Researchers & Policymakers Grapple With Medical Implications Of Cannabis

Bad Hofgastein, Austria – A stronger research agenda for cannabis is urgently required to guide European health policymakers through a bewildering maze of medical and recreational cannabis and cannabinoid products that are fast emerging on the European market, said researchers and policymakers at a panel session of the 2019 European Health Forum (Gastein), which concluded Friday.

Currently, awareness is low and policies are inconsistent regarding the regulation of both medical and recreational cannabis in Europe– a plant whose components includes hundreds of different molecules of very different active ingredients.

Adding to the complexity is the fact that the best known cannabis components, which are THC and cannabidiol (CBD), now appear to have diametrically opposed effects on the brain, and that is stimulating new opportunities for medical applications, but also new questions. CBD’s potential anti-anxiety and anti-psychotic properties are being explored by researchers in the United Kingdom and elsewhere – while a trademarked version of CBD, Epidiolex®, was recently approved by the US Food and Drug Administration as well as by the European Medicines Agency for treatment of a rare form of childhood epilepsy.

(Left-right) Lisbeth Vandem, EMCDDA; Ian Hamilton, Unviersity of York; Paola Kruger, patient advocate; Philip McGuire, Kings College London.

The contrasting impacts of CBD and THC on mental health were underlined by King’s College London Professor Philip McGuire who discussed the results of a recent trial that he led on the use of pure CBD in chronically schizophrenic patients. Those patients’ symptoms were reduced after a period of CBD use as an adjunctive therapy to their regular medication, as compared to patients administered a placebo.

“This is one of the first pieces of evidence that CBD might have anti-psychotic properties,” he told the panel, adding that in MRI scans conducted by researchers, CBD also had very different impacts on brain function than THC, and in some cases “completely opposite effects.”

“We found that the addition of CBD seemed to reduce psychotic symptoms. Its pathways of action on the brain seems to be very different.” While this research is only just emerging, it’s potential is huge because there have not been significantly new anti-psychotic drugs developed for several decades, McGuire told the panel. Based on findings from the recent trial and an as-yet unpublished trial on young adults with prodromal phase psychotic symptoms, he said the research team plans to embark on larger multi-country trials of CBD involving young adults at risk of psychosis in Europe and the United States.

Philip McGuire, King’s College London

“We know THC can cause anxiety and paranoia, and if CBD has the opposite effect then potentially it can be used to treat anxiety and paranoia,” said McGuire in a follow-up interview with Health Policy Watch.  “We have been studying the effects of cannabis on mental health for 20-30 years, initially that was  all about the adverse effects of THC… and then we learned more about CBD and that it seemed to have opposite effects to THC, and that led to thinking about using it as a medicine,” he said.  He added that he hoped that larger trials might lead to eventual regulatory approval for CBD in patients with certain mental health disorders, although he emphasized that the research is still in its early days.

“It’s very new, we have not known about CBD until relatively recently,” he said. “You have to be confident that it is safe and effective… if you have the trials, then the regulation follows because you can show x=z. Otherwise it is just based on opinion.”

Paradoxically, in the medical cannabis applications involving THC-rich products, which are already being used very widely in some countries of Europe, there have been relatively few strictly controlled clinical trials, the panel members noted. Some research, however, has reported positive outcomes for relief of conditions such as irritable bowel syndrome; chronic pain; as well as the symptoms or side effects associated with other chronic diseases or disease treatments, such as cancer.

Diversity of Products and Regulatory Approaches in Europe

Within the WHO European region, there is a growing diversity in the types of cannabis and cannabinoid compounds available, said Liesbeth Vandam, of the European Monitoring Centre for Drugs and Drugs Addiction (EMCDDA), citing a recent agency report.

But regulators, policymakers, health practitioners and the public, all are struggling to keep up with the flood of new products coming onto the market,  Within Europe there are very diverse approaches to regulation of cannabis and cannabinoid products for both medical and recreational use, said Vandam.

These range from cannabis products that are both legal and illegal, as well as natural and synthetic, to over-the counter CBD sold as food supplements, and which are likely to contain only very small amounts of actual CBD.

