The Effects of Ondansetron on Brain Function
Condition: Brain Function; Healthy Adults
Study type: Interventional
Phase: Phase 1

Summary: 
      This project investigates the effects of a single dose of ondansetron on brain function in
      healthy adults. The investigators hypothesize that there will be a dose-dependent reduction
      in activation of the insula and somatosensory brain regions associated with the use of
      ondansetron.
    

Detailed description: 
      Objectives:

      The overall objective of this study is to examine the effects of single doses of 8 mg, 16 mg,
      and 24 mg ondansetron as compared to placebo on neural mechanisms of cognition and perception
      in healthy individuals.

      Background:

      Many psychiatric disorders are associated with altered sensory experiences arising from
      within the body. Examples include increased experience of sensations or urges in muscles,
      skins, joints or visceral organs in tic disorders, OCD patients with symptoms of "not just
      right experiences" or disgust sensitivity, and impulse control disorders (ICDs) such as
      trichotillomania or skin-picking. In OCD, sensory phenomena occur in approximately half of
      patients, are associated with earlier age of onset, and may be harder to treat with classic
      cognitive-behavioral approaches to OCD. Of interest, sensory phenomena in OCD are associated
      with Tourette's syndrome and respond to pharmacological treatments primarily used for tics.
      As such, abnormal sensory processing may be a basic mechanism that links various psychiatric
      disorders.

      The process of attending to body sensations is referred to as interoception, and broadly
      includes the detection of, or attention to, experiences arising from the viscera and soma.
      Research has revealed a cortical interoceptive circuit involving insula, anterior cingulate
      cortex (ACC), and somatomotor cortex.

      Ondansetron (OND) is a good candidate for the modulation of the above-described interoceptive
      circuit. It is a selective 5-HT3 (serotonin) receptor antagonist that acts on both peripheral
      and central receptors. OND has long been used to treat nausea and vomiting due to
      chemotherapy, radiation therapy, anesthesia, and opioid-induced emesis. It has also been used
      alone or as adjunctive therapy for the treatment of both OCD and Tourette's disorder, showing
      some efficacy in small clinical trials. The mechanisms by which ondansetron improves symptoms
      in OCD and tic disorders are unknown, but a recent study found that OND application directly
      into the insula decreased disgust reactions in rats. This data suggests that ondansetron's
      clinical efficacy could be related to effects on interoceptive circuit activity in the insula
      and sensorimotor regions, a possibility that is being explored in the current protocol.
      Typical dosages for anti-emetic action is 8-24 mg. The investigator's pilot data found that a
      single 16 mg dose of ondansetron reduced activation of insula and somatosensory cortex in
      both healthy controls and patients with OCD. As a follow-up to this pilot work, the current
      protocol will compare the effects of three different dosages of ondansetron (8 mg, 16 mg, and
      24 mg) on activation in insula and somatosensory cortex during tasks of cognition and
      perception in healthy adults.
    

Intervention name(s): ondansetron; placebo
Intervention type(s): Drug; Drug
Intervention description(s): Ondansetron 8mg, 16mg, 24mg; placebo pill
Other intervention name(s): Zofran
Intervention MeSH terms: Ondansetron
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: fMRI; Brain function; Sensory processing