Effect of Medical Marijuana on Neurocognition and Escalation of Use

Study Overview
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Brief Summary
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This study will use a randomized controlled design to test whether patients who use medical marijuana, compared to a waitlist control group, experience a change in health outcomes (relief of symptoms, or adverse health outcomes such as new-onset symptoms of cannabis use disorders, neurocognitive impairments) or brain-based changes.

Detailed Description
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This trial is a randomized, longitudinal study of medical marijuana (MM) that will: (1) characterize the impact of MM on indices of addiction, such as CUD, escalation of use, tolerance, and withdrawal among those who stop using, (2) assess, via dosing diaries, the effect of MM use patterns on use of other medications, and perception of underlying disease symptomatology, (3) characterize the impact of MM on neurocognitive performance, including executive function, memory, attention, and decision-making and (4) examine evidence for impact of MM on brain structure and function. This study will enroll 200 adults with no prior history of CUD or heavy marijuana use, who express interest in using MM to treat pain, insomnia, anxiety, and/or depression. Participants will be randomly assigned to either an active MM arm (n = 100), or to a waitlist control arm (WLC) (n = 100). Participants will be assessed at baseline, regularly for 3 months, and at a 6-month and 12-month follow-up for MM use behaviors, development of CUD, perception of disease symptomatology, and neurocognitive performance. Urine collected at each visit will be assessed with quantitative assays. MRI scans will be collected to longitudinally investigate possible brain changes associated with MM use.

Official Title
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Effect of Medical Marijuana on Neurocognition and Escalation of Use

Conditions
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Pain, Insomnia, Depression, Anxiety

Intervention / Treatment
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* Drug: Medical Marijuana


