A career break, a COVID pandemic and an introduction to Medical Cannabis

This time last year, the cannabis industry was something I knew absolutely nothing about. However, a career break from my role within the NHS, paired with some unexpected circumstances due to the COVID pandemic, landed me in the world of plant-based medicines. In the Caribbean nation of Saint Vincent and the Grenadines (where I had travelled to with the plan to undertake a research project on the impact of epilepsy and introduce a diagnostic EEG clinic), I received a crash course in cannabis (thanks to The Director of Cultivation at my sponsoring company) and subsequently developed a keen interest in the potential of this drug to treat a whole range of conditions, including epilepsy. Life in the Caribbean gave me a whole new perspective on many things, one of the most interesting being the use of natural and native plants and herbs as treatments and healing aids, which are sworn upon by locals, as they have been for many years. With discussion about the efficacy of the papaya leaf as a treatment for the Dengue Fever outbreak, it made me think – for all of human history, we have looked to natural substances to heal us. Thyme tea has been used for decades to induce labour and ease pains during childbirth in Jamaica and across the Caribbean. Many of the drugs we use today are preparations of substances we find in our natural environment - Morphine comes from the poppy…Aspirin from the willow tree...So why are we so scared of exploring cannabis as a medicine?

A Brief History of Cannabis

Evidence suggests that cannabis was one of man’s first medicines, with the earliest recorded use in China around 2700BC. It was used throughout Ancient Egypt, Greece, Rome and India, for both spiritual and medical purposes, from reducing inflammation to anaesthesia. By the 19^th century, it was in popular use for a range of ailments and was famously brought to the UK by Dr William O’Shaughessy in the 1820s, where it was used to treat seizures. It’s medical use became so accepted that even Queen Victoria is thought to have used it to ease menstrual and childbirth pains.

Despite this, there was a point in history where public perception dramatically changed as the plant was tactfully re-branded as a dangerous and illegal Schedule 1 drug. The 1930s saw the introduction of Harry Anslinger and propaganda such as ‘Reefer Madness’, with undeniable roots in racism towards Black and Hispanic communities (the word ‘Marijuana’ was even adopted to strengthen the link to Mexicans). In 1978, the ‘War on Drugs’ resulted in changes in drug policy and a harsh crackdown on drug possession and use in the US. Political pressure simultaneously began to rise in the UK; this resulted in the banning of medical cannabis in 1971 and the re-classification of the drug as Schedule 1, deeming it as a harmful drug with absolutely no medical value.

 “Marijuana is the most violence-causing drug in the history of the world”

 “…the primary reason to outlaw marihuana is its effects on the degenerate races.”

                                                                                                                                                                             - Harry Anslinger

In 1972, Nixon’s National Commission on Marijuana and Drug Abuse concluded: “There is little proven danger of physical or psychological harm from the experimental or intermittent use of natural preparations of cannabis." Similar evidence was being presented in the UK but this was largely disregarded. Criminalisation for cannabis possession and use remained harsh, with huge rates of arrest and incarceration. Racist rhetoric appears to be a persistent theme in the cannabis story; criminalisation associated with cannabis disproportionally affects Black communities both in the US and the UK to this day, despite research showing that usage is roughly equal to the white population.

The Current State of Medical Cannabis in the UK

For many years, the Schedule 1 classification of cannabis meant that medical research was prohibited and many patients remained completely unaware of and unable to explore cannabis as a potential medicine (legally at least...) These reasons were purely political and not scientific.

In recent years, largely as a result of high profile patient cases such as that of Alfie Dingley, who has a rare form of epilepsy called PCDH19. He started having seizures at 8 months old and at worst, was suffering 500+ seizures a month, many of which were life-threatening and required hospitalisation. He was unresponsive to anti-epileptic medications and only showed improvement with steroids (not a feasible or safe option for long term treatment). As a final attempt, his parents moved to the Netherlands to access cannabis, after which he went 42 days seizure free for the first time in his entire life. This initiated a nation-wide campaign to urge parliament to re-consider the classification of cannabis, questioning why patients were being denied a treatment which could be potentially life-saving for them, both treating their specific condition and improving their overall quality of life. In November 2018, UK legislation was successfully changed and medical cannabis was re-classified as a Schedule 2 drug, permitted for prescription by a specialist doctor only for very specific and difficult to treat conditions including:

