Effects of Methylphenidate (Ritalin®) on the Neural Basis of Anxiety
Condition: PTSD
Study type: Interventional
Phase: Early Phase 1

Summary: 
      In the present study, investigator will investigate the effects of methylphenidate (40 mg) on
      mPFC activity in healthy male volunteers during fear extinction using functional magnetic
      resonance imaging (fMRI). Additionally, investigators will examine the effects of
      methylphenidate during aversive interoceptve arousal. The present study will help to identify
      brain structures and networks involved in anxiety and will give insights for methylphenidate
      as a possible adjunct to behavioral therapy for patients with anxiety disorders. Further,
      this study may provide important information about the possible use of fMRI to help the
      development of drugs for the treatment of anxiety disorders.
    

Detailed description: 
      Posttraumatic stress disorder (PTSD) affects 5-10% of the general U.S. population at some
      point during their lifetime; however, the prevalence in much higher among certain subgroups,
      including active duty military personnel and veterans. Pharmacotherapy of PTSD has made
      little headway on the past two decades. Methylphenidate (Ritalin®) is a stimulant drug that
      amplifies dopaminergic and noradrenergic signaling in the brain. Dopamine and norepinephrine
      are thought to play a critical role during fear extinction by moderating medial prefrontal
      cortex (mPFC) activity. The magnitude of mPFC activity seems to crucially affect the degree
      of fear extinction. The model of fear extinction is one approach to conceptualize PTSD.
      Thereby a previously neutral stimulus is paired with a highly aversive unconditioned
      stimulus. Fear extinction refers to the decrement in that conditioned fear responses that
      occur with repeated presentation of the conditioned neutral fear stimulus without the
      aversive stimulus. While preclinical data suggest that a single dose of methylphenidate
      enhances fear extinction, it is less clear how methylphenidate affects fear extinction in
      humans. However, exposing PTSD patients to new therapies is difficult. In the present study,
      investigator will investigate the effects of methylphenidate (40 mg) on mPFC activity in
      healthy male volunteers during fear extinction using functional magnetic resonance imaging
      (fMRI). Additionally, investigators will examine the effects of methylphenidate during
      aversive interoceptve arousal. The present study will help to identify brain structures and
      networks involved in anxiety and will give insights for methylphenidate as a possible adjunct
      to behavioral therapy for patients with anxiety disorders. Further, this study may provide
      important information about the possible use of fMRI to help the development of drugs for the
      treatment of anxiety disorders.
    

Intervention name(s): Methylphenidate; Placebo
Intervention type(s): Drug; Drug
Other intervention name(s): Ritalin
Intervention MeSH terms: Methylphenidate
Intervention model: Single Group Assignment
Intervention model description: Double-blind, cross-over design with two drug conditions. Drug conditions are placebo and methylphenidate 40 mg. Order will be balanced and pseudo-random.
Masking: Double
Primary purpose: Basic Science
Keywords: Methylphenidate; Fear extinction; fMRI; mPFC