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| Name | Class |
|---|---|
| University of Colorado, Denver | OTHER |
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This study investigates whether the anxiolytic effects and anti-inflammatory properties of cannabis vary as a function of the ratio of CBD to THC, with the goal that these effects may shed light on the mixed data linking cannabis use and anxiety. Individuals with mild to moderate anxiety who elect to use cannabis (smoked flower or edible) will complete four weeks of observation. Participants complete cognitive tasks, a substance use history, health questionnaires concerning sleep and physical activity, and a blood draw at four different time points (Baseline, after 2 weeks of cannabis use, and immediately before and after self-administration after 4 weeks of use) with the use of a mobile pharmacology laboratory, which goes to a convenient location for each participant to self-administer their cannabis. Participants are then followed for five months to self-report on cannabis use, anxiety, subjective cognitive functioning, sleep quality, and other mental health symptoms.
Marijuana use is on the rise with the number of adults reporting medical and recreational use doubling in the past decade. Among adult medical marijuana users, 39% report using marijuana for the purposes of self-treating or coping with anxiety. Marijuana is approved for medical use in over half the states and is gaining traction for use as an "off-label" add-on therapy for treatment-resistant anxiety and stress-related disorders. Paradoxically, however, while data suggest that marijuana, in particular ∆9-tetrahydrocannabinol (THC), increases anxiety acutely, cross sectional and longitudinal data suggest associations between marijuana use and lower risk for anxiety disorders.
There is some evidence demonstrating that marijuana use is associated with increases in acute anxiety and anxiety disorders. However, other data suggests that marijuana use may be protective for adolescents at-risk for anxiety and decrease the chances of developing an anxiety disorder during college. This finding is consistent with a growing body of evidence from animal models suggesting that marijuana has anxiolytic and anti-inflammatory properties. Clarifying the anxiolytic effects of specific strains that differ in their cannabinoid composition may explain these discrepant findings. Thus, regardless of whether results support or refute the anxiolytic properties of marijuana, findings from this study fill a critical void and can inform public perception.
The study goal is to understand the anxiolytic effects of cannabinoids, in particular the effects of THC-based strains vs. CBD-based strains vs strains containing both THC and CBD in different ratios (1:0, 1:1, or 0:1) on inflammation, cognitive functioning, and anxiety/negative affect. This design will capitalize on the novel opportunity to examine the effects of real world marijuana strains on key outcomes.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cannabis (smoked flower, ingested edible) | Drug | Self-Directed Use (ad-libitum) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Anxiety: Depression Anxiety Stress Scale (DASS21). | The DASS21 is a 21-item scale that measures self-reported change in anxiety, depression, and stress symptoms. Participants are asked to use 4-point severity/frequency scales (higher values indicate greater severity) to rate the extent to which they have experienced each state. Scores for Depression, Anxiety and Stress are calculated by summing the scores for the relevant items. Changes in DASS subscale self-report will be tested in relation to THC and CBD blood levels. For this aim, only the Anxiety subscale was used. Anxiety subscale score range 0-42 Normal 0-6; Mild 7-9; Moderate 10-14; Severe 15-19; Extremely severe 20-42 | Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration) |
| Change in Inflammation: Circulating Levels of Cytokines (Panel of Inflammatory Markers). | Change in inflammation from before to after cannabis use will be tested in relation to THC and CBD blood levels. The sum concentration of the cytokines IL-1a, IL-1b, IL-6, IL-8, IL-12, and TNFα, which are generally regarded as pro-inflammatory, will be utilized. The range for these values can be from 0 to infinity. Higher values indicate higher (worse) levels of inflammation. | Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration) |
