The complexities of medical cannabis clinical trials

But, in the world of medical cannabis, clinical trials can be difficult to navigate. The evidence available so far does appear promising, and has been generated in a relatively short space of time due to the prohibition of the cannabis plant - which only recently ended in 2018.

However, in comparison to other conventional treatment options, medical cannabis research is still relatively limited and fragmented - and can be tricky to undertake because of the amount of variables involved. 

So, in this blog, we decided to explore the complexities involved in medical cannabis clinical trials.

What is a clinical trial?

There are a number of different approaches that can be taken when conducting a clinical trial, but these can be categorised into two main types: interventional and observational trials. 

Interventional trials

Interventional trials focus on the treatment, or medicine, being tested - and the most common kind of interventional trial is the randomised controlled trial (RCT). 

In RCTs, the survey sample is split into groups randomly using a computer. One group is administered the treatment being tested, while the other receives a placebo. The research team then compares these results at the end of the trial period to determine the efficacy and safety of the treatment. 

Observational trials

Observational trials operate differently, focussing on the individual and how they are affected by the treatment of their choice. 

In observational studies, the research team in charge do not dictate what kind of treatment the participants receive. Instead, they simply observe how the participants respond to these approaches, often using self-reported patient surveys to generate their data. 

This way, researchers are able to observe how patients in all different situations, walks of life, and with different symptoms, respond to one type of treatment. 

What variables are involved in medical cannabis trials?

Medical cannabis clinical trials can greatly vary, not only because there are different types of trials - but because there are a large amount of variables in medical cannabis. 

Clinical trial complexities

Gold-standard randomised controlled trials, for example, are often very selective with the participants, or sample groups, they recruit. This is mostly due to personal factors, such as a participant's tolerance, BMI, age, gender, and metabolism, which all influence the end outcome - and this can make it challenging to capture easy, digestible data if a diverse population is recruited. 

In addition to this, it is difficult to conduct an RCT with certain medical cannabis preparations - because for them to be effective, those involved need to have no idea if they’re receiving the treatment or the placebo. 

And, unlike many conventional pharmaceutical products, certain medical cannabis products have a strong aroma and taste that can be hard to replicate or disguise, which can make the robust controls involved in an RCT redundant. 

What variables are involved in medical cannabis?

In the UK, medical cannabis can be prescribed in different preparations or formulations, including dried cannabis flower, prescribed cannabis oil, in an oromucosal oral spray, and in tablet or capsule form. This means it can be administered and absorbed in a variety of ways, and therefore, take a varying amount of time to take effect, be felt for, and stay in the system. 

These products are all also derived from a plant, which in itself presents variables. 

There are hundreds, if not thousands, of known cannabis cultivars, or strains, that belong to the cannabis family, and each of these has its own unique make up, or profile, of cannabinoids and terpenes. These compounds can be found in varying combinations and concentrations - and, consequently, can all have different effects on the person taking them.  

The way in which the cannabis was grown, such as how controlled its environment was, can affect the quality or concentration of cannabinoids and terpenes present, and the dosage administered can also present other variables - which all affect the end outcome in clinical trials. 

And although a clinical trial may be conducted using a particular strain or cultivar of cannabis - these findings cannot then be used to make a sweeping statement about medical cannabis’ efficacy, quite simply, because of the large amount of variables we’ve just discussed.

What research has been produced by medical cannabis clinical trials? 

For many, the most robust, or reputable, evidence comes from gold-standard randomised controlled trials that have data, or figures, that can be calculated to show a statistically significant difference against the placebo used. 

Others prefer real-life evidence, or ‘anecdotal evidence’ because they like to hear about the experiences others have had in similar circumstances to themselves, and this data is usually generated from observational studies or patient testimonials. 

Evidence from randomised controlled trials

Despite the amount of variables involved in medical cannabis clinical trials, there is a mass of reputable, clinical data from randomised controlled trials that demonstrates the therapeutic potential cannabis-derived treatments can have for a number of different conditions.

Systematic reviews of randomised controlled trials involving cannabinoids have demonstrated their efficacy as an anti-emetic and appetite stimulant. 

