

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“We have to be very careful about that and interpret preclinical data appropriately with limitations and acknowledge the importance of clinical trials.”


Spain approves first cannabis based medicine

The approval for Epidyolex was based on the results of four randomised controlled Phase III trials



Spain cannabis: A Spanish flag in the air with an old building behind it

Spain has approved the first cannabis based medicine, Epidyolex for patients with severe conditions such as epilepsy.

Epidyolex, an oral cannabis-based medicine, has been approved in Spain by the Ministry of Health after a large two-year trial. The approval for Epidyolex was based on the results of four randomised controlled Phase III trials. The clinical development of the therapy was spread over 10 different hospitals.

The trial involved over 700 participants with severe forms of epilepsy.

Until recently, there was no distinction between recreational and medicinal cannabis use in Spain which made it difficult to obtain products with higher quantities of 0.02 percent THC.

The medicine will only be available in hospital pharmacies for the treatment of seizures caused by Lennox-Gastaut Syndrome (LGS) and Dravet Syndrome (DS).

Spain and medical cannabis

Speaking at a press conference, neurologist Vicente Villanueva, head of the Refractory Epilepsy Unit of the Hospital Universtiari i Politècnic La Fe de València said the trials have found a 40 percent reduction in seizures.  “As clinicians and researchers, we are satisfied to have these new options”, 

Antonio Gil-Nagel Rein, a neurologist and director of the Epilepsy Program of the Hospital Ruber Internacional de Madrid reported: “The potential improvement of the quality of life in an area where therapeutic options are very small is good news. Access to a new drug with a novel and clinically proven mechanism of action is a reason for hope for patients and satisfaction for specialists.”

Epidyolex received approval from the European Commission in September 2019. This made it the first cannabis-based prescription medicine to receive authorisation.

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Read more: Can cannabis reduce the side effects of anti-seizure medication?

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Royal Society of Medicine and Integro Clinics announce pain and cannabis medicines event

The event takes place on October 11 from 8:30 to 17:30. It will explore the potential of cannabis medicines in the field of pain medicine in the UK



Event: The Royal Society of Medicine logo in green and red on a white background

The Royal Society of Medicine has announced a collaborative event, Pain and cannabis medicines: Everything you want to know (but were too afraid to ask) in association with Integro Medical Clinics.

The event takes place on October 11 from 8:30 to 17:30. It will explore the potential of cannabis medicines in the field of pain medicine in the UK

Since the legalisation of cannabis medicines on prescription in November 2018, patients and clinicians alike have been awaiting more data or information regarding these medicines. 

The event aims to provide those attending with a comprehensive understanding of the uses of cannabis medicines and the practicalities of using them in their own practice. It will consist of presentations on the history, regulatory environment and pharmacology of cannabis medicines including the use of different cannabis-based medical preparations in treating pain and related symptoms in a wide variety of clinical fields in the context of the current UK regulatory framework. 

Event presentations

The day will feature presentations from international leaders in cannabis medicines such as Professor Raphael Mechoulam, the chemist who discovered the endocannabinoid system and THC, Dr Anthony Ordman, Leading UK Consultant in Pain Medicine and previous President of the Pain Medicine Section of the Royal Society of Medicine and Dr Arno Hazekamp PhD, who worked as Head of Research and Education at Bedrocan, the first European company to produce EU GMP grade cannabis medicines.  

If you wish to sign up, please click here.

Event speakers
Dr Anthony Ordman, Consultant in Pain Medicine

Event: A black and white headshot of Dr Anthony Ordman Founder of the highly respected Chronic Pain Clinic at London’s Royal Free Hospital, he is one of the UK’s most experienced specialists in the treatment of pain. For his contributions to Pain Medicine, Dr Ordman was awarded a Fellowship of the Royal College of Physicians in 2005, and he is the Immediate Past President of the Pain Medicine Section of the Royal Society of Medicine. Dr Ordman is also Senior Medical Consultant and Lead Clinician at Integro Medical Clinics and has a special interest in the potential benefits of cannabis medicines in pain medicine.

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Alex Fraser, Patient Access Lead at GrowPharma

Event: A black and white headshot of guest speaker Alex FraserAlex Fraser is a leading medical cannabis patient advocate. He is a patient himself having been diagnosed with Crohn’s Disease in 2010 at 19 years old. In 2014 he founded the United Patients Alliance and has since appeared on mainstream media multiple times, including on the BBC and ITV, to highlight the urgent need for access to cannabis medicines for the many patients who may benefit from them. He has taken delegations of patients to parliament to give testimony to politicians at the highest levels and organised educational events, rallies and protests calling for law change on medical cannabis. In February 2019 Alex joined Grow Pharma, one of the leading suppliers of cannabis medicines in the UK, as their patient access lead. He utilises his extensive knowledge of medical cannabis, his understanding of patient needs and his network in the industry to ensure patient voices are heard and represented. His work includes informing top-level policymakers, educating healthcare professionals and conceiving and running projects that increase general awareness and provide practical help for patients.

