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Understanding cannabis research – what the experts wish you knew

Two experts on how to understand the limitations of cannabis studies.



Understanding cannabis research - what the experts wish you knew

Estimated reading time: 7 minutes

We asked two experts what they wish consumers knew, when it comes to understanding the limitations of cannabis research.

There is so much research out there now on cannabis – in fact, US advocacy organisation NORML reported that almost 4,000 papers were published in 2021, a record number compared to previous years. 

While this is great news and shows how the world is waking up to the medical benefits of cannabis, if studies are taken out of context or not read correctly, it can lead to a lot of hype – and hope – without the evidence to back it up.

It’s tempting to believe that positive findings from one study might mean a long-awaited cure or a much-needed replacement for prescription medication. 

But stopping conventional medicine, which has been prescribed by your doctor, can be dangerous and your specialists should always be part of a conversation around potential alternatives or complementary therapies.

This starts with exercising caution when reading studies, particularly when it comes to those around CBD. Consumers may not be aware of limitations that can make a huge difference in how the results are read. 

“People should be cautious generally of all studies that make health claims,” warned Rayyan Zafar, PhD fellow at Imperial College London and Drug Science researcher.

“A lot of the studies have been done in very small samples of patients, using doses of CBD that are not readily available to consumers and under very particular dosing regimens, and so the generalisability of these findings is limited.”

Animal v human trials

Dr Elisabeth Philipps, is a clinical neuroscientist and leading expert on the endocannabinoid system (ECS) and cannabinoid medicine.

She highlighted the importance of carrying out human trials to really understand how cannabinoids work in the body.

“Not all studies that come out are what we call clinical studies as they aren’t in humans.

“Ultimately that’s where we are going to glean the best information as to how cannabinoids work in the body,” said Philipps.

“What consumers need to take note of is understanding whether clinical studies are carried out in humans or in vitro, which may mean experiments have been looked at in just cells.

“In vitro or animal studies may help to inform how we take a product forward, but it doesn’t always give us the best picture as to how this is going to work in the body. The human body is highly complex and we can’t replicate that in a lab or petri dish.”

Zafar added: “When an idea for a drug first comes to scientists, a round of preclinical testing is done which means before humans. This is to see whether the drug interacts with the biological target it is trying to reach. 

“Scientists use this round of testing to determine whether the drug would be feasible and safe to use in humans and it is done to minimise harm and cost to humans.”

Animal studies can show the safety and suggest how something works but it may be different within the human body. 

Philipps explained: “In terms of animal studies, they can give us a greater understanding around the toxicology or safety side, but the systems are so different. In animals, they have different fat compositions and liver metabolisms. We can only really work out what is happening when we put it into the human body.”

Product variation

Another thing that consumers may not be aware of is the difference in quality of products being used in studies, versus the quality of those available to buy. 

A recent study shows that a lot of products are mislabelled with the incorrect amount of CBD, before being sold in stores or online. 

So even if a consumer finds the product helps anecdotally, the levels of CBD they are taking will not be the high pharmaceutical grade available to scientists who are conducting studies. 

Elisabeth explained: “[Papers] should list what the products are and if they are off the shelf. With novel food regulations in the UK, there will be a far more stringent set of rules which will ensure the products on the shelf are going to be safe and that they are going to contain the amount of CBD they say they do. They are not necessarily going to be the ones used in the studies though.”

There is also not a good deal of standardisation in over the counter products, meaning that quality and consistency can vary considerably.

“There can be a lot of variability between batches of CBD bought over the counter and this is as there is not a great deal of standardisation yet in this area,” said Zafar. 

“For studies, more specific and set concentrations of products are likely used, although I couldn’t comment on quality as there is a lot of variability across the board.

“Typically shop-bought CBD gives maximum of 50mg a day, whereas in some studies 400 to 800mg is prescribed, which is very expensive to purchase and could only really be done so via a prescription.”

Dr Philipps added: “A lot of the clinical studies use much higher doses of sometimes up to 10 times what you will take as a food supplement. It’s also about being aware that the dose can be different between the study and what’s being recommended, so finding your dose rate.

“We know that it’s safe for higher doses of CBD because of the Epidiolex oil that is given to children for certain types of epilepsy. That’s been passed on by the MHRA so we know the toxicology and safety studies are there.”

Size, gender and ethnicity

Other issues are presented by study size and gender and ethnicity ratios. 

“A lot of the studies are in their infancy at the moment and we need to understand that we are not seeing large scale studies,” said Philipps.

“It’s great to have these studies but it’s only when we look at thousands of people that we can truly understand the impact on anxiety or pain. 

“Immune studies can often be conducted on people with a healthy immune system to see how a nutrient works in the body. That’s all very well, but someone healthy is going to be very different from someone who has a weakened immune system.

“We are seeing a real skew around gender, age and ethnicity too.”

Women and minority ethnic groups have historically been underrepresented in clinical research, despite their diverse health profiles.

The Covid-19 pandemic highlighted this once again. Despite ethnic minorities in the UK being found to be at a significantly greater risk from Covid-19, a National Institute for Health Research (NIHR) report found ethnic minorities constitute only nine per cent of participants in studies. 

Although little research has been done to date on it specifically, the same can be said of cannabis-related studies, according to Dr Philipps.

A 2019 study from the University of York found women were underrepresented in studies on cannabis and psychosis, meanwhile a 2020 paper found that almost all existing studies on CBD and mental health at the time, were conducted using only male subjects. 

This is important as cannabinoids may affect women and ethnic minorities differently due to hormones, brain chemistry, as well as societal and cultural factors. 

“Clinical controlled research happens in very specific sets of conditions for profuclar patient groups. This means that often their generalisability is limited,” said Zafar.

“Every study will have inclusion and exclusion criteria based on the disorder of interest being studied. Sometimes these are restricted to certain genders as there are disorders that occur more frequently or exclusively in specific sex.

“The greater the number of individuals in a study allows for greater confidence in the results as we can see the effects of the drug in more individuals.”

He pointed out that real-word evidence, such as that being collected by Drug Science, may help bridge the gap, by supplementing controlled studies.

“Real-world evidence in the form of patient data registry and patient-reported outcomes can greatly supplement controlled studies as it shows the real-world effectiveness of a drug,” he continued.

“We are doing this at Drug Science with Project Twenty21, where we are assessing the impact of medical cannabis in the real world in patients with a wide range of conditions.”

Overall Zafar warns patients and consumers to take initial findings “with a pinch of salt” and wait for the results of larger trials before making any drastic changes to their care.

He added: “I wish consumers knew to take them with a pinch of salt, as often they require an in-depth knowledge of the field to understand the true effects of what is being described, and that when there are positive results in smaller trials to wait for larger confirmatory trials to support earlier findings.”

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