 v  Children with rare, severe forms of epilepsy

 v  Adults with nausea and vomiting due to chemotherapy

 v  Adults with muscle pain due to multiple sclerosis

However, medical cannabis prescriptions remain minimal; in fact there have only been around 20 prescriptions made by the NHS since legislation was passed. This neglects a huge number of patients who are potentially treatable with cannabis, or means that those fighting to access the drug are forced to seek illegal access or pay the extremely high costs associated with seeking this medicine privately. Doctors are generally not supported to prescribe cannabis-based medical products, as the Schedule 2 classification states that they must take “personal responsibility to prescribe without sufficient evidence”. A wider public scepticism remains due to the lack of education, understanding and empirical evidence (a lack of ‘gold-standard’ randomised-controlled trials). The narrative of cannabis use being ‘morally-wrong’ has also remained strong and is likely one of main reasons currently complicating patient access routes. Even in my practice, I’ve experienced the shocked faces and dismissive attitudes when patients mention that they’ve even tried CBD oil as a last resort (despite pure CBD oil currently being legal and widely available in the UK, due to the absence of THC - the component of cannabis which makes you feel ‘high’…). It is clear that we still have some way to go in providing safe and effective medical cannabis in the UK, as well as breaking down barriers in public perception and general scepticism around the drug.

 A little bit about the plant…

There are three sub-species of the cannabis plant, which classically have differing physical features and effects on consumption.

Sativa and Indica are the main ones you’ll hear mentioned when it comes to medical use. Sativa strains are typically associated with “mind energising” effects and Indica strains are associated with “mind relaxing” effects. It is now, however, difficult to distinguish and identify pure Sativa or Indica species and most plants are now a hybrid, simply with Sativa or Indica dominance.

The plant can be either male or female, with the female plants preferred for medicinal purposes. This is because unfertilised or seedless female plants (also known as Sinsemillia) feature the highest concentration of cannabinoids.

There are over 100 known phyto-cannabinoids (from the plant) found within the ‘trichomes’ of the cannabis plant, the mostly commonly known ones being Cannabidiol (CBD) and Tetrahydrocannabinol (THC). As I mentioned earlier, THC is the main psychoactive component of cannabis. CBD and THC (and all the other cannabinoids) exert their effects throughout the body via the Endocannabinoid System (and various other systems). The ratio of CBD:THC is often key in medical cannabis, although other components may also be involved.

The Main Effects of CBD and THC

CBD	THC
Analgesic
Anti-convulsant	Anti-inflammatory
Neuroprotective	Anti-emetic
Anti-cancer	Muscle relaxant
Anti-anxiety	Anti-oxidant

Alternatively, ‘Hemp’ refers to special variety of the plant containing high amounts of CBD and minimal THC  (<0.2% THC in the UK) and its often the basis of over-the-counter CBD oils. Hemp is grown industrially and is used for its fibres (for textile and building materials), seeds (regarded a highly nutritional snack) and much more.

As well as cannabinoids, there are many other components found within the cannabis plant. Terpenes are the chemicals which give cannabis its characteristic smell, and include Myrcene, Linalool and Beta-Caryophyllene (to name just a few…). These chemicals have additional effects in the body and therefore also have medical properties. Flavinoids give various plants, including cannabis, their colour, and an ‘Entourage Effect’ has been indicated between cannabinoids, terpenes and flavonoids. More research is needed in this area but essentially, this means that they all work synergistically to exert and modulate each of their effects.

Introducing the Endocannabinoid System

The Endocannabinoid System (ECS) is formed of endogenous cannabinoids and receptors, which are located throughout all body systems, likely explaining the widespread effects of cannabis. These endo-cannabinoids (from the body) include Anandamine and 2-AG.

Both endocannabinoids and phytocannabinoids bind receptors called CB₁ and CB₂, which are primarily located in the brain/nervous system and immune system, respectively. The systems predominant function is in homeostasis (maintaining the body’s natural balance) and neuromodulation (regulating the release of chemical signals with the brain), with wider effects on sleep, memory, regulation of appetite, insulin sensitivity, modulating our stress response and embryonic development. Interestingly, Anandamine has a similar structure to THC is associated with feelings of euphoria i.e. ‘the runner’s high’.

