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Inside The Largest Ever Independent Cannabis Study In The UK

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Earlier this month, UK's King's College of London launched Cannabis & Me, a scientific study into the effects of cannabis on mental health, considered the largest cannabis study of its kind.

The study, which aims to involve 6,000 participants, will research environmental and biological factors behind the different effects of cannabis consumption on the human brain and provide information to physicians in the UK and across the world for prescribing cannabis safely.

The Medical Research Council (MRC) granted $2.8 million (£2.5 million) of funding for the study in 2020, but the COVID-19 pandemic has delayed its start.

Cannabis & Me's lead researcher, Dr. Marta di Forti, has extensive experience studying cannabis from a psychiatric perspective.

She published several studies about causal links between cannabis use and psychotic disorders over the years, and, in 2019, she obtained funding from the Maudsley Charity to develop the UK's first and only Cannabis Clinic for Patients with Psychosis.

How the study works

Cannabis & Me's study consists of a 40-minute online survey, which aims to explore "the different effects that people experience when they use cannabis and how these might relate to other recreational drug use, live events, including trauma or illnesses, but also positive situations and social context."

Furthermore, researchers aim to understand how internal and external factors might influence the use of cannabis and vice-versa.

Participants will be split into two groups: Those currently using cannabis and those who have never used it in their lifetime or have only used it a maximum of three times.

Participants have to meet several criteria, including being over 18 years old, resident in the London area, fluent in English, willing to take part in a face-to-face assessment, willing to donate a blood sample, and to take part in virtual reality (VR) experience, and being without a previous or current diagnosis of psychotic disorders and without currently receiving treatment for psychotic disorders.

Successively, both groups will be invited to meet the research team and complete a face-to-face assessment.

Why is this study important for cannabis research?

To understand the reasons behind the need for this study is necessary to have a glance at the legal status of cannabis around the world.

Although it is still illegal at the federal level, more and more US states have legalized medical and adult-use cannabis in recent years.

Meanwhile, European countries have started a public debate over cannabis legalization at the national level, and some countries are attempting to regulate its use in different ways.

As a result, cannabis is changing its perception at the social level, and recent reports have shown how its consumption is growing.

But even though cannabis research is making progress in understanding better this plant that has been stigmatized for decades and criminalized by adopting restrictive policies, little is still known about risks associated with cannabis use and, most importantly, how to avoid them.

Dr. Di Forti explained that this study aims to use data to provide more balanced information in terms of public health.

This study will help assess risks associated with cannabis use, how they can be avoided, and how people can make informed choices if they use cannabis for medicinal or recreational reasons.

Furthermore, through the data of this study, researchers want to provide a series of tools to physicians who prescribe medical cannabis to make them more confident about how to prescribe medical cannabis products, monitor side effects, and be aware of potential risks.

"Given that I am a psychiatrist, the harm I am interested in is the one related to the brain. I am talking about a minority of cannabis users developing psychosis, even transient or more persisting. I want to see if we can screen out those who have benefited from cannabis and keep safe those patients that show psychotic symptoms and that visit my clinic every week," Dr. Di Forti said.

The study will involve around a dozen researchers and experts with a wide array of expertise and specializations.

Dr. Di Forti plans to reach a number of participants of 6,000 units: 3,000 cannabis users and 3,000 non-cannabis users or former cannabis users.

Epigenetics, DNA testing, biology, and VR experience at the service of cannabis research

The data from the latter group will help understand cannabis epigenetics.

As epigenetics studies how people's behavior and environment can cause changes that affect their genes, researchers want to understand whether cannabis follows the same path as tobacco and alcohol, which affect epigenetic profiling and tend to be partially or completely washed out when quitting.

As our DNA can be switched on and off depending on internal and external factors, researchers want to understand how it behaves when people use cannabis and what the difference is between those who have beneficial effects from cannabis and those who develop psychotic disorders following its use.

Dr. Di Forti explained that the main scientific literature on cannabis and its associated side effects mainly consisted of epidemiological studies.

Although there have been some cannabis studies that looked out of the genetic side to understand whether some cannabis users develop psychosis because they are genetically predisposed, results have been relatively inconclusive.

"What we know is that if you have a predisposed genetics psychosis or have a family history with psychosis and put on top cannabis consumption, your chances to develop psychosis increase. But we don't know if cannabis can change how the DNA can switch on and off depending on environmental exposure and whether its expression can be halted," she said.

Furthermore, some studies suggest that people with psychosis show abnormality in their endocannabinoid system.

In fact, part of the study aims to focus on the biological aspects of cannabis use.

Through a blood test, researchers will study the DNA structure and determine whether the genes involved in the metabolism of THC, CBD, and other cannabinoids vary in how people metabolize cannabis through the endocannabinoid system.

This will help understand whether the different effects of cannabis consumption are also related to the biological interaction between the endocannabinoid system and cannabis compounds.

"There is a possibility that out there some people are unable to metabolize cannabis because of their genetics or endocannabinoid system," Dr. Di Forti said.

Regarding the effects of the social environment on cannabis users, researchers will ask participants whether they have trauma history and to seek psychological relief in cannabis to understand if users are benefiting from it.

Furthermore, participants of this study will be involved in virtual reality (VR) experiences, such as finding themselves in an everyday social context.

The study aims to understand how cannabis use can alter the perception of the external environment, and researchers will use a VR experience to assess such an alteration.

Therefore, researchers will propose to participants several scenarios through a VR experience to measure the reactions of cannabis users, which would help explain several adverse effects of cannabis consumption, such as paranoia.

The study was scheduled to last for five years and end in 2025. But as the COVID-19 pandemic delayed its launch, Dr. Di Forti said they would ask for an extension.

The main cost of this study includes researchers' salaries, genetic, epigenetic, and blood tests, as well as infrastructure costs.

Researchers will be able to publish the first data in a year and a half, while biological data are likely to be released in two years.

The online survey to take part in this study will be closed in 18 months.

Since early September, over 280 people have joined the study, and researchers are already calling them to get psychological data.

Criticism of Dr. Di Forti's work about cannabis and psychotic disorder

The launch of the Cannabis & Me study has received some criticism from cannabis anti-prohibitionist activists and cannabis industry insiders, raising concerns around impartiality.

From their perspective, Dr. Di Forti's work portrayed in the media has contributed to adding a burden to the stigma around cannabis.

In particular, a study by Dr. Di Forti and others published in The Lancet Psychiatry journal in 2015 found that "the risk of individuals having a psychotic disorder showed a roughly three-times increase in users of skunk-like cannabis compared with those who never used cannabis."

Another study, published in the same journal in 2019, found that daily use of high potency cannabis is "strongly linked to the risk of developing psychosis."

Asked to comment on the criticism from a part of the cannabis community regarding her work on cannabis, Dr. Di Forti said that the general debate over cannabis is polarized.

"It's trivial to say that, because cannabis is a plant, no harm can come from it. Many plant extracts used in medicine are used as poison as well. Equally, it's not fair to say that cannabis is entirely harmful because we know that only a minority of people is harmed by cannabis," she said.

Dr. Di Forti hopes this study will help reconsider the two sides of the argument.

She explained that her goal is to understand why a minority of cannabis users experience psychological and cognitive disorders and want to help these people prevent adverse effects of cannabis and keep them safe.

"I am not concerned about cannabis becoming more available. I am concerned about people having the tools to use it safely," she said.

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