Others have shown cannabinoids can relieve spasticity, neuropathic and chronic pain, and their effects on those with irritable childhood epilepsy are also well documented in randomised controlled trials. 

The success of these randomised controlled trials has led to the licensing of three cannabis-derived medicines that can now be prescribed by the NHS. These are:

• Epidiolex for Lennox-Gastaut Syndrome and Dravet Syndrome
• Sativex for multiple sclerosis spasticity
• Nabilone for chemotherapy induced nausea and vomiting

Evidence from observational studies

Since 2021, Drug Science have regularly published data from T21: the UK’s largest observational study of patients using medical cannabis. According to their latest report, over 4430 people are now taking part, and over 500 have been participating for over two years, allowing them to track patient responses over a much longer period of time than any conventional RCT. 

Their study has closely tracked the effects medical cannabis has had on the lives of those with PTSD, depression, anxiety, chronic pain, fibromyalgia, multiple sclerosis, and so many more conditions. These collective findings remain largely positive and reflect medical cannabis is generally well tolerated and beneficial to a patient’s overall health and well-being when applied appropriately.

Another great resource for credible information is the Medical Cannabis Alliance (MCA). In February 2024, they presented the findings of their latest patient response survey and found that 96% say their quality of life has improved since starting cannabis-based treatments. 

In this survey, the most common conditions being treated with medical cannabis preparations were anxiety, chronic pain, depression, insomnia, and arthritis. They found that 81% of respondents said their symptoms improved, 73% felt better in general, and 60% had reduced the quantity of other prescription medications they use since starting these treatments. 

How can the medical cannabis industry overcome the obstacles involved in clinical research?

To facilitate standardisation and meet more robust clinical trial requirements, manufacturers of medical cannabis should ensure every effort is made to ensure their batches are uniform, and can be replicated time and again for consistency. 

For this reason, following standard operating procedures and Good Manufacturing Practice protocols is essential, and providing certificates of analysis ensures cannabis-based products can be traced for safety and quality purposes. 

Investing, collaborating, and contributing to clinical research that furthers medical cannabis is another, imperative step the industry should take to ensure these options gain more awareness, and acceptance within both the medical community, and wider society. 

Whether this happens in the lab, in patient response surveys, or research reports into the attitudes, awareness, or perceptions of medical cannabis - it is all valuable research that may help medical cannabis propel further into the mainstream of what modern healthcare is today. 

Final Thoughts

To close the article, we also spoke to our Chief Operating Officer, Graham Woodward, an experienced CQC inspector, psychiatric nurse, and former clinical director, about his thoughts on the matter. 

Graham said: 

“When the government changed the law in the UK, it was changed so that children could get cannabis treatments for intractable epilepsy, and I don’t think they realised adults were going to be accessing it. By doing that, they’ve now allowed cannabis to be prescribed as CBPMs without doing clinical trials with adults, and it feels almost that we’ve come too far now to go back. We’ve got incredible amounts of real-life evidence and data that shows how medical cannabis works for certain conditions, and in some cases it really, really works.

I’m astounded that now working in the medical cannabis field, looking at my years working in psychiatry within the NHS there are a vast amount of SSRIs and antipsychotics that have this RCT clinical backing, and are regularly prescribed, but in the main, cause intolerable side effects and ineffective. Then the cannabis plant comes along, without the same clinical backing, yet still heaps of observational evidence, and it works really well for some of these people. It almost makes a mockery of the whole thing.

We need to spread accurate, and credible information about the benefits, and limitations of medical cannabis to properly educate people on the matter. While there are a lot of complexities involved in using cannabis preparations in randomised controlled trials, we can pioneer with producing more and more observational data.

I have previously asked the NHS whether private clinics can contribute to the data they are collecting from NHS cannabis prescribers, perhaps asking our patients to submit EQ-5D or GAD7 questionaries, but at the time they were only looking to capture data on Sativex, Epidyolex, and Nabilone. But, we remain hopeful there may be further opportunities in the future to collaborate.”