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Largest Ever Study Into the Effects of Cannabis on the Brain

The largest-ever independent study into the effects of cannabis on the brain is being carried out in the UK.

Even though cannabis is the most commonly used illegal drug in the UK and medicinal cannabis has been legalised here since 2018 little is known about why some people react badly to it and others seem to benefit from it.

According to Home Office figures on drug use from 2019, 7.6% of adults aged 16-59 used cannabis in the previous year.

Medicinal cannabis in the UK can only be prescribed if no other licenced medicine could help the patient. At the moment, GPs can't prescribe it, only specialist hospital doctors can. The NHS  says it can only be used in three circumstances: in rare, severe epilepsy; to deal with chemotherapy side effects such as nausea; or to help with multiple sclerosis.

So, with cannabis being used both recreationally and medicinally, King's College London is carrying out a wide-reaching scientific study into its effect on the human brain.

As part of the Cannabis&Me study, KCL needs to get 3000 current cannabis users and 3000 non-cannabis users to take part in an online survey, with a third of those survey respondents then taking part in a face-to-face assessment that includes virtual reality (VR) and psychological analysis. The study also aims to determine how the DNA of cannabis users and their endocannabinoid system impacts their experiences, both negative and positive, with the drug. 

The study is spearheaded by Dr Marta Di Forti and has been allocated over £2.5 million in funding by the Medical Research Council. 

photo of Dr Marta Di Forti
Dr Marta Di Forti

Medscape UK asked Dr Di Forti about the study:

How do you describe the study? 

"It’s a really unique study. We are aiming to see what’s happening to people using cannabis in the privacy of their homes for medicinal, recreational reasons, or whatever other reason.

"The debate on cannabis has always been quite polarised. There have been people who experience adversities with cannabis use, especially psychosis, whose families may perhaps like cannabis to be abolished if possible. Then there are other people who are saying they get positive benefits from using cannabis."

So where does the study come in?

"The study wants to bring the two sides of the argument together and understand what’s really happening. The group I see as a clinician comes to severe harm when they use cannabis regularly. We want to find out who they are and whether we can identify them. While we need to make sure they never come to harm when using cannabis, we need to consider others who won’t come to harm from using cannabis and give them a chance to use it in a way that’s beneficial."

How does the study work?

"The first step of the study is to use an online questionnaire that can be filled in by anyone aged 18-45 who lives in the London area or can travel here if selected. The first set of questions are a general idea of their cannabis use: 'Why do they use it?' 'What are its benefits?' Then, general questions on what their life has been like up to that point: 'Did they have any adversities in childhood?' 'How is their mood and anxiety levels?' 'Do they experience any paranoid responses in everyday life?' It probably takes between 30-40 minutes to fill out the questionnaire."

Can you explain about paranoid responses?

"We go through the questionnaires looking at people's paranoid response to everyday life, not in a clinical disorder term, just in terms of the differences in how we respond to certain circumstances. For example: 'How do you feel if someone's staring at you on the Tube?' Some people are afraid, some feel uncomfortable, some people don’t notice, and others think a person is staring at them as they look good or another such positive feeling. So, we give people a paranoia score and will invite some at the top and some at the bottom of that score for a face-to-face assessment. We want to select those people who are using cannabis daily and they are getting either no paranoia or high paranoia."

What happens at the face-to-face assessments?

"We do two things which are very novel. We ask them to take part in a virtual reality experience. They are in a lovely shop and within this experience they come across challenges, which may or may not induce a benign paranoia response. We will ask them to donate a sample of blood before they go into the VR set. We will test for tetrahydrocannabinol (THC) and cannabidiol (CBD). We will also look at the metabolites of the two. People don't take into account how differently individuals metabolise cannabis, which could be one of the reasons why some people can tolerate it and others can't."

There's also a genetic aspect of the study?

"From the same sample, we will extract DNA to look at the genetics across the genome and compared genetic variations between high and low paranoia in the context of cannabis use. Also, we will look at the epigenetics, as we have learned from neuroscience, and also cancer, that sometimes a substance we ingest has an effect on our health. It's perhaps an interaction with the way our DNA is written but also with the changes to the way our DNA is read and translated into biology if exposed to that substance. We know that smoking tobacco does have an impact at an epigenetic level on the DNA. We do know that in people who stop smoking, these impacts on the epigenetics is partially reversed. This work hasn’t been done properly for cannabis.

"There have been four published studies that have looked at the effect of cannabis use on epigenetic but they have been quite inconclusive, and they haven't looked at large numbers of current users taking into account how much they are using. Moreover, we do know that when THC and CBD get into our bodies, they interact with something that is already embedded in our biology which is the endocannabinoid system. Therefore, in the blood samples we also aim to measures the levels of the endocannabinoids we naturally produce.

"All of this data will then be analysed to see if we can get close to understanding what makes some cannabis users susceptible to paranoia while others who are using cannabis get some benefits, even in the domain of mental health."

Who are you looking for to take part in your study?

"What we don't want is to get only people who are the classic friends and family of academics to do the study. We want a representative sample of people out there who are using cannabis. My ideal candidate would be someone who hates me and usually sends me abusive emails saying I'm against cannabis, which is wrong. All I want to find out is who is susceptible to harm which will keep everybody else safe. We are not trying to demonise cannabis, it's exactly the opposite. We would like people from all ethnic and socioeconomic backgrounds to join to give voice to everyone out there using cannabis, the reasons why, and the effects they experience."

Will this study perhaps give more information of when it's appropriate to prescribe medicinal cannabis, as it’s still quite unusual for it to be prescribed in the UK isn't it?

"Absolutely spot on. That’s exactly the point. We want to hear from people who are receiving medicinal cannabis as a prescription, as they are likely to take it on a daily basis and daily use is what epidemiological studies have linked to the highest risk of psychosis. There will be people taking THC everyday for pain, nausea, for Crohn’s disease, and more.

"Normally when you receive a prescription for a medication the physician in charge will tell you the potential side effects which will be monitored to make sure it’s safe, and you may have to swap to a different medication. Now this isn't really happening with medicinal cannabis, which is one of the reasons clinicians are anxious about prescribing it and they have been criticised for not prescribing it very much. There's much less structure and guidance about 'psychosis-related' side effects monitoring. If we can really identify those people who are likely to develop psychosis or disabling paranoia when they use cannabis, physicians might be more prepared to prescribe more widely when indicated.

"You could even have a virtual reality scenario available as a screening tool when you get prescribed medicinal cannabis, to see if there are changes in your perception of the world, which is ultimately what psychosis is about. Could this be a way of implementing safe prescribing which will encourage physicians to use safe cannabis compounds and make some people less anxious about it?

"This study is not here to highlight the negativity of cannabis, on the contrary it's to understand how it can be used recreationally, but even more important, medicinally in a safe way so people that are coming to no harm can continue to do so and people who are at risk can be kept safe, or at least monitored adequately."

Lead Image Credit: Image Source/Getty Images

In-article Image Credit: Dr Marta Di Forti