| Patient Global Impression of Change: Global Impression of Change Scale (PGIC). | Patient Global Impression of Change Scale (PGIC) measures self-reported change on a 1-7 scale (i.e. from 1 (very much worse) to 7 (very much improved) in anxiety. Changes in this measure will be tested in relation to THC and CBD blood levels. Scale possible score range 0-7, with higher scores indicating the largest amount of possible change. | This was administered only once, at the 4 week timepoint, asking participants to reflect on how much change they had experienced over the past 4 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Cognitive Impairment: NIH Toolbox Cognitive Battery, Flanker Inhibitory Control Attention Task (FICA) and International Shopping List Test (ISLT). | Co-outcomes testing multiple domains of thinking, memory, and perception (NIH Toolbox), cognitive impairment in the domains of immediate and delayed recall (ISLT), attention and inhibitory control (FICA). Cognitive outcomes are measured in standard scores (e.g. Range of >70 to >140 (Mean of 100 and SD of 15) with higher scores indicating better performance) and can be averaged to reflect a Standard score of overall cognitive function. |
| Measure | Description | Time Frame |
|---|---|---|
| Exploratory: Daily Follow-Up Messages | Brief self-report from participants on anxiety and sleep in the past 24 hours. These are all 1-item novel questions in a daily, text based survey. Anxiety and sleep are on a scale of 1-10, with higher numbers being more anxiety or better sleep. Score is an average rating over 30 days. | One survey per day for 30 days (at the start of the 4 week study) |
Inclusion Criteria:
Exclusion Criteria:
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Community Sample
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| Name | Affiliation | Role |
|---|---|---|
| Cinnamon Bidwell, PhD | University of Colorado, Boulder | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Innovation and Creativity | Boulder | Colorado | 80304 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41864773 | Derived | Lisano JK, Rosa L, Giordano G, Bryan AD, Bidwell LC. Physical Activity Level Moderates Cannabis-Associated Reductions in Negative Affect in Anxious Individuals. Clin Ther. 2026 Mar 20:S0149-2918(26)00041-X. doi: 10.1016/j.clinthera.2026.02.007. Online ahead of print. | |
| 40916181 | Derived | Martin-Willett R, Skrzynski CJ, Bryan AD, Bidwell LC. Effects of Cannabinoids on Emotional States and Alcohol Use Among Underrepresented Groups: Moderation by Perceived Discrimination. Hum Psychopharmacol. 2025 Sep;40(5):e70016. doi: 10.1002/hup.70016. |
| Label | URL |
|---|---|
| OASIS Website, CU Change Lab, University of Colorado-Boulder | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Non-Use | No use of cannabis |
| FG001 | THC Group | Participants used THC dominant products |
| FG002 | CBD Group | Participants used CBD dominant products |
| FG003 | THC+CBD Group | Participants used products with roughly equivalent proportions of THC and CBD |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Non-Use | No use of cannabis |
| BG001 | THC Group | Participants used THC dominant products |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Anxiety: Depression Anxiety Stress Scale (DASS21). | The DASS21 is a 21-item scale that measures self-reported change in anxiety, depression, and stress symptoms. Participants are asked to use 4-point severity/frequency scales (higher values indicate greater severity) to rate the extent to which they have experienced each state. Scores for Depression, Anxiety and Stress are calculated by summing the scores for the relevant items. Changes in DASS subscale self-report will be tested in relation to THC and CBD blood levels. For this aim, only the Anxiety subscale was used. Anxiety subscale score range 0-42 Normal 0-6; Mild 7-9; Moderate 10-14; Severe 15-19; Extremely severe 20-42 | Posted | Mean | Standard Deviation | units on a scale | Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration) |
|
Participants were monitored from Baseline to 4 weeks.
This study was quasi-observational and minimally invasive.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Non-Use | No use of cannabis | 0 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. L. Cinnamon Bidwell | University of Colorado Boulder | 3037355180 | CUChange@Colorado.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 1, 2023 | Apr 25, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001008 | Anxiety Disorders |
| D000098647 | Generalized Anxiety Disorder |
| D007249 | Inflammation |
| D002189 | Marijuana Abuse |
| ID | Term |
|---|---|
| D001523 | Mental Disorders |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D019966 | Substance-Related Disorders |
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| ID | Term |
|---|---|
| C587251 | nabiximols |
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Blood samples (including DNA analysis) gut microbiome samples (including microbial DNA analysis)
| Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration) |
| Self-Reported Affect in the Context of Negative Affect Induction Task | Participants reported levels of negative affect on a novel scale from -50 (worst) to +50 (best) while undergoing a guided rumination to induce negative affect. | Acute change in affect from before the negative affect induction task to post-breathing |
| Change in Depression: Depression Anxiety Stress Scale (DASS21). | The DASS21 is a 21-item scale that measures self-reported change in anxiety, depression, and stress symptoms. Participants are asked to use 4-point severity/frequency scales (higher values indicate greater severity) to rate the extent to which they have experienced each state. For this aim, only the Depression subscale was used. Depression subscale score range 0-21 Normal (0 to 4), Mild (5 to 6), Moderate, (7 to 10), Severe (11 to 13), Extremely Severe (14 and above) | Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration) |
| Health and Wellbeing | Self-report measure across primary domains of diet, assessment of sleep quality, and health-related well-being. Each domain was assessed with the following single items: Diet: "In general, how healthy is your overall diet? Would you say" (response options 0- excellent; 1- very good; 2- good; 3- fair; 4- poor) Sleep Quality: "During the past 2 weeks, how would you rate your sleep quality overall?" (response options 0- very good; 1- fairly good; 2- fairly bad; 3- very bad") Health Related Wellbeing: "In general, how would you describe your health?" (response options 0- excellent; 1- very good; 2- good; 3- fair; 4- poor) | Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration) |
| Motor Battery: Balance and Motor Function | Motor control assessed via dynamic sway, proprioception, and finger tapping rate. Motor outcomes can be aggregated via Z-score to reflect a Z-score of overall motor function. We calculated the sum of Motor Battery Balance (Eyes Open, Eyes Closed, and Head Back) z-scores. A score of 0 means a participant's balance is at the mean for the sample. Higher scores (scores greater than 0) correspond to worse balance compared to the sample. Scores lower than 0 indicate better balance compared to the sample. | Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration) |
| Objective Physical Activity/Exercise | Physical activity via objective daily data on wearable watch as measured by average minutes of moderate to vigorous physical activity (MVPA). | 4 weeks |
| Physical Activity/Exercise | Physical activity via subjective self-report data using the Stanford Leisure-Time Activity Categorical item with 6 item responses (L-CAT; 1-6). Scores are reported as a mean between 1 and 6, larger numbers correspond to higher levels of activity. | 4 weeks |
| Change in Stress: Depression Anxiety Stress Scale (DASS21). | The DASS21 is a 21-item scale that measures self-reported change in anxiety, depression, and stress symptoms. Participants are asked to use 4-point severity/frequency scales (higher values indicate greater severity) to rate the extent to which they have experienced each state. For this aim, only the Stress subscale was used. Stress subscale score range 0-33 Normal (0 to 14), Mild (15 to 18), Moderate, (19 to 25), Severe (26 to 33) | Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration) |
| Exploratory: Monthly Follow-Up Surveys | Self-report from participants on anxiety (DASS anxiety subscale), sleep (novel sleep quality question ranging from 1-10 and 10 being best sleep), subjective cognitive functioning (perceived cognitive ability from the Functional Assessment of Cancer Therapy-Cognitive Function scale as was already reported in secondary measures- see for full description), and general health health (novel health question as was also reported in secondary measures- see for full description). | 5 months (post-study completion) |
| 40522823 | Derived | Skrzynski CJ, Rosa L, Drake A, Bryan AD, Bidwell LC. Experimental study on cannabis use and affect: Effects on reactivity to and recovery from negative stimuli. J Psychopathol Clin Sci. 2025 Aug;134(6):639-650. doi: 10.1037/abn0001023. Epub 2025 Jun 16. |
| 38252547 | Derived | Bidwell LC, Martin-Willett R, Skrzynski C, Lisano J, Ortiz Torres M, Giordano G, Hutchison KE, Bryan AD. Acute and Extended Anxiolytic Effects of Cannabidiol in Cannabis Flower: A Quasi-Experimental ad libitum Use Study. Cannabis Cannabinoid Res. 2024 Aug;9(4):1015-1027. doi: 10.1089/can.2023.0187. Epub 2024 Jan 22. |
| BG002 |
| CBD Group |
Participants used CBD dominant products |
| BG003 | THC+CBD Group | Participants used products with roughly equivalent proportions of THC and CBD |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Anxiety: DASS 21 | Subscale score range 0-42 Normal 0-6; Mild 7-9; Moderate 10-14; Severe 15-19; Extremely severe 20-42 | Mean | Standard Deviation | units on a scale |
|
| OG001 | THC Group | Participants used THC dominant products |
| OG002 | CBD Group | Participants used CBD dominant products |
| OG003 | THC+CBD Group | Participants used products with roughly equivalent proportions of THC and CBD |
|
|
| Primary | Change in Inflammation: Circulating Levels of Cytokines (Panel of Inflammatory Markers). | Change in inflammation from before to after cannabis use will be tested in relation to THC and CBD blood levels. The sum concentration of the cytokines IL-1a, IL-1b, IL-6, IL-8, IL-12, and TNFα, which are generally regarded as pro-inflammatory, will be utilized. The range for these values can be from 0 to infinity. Higher values indicate higher (worse) levels of inflammation. | Participants were included in inflammatory marker analyses if they had biomarkers available for both timepoints (baseline and 4 weeks). Thus, sample size here is not the same as sample size for self-report based outcomes. | Posted | Mean | Standard Deviation | pg/mL | Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration) |
|
|
|
| Primary | Patient Global Impression of Change: Global Impression of Change Scale (PGIC). | Patient Global Impression of Change Scale (PGIC) measures self-reported change on a 1-7 scale (i.e. from 1 (very much worse) to 7 (very much improved) in anxiety. Changes in this measure will be tested in relation to THC and CBD blood levels. Scale possible score range 0-7, with higher scores indicating the largest amount of possible change. | Posted | Mean | Standard Deviation | score on a scale | This was administered only once, at the 4 week timepoint, asking participants to reflect on how much change they had experienced over the past 4 weeks. |
|
|
|
| Secondary | Cognitive Impairment: NIH Toolbox Cognitive Battery, Flanker Inhibitory Control Attention Task (FICA) and International Shopping List Test (ISLT). | Co-outcomes testing multiple domains of thinking, memory, and perception (NIH Toolbox), cognitive impairment in the domains of immediate and delayed recall (ISLT), attention and inhibitory control (FICA). Cognitive outcomes are measured in standard scores (e.g. Range of >70 to >140 (Mean of 100 and SD of 15) with higher scores indicating better performance) and can be averaged to reflect a Standard score of overall cognitive function. | Posted | Mean | Standard Deviation | score on a scale | Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration) |
|
|
|
| Secondary | Self-Reported Affect in the Context of Negative Affect Induction Task | Participants reported levels of negative affect on a novel scale from -50 (worst) to +50 (best) while undergoing a guided rumination to induce negative affect. | Posted | Mean | Standard Deviation | score on a scale | Acute change in affect from before the negative affect induction task to post-breathing |
|
|
|
| Secondary | Change in Depression: Depression Anxiety Stress Scale (DASS21). | The DASS21 is a 21-item scale that measures self-reported change in anxiety, depression, and stress symptoms. Participants are asked to use 4-point severity/frequency scales (higher values indicate greater severity) to rate the extent to which they have experienced each state. For this aim, only the Depression subscale was used. Depression subscale score range 0-21 Normal (0 to 4), Mild (5 to 6), Moderate, (7 to 10), Severe (11 to 13), Extremely Severe (14 and above) | Posted | Mean | Standard Deviation | score on a scale | Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration) |
|
|
|
