Psychedelic research TWG

Mission statement/Aims

A strict, widely agreed upon definition describing which drugs are truly “psychedelics” remains elusive. However, it is widely held that the primary effect of psychedelic drugs is the triggering of non-ordinary states of consciousness (known as psychedelic experiences or "trips"). This state includes specific cognitive, affective, and sensory changes, including, but not limited to; an altered sense of “self”, blissful mood and alterations in the visual field. This state is often perceived as exceptionally profound or meaningful.

The psychedelics with the largest scientific and cultural influence, are LSD (lysergic acid diethylamide), psilocybin (O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine), mescaline (3,4,5-trimethoxy-phenethylamine), and DMT (N,N-dimethyltryptamine). These, and almost all novel psychedelics, each fall into one of three families of chemical compounds: phenethylamines, lysergamides, and tryptamines. Current evidence suggests that all psychedelics produce their acute effects via serotonin 2A receptor agonism which modulates the activity of key circuits in the brain involved with sensory perception and cognition. The exact nature of how psychedelic induced changes in neural function are linked to changes in perception and cognition is still unknown. Functional brain imaging suggests that psychedelic induced disruption of within-network connectivity and increased functional connectivity between functional networks are likely the most relevant mechanisms underpinning the psychedelic experience. We will also include the study of compounds related to psychedelics, e.g., dissociatives such as the NDMA antagonist ketamine.

Psychedelics are intriguing pharmacological agents for two primary reasons. Firstly, their profound acute effects on perception, affect and cognition enable researchers to develop a closer understanding of these processes in the un-altered state and to develop an understanding of the role of monoamine neurotransmitters, primarily serotonin, in modulating these processes. Secondly, psychedelics, in combination with psychological support and therapy, have shown rapid and large treatment effects in a range of psychiatric disorders, including major depressive disorder, addictive disorders including smoking and alcohol, and existential distress associated with end-of-life. Additionally, persisting positive effects on mood, behaviour and personality have been reported following a single dose in healthy volunteers lasting at least several months.

Many questions around the acute and persisting effects of psychedelics remain unanswered; for instance, very little work has investigated which (additional) receptors are involved in neuropharmacology of the effects behind the different compounds, persisting effects on functional brain activity, the differences in acute and persisting effects between compounds have not been elucidated, and the link between acute and persisting effects has not been clearly established. This TWG aims to share findings that are transforming our understanding of psychedelics, setting the stage for the identification of mode of action and potential benefit for new treatments of neuropsychiatric disorders.

The present TWG in Psychedelic Research will comprise internationally recognized European centres with a track-record within psychedelic research. These sites are comprised of both preclinical and clinical scientists who will work jointly to perform high-level translational research projects enabling to substantially improve mechanistic and functional knowledge about the exact mode of action of psychedelics.

Overall, the ECNP TWG will:

1. Represent the methodological and technical skills and scientific expertise required for the development of relevant human and animal studies in order to set up collaborative projects.
2. Examine the exact mechanisms and related pathways of psychedelics.
3. Share collected data among the constitutive centres of the present TWG to carry out pilot or ancillary studies testing new hypotheses or replicating previous findings.
4. Invest in shared stocks of GMP produced psychedelics.
5. Identify laboratories within the TWG capable of measuring serum drug levels and biomarkers of relevance.
6. Support policy-making vis-à-vis politicians and regulators.

The emerging importance of psychedelics for understanding the brain and for treating psychiatric and neurologic disorders makes it timely to create a European TWG in the field of psychedelic research where we include both clinical and basic research centres with widely renowned competencies and experience in this field. This network differs from all other ECNP networks as it will be the only network to investigate the mechanism of action of psychedelic compounds.