Intra-Sessional Autonomic Arc Detection in Ketamine-Assisted Therapy for PTSD: A Signal Characterisation Pilot Study

Post-traumatic stress disorder (PTSD) affects an estimated 9.2% of Canadians over a lifetime, with particularly high prevalence among first responders, veterans, and survivors of interpersonal violence. Conventional first-line treatments leave a significant proportion of patients with residual symptoms, and access to evidence-based care remains limited in rural and remote settings. Ketamine-assisted therapy (KAT) has demonstrated rapid anxiolytic and antidepressant effects in multiple randomised controlled trials and represents a promising approach for treatment-refractory PTSD. However, the mechanisms through which KAT produces therapeutic change, and the conditions that determine whether a given session produces durable benefit, are incompletely understood.

The REBUS (Relaxed Beliefs Under Psychedelics) account provides the theoretical foundation for this study. Under this framework, ketamine temporarily reduces the precision-weighting of high-confidence predictive priors - including deeply entrenched trauma-related threat appraisals - creating a window of increased neuroplasticity during which the generative model is most available for revision. This window is hypothesised to correspond to a specific autonomic configuration: a shift from peak sympathetic activation toward increasing ventral vagal dominance, characterised by falling electrodermal activity, rising HRV coherence, and emerging parasympathetic predominance. This configuration is referred to as the Transition Window. The Transition Window is theoretically critical because articulation of psychological content delivered during this state is predicted to produce genuine prior-precision reduction, whereas identical articulation delivered outside this window is predicted to produce verbal acknowledgement without the underlying autonomic reorganisation that constitutes genuine release.

The foundational challenge for testing this prediction empirically is that no validated method has existed for detecting the Transition Window in real time. This study addresses that gap by applying the JungleCODE arc-position detection algorithm to continuous intra-sessional physiological data from KAT participants.

JungleCODE (Open Medicine Studio; patent pending, PCT filed) is a proprietary signal processing algorithm that analyses continuous heart rate variability (HRV) time-series data - and, where available, electrodermal activity (EDA) - to estimate arc position on a clinically defined aporia-to-ataraxia spectrum. Aporia refers to the state of peak arousal, maximal predictive prior precision, and high sympathetic drive. Ataraxia refers to the state of regulatory restoration, reduced prior precision, and ventral vagal dominance. Unlike single-biomarker threshold approaches, JungleCODE is a trajectory detection algorithm: it identifies where in a continuous arc the person is located based on the directional pattern of change over time, not the absolute value at any given moment. The algorithm outputs arc-position scores at 30-second intervals along with transition event flags, trajectory classification, and autonomic phase designation.

This study is observational and non-interventional. Participants independently arrange their own ketamine-assisted therapy sessions with a licensed British Columbia physician or nurse practitioner. The researcher does not administer ketamine or any other substance and has no clinical role during the session. All clinical decisions and safety oversight during the KAT session remain entirely with the licensed treating provider. The researcher's role is continuous physiological monitoring via an EmbracePlus wrist-worn wearable biosensor and a structured post-session interview.

The EmbracePlus (Empatica Inc.) is a medical-grade research biosensor that records the interbeat interval stream at 64 Hz, EDA phasic and tonic components, skin temperature, and accelerometry. Data is streamed via Bluetooth to a secured local device and transferred to the Open Medicine Studio sovereign data layer - a self-managed, physician-controlled PostgreSQL database hosted in AWS ca-central-1, encrypted at rest using physician-held customer-managed keys - within 24 hours of each monitoring session.

The study proceeds across three phases for each participant. The preparation phase, conducted three to seven days before the KAT session, establishes the participant's individual arc baseline through continuous wearable monitoring during normal daily activity and sleep. A structured pre-session interview, audio-recorded with participant consent, is conducted within 48 hours of the session. The intra-sessional phase involves continuous EmbracePlus monitoring throughout the KAT session, from preparation through dosing to immediate integration onset. The researcher is not present at the session site unless explicitly invited by the treating provider; where present, the researcher acts solely as an observer and has no clinical role. Precise session timestamps are recorded to enable temporal mapping of arc-position events onto session phases. The integration phase involves three to five day wearable monitoring windows at one, two, and four weeks post-session, with brief structured check-in interviews and administration of the PCL-5 at two and four weeks.

The primary outcome is characterisation of the intra-sessional autonomic arc trajectory - including arc depth, inflection timing, transition event identification, and trajectory classification - as detected by the JungleCODE algorithm applied to the continuous EmbracePlus data stream. Secondary outcomes include the temporal correspondence between arc-position transition events and KAT session phase timestamps, the integration-phase arc trajectory compared to individual pre-session baseline, and the correspondence between arc-position transition event timing and participant-reported subjective experience assessed via the Post-Session Subjective Integration Scale. PTSD symptom severity as measured by PCL-5 is collected as an exploratory measure; this pilot study is not powered to assess symptom outcomes.

This is a pilot signal characterisation study with a target enrolment of two to six participants. No hypothesis tests are pre-specified. Analysis is descriptive, focused on arc trajectory visualisation, transition event identification, and feasibility metrics including device wear compliance, data quality, and participant retention. The findings will be used to calibrate the JungleCODE algorithm for the KAT context, characterise inter-individual variability in arc trajectory parameters, and identify candidate arc-event signatures for subsequent hypothesis testing in larger controlled trials.

All data is governed by the Open Medicine Studio Sovereign Data Management Blueprint (JC-DMB-001 v1.0) and is held in compliance with the BC Personal Information Protection Act (PIPA) and the federal Personal Information Protection and Electronic Documents Act (PIPEDA). Participants are assigned pseudonymous codes at enrolment; the linkage list is held by the PI on an encrypted offline device separate from all study data. No identifiable data is stored in or transmitted to any third-party system.

Ethics oversight is provided by the Canadian SHIELD Ethics Review Board (CSERB; OHRP Registration IORG0003491; FDA Registration IRB00004157). The study is registered on ClinicalTrials.gov prior to enrolment of the first participant, consistent with ICMJE requirements.