| Secondary | Health and Wellbeing | Self-report measure across primary domains of diet, assessment of sleep quality, and health-related well-being. Each domain was assessed with the following single items: Diet: "In general, how healthy is your overall diet? Would you say" (response options 0- excellent; 1- very good; 2- good; 3- fair; 4- poor) Sleep Quality: "During the past 2 weeks, how would you rate your sleep quality overall?" (response options 0- very good; 1- fairly good; 2- fairly bad; 3- very bad") Health Related Wellbeing: "In general, how would you describe your health?" (response options 0- excellent; 1- very good; 2- good; 3- fair; 4- poor) | Posted | Mean | Standard Deviation | units on a scale | Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration) |
|
|
|
| Secondary | Motor Battery: Balance and Motor Function | Motor control assessed via dynamic sway, proprioception, and finger tapping rate. Motor outcomes can be aggregated via Z-score to reflect a Z-score of overall motor function. We calculated the sum of Motor Battery Balance (Eyes Open, Eyes Closed, and Head Back) z-scores. A score of 0 means a participant's balance is at the mean for the sample. Higher scores (scores greater than 0) correspond to worse balance compared to the sample. Scores lower than 0 indicate better balance compared to the sample. | Posted | Mean | Standard Deviation | z-score | Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration) |
|
|
|
| Secondary | Objective Physical Activity/Exercise | Physical activity via objective daily data on wearable watch as measured by average minutes of moderate to vigorous physical activity (MVPA). | Posted | Mean | Standard Deviation | minutes | 4 weeks |
|
|
|
| Secondary | Physical Activity/Exercise | Physical activity via subjective self-report data using the Stanford Leisure-Time Activity Categorical item with 6 item responses (L-CAT; 1-6). Scores are reported as a mean between 1 and 6, larger numbers correspond to higher levels of activity. | Posted | Mean | Standard Deviation | score on a scale | 4 weeks |
|
|
|
| Secondary | Change in Stress: Depression Anxiety Stress Scale (DASS21). | The DASS21 is a 21-item scale that measures self-reported change in anxiety, depression, and stress symptoms. Participants are asked to use 4-point severity/frequency scales (higher values indicate greater severity) to rate the extent to which they have experienced each state. For this aim, only the Stress subscale was used. Stress subscale score range 0-33 Normal (0 to 14), Mild (15 to 18), Moderate, (19 to 25), Severe (26 to 33) | Posted | Mean | Standard Deviation | score on a scale | Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration) |
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| Other Pre-specified | Exploratory: Daily Follow-Up Messages | Brief self-report from participants on anxiety and sleep in the past 24 hours. These are all 1-item novel questions in a daily, text based survey. Anxiety and sleep are on a scale of 1-10, with higher numbers being more anxiety or better sleep. Score is an average rating over 30 days. | Posted | Mean | Standard Deviation | units on a scale | One survey per day for 30 days (at the start of the 4 week study) |
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| Other Pre-specified | Exploratory: Monthly Follow-Up Surveys | Self-report from participants on anxiety (DASS anxiety subscale), sleep (novel sleep quality question ranging from 1-10 and 10 being best sleep), subjective cognitive functioning (perceived cognitive ability from the Functional Assessment of Cancer Therapy-Cognitive Function scale as was already reported in secondary measures- see for full description), and general health health (novel health question as was also reported in secondary measures- see for full description). | Posted | Mean | Standard Deviation | units on a scale | 5 months (post-study completion) |
|
|
|
| 42 |
| 0 |
| 42 |
| 0 |
| 42 |
| EG001 | THC Group | Participants used THC dominant products | 0 | 86 | 0 | 86 | 0 | 86 |
| EG002 | CBD Group | Participants used CBD dominant products | 0 | 92 | 0 | 92 | 0 | 92 |
| EG003 | THC+CBD Group | Participants used products with roughly equivalent proportions of THC and CBD | 0 | 80 | 0 | 80 | 0 | 80 |
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| D064419 | Chemically-Induced Disorders |
| 4 Week |
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| 4 Weeks |
|
| 4 weeks |
|
| 4 Week Self Reported Diet |
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| Baseline Sleep Quality |
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| 4 Week Sleep Quality |
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| Baseline Health-Related Wellbeing |
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| 4 Week Health-Related Wellbeing |
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| Change in Balance score at 4 weeks |
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| Change in scores at 4-weeks on L-CAT |
|
| Sleep Quality Rating |
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| Sleep |
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| Subjective Cognitive Impairment |
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| General Health |
|