Some national regulatory agencies have legalized the medical use of cannabis-rich in THC for the treatment of pain and other chronic conditions, but with little recognition of the potential for medical applications of CBD. Other countries may allow CBD-rich products to be sold over-the counter, while cannabis products with higher levels of THC may be harder to obtain, including by prescription.

“Cannabis products have become increasingly diverse in Europe,” says the recent EMCDDA report, cited by Vandam. It notes that more detailed information needs to be collected on the precise components of various products being made available, at national and European levels, in order to better monitor health effects.”

Rising levels of THC in recreational cannabis. Credit: Ian Hamilton, University of York.

Other concerns expressed by the panelists included the steadily increasing THC potency of recreational cannabis products on the market today, as well as a cross-over influences from the medical cannabis market, which some fear could stimulate increased recreational use and abuse, particularly in adolescents and young adults whose developing brains are more vulnerable to THC.

The ratio of psychoactive THC to CBD in street cannabis in the UK has increased eight-fold between 1995 and 2014, noted Ian Hamilton, a senior  lecturer on addiction and mental health at the UK’s University of York,. In the United Kingdom, recreational cannabis is still illegal, and medical cannabis was approved for use only last year, but use has been very constrained by its high price and doctor’s reluctance to prescribe, he said.

Increased THC potency in street cannabis products has also been observed elsewhere across Europe, according to the recent EMCDDA study, said Vandam.

Needed: Coherent Research Agenda

Overall, she says, “there is a strong need for additional research and clinical studies including larger and better-designed trials; studies looking at dosage and interactions between medicines; and studies with longer-term follow-up of participants.”

Ian Hamilton, University of York, United Kingdom

Among the research and policy issues, adds Hamilton, are lack of agreed-upon definitions for the products tested and used, as well as for the recreational users, in terms of what levels of use might actually constitute dependency or addiction, with significantly greater health impacts.

“The UK government has struggled to come up with a policy for cannabis-based products, and they have struggled to be clear in their definitions,” he said. But key questions still remain open, such as whether policies also cover raw cannabis products, or cannabis-derived oils?

“In [addiction] research, the other problem is that different researchers define a regular [cannabis user] in different ways.  There needs to be more standardization in the terminology. There needs to be some agreement; otherwise we have all of these interesting bits of research, but we cannot compare them.”

Malta is another European country that has recently moved forward with the legalization of medical cannabis, including granting licenses for cannabis cultivation, noted Natasha Azzopardi-Muscat, a health professional with the National Directorate for Health Information & Research and President of the European Public Health Association.

“It’’s very clear, many countries are facing a new frontier, and we all have to learn together,” said Azzopardi-Muscat, who moderated the cannabis session.

She said that she was concerned, in particular, with the “blurring of the use between cannabis as a medicinal product and cannabis as a recreational product, and that is where we need to do further homework.

“Nobody quarrels to cannabis being elevated to the status of medicinal product if it can satisfy the traditional scientific thresholds for quality, safety, efficacy that are normally ascribed to medicines,” she added.

“But there is a wide difference between the wide varieties of the plant and its constituents – the different types of cannabinoids.  That is where the science starts to become really complicated, and the policy and regulatory issues become increasingly difficult.

“The key take-home lesson is that this is an issue which is scientifically very complex, which policymakers are going to find very difficult to regulate. And there isn’t a clear pool of expertise – it is fragmented between different research areas and activities.”

She said that she hoped the new flagship European Union research initiative, Horizon Europe, can provide a “window of opportunity to promote a clear research agenda that would be able to support policy agendas.

“My key message is to push the research agenda, involving both clinicians and public health specialists in a carefully structured debate. There is a window of opportunity to address this issue in Horizon Europe,” she said.  “I do see this as something that may be discussed on the European health policy agenda, but by then we may be too late, and we may be struggling to regulate a horse that has bolted.”

Natasha Azzopardi-Muscat, President, European Public Health Association

 

Image Credits: EHF-Gastein , EHF-Gastein, Ian Hamilton, University of York.

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