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Pathological GamblingPhase 2NCT02337634

Milk Thistle in Pathological Gambling

A Phase 2 study testing Milk Thistle in people with Pathological Gambling and Gambling Disorder, run by University of Chicago at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Pathological Gambling, Gambling Disorder
What is being tested?
Milk Thistle
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
55 participants
Where
1 siteUnited States
Study dates
Jan 2015to Dec 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Men and women age 18-75;
  • Diagnosis of current gambling disorder based on DSM-5 criteria and confirmed using the clinician-administered Structured Clinical Interview for Pathological Gambling (SCI-PG) (12);
  • Gambling behavior within 2 weeks prior to enrollment;
  • Women of child bearing age are required to have a negative result on a beta-human chorionic gonadotropin pregnancy test;
  • Women of childbearing potential utilizing a medically accepted form of contraception defined as double barrier, oral contraceptive, injectable contraceptive, implantable contraceptive devices, and abstinence

Who cannot join

  • Infrequent gambling (i.e. less than one time per week) that does not meet DSM-5 criteria for gambling disorder;
  • Unstable medical illness or clinically significant abnormalities on laboratory tests, EKG, or physical examination at screen as determined by the investigator;
  • History of seizures;
  • Myocardial infarction within 6 months;
  • Current pregnancy or lactation, or inadequate contraception in women of childbearing potential;
  • A need for medication other than milk thistle with possible psychotropic effects or unfavorable interactions as determined by the investigator;
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  • Clinically significant suicidality (defined by the Columbia Suicidal Scale);
  • Lifetime history of bipolar disorder type I or II, schizophrenia, or any psychotic disorder;
  • Initiation of psychotherapy or behavior therapy within 3 months prior to study baseline;
  • Previous treatment with milk thistle

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Chicago

    Chicago, Illinois, 60637

Other trials in United States

About this study

Official title: Silymarin Treatment of Pathological Gambling: A Double-Blind, Placebo-Controlled Study

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.

Read the 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.

Being tested
Placebo, Milk Thistle
Medical subject headings
Gambling

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

    Also called Sugar Pill

    Taken as two 150mg capsules BID for 2 weeks, then 300mg BID for remainder of the study.

  • Milk ThistleDrug

    Also called Silymarin

    Taken as two 150mg capsules BID for 2 weeks, then 300mg BID for remainder of the study.

Study groups in NCT02337634
Study groupRoleWhat they receive
PlaceboPlacebo comparatorMatched dosage of milk thistle daily.
Receives: Drug: Placebo
Milk ThistleActive comparatorCapsule form, 150mg BID to 300mg BID
Receives: Drug: Milk Thistle

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS)

    Every 2 weeks the subject will take the PG-YBOCS for the duration of the 8-week study. At each of these visits the outcome will be assessed, but only one value (change from baseline to week 8) will be reported. The scale itself assesses severity of gambling, with higher scores indicating worse outcomes. The scale includes two subscales: a thought/urge subscale and a behavior subscale. Each subscale contains 5 items to be rated with a score of 0-4. Subscale scores are summed to get a total score. Possible total scores range from 0-40.

    Measured: Once every two weeks for the 8 weeks of the study

Secondary outcomes (7)
  1. Clinical Global Impression-Improvement and Severity Scales (CGI-I and CGI-S)

    The entire study for an individual subject will last 8 weeks. Every 2 weeks the subject will take the CGIs for the duration of the 8 weeks. Results are reported as the change in Week 8-Week 0 scores. The scales themselves assess overall disorder severity, with higher scores indicating worse outcomes (i.e., less improvement or greater severity). Possible total scores range from 1-7.

    Measured: Once every two weeks for the 8 weeks of the study

  2. Gambling Symptom Assessment Scale (G-SAS)

    Every 2 weeks the subject will take the G-SAS for the duration of the 8-week study. This is a 12-item, reliable and valid, self-rated scale assessing gambling urges, thoughts, and behaviors during the previous seven days. At each of these visits the outcome will be assessed, but only one value (change from baseline to week 8) will be reported. The scale itself assess severity of gambling symptoms, with a higher score indicating a worse outcome. Each item can be rated with a score of 0-4, with the sum of the 12 items equaling the total score. Possible total scores range from 0-48.

    Measured: Once every two weeks for the 8 weeks of the study

  3. Hamilton Anxiety Rating Scale (HAM-A)

    The entire study for an individual subject will last 8 weeks. Every 2 weeks the subject will take the HAM-A for the duration of the 8 weeks. Results are reported as the change in Week 8-Week 0 scores. The scale itself assess levels of anxiety, with higher scores indicating worse outcomes. Possible total scores range from 0-56.

    Measured: Once every two weeks for the 8 weeks of the study

  4. Sheehan Disability Scale (SDS)

    The entire study for an individual subject will last 8 weeks. Every 2 weeks the subject will take the SDS for the duration of the 8 weeks. Results are reported as the change in Week 8-Week 0 scores. The scale itself assesses level of disability resulting from gambling (or target disorder), with higher scores indicating worse outcomes. Possible total scores range from 0-30.

    Measured: Once every two weeks for the 8 weeks of the study

  5. Hamilton Depression Rating Scale (HAM-D)

    The entire study for an individual subject will last 8 weeks. Every 2 weeks the subject will take the HAM-D for the duration of the 8 weeks. Results are reported as the change in Week 8-Week 0 scores. The scale itself assesses level of depression, with higher scores indicating worse outcomes. Possible total scores range from 0-52.

    Measured: Once every two weeks for the 8 weeks of the study

  6. Perceived Stress Scale (PSS)

    The entire study for an individual subject will last 8 weeks. Every 2 weeks the subject will take the PSS for the duration of the 8 weeks. Results are reported as the change in Week 8-Week 0 scores. The scale itself assesses the level of perceived stress the individual experiences, with higher scores indicating worse outcomes. Possible total scores range from 0-40.

    Measured: Once every two weeks for the 8 weeks of the study

  7. Quality of Life Inventory (QOLI)

    The entire study for an individual subject will last 8 weeks. This inventory will be completed at the first and last visit of the study, with only these two points being assessed. Results are reported as the change in Week 8-Week 0 scores. The scale itself assess the subjects overall perceived quality of life, with higher scores indicating better outcomes. Possible total scores range from 1-77.

    Measured: Once every two weeks for the 8 weeks of the study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jan 2015 (estimated)
  2. Study startJan 2015
  3. Primary completionDec 2022
  4. Study completionDec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02337634
Sponsor's protocol ID
14-0480
Status last verified
Feb 2024
First submitted
8 Jan 2015
Last updated
7 Jul 2026
Data monitoring committee
Yes

Publications

  • Grant JE, Driessens C, Chamberlain SR. Silymarin (Milk Thistle) Treatment of Adults With Gambling Disorder: A Double-Blind, Placebo-Controlled Trial. Clin Neuropharmacol. 2024 Mar-Apr 01;47(2):54-58. doi: 10.1097/WNF.0000000000000585.

    PubMed 38478366
  • Dowling N, Merkouris S, Lubman D, Thomas S, Bowden-Jones H, Cowlishaw S. Pharmacological interventions for the treatment of disordered and problem gambling. Cochrane Database Syst Rev. 2022 Sep 22;9(9):CD008936. doi: 10.1002/14651858.CD008936.pub2.

    PubMed 36130734

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Milk Thistle in people with Pathological Gambling and Gambling Disorder, run by University of Chicago at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) (time frame: Once every two weeks for the 8 weeks of the study). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02337634, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2026.

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