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Related Experiment Video

Updated: Nov 1, 2025

Extinction Training During the Reconsolidation Window Prevents Recovery of Fear
11:17

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Cannabinoid polymorphisms interact with plasma endocannabinoid levels to predict fear extinction learning.

Luke J Ney1, Allison Matthews1, Chia-Ming Ken Hsu1

  • 1School of Psychology, University of Tasmania, Hobart, Australia.

Depression and Anxiety
|June 21, 2021
PubMed
Summary

Genetic variations in the endocannabinoid system impact fear extinction learning in individuals with posttraumatic stress disorder (PTSD). Fatty acid amide hydrolase (FAAH) gene variants and arachidonoyl ethanolamide (AEA) levels influence extinction, suggesting potential therapeutic targets for PTSD.

Keywords:
endocannabinoidsfear conditioningfear extinctionposttraumatic stress disorder

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Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • The endocannabinoid system is a potential therapeutic target for posttraumatic stress disorder (PTSD).
  • Exposure therapy, a gold-standard PTSD treatment, relies on fear extinction learning.

Purpose of the Study:

  • To investigate the role of genetic endocannabinoid polymorphisms in fear extinction.
  • To compare fear extinction in PTSD patients and healthy individuals.

Main Methods:

  • Genotyping of endocannabinoid polymorphisms from saliva samples.
  • Assessment of fear conditioning and extinction using skin conductance.
  • Analysis of genetic effects on extinction learning in 220 participants (PTSD and healthy).

Main Results:

  • Cannabinoid receptor 1 (CNR1) polymorphisms (rs2180619, rs1049353) were linked to poorer extinction in PTSD.
  • Fatty acid amide hydrolase (FAAH) polymorphism (rs324420) was associated with worse extinction in PTSD.
  • In healthy controls, FAAH rs324420's effect on extinction was moderated by plasma arachidonoyl ethanolamide (AEA) levels.

Conclusions:

  • Cannabinoid receptor 1 and AEA are implicated in human extinction learning.
  • FAAH rs324420 moderates fear extinction via AEA levels in healthy individuals.
  • FAAH inhibitors may offer a novel therapeutic strategy for anxiety in PTSD, warranting further clinical investigation.