Science Medical cannabis conundrum

The phytocannabinoid CBD is proven to be effective in treating illness and pain, but safety and ethical concerns are limiting a growth industry

In 2017, Mikael Sodergren, a liver and pancreatic cancer surgeon at Imperial College healthcare NHS trust, was becoming increasingly interested in the potential role of medical cannabis in treating pain, especially the discomfort experienced by patients after complex operations.

“I hope that I do a lot of good, but unfortunately in the short term, I inflict a lot of pain with cancer surgery,” he said. “So we’re reliant on pretty nasty painkillers, such as highstrength intravenous opioids, which we’re trying to move away from.”

Over the past 15 years, an increasing number of scientists have become interested in the potential benefits of medical cannabis for treating all kinds of illness, from multiple sclerosis to anxiety, sleep disorders and posttraumatic stress disorder.

The reason is that phytocannabinoids – chemicals that occur naturally in the cannabis plant – bind to receptors on the body’s endocannabinoid system, a complex cell-signalling network stretching throughout the body, which is involved in neurological functions ranging from pain-sensing to regulating the sleep-wake cycle.

The phytocannabinoid that has received the most attention of all is CBD. Some studies have suggested it might be capable of desensitising pain neurons connected to the endocannabinoid system, while it has been shown repeatedly to have antiinflammatory effects, which can help reduce seizures in those with childhood epilepsy.

Medical cannabis is a complex and contentious field, because it is not just one drug. There are more than 400 different phytocannabinoids in the cannabis plant and while some treatments consist solely of CBD, others use the whole plant extract. The more controversial treatments blend varying concentrations of CBD and tetrahydrocannabinol (THC), the psychoactive element of cannabis, which elicits the “high” experienced by recreational users. While some studies suggest THC might be effective at enhancing the effects of CBD, it has also been linked with an increased risk of psychosis.

“Most major safety concerns are related to THC products, but there are also some safety concerns around the use of CBD products,” said Susan Weiss, director of the Division of Extramural Research at the National Institute on Drug Abuse, in the US. “The main safety concerns involve the use of a smoked product, which can lead to a chronic cough and bronchitis, and risks for certain populations such as those with a family history of schizophrenia or psychosis.”

While laws were changed in November 2018, allowing medical cannabis to be legally prescribed in the UK for the first time, the National Institute for Health and Care Excellence (Nice)

‘We’ve seen this with tobacco, which was once advertised as a way to reduce anxiety’

has only licensed three CBD-based treatments for use on the NHS. These are available only for three rare types of childhood epilepsy, the vomiting and nausea associated with chemotherapy and multiple sclerosis-related spasticity.

It is estimated that up to 1.4 million people in the UK are using cannabis for medical purposes, but while some of these individuals are being prescribed products by private GPs and pharmacies, others are buying CBD oils of different concentrations from health food shops or the whole plant extract from recreational dealers.

Private clinics around the globe have begun to create medicalcannabis registers to collate data on the types of cannabis that have proved effective and on any potential safety issues, which they hope will persuade Nice, and other regulators, to improve access to medical cannabis.

Data collection

In December 2019, Sodergren established the UK Medical Cannabis Registry, to follow patients who have been prescribed various medical cannabis products by clinicians at the private Sapphire Medical Clinics practice for a range of different ailments.

In May 2021, results were released for the first 129 patients. These showed significant improvements in anxiety, pain and sleep-quality measurements after one and three months. Intriguingly in the context of pain, the treatments appeared to be better tolerated than conventional opioids.

Similar registers are being run by the non-profit research organisation Drug Science, while the Cannabis Care clinic in Auckland, New Zealand, has been following 253 patients on CBDbased treatments.

Sodergren is hopeful this could lead to medical cannabis being regarded as a mainstream method of treating pain. “It’s coming,” he said. “I think in five to 10 years we’re going to have an NHS-licensed drug for pain.”

However, others feel the evidence base remains sparse, especially for complex conditions such as anxiety. Because the UK Medical Cannabis Registry data covers a range of different forms of medical cannabis, some say it does not help with the tricky question of working out the best formulation and dose to use for a particular disease.

“The main issue we have is that medical cannabis use is still very poorly defined,” said Marta Di Forti, a psychiatrist at King’s College London. “When I have patients who want to buy CBD over the counter and try it, my recommendation is that they start with the lowest recommended dose and monitor if they experience any adverse side-effects, because we still know so little.”

The consensus is that CBD-based medical cannabis is likely to become more widely available as a treatment for different forms of epilepsy, because of its known anti-seizure effects. The CBD-based medication Epidyolex is already licensed by Nice to treat three rare childhood epilepsies.

Recreational lobbies

Some scientists are concerned about how the growing interest in medical cannabis has been linked to organisations aiming to open up parallel and lucrative recreational markets for the drug. Last year, an investigation by the British Medical Journal uncovered connections between organisations researching the use of medical cannabis, such as Drug Science and the Centre for Medicinal Cannabis, with companies lobbying for wider access to recreational cannabis in order to cash in on a great, green windfall.

The potential rewards are obvious. According to Prohibition Partners, a marketing consultancy with a stated mission to open up the international cannabis industry, the entire UK cannabis market could be worth $1.7bn by 2024, if recreational use is also legalised in the next three years.

But not everyone is comfortable with the recreational and medical cannabis industries being entwined. “Wherever there is a financial interest, and we don’t have enough information scientifically to counterbalance the push for this product, I become very worried as a clinician,” said Di Forti. “We’ve seen this in the past with tobacco, which was once advertised as a way to reduce anxiety. I don’t want to see history repeating itself.”

Cannabis researchers say that some of the safety concerns over medical cannabis have been overblown, as they are based on data from recreational users, who are often consuming higher and more unregulated doses of the drug. “Cannabis containing THC is still highly stigmatised unfortunately,” said Anne Schlag, head of research at Drug Science. “Some of the issues associated with recreational use are not always applicable to medical use.”

Sodergren is keen to distance the debate about whether recreational cannabis should be legalised from research into the medical applications.

“The recreational perspective is really unhelpful to the development of medical cannabis in the UK,” he said. “What the academic medical profession needs is five to 10 years to tease out the indications what it’s going to be useful for and to really understand where these medicines fit in our treatment of illnesses. Having this parallel debate about recreational cannabis just isn’t helpful to that process at all.”

For Gary Stephens, a professor of pharmacology at the University of Reading, the way forward is to focus on medical cannabis products that do not contain THC, to separate the medicinal element of these treatments from the recreational side.

“When people first started using medicinal cannabis in the US, there was a big backlash, particularly when it came to use in children,” he said. “Getting Epidyolex, a CBD-based medicine, into the clinic has helped with that. We’re not giving them anything that gets them euphoric, we’re giving them something useful.”