# 1/2 A Brief Automated Neurocognitive Training to Enhance the Real-World Impact of Ketamine's Rapid Antidepressant Effect

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $878,720

## Abstract

Project Summary. Intravenous ketamine, which displays rapid antidepressant properties, is posited to reverse symptoms
by rapidly enhancing neuroplasticity. Although community-based ketamine clinics have proliferated in the US and
worldwide in recent years, a significant barrier to clinical adoption is the lack of evidence-based strategies to enhance the
durability of ketamine’s effects, creating substantial barriers to access and longer-term maintenance of gains. In a previous
efficacy study among depressed outpatients, we posited that ketamine would rapidly increase plasticity within the
information processing domain, allowing for rigid, negative biases in cognition (specifically, negative self-
representations) to be rapidly made malleable. We further expected these neurocognitive changes would provide a clinical
window of opportunity in which to introduce digital cognitive training techniques, which would consolidate adaptive
forms of cognitive processing (specifically, positive implicit representations of self) while neuroplasticity remains high.
By instantiating adaptive forms of processing after first 'priming' the brain with ketamine, we developed a novel
synergistic treatment approach (ketamine + Automated Self Association Training; ‘ASAT’) that extended the acute effects
of a single ketamine infusion far beyond its typical 7-14 day window, showing statistically significant effects on
depression [relative to saline paired with ASAT (no-drug control arm)] that persisted for 3 months after a single infusion
of ketamine—an approximately 9-fold increase in durability of effect relative to ketamine paired with sham digital
training (no-training control arm). In the current multi-site ‘Hybrid Type 1’ effectiveness-implementation randomized
controlled trial, 600 ketamine-seeking depressed outpatients receiving intravenous ketamine ‘induction’ (6-12 serial
infusions over 3-8 weeks) at one of 8 well-established real-world clinics throughout the US will be randomized to receive
either adjunctive active ASAT or sham ASAT. After an initial in-clinic ‘onboarding’ session, patients will self-administer
ASAT (or sham) at home, in three ‘bursts’ (each ‘burst’ = eight ~15min sessions delivered 2x/day over 4 consecutive
days), sequenced to begin just after (1) the first ketamine induction dose (Aim 1), (2) the last ketamine induction dose
(Aim 2), and (3) 3 months after the first dose (Exploratory Aim). Patients will complete depression severity measures
and performance-based measures of cognitive target engagement (implicit self-associations), acutely and across a 12-
month naturalistic follow-up, enabling comprehensive assessment of ASAT’s potential enhancing (Aim 1) and extending
(Aim 2) effects on depression relief. Validated data-driven ‘combined moderator’ methods will be used to identify
baseline patient profiles (Aim 3) that predict favorable response to ketamine (all patients) and specific response to
ketamine+ASAT (relative to ketamine+sham). Com...

## Key facts

- **NIH application ID:** 10866705
- **Project number:** 1R01MH136179-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Rebecca Price
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $878,720
- **Award type:** 1
- **Project period:** 2024-07-05 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10866705

## Citation

> US National Institutes of Health, RePORTER application 10866705, 1/2 A Brief Automated Neurocognitive Training to Enhance the Real-World Impact of Ketamine's Rapid Antidepressant Effect (1R01MH136179-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10866705. Licensed CC0.

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