# Can Blocking the Orexin System Enhance Sleep’s Benefits to Therapeutic Exposure for PTSD?

> **NIH NIH K01** · HOWARD UNIVERSITY · 2020 · $148,114

## Abstract

PROJECT SUMMARY/ABSTRACT
Cognitive behavioral therapies (CBT), a first line treatment for posttraumatic stress disorder (PTSD), have
limitations particularly in treating hyperarousal symptoms. It is, therefore, imperative to identify strategies to
improve effectiveness of treatments for PTSD. Disturbed sleep is common in PTSD. Sleep has been implicated
in learning processes that are a key to adaptive processing of trauma memories. Findings of our preliminary
study of people with PTSD suggest that sleep characteristics indicating increased nocturnal arousal
compromise therapeutic effects of written narrative exposure (WNE) intervention (writing about one’s traumatic
experience). Orexins (hypocretins) are neuropeptides implicated in regulating both sleep/wake and stress
responses and emotional behaviors. A dual orexin receptor antagonist, suvorexant, has been found to
enhance sleep characteristics associated with emotional adaptation in humans. Administration of an orexin
receptor-1 antagonist to mice facilitated extinction of conditioned fear, an animal model of recovery from PTSD
and anxiety disorders. The long-term objectives of the candidate’s research program are to elucidate
neurophysiological mechanisms underlying the potential for sleep to contribute to resilience and PTSD
recovery and apply this knowledge to improve PTSD prevention and treatment. To accomplish these
objectives, the following specific aims will be pursued: 1) to examine effects of pharmacologically blocking the
orexin system after WNE on sleep, PTSD symptoms, and intersession habituation; and 2) to use an animal
model to elucidate neural mechanisms underlying the effects of inhibiting the orexin system on sleep and
memory consolidation following fear extinction. In the proposed clinical project, adult participants with PTSD
will complete WNE in the evening and morning with intervening sleep, and either suvorexant (FDA-approved
for treatment of insomnia) or placebo will be administered prior to going to bed following the evening WNE.
This proposed study is the first to investigate the contribution of the orexin system to therapeutic effects of
exposure-based treatment for PTSD through sleep. In the animal study, orexin neurons in the hypothalamus
will be inhibited using optogenetic methods following a fear extinction training. For the career development
plan, the candidate will participate in didactic and in-lab training activities in neuroscience and advanced
research methodologies of both clinical and animal studies. The new skill set to be acquired during the K01
period will complement the candidate’s current expertise and enable her to develop an independent
translational research program that strategically utilizes clinical and animal study methods to elucidate
mechanisms underlying sleep’s contribution to resilience and PTSD recovery.

## Key facts

- **NIH application ID:** 9888444
- **Project number:** 5K01MH110647-04
- **Recipient organization:** HOWARD UNIVERSITY
- **Principal Investigator:** Ihori Kobayashi
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $148,114
- **Award type:** 5
- **Project period:** 2017-04-04 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9888444

## Citation

> US National Institutes of Health, RePORTER application 9888444, Can Blocking the Orexin System Enhance Sleep’s Benefits to Therapeutic Exposure for PTSD? (5K01MH110647-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9888444. Licensed CC0.

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