The Widespread Effects of Different Cannabinoids in the Body

Body System	Effect
Central Nervous System	Euphoria, aggravation of psychosis, sedation, changes in perception, cognitive performance, motor function etc.
Cardiovascular System	Changes in heart rate, vasodilation, increased cardiac output, postural hypotension
Respiratory System	Bronchodilation
Gastrointestinal System	Decreased gastric motility, decreased gastric emptying, effects on nausea, vomiting and diarrhoea
Musculoskeletal System	Muscle relaxation/reduction in spasms
Immune System	Complex immunomodulatory effects, altered allergic reactions
Reproductive System	Many complex effects on reproductive hormones and sexual function

 But what about the risks?

Clearly there are some risks associated with cannabis; however, It is important to make the distinction here between medical and recreational use. Risks may include dependency (although rates are thought to be ~9% compared to alcohol at 15% and tobacco at 23% …),  psychosis (in those with a family or personal history of schizophrenia/psychosis) and possible cognitive decline; however, most studies on this have been based on recreational and not medical cannabis, which typically contains significantly higher proportions of THC and often a completely different context of usage. The most common ways to consume cannabis medically includes vaping, oils, capsules or tinctures; obviously, smoking cannabis is not recommended as part of your medical treatment regime, as this has associated risks due to smoke inhalation and carcinogens. Research has also suggested potentially harmful effects of cannabis on the young developing brain – but, from my understanding this often comes down to assessing risks vs. benefits in each particular case. Unlike many other drugs (such as opioids), there are no recorded cases of cannabis overdose – the theory behind this is that CB₁ receptors are not present within the brainstem, meaning it has little known effects on this ‘life-sustaining’ area of the brain which is responsible for regulating breathing etc. Moreover, emerging evidence suggests that cannabis might actually play a role in treating opioid addiction, alleviating opioid withdrawal symptoms and decreasing the likelihood of relapse.

Support for the use of Medical Cannabis for Epilepsy

As previously mentioned, epilepsy was one of the earliest recorded conditions treated with cannabis, and it has been the condition central to most of the high profile cases gaining attention in the media. The precise mechanisms which mean cannabis is able to help in some epilepsy cases remain quite unclear; however we know that cannabinoids play a role in ‘retrograde signalling’, i.e. modulating the release of neurotransmitters from neurones in the brain. Cannabinoids have been described as a sort of ‘circuit breaker’, interrupting excess activity in hyper-excitable tissues. In animal studies, blocking CB₁ receptors results in severe seizures, supporting the key role this system plays in normal brain function and controlling seizure activity. Cannabinoids also exert their effects via various other receptor systems and it is possible that cannabis works in epilepsy for a number of different reasons. Although sparse, there are reduced interictal and ictal epileptiform discharges (in English, the abnormalities we see in the EEG at rest and during a seizure) associated with cannabis use; this is an interesting area for possible future research.

All those years ago, Dr O’Shaughnessy reported being able to stop febrile seizures in a 40 day old infant using cannabis, leading him to declare that “the profession has gained an anti-convulsive remedy of the greatest value”. In 2013, this statement was demonstrated publicly for the first time by Charlotte Figi, a young girl diagnosed with Dravet Syndrome, a rare epilepsy syndrome often associated with SCN1A mutation. The condition results in severe seizures and cognitive decline; in this case, Charlotte, was having up to 300+ seizures each week and lost her ability to walk, talk and eat by the age of 5. After trying the ketogenic diet and a whole host of other anti-epileptic drugs (most of which were associated with serious side effects), Charlotte’s parents fought for access to medical cannabis. They initially thought the results were “ a fluke”, as for this first time ever, several hours went by without Charlotte having a seizure. The high CBD: low THC strain they used was re-branded ‘Charlotte’s Web’ and has subsequently been sought after by many other patients. This case was the focus of a landmark CNN Special Report by Dr Sanjay Gupta, investigating the reasons behind why he “changed his mind about weed” and many other people’s too. At the time, Charlotte was described as  "the girl who is changing medical marijuana laws across America”.

