There's been a quite informative publication by a newly created EU Drug Agency that covered frequently asked questions about psychedelics. I went through the content and I must admit that I was surprised to see a very balanced document without the stigmatizing content in it.
Below I'll quote some of the content from that report simply because it is worth spreading further.
What are psychedelic substances?
There are different ways in which psychedelic substances can be categorised, usually determined by their mechanisms of action (i.e. how they work in the brain). One common way of categorising these substances, particularly in clinical trials involving psychedelics for mental health conditions, is to divide them into typical (or classical) serotonergic psychedelics and atypical psychedelics (EMA, 2023). Other categorisations have also been proposed, such as separating psychedelic substances from dissociative drugs and ‘other’ substances that affect various brain functions and may cause psychedelic and/or dissociative effects (NIDA, 2023). As research is quickly progressing in this area, and understanding of the properties of these substances deepens, there may be future changes in their classifications.
Typical or classical serotonergic psychedelics generally include, but are not limited to:
LSD (lysergic acid diethylamide)
psilocybin (sometimes referred to as ‘magic mushrooms’)
DMT (N,N-Dimethyltryptamine, a component of ‘ayahuasca’ and/or ‘yagé’)
5-MeO-DMT (5-Methoxy-DMT, a component of Bufo alvarius venom or ‘yoppo’)
mescaline (sometimes referred to as ‘peyote’ or ‘San Pedro’).
Atypical psychedelics generally include, but are not limited to:
dissociative anaesthetics, or simply dissociatives, such as ketamine, esketamine and phencyclidine (PCP, also known as ‘angel dust’) and their analogues, as well as dextromethorphan (DXM)
entactogens (e.g. MDMA)
ibogaine
salvinorin (sometimes referred to as ‘magic mint’).
Classical psychedelics act on the serotonergic system in the brain, as agonists of the type 2A serotonin receptors (5HT-2A). They produce effects that impact perception, mood and cognition, and may cause visual distortions, altered sensory experiences, and a sense of expanded awareness, contributing to a complex and multifaceted effect often referred to as an ‘altered state of consciousness’. The subjective effects, however, vary greatly depending on dose, but also between individuals and from one episode of use to the next within the same person.
Atypical psychedelics share some of the psychoactive effects of typical or classical psychedelics while having a distinct pharmacological mechanism of action. While atypical psychedelics can also induce altered states of consciousness, the subjective experience may also be qualitatively distinct from what is induced by typical or classical psychedelics (Yaden and Griffiths, 2021). To date, the most commonly trialled psychedelics for mental health conditions have been (es)ketamine, psilocybin, MDMA, DMT (including 5-MeO-DMT) and LSD (see 'Why are psychedelics currently being researched in the medical field?').
On a side note: I'd add cannabis to the list of psychedelics. Even though it may seem controversial my thinking on that point is aligned on the one provided by the UC Berkeley in their online program "Psychedelics and the mind" which I went through right after it was launched officially.
Are psychedelics controlled substances?
Currently, three UN conventions describe the basic framework for controlling the production, trade and possession of several hundred psychoactive substances (most of which have a recognised medical use). With some exceptions, most typical and atypical psychedelic substances are controlled under Schedule I of the United Nations Convention on Psychotropic Substances of 1971 (United Nations, 1971), which requires countries to enact national responses including penalties for unauthorised actions. These conventions have been signed by all EU Member States. Ketamine has not been scheduled in the UN conventions.
For more information on penalties, or rehabilitative responses, for the core offences of drug use, possession for personal use, and supply-related offences across countries in Europe, see the EUDA web page ‘Penalties at a glance’. As laws differ across EU Member States and are subject to change, it is important to consult the relevant national competent authority for the most up-to-date information.
Why are psychedelics used?
Psychedelic substances are used in diverse contexts and for different reasons. This includes use in recreational settings among people who use drugs; for religious, spiritual and cultural reasons; and among certain indigenous and non-indigenous groups. Several classical psychedelic substances, such as DMT (in the form of ayahuasca) and mescaline, have a long history of ritualistic and/or religious use in collective practices across indigenous and non-indigenous groups around the world (particularly in Latin America) (NIDA, 2023). Psychedelic use in these contexts is well documented by researchers including anthropologists, where the consumption of psychedelics has been described as being a catalyst for social affiliation, cultural integration and belief (see e.g. Rodríguez Arce and Winkelman, 2021).
Clinical researchers are also investigating the therapeutic properties of a variety of psychedelics for specific mental health conditions (see 'Why are psychedelics currently being researched in the medical field?'). In conjunction, there appears to be a new wave of psychedelic use in Europe, where people are using psychedelics for wellness, therapeutic or spiritually oriented interventions (see 'What information exists on the prevalence and patterns of use of psychedelics in Europe?' and 'What are ‘psychedelic retreats’?').
What are ‘psychedelic retreats’?
Psychedelic retreats appear to be part of a wide range of psychedelic-related practices and interventions that now exist in Europe. Such practices are reported to range from naturalistic/spiritual events (which appear to be commonplace for psychedelic retreats) to interventions that mimic the psychedelic-assisted therapy used in some clinical trials. Specifically, psychedelic retreats appear to be structured and guided experiences in which groups of individuals engage in the use of psychedelic substances, such as psilocybin (‘magic mushrooms’), LSD, DMT (ayahuasca), ketamine and MDMA. They are reported to take place in nature or specially designed facilities, led by facilitators or guides, and may take place over one or several days. The primary goals of psychedelic retreats appear to revolve around therapeutic, spiritual or self-development purposes. Some legal psychedelic retreats are reported to operate in the Netherlands, although in other EU Member States they generally seem to be unlicensed or illegal.