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 18-65 years, inclusive; Competent and willing to provide written informed consent; Desire to use medical marijuana for self-reported pain, sleep, or affective (mood and/or anxiety including PTSD) symptoms. Not in possession of a medical marijuana card, but expressing intent to get one. Able to communicate in English language. Exclusion Criteria: Current daily marijuana use (prior to enrollment) Current substance use disorders (e.g. cocaine, opiate, stimulant). Light to moderate alcohol use is permitted (defined as 16 or less on the AUDIT), and nicotine dependence is permitted because of the high co-use of nicotine and marijuana. Participants cannot meet current SCID criteria for a use disorder on any illicit substance other than nicotine. Pregnant (verified by a urine test). In the opinion of the investigator, not able to safely participate in this study because of any medical or psychological issues (e.g. psychosis) that might compromise their safety.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Medical Marijuana Arm<br>This group can begin using medical marijuana immediately. | Drug: Medical Marijuana<br>* Patients in this group can choose when, where, and how much medical marijuana to use.<br>* Other names: Cannabis;|
| No Intervention: Waitlist Control Arm<br>This group agrees to wait 3 months before using medical marijuana. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Difference in Number of Cannabis Use Disorder Symptoms Averaged Over 2, 4, and 12 Weeks | The DSM-5 Cannabis Use Disorder (CUD) Checklist will evaluate symptoms of CUD (number of symptoms). The scale ranges from 0-11, with a higher score indicating a greater number of cannabis use disorder symptoms. A trained member of study staff assessed number of CUD symptoms through a structured interview. Each item was scored as 1 if the participant endorsed the symptom, and scored as 0 if they did not endorse the symptom. Reported results are an average taken over weeks 2, 4, and 12 to be consistent with the regression model estimates. | 2 weeks, 4 weeks, and 12 weeks | 
| Mean Difference in Depression Subscale Scores From the HADS Averaged Over 2, 4, and 12 Weeks | For those with depression symptoms, the depression subscale of the Hospital Anxiety and Depression Scale (HADS) will be used to assess symptoms. The subscale ranges from 0-21, with a higher score indicating worse depression outcomes. Reported results are an average taken over weeks 2, 4, and 12 to be consistent with the regression model estimates. | 2 weeks, 4 weeks, and 12 weeks | 
| Mean Difference in Anxiety Subscale Scores From the HADS Averaged Over 2, 4, and 12 Weeks | For those with anxiety symptoms, the anxiety subscale from the Hospital Anxiety and Depression Scale (HADS) will be used to assess symptoms. This subscale ranges from 0-21, with higher scores indicating worse anxiety outcomes. Reported results are an average taken over weeks 2, 4, and 12 to be consistent with the regression model estimates. | 2 Weeks, 4 Weeks, and 12 Weeks | 
| Mean Difference in Pain Severity Scores on the BPI Average Over 2, 4, and 12 Weeks | For those with pain, the Brief Pain Inventory (BPI) severity subscale was used to assess pain symptoms. This scale ranges from 0-10, with a higher score indicating greater pain severity. Reported results are an average taken over weeks 2, 4, and 12 to be consistent with the regression model estimates. | 2 weeks, 4 weeks, and 12 weeks | 
| Mean Difference in Sleep Scores on the AIS Averaged Over 2, 4, and 12 Weeks | For those with insomnia, the Athens Insomnia Scale (AIS) will be used to assess insomnia symptoms. This scale ranges from 0-24, with higher scores indicating worse sleep outcomes. Reported results are an average taken over weeks 2, 4, and 12 to be consistent with the regression model estimates. | 2 weeks, 4 weeks, and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Difference in Physical Health Scores on the SF-12 Averaged Over 2, 4, and 12 Weeks | The Short Form-12 Health Survey (SF-12) Physical Health Summary Scale was used to assess self-report of physical health. SF-12 scores are based on an Item Response Theory model, in which they are z-scores rescaled to have a mean of 50 (SD=10) in any typical population. There are no range limits to this measure. Higher scores indicate better physical health functioning. Reported results are an average taken over weeks 2, 4, and 12 to be consistent with the regression model estimates. | 2 weeks, 4 weeks, and 12 weeks | 
| Mean Difference in Mental Health Scores on the SF-12 Averaged Over 2, 4, and 12 Weeks | The Short Form 12 Health Survey (SF-12) Mental Health Summary Scale was used to assess self-report of mental health. SF-12 scores are based on an Item Response Theory model, in which they are z-scores rescaled to have a mean of 50 (SD=10) in any typical population. This measure has no range limits. Higher scores indicate better mental health functioning. Reported results are an average taken over weeks 2, 4, and 12 to be consistent with the regression model estimates. | 2 weeks, 4 weeks, and 12 weeks | 
| Mean Difference in Attention Switching Task: Congruency Cost Scores on the CANTAB Averaged Over 4 and 12 Weeks | Congruency cost was assessed wth the Attention Switching Task (AST), which assesses attention shifting and executive function via a simple task assessing the direction (pointing left or right) and position (on the left or right side) of an arrow, and is part of the Cambridge Neuropsychological Test Automated Battery (CANTAB). The range of this measure is -1900 to 1900 ms. It is calculated as the difference in the median latency for incongruent trials (i.e., trials where the direction of the arrow differs from the side it appears) minus the median latency for congruent trials (i.e., trials where the direction of the arrow matches the side it appears). Positive values indicate faster responses to congruent trials. Reported results are an average taken over weeks 4 and 12 to be consistent with the regression model estimates. | 4 weeks and 12 weeks | 
| Mean Difference in Attention Switching Task: Switching Cost Scores on the CANTAB Averaged Over 4 and 12 Weeks | Switching cost was assessed with the Attention Switching Task (AST), which assesses attention shifting and executive function via a simple task assessing the direction (pointing left or right) and position (on the left or right side) of an arrow, and is part of the Cambridge Neuropsychological Test Automated Battery (CANTAB). The range for this measure is -1900 to 1900 ms. It is calculated as the difference in the median latency for blocks of switching trials (i.e., blocks of trials where the response rule switches between indicating the direction of the arrow or the position of the arrow) minus the median latency for blocks of non-switching trials (i.e., blocks of trials where the response rule is always either to indicate the direction of the arrow or the position of the arrow across all trials). Positive scores indicate faster responses to non-switching trials. Reported results are an average taken over weeks 4 and 12 to be consistent with the regression model estimates. | 4 weeks and 12 weeks | 
| Mean Difference in Rapid Visual Information Processing (RVP) Task: Discriminability Scores on the CANTAB Averaged Over 4 and 12 Weeks | Discriminability was assessed with the Rapid Visual Information Processing (RVP) Task, which assesses sustained attention and is part of the Cambridge Neuropsychological Test Automated Battery (CANTAB). Discriminability scores are based on a transformation of response times and accuracy using the EZ-Diffusion model. There are no limits for this measure. Higher scores indicate that subjects can better discriminator between targets and distractors. Reported results are an average taken over weeks 4 and 12 to be consistent with the regression model estimates. | 4 weeks and 12 weeks | 
| Mean Difference in Paired Associates Learning (PAL) Task: Total Errors Scores on the CANTAB Averaged Over 4 and 12 Weeks | Total errors were assessed with the Paired Associates Learning (PAL) task, which assesses visual memory and is part of the Cambridge Neuropsychological Test Automated Battery (CANTAB). The range for this measure is 0 to 70 errors. Higher scores indicate that the subject committed more errors (worse performance). Reported results are an average taken over weeks 4 and 12 to be consistent with the regression model estimates. | 4 weeks and 12 weeks | 
| Mean Difference in Spatial Working Memory (SWM) Task: Repetition Errors Scores on the CANTAB Averaged Over 4 and 12 Weeks | Repetition errors were assessed with the Spatial Working Memory (SWM) task, which assesses spatial working memory and executive function. It is part of the Cambridge Neuropsychological Test Automated Battery (CANTAB). The range for this measure is 0 to 63 errors. Higher scores indicate that more repetition errors were committed (worse performance). Reported results are an average taken over weeks 4 and 12 to be consistent with the regression model estimates. | 4 weeks and 12 weeks | 
| Mean Difference in Verbal Recognition Memory (VRM) Task: d' Scores on the CANTAB Averaged Over 4 and 12 Weeks | Discriminability was assessed with the Verbal Recognition Memory task (VRM), which assess verbal memory. It is part of the Cambridge Neuropsychological Test Automated Battery (CANTAB). Discriminability scores are based on a transformation of hit and false alarm rates using a signal detection theory (SDT) model.There are no limits for this measure. Higher scores indicate that a subject was able to better discriminate between previously studied and novel words. Reported results are an average taken over weeks 4 and 12 to be consistent with the regression model estimates. | 4 weeks and 12 weeks | 
| Mean Difference in Verbal Recognition Memory (VRM) Task: Free Recall Memory Scores on the CANTAB Averaged Over 4 and 12 Weeks | Free Recall Memory was assessed with the Verbal Recognition Memory task (VRM), which assesses verbal memory. It is part of the Cambridge Neuropsychological Test Automated Battery (CANTAB). The range for this measure is 0 to 18 words recalled. Higher scores indicate that subjects were able to correctly recall more previously studied words. Reported results are an average taken over weeks 4 and 12 to be consistent with the regression model estimates. | 4 weeks and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, medical marijuana, cannabis, pain, insomnia, depression, anxiety, addiction, dependence, neurocognition