Milk Thistle in Pathological Gambling
Condition: Pathological Gambling; Gambling Disorder
MeSH terms: Gambling
Study type: Interventional
Phase: Phase 2

Summary: 
      The goal of the proposed study is to evaluate the efficacy and safety of silymarin in
      individuals with gambling disorder. The hypothesis to be tested is that silymarin will be
      more effective and well tolerated in subjects with gambling disorder compared to placebo. The
      proposed study will provide needed data on the treatment of a disabling disorder that
      currently lacks a clearly effective treatment.
    

Detailed description: 
      Gambling disorder is a significant public health problem that often results in a distinctive
      pattern of persistent and disabling psychological symptoms. Although once thought to be
      relatively uncommon, studies estimate that gambling disorder has a lifetime prevalence among
      adults of 1.6% and past-year prevalence of 1.1%. Patients with gambling disorder also
      experience significant social and occupational impairment as well as financial and legal
      difficulties.

      Individuals with gambling disorder report chronically high levels of stress, and
      vulnerability to gambling addiction is enhanced by stressful events (4), particularly as
      stress may result cognitive problems leading to impulsive and unhealthy decisions. A stress
      response is elicited when sensations and Observations do not match existing or anticipated
      expectations. A primary endocrine response to stress is the secretion of glucocorticoids
      through the activation of the hypothalamic-pituitary-adrenal axis. Although their release
      serves to maintain homeostasis during acute episodes of stress, prolonged stress responses
      have been associated with structural brain damage both in humans and animals. In humans,
      stress also enhances addictive craving, and relapse to addiction is more likely to occur in
      individuals exposed to high levels of stress. Since oxidative stress may be implicated in the
      etiology of addictive behaviors, use of antioxidants to reduce relapse, improve cognitive
      functioning, and reduce addictive urges may be a sensible step.

      Silymarin, a flavonoid and a member of the Asteraceae family, is extracted from the seeds of
      milk thistle (Silybum marianum) and is known to own antioxidative and anti-apoptotic
      properties. Silymarin has been reported to decrease lipid peroxidation. Furthermore, it has
      been demonstrated that its anti-oxidative activity is related to the scavenging of free
      radicals and activation of anti-oxidative defenses: increases in cellular glutathione content
      and superoxide dismutase activity. Milk thistle has been used for a range of psychiatric
      disorders including methamphetamine abuse and obsessive compulsive disorder, two psychiatric
      disorders with similarities to gambling disorder. The flavanoid complex silymarin in
      preclinical studies has been found to increase serotonin levels in the cortex, and ameliorate
      decreases in dopamine and serotonin in the prefrontal cortex and hippocampus associated with
      methamphetamine abuse. In the frontal cortex one of the functions of dopamine is to increase
      the signal to noise ratio, increased dopamine correlating with increased frontal performance.
      Studies have shown that the higher cortical dopamine levels are associated with improved
      frontal cortical cognitive performance. Cortical inhibition is felt to be the basis for
      top-down control of motivated behaviors. A recent randomized controlled study with milk
      thistle was conducted in Iran Thirty five participants with moderate OCD were randomly
      assigned to 200 mg of milk thistle leaf extract or 10 mg of fluoxetine three times daily for
      eight weeks. Results revealed no significant difference in treatment effects between milk
      thistle and fluoxetine from baseline to endpoint as both interventions provided a highly
      significant reduction in symptoms.

      Silymarin or Milk Thistle may therefore offer promise for the treatment of individuals with
      gambling disorder. Pharmacological management of gambling symptoms has produced mixed
      results, with some studies showing a superiority of medication to placebo.

      The current pilot study examines the tolerability and efficacy of milk thistle in the
      treatment of gambling disorder. We hypothesize that milk thistle will reduce the severity of
      gambling symptoms and improve patients' overall functioning.
    

Intervention name(s): Placebo; Milk Thistle
Intervention type(s): Drug; Drug
Intervention description(s): Taken as two 150mg capsules BID for 2 weeks, then 300mg BID for remainder of the study.; Taken as two 150mg capsules BID for 2 weeks, then 300mg BID for remainder of the study.
Other intervention name(s): Sugar Pill; Silymarin
Intervention MeSH terms: Silymarin
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment