The effect of intranasal oxytocin treatment on conditioned fear extinction and recall in a healthy human sample

Psychopharmacology (Berl). 2013 Sep;229(1):199-208. doi: 10.1007/s00213-013-3099-4. Epub 2013 May 5.


Rationale: To improve outcomes for patients undergoing extinction-based therapies (e.g., exposure therapy) for anxiety disorders such as post-traumatic stress disorder (PTSD), there has been interest in identifying pharmaceutical compounds that might facilitate fear extinction learning and recall. Oxytocin (OT) is a mammalian neuropeptide that modulates activation of fear extinction-based neural circuits and fear responses. Little is known, however, about the effects of OT treatment on conditioned fear responding and extinction in humans.

Objectives: The purpose of the present study was to assess the effects of OT in a fear-potentiated startle task of fear conditioning and extinction.

Methods: A double-blind, placebo-controlled study of 44 healthy human participants was conducted. Participants underwent a conditioned fear acquisition procedure, after which they were randomized to treatment group and delivered OT (24 IU) or placebo via intranasal (IN) spray. Forty-five minutes after treatment, participants underwent extinction training. Twenty-four hours later, subjects were tested for extinction recall.

Results: Relative to placebo, the OT group showed increased fear-potentiated startle responding during the earliest stage of extinction training relative to placebo; however, all treatment groups showed the same level of reduced responding by the end of extinction training. Twenty-four hours later, the OT group showed significantly higher recall of extinction relative to placebo.

Conclusions: The current study provides preliminary evidence that OT may facilitate fear extinction recall in humans. These results support further study of OT as a potential adjunctive treatment for extinction-based therapies in fear-related disorders.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Conditioning, Psychological / drug effects*
  • Conditioning, Psychological / physiology
  • Extinction, Psychological / drug effects*
  • Extinction, Psychological / physiology
  • Fear / drug effects*
  • Fear / physiology
  • Fear / psychology*
  • Female
  • Humans
  • Male
  • Mental Recall / drug effects*
  • Mental Recall / physiology
  • Oxytocin / administration & dosage*
  • Reflex, Startle / drug effects
  • Reflex, Startle / physiology
  • Treatment Outcome
  • Young Adult


  • Oxytocin