Dose-related reductions in prefrontal recruitment during cognitive reappraisal following oral delta-9-tetrahydrocannabinol in posttraumatic stress disorder.
Connor J Haggarty, Christine A Rabinak
Neuropsychopharmacology July 16, 2026 DOI: 10.1038/s41386-026-02502-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, placebo-controlled trial Peer reviewed |
|---|---|
| Sample size | 37 |
| Population | Adults with posttraumatic stress disorder (PTSD) |
| Dose | 5 mg dronabinol or 10 mg dronabinol, single oral dose |
| Topics | Cannabis PTSD |
| Key findings | Relative to placebo, both 5 mg and 10 mg oral dronabinol were associated with reduced activation during reappraisal of negative images in prefrontal and parietal regions implicated in top-down control, with broader and stronger attenuation at 10 mg. In-scanner negative affect ratings and post-scan valence and arousal ratings did not differ reliably by dose, which the authors interpret as consistent with a potential neural-subjective dissociation. |
Abstract
Posttraumatic stress disorder (PTSD) is characterized by difficulties in emotion regulation and altered recruitment of prefrontal control systems during cognitive reappraisal. Cannabinoid signaling has been implicated in stress and affect regulation, yet dose-dependent effects of acute delta-9-tetrahydrocannabinol (THC) on the neural mechanisms supporting reappraisal in PTSD remain unclear. In a randomized, double-blind, placebo-controlled design, adults with PTSD received a single oral dose of placebo (N = 12), 5 mg dronabinol (synthetic THC; N = 12), or 10 mg dronabinol (N = 13) prior to fMRI during a validated cognitive reappraisal task. Relative to placebo, both THC doses were associated with reduced activation during reappraisal of negative images (Reappraise-Negative > Maintain-Negative) across prefrontal and parietal regions implicated in top-down control, with broader and stronger attenuation at 10 mg. In contrast, in-scanner negative affect ratings were robustly sensitive to task conditions but did not differ by dose. Post-scan valence and arousal ratings confirmed expected stimulus effects without reliable dose effects. Exploratory analyses revealed limited correspondence between regional activation and subjective affect. These findings indicate that acute oral THC is associated with dose-dependent reductions in recruitment of prefrontal control circuitry during cognitive reappraisal in PTSD without detectable changes in self-reported affect, consistent with a potential neural-subjective dissociation, although smaller behavioral effects may not have been detectable in the current sample.
Comparable studies
Other randomized controlled trials on PTSD, most cited first.
Citations in the library
Cites 16
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- Dose-dependent effect of acute THC on extinction memory recall and fear renewal: a randomized, double-blind, placebo-controlled study. Psychopharmacology February 1, 2026
and 11 more in the library