A second chance to psychedelics

There is a lot of stigma around psychedelics like LSD, MDMA (as in ecstasy) and psilocybin (a naturally occurring compound found in "magic mushrooms"), as they are often associated to harmful behaviour and abuse. Their use was restricted in 1971, when they were added to the United Nation’s Convention of Psychotropic Substances as drugs claimed to create a serious risk to public health, with no therapeutic value.

However, there was a medical interest in these drugs for different psychiatric conditions. But most of the treatments performed in the ‘60s and the ‘70s would be considered experimental today and, in some cases, even unethical. For example, due to lack of patients’ consent or due to repeated or high administered doses. ?

In addition, most of the evidence generated was of low scientific grade due to methodological inadequacies, lack of comparison against placebo, too much anecdotal observation and not enough statistical analysis. Despite some positive observations, the UN classification I mentioned above diminished the research interest, and this almost disappeared in the 80s.

Over the past decade, there has been a shift in the way psychedelics are perceived, with academics and researchers showing a renewed interest in what is called psychedelics assisted therapy, when single-dose psychedelics are used in combination with psychotherapy. Research has focused on using psychedelics assisted therapy against resistant depression, post-traumatic stress disorder (PTSD) and substance abuse.

In light of promising early clinical evidence from randomised trials, the U.S. Food and Drug Administration (FDA) designated the psilocybin therapy as "breakthrough therapy" against major depressive disorder and treatment-resistant disorder. The Australian Therapeutic Goods Administration (TGA) took this one step further and authorised some psychiatrists to use psilocybin for treatment-resistant depression and MDMA for PTSD.

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So where is the EU in all this?

We at the European Medicines Agency acknowledge that psychedelics assisted therapy looks promising to tackle several mental health conditions. At the same time, we are concerned about the challenges developers may face in meeting the scientific and regulatory expectations for getting a marketing authorisation for these products. We must see scientifically rigorous evidence to support efficacy and safety of psychedelics. There are currently 11 ongoing clinical trials in the EU with psilocybin, four trials are ongoing with MDMA and one trial with LSD. While the clinical trials that have been run so far show promising results, they are too small to base a regulatory decision on. Complex study designs are critical to generate robust, less fragmented evidence.

Experts across the EU medicines regulatory network have been engaged with developers of psychedelic therapies since 2019 in a few ?EMA scientific advice and protocol assistance procedures. We know that these products are mostly developed by small pharmaceutical companies and academics. Navigating the regulatory process may be overwhelming for them, but EMA is open to start the discussions, to offer guidance and support. We invite those interested to approach us if they have projects in the pipeline. The Agency’s Innovation Task Force is another great way to get in touch.

EMA and members of its Central Nervous System Working Party are actively engaged with researchers from the European College of Neuropsychopharmacology (ECNP). This close cooperation resulted in commentary published in The Lancet on regulatory and scientific challenges.

Between 19 and 20 March, the ECNP is organising a conference bringing together a mix of scientists, industry leaders, patient representatives and regulators to identify what it takes to move forward with psychedelics used as therapies for medical conditions. Together with Marion Haberkamp , head of Neurology, Psychiatry and Ophthalmology at the Federal Institute of Drugs and Medical devices (BfArM), I will be chairing a session on regulatory aspects regarding clinical trials. I have been part of the organising committee for this conference, and I am really looking forward to engaging with stakeholders in this field.

Diving into understanding the opportunities that psychedelics may bring has never been more relevant, given the toll mental health issues are taking on public health nowadays.

Steffen Thirstrup , Chief Medical Officer at EMA?