The first day kicked off with a women-led keynote focused on the psychological and biological aspects of psychedelics’ therapeutic potential.

In her introductory remarks, Dr. Nora Volkow, Director of the National Institute on Drug Abuse (NIDA), described a pendulum shift in the field and the potential that can be harnessed from these substances to develop new therapeutics. As long as “we don’t mess it up”, that is!

The first keynote was delivered by Dr. Rachel Yehuda (Icahn School of Medicine at Mount Sinai, United States). As a leader in traumatic stress studies and post-traumatic stress disorder (PTSD), her seminar focused on the role of psychotherapy in driving clinical outcomes for psychedelic-assisted therapy (PAT) for PTSD.

After laying the groundwork surrounding the biological basis of trauma, Yehuda discussed the role of psychotherapy and recovery signals versus the drug effects during PAT. Of note, she described the Goldilocks problem of psychotherapy causing a hyperarousal state and pharmacotherapy inducing a hypoarousal state in those with PTSD. Her work, along with many others, is aiming to find that middle ground using psychedelics like MDMA.

Lykos Therapeutics’ (formerly MAPS PBC) MDMA-assisted therapy (MDMA-AT) protocol features many hours of therapeutic face-time outside of dosing sessions. Yehuda said that this amount of preparation and integration must play a role on its own.

After sharing some unpublished data related to her own studies with MDMA-AT in those with PTSD, she ended by highlighting that clinical trials directly comparing PAT with or without psychotherapy in clinical populations, which have not yet been conducted, may shed light on this issue.

The second seminar of the keynote was given by Dr. Gül Dölen (University of California, Berkeley, United States). Her seminar touched the other side of the aisle, with a discussion on her preclinical studies on neuroplasticity and critical periods.

This work was originally published in 2023 (see Nardou et al., 2023) and used a social preference protocol in rodents to demonstrate the power of psychedelics to reopen a period of increased sociability in adults that is typically seen in juveniles. This increased sociability is thought to be indicative of a reopening of the period involved in social reward learning. In this paper, the authors demonstrate that MDMA, psilocybin, LSD, ketamine and ibogaine all induce this social reward learning, but other drugs like cocaine do not. Dölen suggests that the durability of PAT may be related to the learning that takes place during integration, but this is often context dependent.

Recently, a preprint was posted on BioRxiv testing the reproducibility of psychedelic behavioural experiments in rodent models. One of the models tested social reward experiments similar to the ones used by Dölen’s lab. In her seminar, she pointed out that many replication issues come down to the smallest of details, including things like room temperature and the type of cage materials, or more obvious details like timing of drug administration and the type of cues being paired with behaviour.

This discussion emphasised the point that animal models are tedious and not made to perfectly replicate the human experience, something that became a theme of the GRC.

Dölen ended her seminar by sharing her hypothesis that psychedelic-induced neuroplasticity provides a window in which psychotherapy can further augment the positive outcomes of psychedelics. PAT needs the therapy aspect, she argued, as recommended by some psychiatrists and psychotherapists working directly on these clinical trials.

The next major venture for her lab is the PHATHOM project, which aims to assess the potential of psychedelics in augmenting physical therapy among stroke patients.