Fast forward to 2017 where we saw clinical trials for CBD-based pharmaceutical drug Epidiolex for two intractable epilepsy syndrome of childhood called Dravet Syndrome and Lennox-Gastaut Syndrome. These trials provided, for many, the first ‘scientific evidence’ that the drug was better than placebo in reducing seizure frequency. The studies, however, also demonstrated the adverse effects which could be associated with the drug; indicating an urgent need for further study into the immediate and long-term effects. It has also been argued that natural CBD or broad spectrum oils may be better in terms of outcomes and also side effects than pharmaceutically prepared formulas. Epidiolex is licensed for use in the UK and recommended by NICE currently for these two syndromes specifically. NICE has not recommended cannabis-based medicines for any other epilepsies in the NHS, indicating that more high quality evidence is needed. Any further decisions to prescribe a cannabis-based medicine for epilepsy in the UK must be done via a ‘specials’ process and this is evaluated on a case-by-case basis. Other medicines, such as Dutch products Bedica and Bedrolite (containing both CBD and THC) have been prescribed by specialist doctors; however, as mentioned earlier, prescriptions still remain minimal in the UK due to understandable hesitation from Clinicians who are currently without support.

At the end of last year, a study of 10 patients prescribed cannabis-based medicinal products revealed an astonishing average 97% monthly seizure reduction. This study also highlighted the idea that the efficacy of CBD may be greater when combined with THC; again suggesting the potential beyond the only currently licensed medicine in the UK, Epidiolex. A key take home message from this study was the huge financial burden on patients and families currently using medical cannabis products not available on the NHS, with the average cost of £1816.20 per month. The study also cited a recent report from the Centre for Medical Cannabis which estimated that up to 14 million people in the UK are currently self-medicating with cannabis, including up to 12% of the epilepsy population. Along with the need for larger scale research, these findings surely call for steps to be taken to ensure safe and affordable access to medical cannabis for those who are using it regardless.

Even with "a lack of empirical data", the benefits of medical cannabis for some patients is undeniable. and there’s no ignoring the fact that it does appear to be a ‘miracle drug’ for some. Through my work with Drug Science, I have had the opportunity to speak to the founders of EndOurPain, a campaign for safe and legal access to medical cannabis in the UK.  I have heard the touching personal stories of the families who are benefitting hugely from cannabis, but sadly continue to face ongoing struggles in obtaining access to a drug which has dramatically reduced their child’s seizures and improved their overall quality of life.

Take Home Message

Cannabis-based medical products aren’t a 'one size fits all' and it’s all about finding the right strain for each particular disorder and case, the right ratio of cannabinoids, terpenes and other components, the right dosage and the right method of administering the medication…then there’s balancing any side effects and dealing with drug tolerance. We also have to consider the fact that although it does appear to be a ‘miracle drug’ in some cases, there are also cases where it doesn’t work as well. Saying that, the undeniable point and the main thing I’ve learned during my first year being involved in the medical cannabis world so far is the huge difference that this medicine has made to so many lives. I sympathise greatly with the parents who have fought for the use of medical cannabis products to improve the quality of life for their children, and who have acted as advocates to make the drug an option for others. And I fail to understand why we continue to deny so many patients the potential to explore a drug which may benefit them so much. The difficulties currently faced by parents accessing medical cannabis are becoming more apparent and more urgent, as the realities of Brexit mean patients have already faced fears that they will no longer be able to access medications such as Bedrocan, therefore potentially putting their children at risk of severe relapse, seizure re-occurrence and all the complications that accompany that (including status epilepticus, intensive care admission and the worst care scenario). Even those with consistent access have to face huge financial burdens as they currently have to pay for the currently un-licensed medications privately in the UK. 

Although I’ve been focusing on epilepsy, stronger evidence exists for the use of cannabis in conditions such as chronic pain and anxiety. As the drug often helps with sleep, mood and appetite, it can generally assist with quality of life and has even been beneficial in end of life care. Some have argued that exploring cannabis use clinically has re-emphasised the focus on patient quality of life, a concept which can be somewhat lost in other areas of medicine. It seems that the potential of this drug is endless, with benefits being also explored in dementia, PTSD, various dermatological conditions and women’s health...

The medical cannabis revolution is undoubtedly an exciting one and I look forward to seeing the future of the drug. Drug Science is playing a crucial role in advancing the current status of medical cannabis in the UK and nation-wide observational study Project Twenty21 aims to collate data on the safe and effective use of medical cannabis for several conditions, with an epilepsy study branch due to launch soon. We have hopes that this will provide evidence for NHS funding where the benefits of treatment with medicinal cannabis is proven to outweigh the potential risks.

It is clear we still some way to go when it comes to attitudes towards and education on medical cannabis, as well as providing safe, legal and affordable and access – but I feel like we’re heading in the right direction.