Psychedelic retreats and similar practices have a long-established tradition in Latin America and recently appear to have grown in number in Europe. As little is known about the range of psychedelic practices in Europe, the EUDA has an ongoing project to map these practices and the services they claim to offer.
What are the risks of using psychedelics?
The risks of using psychedelics depend on a number of factors, such as the substance (including dosage, potency/purity, and the presence of adulterants), patterns and settings of use, for example whether it relates to recreational patterns of use or for unregulated therapeutic purposes.
For example, there are well-documented risks related to recreational patterns of MDMA use, including acute poisonings and deaths, partly due to the presence of ecstasy tablets with a high MDMA content and partly due to adulteration of ecstasy tablets with other harmful substances (EMCDDA, 2023; Trimbos-instituut, 2023). Ketamine has been linked to various dose-dependent acute and chronic harms, including neurological and cardiovascular toxicity, mental health problems and urological complications, such as bladder damage from intensive use or the presence of adulterants.
For some psychedelics, particularly the new synthetic psychedelics, there is limited data on the risks stemming from long-term or intensive use. As with all synthetic drugs, there are inherent risks related to potency and purity when used in recreational settings, including the risks of consuming substances that have been mislabelled or mis-sold.
The specific risks of consuming psychedelics for unregulated therapeutic purposes remain poorly understood.
In the context of psychedelic-assisted psychotherapy, there appear to be unique risks related to the vulnerability of the consumer when experiencing an ‘altered state of consciousness’. Specifically, research has highlighted increased vulnerability of patients, the potential for power imbalance between patients and clinicians, and subsequent risks of harm or abuse within treatment, due to the effects of the substances themselves combined with the psychotherapeutic modalities employed (McNamee et al., 2023; Meikle et al., 2024). These particular risks may be heightened in unlicensed or illegal settings (e.g. ‘psychedelic retreats’), where such substances are consumed for wellness, therapeutic or spiritually oriented interventions, in the absence of trained or regulated medical professionals. The EUDA has an ongoing project with the aim of developing a better understanding of the risks related to such unregulated psychedelic practices.
In the context of clinical research with psychedelics, some mild to adverse events have been reported. Adverse events are any unwanted medical occurrences during a clinical study where pharmaceutical products were administered. Most adverse events from clinical trials with psychedelics are reported to occur during the acute effect of the substance and resolve spontaneously (such as related to acute anxiety). However, it is important to consider that there appear to be significant asymmetries in the quantity and quality of safety data that is available for different psychedelic substances (Breeksema et al., 2022). How such risks will be mitigated if these substances are used for medical treatment outside of clinical trials remains an important concern, particularly regarding reported occurrences of challenging experiences (sometimes referred to as ‘bad trips’) and the aforementioned issues around patient suggestibility and vulnerability to abuse.
Why are psychedelics currently being researched in the medical field?
Since 2010 there has been a rapid expansion of clinical trials and other studies in the medical field involving both classical and atypical psychedelic substances for specific mental health conditions, particularly ones that are resistant to conventional treatment. Esketamine, psilocybin, MDMA, DMT and LSD have been the most frequently trialled substances. Psilocybin has, for example, been trialled in the treatment of depression (particularly treatment-resistant depression and major depressive disorder), obsessive compulsive disorder, eating disorders and nicotine and alcohol use disorders. Clinical trials conducted with MDMA have mainly focused on the treatment of post-traumatic stress disorder (PTSD), alcohol use disorder and symptoms of social anxiety in patients with autism spectrum disorder. Meanwhile, LSD has been trialled to treat end-of-life anxiety and substance-related disorders. This recent wave of clinical trials has also stimulated research with psychedelics in animal models and healthy individuals (see e.g. Carhart-Harris et al., 2012; De Gregorio et al., 2021; Odland et al., 2022) in a bid to understand the safety of psychedelic drugs as well as their underlying neurobiology and mechanisms.
According to the available data from these clinical trials, some psychedelics have shown promise in alleviating specific symptoms associated with difficult-to-treat neuropsychiatric disorders. The level of evidence appears relatively consistent when treating PTSD with MDMA-assisted therapy (see e.g. Mitchell et al., 2021). In addition, psilocybin-assisted therapy may reduce depressive symptoms in patients with treatment-resistant depression and major depressive disorder (see e.g. Goodwin et al., 2022; von Rotz et al., 2023). However, across many studies, a clear definition of the adjunct psychological intervention appears to have been limited, and as such, in some cases, it may be difficult to distinguish the interaction between the psychedelic itself and the associated therapy, and the degree to which each of these components influences results. There also appears to be limited data about potential benefits for other psychiatric indications, such as the treatment of substance-related disorders with DMT (ayahuasca) and ibogaine. A complicating factor is reported to be that a large number of studies still present methodological challenges (Butlen-Ducuing et al., 2023; EMA, 2023) and limitations, particularly related to blinding (a process designed to minimise bias by preventing participants and organisers, and sometimes those analysing the data, from knowing which treatment or intervention participants are receiving), which may compromise the interpretation of results.
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