A Phase 2 interventional study of Placebo and Milk Thistle in Pathological Gambling and Gambling Disorder, sponsored by University of Chicago. Completed at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-07-07.
Sponsored by University of Chicago · Phase 2, Interventional, and Treatment
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.
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.
158 studies on the registry are indexed under Gambling; 42 are open to participants now.
This study's enrollment of 55 is below the median of 66 across 128 interventional studies indexed under Gambling.
Browse Gambling studies →University of Chicago is the lead sponsor of 924 studies on the registry; 185 are open to participants now.
Of its 103 completed or terminated interventional studies of FDA-regulated products, 72 (70%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Matched dosage of milk thistle daily.
Drug: Placebo
Capsule form, 150mg BID to 300mg BID
Drug: Milk Thistle
Taken as two 150mg capsules BID for 2 weeks, then 300mg BID for remainder of the study.
Also known as: Sugar Pill
Taken as two 150mg capsules BID for 2 weeks, then 300mg BID for remainder of the study.
Also known as: Silymarin
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.
Time frame: Once every two weeks for the 8 weeks of the study
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.
Time frame: Once every two weeks for the 8 weeks of the study
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.
Time frame: Once every two weeks for the 8 weeks of the study
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.
Time frame: Once every two weeks for the 8 weeks of the study
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.
Time frame: Once every two weeks for the 8 weeks of the study
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.
Time frame: Once every two weeks for the 8 weeks of the study
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.
Time frame: Once every two weeks for the 8 weeks of the study
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.
Time frame: Once every two weeks for the 8 weeks of the study
| Milestone | Placebo | Milk Thistle |
|---|---|---|
| Started | 26 | 17 |
| Completed | 22 | 16 |
| Not completed | 4 | 1 |
| Withdrew: Protocol violation | 3 | 1 |
| Withdrew: Lost to follow-up | 1 | 0 |
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.
| units on a scale | Placebo | Milk Thistle |
|---|---|---|
| Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) | -11.76 ± 7.18 | -11.86 ± 7.75 |
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.
| units on a scale | Placebo | Milk Thistle |
|---|---|---|
| Change in CGI-I score | -0.90 ± 1.67 | -1.71 ± 1.14 |
| Change in CGI-S score | -1.5 ± 1.41 | -1.5 ± 1.38 |
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.
| units on a scale | Placebo | Milk Thistle |
|---|---|---|
| Gambling Symptom Assessment Scale (G-SAS) | -15.54 ± 9.91 | -19.72 ± 8.55 |
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.
| units on a scale | Placebo | Milk Thistle |
|---|---|---|
| Hamilton Anxiety Rating Scale (HAM-A) | -3 ± 2.5 | -0.43 ± 0.96 |
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.
| units on a scale | Placebo | Milk Thistle |
|---|---|---|
| Sheehan Disability Scale (SDS) | -9.94 ± 10.15 | -8 ± 9.57 |
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.
| units on a scale | Placebo | Milk Thistle |
|---|---|---|
| Hamilton Depression Rating Scale (HAM-D) | -2.56 ± 2.51 | -2.33 ± 2.07 |
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.
| units on a scale | Placebo | Milk Thistle |
|---|---|---|
| Perceived Stress Scale (PSS) | -5.44 ± 3.84 | -3.88 ± 5.99 |
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.
| units on a scale | Placebo | Milk Thistle |
|---|---|---|
| Quality of Life Inventory (QOLI) | 10.92 ± 28.61 | 1.3 ± 41.42 |
Collected over Adverse events were collected from the time participants signed consent until their final Week 8 visit.. Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 0/26 (0%) | 0/26 (0%) | 3/26 (11.5%) |
| Milk Thistle | 0/17 (0%) | 0/17 (0%) | 4/17 (23.5%) |
| Event | Placebo | Milk Thistle |
|---|---|---|
| HeadacheNervous system disorders | 1/26 | 3/17 |
| NauseaGastrointestinal disorders | 2/26 | 0/17 |
| Reduced appetiteGastrointestinal disorders | 0/26 | 1/17 |
| DiarrheaGastrointestinal disorders | 1/26 | 0/17 |
| VomitingGastrointestinal disorders | 1/26 | 0/17 |
| Dry mouthGeneral disorders | 1/26 | 0/17 |
| Increased appetiteGastrointestinal disorders | 1/26 | 0/17 |
One participant assigned to placebo dropped out before being randomized, leaving placebo total at N = 25.
| Age, Categorical(Participants) | Placebo | Milk Thistle | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 24 | 16 | 40 |
| >=65 years | 1 | 1 | 2 |
| Age, Continuous(years) | Placebo | Milk Thistle | Total |
|---|---|---|---|
| Mean | 50.48 ± 12.99 | 48.25 ± 13.64 | 49.6 ± 13.24 |
| Sex: Female, Male(Participants) | Placebo | Milk Thistle | Total |
|---|---|---|---|
| Female | 7 | 10 | 17 |
| Male | 18 | 7 | 25 |
| Race/Ethnicity, Customized(Participants) | Placebo | Milk Thistle | Total |
|---|---|---|---|
| Caucasian | 5 | 4 | 9 |
| African American | 17 | 13 | 30 |
| Hispanic/Latino | 1 | 0 | 1 |
| Native American | 1 | 0 | 1 |
| Not reported | 1 | 0 | 1 |
| Region of Enrollment(participants) | Placebo | Milk Thistle | Total |
|---|---|---|---|
| United States | 25 | 17 | 42 |
| Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) Score(units on a scale) | Placebo | Milk Thistle | Total |
|---|---|---|---|
| Mean | 20.62 ± 3.40 | 21.17 ± 3.1 | 20.84 ± 3.36 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Jan 2015 to primary completion in Dec 2022, 95 months.
Results were first posted in Sep 2024, 1 year 9 months after primary completion.
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This study is completed, as verified in Feb 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Milk-thistle extract