Professor Raphael Mechoulam, Professor of Medicinal Chemistry at the Hebrew University of Jerusalem in Israel

Event: A black and white headshot Most well-known for the total synthesis of delta-9 tetrahydrocannabinol (THC) and the discovery of the Endocannabinoid System. Since the inception of his research in the 60s, Professor Mechoulam has been nominated for over 25 academic awards, including the Heinrich Wieland Prize (2004), an Honorary doctorate from Complutense University (2006), the Israel Prize in Exact Sciences – chemistry (2000), the Israel Chemical Society Prize for excellence in research (2009) and EMET Prize in Exact Sciences – Chemistry (2012

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Dr Sally Ghazaleh, Consultant Pain Specialist

Event: A black and white headshot of a guest speakerDr Sally Ghazaleh, is a Pain Management Consultant at the Whittington Hospital, and the National Hospital of Neurology and Neurosurgery, London. She qualified from the University of Szeged Medical School, Hungary in 2000, and then completed her specialist training in the Anaesthesia and Intensive Care Medicine at Semmelweis University in 2007. She went on a fellowship at University College Hospital, London, to gain her higher degree in Pain Medicine

During her time at the pain management Centre at University College Hospital, she gained extensive experience in dealing with and managing patients with complex multiple pain problems. She is accomplished at a variety of interventional and non-interventional treatments for this specific patient group. Sally specializes in managing patients with lower back pain, neck pain, neuropathic pain, abdominal pain, cancer pain, complex regional pain syndrome, post-stroke pain and Fibromyalgia. She has a particular interest in bladder and abdominal pain in women, and women’s health in general.

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Celebrities including Drake call for a general pardon for those involved in cannabis offences.

There are over 150 signatures from rappers, artists, producers, law enforcement and more.



Celebrities: A judges gavel on a wooden table next to a green cannabis leaf

Over 150 celebrities including the rapper Drake and NBA athletes have signed an open letter to President Biden calling for a general pardon of non-violent cannabis offences.

NBA athlete Al Harrington, rapper Drake, world champion boxer Badou Jack, rapper and activist Killer Mike, NBA star John Wall along with Meek Mill and Julio Jones announced at a live-streamed event that they have co-written and signed a letter addressed to President Joe Biden. The letter requests a general pardon for ‘all persons subject to federal criminal or civil enforcement on the basis of a nonviolent marijuana offence.”

The idea for the letter to president Biden came from Weldon Angelos of the Weldon Project/ Mission Green and Academy for Justice Director Erik Luna. The Weldon Project aims to help fund social change and financial aid for those who are still serving prison time for cannabis-related offences. Angelo was an emerging musician before he was sent to prison for selling less than $1,000 worth of cannabis.  Despite it being his first offence,  Angelos went on to service 13 years of his term before eventually being released in 2016. He founded the project upon being released.

The letter includes signatures from 150 athletes, artists, law enforcement officials, academics, business leaders, producers, lawmakers, policy experts, reform advocates and other professionals.

It reads: “This resolve is witnessed today in both red and blue states, from coast to coast, as the American people call for an end to cannabis prohibition. Whatever one thinks of other drugs and other defendants, incarcerating cannabis offenders in federal prisons is a misuse of our nation’s resources and grossly hypocritical, given that a clear majority of Americans oppose cannabis prohibition and about half admit to using the drug during their lifetime.”

The live-streamed event discussed the letter to President Biden while placing an emphasis on a call for a general pardon. Speaking with Benzinga, Angelos said that the celebrities who had signed the letter had done so in support of a fellow artist, Ralo who is facing eight years for a cannabis offence. Despite several states switching to safe, regulated cannabis programs.

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“When Biden ran for president, he promised to take action and use the pardon power of the presidency to release those serving prison time for marijuana and pardon their felony convictions,” Angelos said. “At a time when dispensaries are as prevalent as liquor stores in some states, it is time for President Biden to now make good on that promise.”

In a press release, Ralo said: “I appreciate my friends and peers in the hip-hop community, such as Drake & Killer Mike, for supporting my clemency because it’s just not right that corporations are allowed to violate federal law and become millionaires while people like myself go to prison for years,”

He added: “This is hypocrisy. But I am hopeful that Joe Biden will honour his campaign promise and grant us clemency, without delay, so that we can return home to our families and communities.”

Angelos also highlighted that the long term effects for those incarcerated ‘go beyond the prison walls’ making it difficult for former prisoners to get jobs, access to affordable housing or educational loans. “They’re limited in so many ways that people don’t realize when they just want to begin again and contribute to society. Enough is enough. No one should be locked up in federal prison for marijuana.”

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