# Functional neuroimaging of fatty acid amide hydrolase inhibition in posttraumatic stress disorder: a randomized clinical trial

> **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637)
> **Publisher:** CED Clinic (https://cedclinic.com)
> **Canonical URL:** https://cedclinic.com/research/amidohydrolases-for-post-traumatic-stress-disorders-randomized-controlled/
> **Published:** 2026-10-19T22:44:44-04:00 | **Last Modified / Clinically Audited:** 2026-10-19T22:44:49-04:00
> **Clinical Summary:** This study looked at adults with post-traumatic stress disorder, a condition that can follow frightening events.

---

The endocannabinoid ligand anandamide (AEA) plays a role in fear extinction, the conceptual foundation of the gold standard treatment for posttraumatic stress disorder (PTSD), exposure-based psychotherapy. Converging evidence from animal models and non-clinical human studies highlights the potential to enhance fear extinction pharmacologically by inhibiting the AEA catabolic enzyme, fatty acid amide hydrolase (FAAH). However, in our randomized clinical trial (n = 100), a FAAH inhibitor did no better than placebo at enhancing the response to exposure-based therapy in PTSD. Here, we used functional magnetic resonance imaging to investigate the neurobiological effects of FAAH inhibitor treatment on resting-state functional connectivity and the neural correlates of emotional processing (n = 76 scanned). We found that greater symptom improvement was significantly related to lower functional connectivity between ventromedial prefrontal cortex (vmPFC) and right dorsolateral prefrontal cortex (dlPFC), as well as lower task activation of the right dlPFC. Further, we found that self-reported symptoms at the time of scan were associated with increased functional connectivity of the vmPFC and the amygdala across the cortex (mainly in the ventral attention network and sensorimotor network, respectively). However, while we confirmed that 4 weeks of FAAH inhibition significantly increased AEA, there were no significant differences in functional connectivity or task activation between treatment groups. These findings suggest that FAAH inhibition does not affect intrinsic functional connectivity or emotional task response in PTSD, and that the dlPFC may play an important role in the response to exposure-based psychotherapy.

 

### Related

---

### Verification & Medical Governance

- **Lead Clinical Author:** Benjamin Caplan, MD
- **Credentials:** Board Certified in Family Medicine (ABFM), Former CMO Canna Care Docs (250,000+ patients supervised), Founder & CMO CED Clinic & CED Foundation, Author of *The Doctor-Approved Cannabis Handbook* (Penguin Random House).
- **Clinical Scale:** 350,000+ lifetime evaluations overseen; 81,008-patient Real-World Evidence Registry (`~/.ced_rwe_vault.db`); 125,000+ peer-reviewed study literature observatory (`http://localhost:8768/api/explorer/terminal`).
- **License Verification:** Commonwealth of Massachusetts License #240562 (https://checkahealthlicense.mass.gov/).
- **NPI Registry:** 1962722637 (https://npiregistry.cms.hhs.gov/provider-view/1962722637).
- **Ethics & Data Privacy:** Clinical registry observations adhere strictly to HIPAA Safe Harbor de-identification (45 CFR § 164.514(b)) and criteria for secondary research exemption under 45 CFR § 46.104(d)(4).