The therapeutic potential of psychedelics: the European regulatory perspective

Abstract

In the EU, mental health problems affect more than one in six people with considerable impacts for individuals and society and economic costs that exceed 4% of gross domestic product across the EU. 1 Organisation for Economic Co-operation and DevelopmentA new benchmark for mental health systems: tackling the social and economic costs of mental ill-health. OECD Health Policy Studies. OECD Publishing, Paris2021 Google Scholar , 2 Organisation for Economic Co-operation and DevelopmentEuropean UnionHealth at a glance: Europe 2018: state of health in the EU cycle. OECD Publishing, Paris2018 Google Scholar There is a need for effective, safe new treatments for mental disorders. In the past decade there has been a renewed interest worldwide in psychedelics as potential treatments for various mental health conditions, 3 Tullis P The rise of psychedelic psychiatry. Nature. 2021; 589: 506-509 Crossref PubMed Scopus (16) Google Scholar such as treatment-resistant depression, addictive disorders, post-traumatic stress disorder, and end-of-life psychological distress. 4 Goodwin GM Aaronson ST Alvarez O et al. Single-dose psilocybin for a treatment-resistant episode of major depression. N Engl J Med. 2022; 387: 1637-1648 Crossref PubMed Scopus (17) Google Scholar , 5 Johnson MW Garcia-Romeu A Griffiths RR Long-term follow-up of psilocybin-facilitated smoking cessation. Am J Drug Alcohol Abuse. 2017; 43: 55-60 Crossref PubMed Scopus (225) Google Scholar , 6 Agin-Liebes GI Malone T Yalch MM et al. Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. J Psychopharmacol. 2020; 34: 155-166 Crossref PubMed Scopus (107) Google Scholar , 7 Holze F Gasser P Müller F et al. Lysergic acid diethylamide–assisted therapy in patients with anxiety with and without a life-threatening illness: a randomized, double-blind, placebo-controlled phase II study. Biol Psychiatry. 2023; 93: 215-223 Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar These psychoactive compounds have overlapping effects via different mechanisms of actions which, in the context of therapeutic use, remain to be established. 8 Grieco SF Castrén E Knudsen GM et al. Psychedelics and neural plasticity: therapeutic implications. J Neurosci. 2022; 42: 8439-8449 Crossref PubMed Scopus (0) Google Scholar Psychedelic substances induce alterations of consciousness, including visual effects, transient feelings of oneness with the universe, transcendence of time and space, and ego dissolution, but can also induce anxiety and psychological distress, 9 Reiff CM Richman EE Nemeroff CB et al. Work Group on Biomarkers and Novel Treatments, a Division of the American Psychiatric Association Council of ResearchPsychedelics and psychedelic-assisted psychotherapy. Focus (Am Psychiatr Publ). 2021; 19: 95-115 PubMed Google Scholar which can be alleviated through interpersonal support during administration. 10 Barrett FS Bradstreet MP Leoutsakos JS Johnson MW Griffiths RR The Challenging Experience Questionnaire: characterization of challenging experiences with psilocybin mushrooms. J Psychopharmacol. 2016; 30: 1279-1295 Crossref PubMed Scopus (0) Google Scholar , 11 Johnson M Richards W Griffiths R Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008; 22: 603-620 Crossref PubMed Scopus (467) Google Scholar Classic psychedelics act via 5-HT2A receptor agonism and include mescaline, N,N-dimethyltryptamine, lysergic acid diethylamide, and psilocybin. Atypical psychedelics (eg, 3,4-methylenedioxymethamphetamine and ketamine), have different pharmacological mechanisms of action and also differ in terms of legal status (eg, ketamine and esketamine are approved as medicines in the EU). We do not, therefore, include atypical psychedelics in this discussion of the European regulatory context for potential therapeutic uses of psychedelics in mental disorders. The issues we raise here are informed by our work for the European Medicines Agency (EMA), the EMA's Central Nervous System Working Party, and the European College of Neuropsychopharmacology (ECNP).