Psychedelic Medicine and Neuromodulation: From Bench to Bedside Advancing Real-World Implementation of Next-Generation Psychiatric Treatments

Psychedelic medicine has emerged as one of the most promising frontiers in psychiatry and neurology, characterized by the capacity of compounds such as psilocybin, MDMA, LSD, DMT, and ketamine (including esketamine) to rapidly induce neuroplasticity, disrupt rigid maladaptive neural networks, and facilitate profound therapeutic change in conditions including treatment-resistant depression, PTSD, anxiety disorders, substance use disorders, eating disorders, and chronic pain syndromes. These agents engage serotonin 5-HT2A receptors, promote BDNF expression, and transiently dissolve the default-mode network, producing measurable changes in functional connectivity that correlate with sustained clinical improvement. Parallel to this renaissance, neuromodulation technologies—including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), focused ultrasound, vagus nerve stimulation (VNS), and deep brain stimulation (DBS)—offer precise, circuit-specific modulation of cortical and subcortical networks implicated in the same disorders.

The convergence of psychedelic medicine and neuromodulation represents a powerful synergistic opportunity: psychedelic-induced plasticity may amplify the lasting effects of neuromodulatory interventions, while targeted brain stimulation may stabilize, prolong, or direct the acute psychedelic state toward specific therapeutic outcomes. There is a rapidly expanding body of preclinical, neuroimaging, and early-phase clinical evidence supporting these hybrid approaches, yet critical gaps remain in mechanistic understanding, standardized protocols, safety optimization, and integration with psychotherapy.

Despite robust Phase II and III data for several psychedelic agents and FDA-cleared neuromodulation devices, the field continues to navigate regulatory, ethical, and implementation challenges. Questions persist regarding optimal sequencing and dosing of combined interventions, biomarkers of response, long-term safety, equity of access, and differentiation from conventional pharmacotherapy or psychotherapy. These issues mirror the historical trajectory of other paradigm-shifting treatments and warrant systematic, multi-disciplinary investigation.

A growing international community of clinicians, neuroscientists, pharmacologists, psychologists, and ethicists has convened at major conferences (e.g., Psychedelic Science, International Society for Neuromodulation, and specialized hybrid workshops) to forge consensus on nomenclature, trial design, and best-practice guidelines. This Research Topic will showcase the latest empirical findings, theoretical frameworks, and translational advances at the intersection of psychedelic medicine and neuromodulation. Contributions from experts across psychiatry, neurology, neuroscience, psychology, neuroimaging, and public health are invited to accelerate the safe, effective, and equitable integration of these modalities into clinical care.

The overarching goals of this Research Topic are to:

1. Synthesize current mechanistic insights into how psychedelics and neuromodulation interact at molecular, circuit, and systems levels.

2. Advance evidence-based protocols for combined or sequential interventions.

3. Identify biomarkers, predictors of response, and long-term outcomes.

4. Address ethical, regulatory, and implementation barriers to broaden access while maintaining rigorous safety standards.

We welcome original research articles, reviews, systematic reviews, clinical trial protocols, perspective pieces, and case series on the following (non-exhaustive) topics:

- Underlying neurobiological and psychological mechanisms of psychedelic-induced neuroplasticity and its modulation or potentiation by neuromodulatory techniques

- Synergistic or sequential protocols combining classic or atypical psychedelics with non-invasive (TMS, tDCS, focused ultrasound) or invasive (DBS, VNS) neuromodulation

- Neuroimaging (fMRI, MEG, EEG, PET, MRS) and electrophysiological correlates of single vs. combined interventions

- Screening, assessment, personalized patient selection, intervention protocols, dosing paradigms, psychotherapy integration, and long-term clinical outcomes (≥12 months)

- Safety, tolerability, adverse events, and risk-mitigation strategies across diverse populations

- Phenomenology of psychedelic experiences when augmented by neuromodulation, including lived-experience perspectives and qualitative analyses

- Ethical, legal, regulatory, equity considerations, comparative effectiveness research, and public-health initiatives

This multi-disciplinary Research Topic aims to drive forward the field through high-quality contributions. We particularly encourage submissions from early-career researchers, clinician-scientists, and teams incorporating patient-partnered or community-based approaches.

Topic Editor Owen Muir declares financial and professional relationships with Radial, Neurolief, Brainway, Magnus, SDP, NIH (R41), iRxReminder, SoniRemedy, Springer Health, Vidara Health, OutrO Health, Purple Gaze, Ampa Health, Springer, MindMed, Soneira, and GrayMatters, in roles such as CMO, PI, owner, grant, consultant, advisor, and book author; these relationships involve research, consulting, equity, and publishing activities. Topic Editor Burton J. Tabaac serves as a scientic advisor to Rose Hill Life Sciences. The other Editors declare no competing interests relating to the Research Topic subject.