Buspirone, Stress, and Attentional Bias to Marijuana Cues
Condition: Cannabis Use Disorder
MeSH terms: Marijuana Abuse
Study type: Interventional
Phase: Phase 2

Summary: 
      This project has two primary goals. The first goal is to further scientific understanding
      about marijuana abuse by examining two recognized factors in marijuana use and relapse: (1)
      stress/anxiety and (2) atypical reactivity to marijuana-related stimuli (e.g., attentional
      bias). The second goal is to attenuate the influence of stress/anxiety and attentional bias
      to marijuana stimuli via administration of buspirone.

      Buspirone is uniquely suited to this project because it has effects on neurotransmitter
      systems known to modulate both stress/anxiety and attentional bias.
    

Detailed description: 
      For nearly 40 years marijuana has remained the most widely used illicit drug in the US, with
      more than 50% of first-time users < age 18. Marijuana accounts for ≈ 60% of illicit substance
      use disorders (SUD) in the US, bearing by percent the largest US public health burden among
      illicit substances. Across preclinical, human laboratory, and clinical interview data, there
      is compelling evidence that the phenomenon of cue reactivity is related to drug seeking and
      relapse. Attentional bias is a measurable component of cue reactivity, and can be
      operationally defined as differential attention (e.g., reaction time difference) towards
      drug-related stimuli vs. neutral stimuli. This phenomenon has been demonstrated in SUD
      populations across many classes of abused drugs, including alcohol, nicotine, stimulants,
      opiates, and - importantly - marijuana. Cue reactivity and attentional bias are exacerbated
      by acute and chronic stress and anxiety. Notably, stress is a well-documented predictor of
      marijuana abuse and marijuana relapse. Therapeutic interventions that attenuate attentional
      bias to marijuana cues are a potentially important component in the treatment of marijuana
      SUD. Due to the well-documented association with stress, an intervention that simultaneously
      addresses both stress and attentional bias could be uniquely efficacious. Currently, few
      pharmacotherapies exist for marijuana SUD, and none are presently known to address
      attentional bias to marijuana cues. This application will explore the potential of the
      anxiolytic buspirone to modify attentional bias and stress. Buspirone is a unique compound
      marked by modulation of both serotonin (5-HT1A) and dopamine D3 receptors. Importantly, the
      5-HT1A receptor is known to play a key role in stress related anxiety, and preclinical work
      indicates that D3 antagonists significantly decrease cue reactivity to a number of abused
      drugs. This combination of effects suggests buspirone may be advantageous in targeting both
      stress and attentional bias as factors that contribute to problem marijuana use.

      Accordingly, this project seeks to examine the effects of chronic buspirone administration on
      attentional bias and stress/anxiety in marijuana SUD. Using laboratory-based methodologies
      sensitive to attentional bias towards marijuana cues and well validated measures of stress
      and anxiety, we will examine if buspirone's unique mechanism of action will (a) produce an
      attenuation of attentional bias to marijuana cues, and (b) be most pronounced under
      conditions in which attentional bias is related to high levels of stress and anxiety.
    

Intervention name(s): Buspirone; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Buspirone is an anxiolytic compound marked by modulation of both 5-HT1A and D3 receptors. Buspirone is administered orally twice per day (9:00 AM and 6:00 PM) for 3 weeks. 10 mg buspirone is administered on days 1-4, then the dose is increased by 10 mg every 3 days to a maximum of 40 mg buspirone on days 10-19.; Placebo is administered orally twice per day (9:00 AM and 6:00 PM) for 3 weeks.
Other intervention name(s): corn starch
Intervention MeSH terms: Buspirone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: marijuana; attentional bias; stress; buspirone