Changes in Cognition and Psychiatric Disorder Symptoms During Cannabis Abstinence Using a Novel Discordant Twin Design

Study Overview
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Brief Summary
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This study will test whether 42 days of cannabis abstinence, compared to continued cannabis use, is associated with improvements in cognition and psychiatric disorder symptoms. Identical twins, who are concordant on cannabis use, will be experimentally-manipulated to be discordant for 42 days. Each twin, within a twin pair, will be randomly assigned to either the contingency management condition, incentive-based protocol to promote cannabis abstinence, or control condition, no changes in cannabis use requested.

Detailed Description
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The proposed project is a randomized controlled trial to compare cognition and psychiatric disorder symptoms between monozygotic (MZ) twin pairs, who are concordant on frequency of cannabis use. Each twin, within the twin pair, will be randomly assigned to either contingency management (CM), monetary incentives provided to reinforce cannabis abstinence, or control, no changes in cannabis use required or reinforced. Participants in the CM condition will receive an increasing schedule of payments at each visit reinforcing continued cannabis abstinence. All participants will receive increases in the payment schedule for attendance of each subsequent assessment. Participants will be assessed on measures of cognition including attention, memory, and processing speed as well as anxiety, depression, and ADHD symptoms. In addition, at each visit participants will complete a qualitative and quantitative drug test. The qualitative drug test will be used to determine if new cannabis use has occurred since the last visit, and will determine if the participant receives payment for abstinence. The investigators will also use previously collected genotype for each participant. The first aim of this study is to characterize cognitive recovery, across all potential cognitive domains, using an experimental manipulation to achieve discordance between MZ twins on cannabis use. The hypothesis for the first aim is that the abstinent group will have greater improvements in memory and processing speed compared to controls. However, there will not be any group differences between the abstinent group and the control group on attention, language, and executive function performance. The second aim of the proposed project is to characterize psychiatric disorder symptoms by comparing psychiatric disorder symptom changes among the cannabis abstaining twin to their cannabis using co-twin across 42 days. The abstinent group will endorse more psychiatric symptoms during the withdrawal period (up to 14 days) but will endorse fewer psychiatric symptoms at day 28 and 42 compared to the control group. The third aim (exploratory) of the proposed project is to examine how genetic risk for psychiatric disorders interacts with environment (i.e., cannabis abstinence versus continued use) to influence cognitive functioning. The hypothesis for aim 3 is that anxiety, depression, and ADHD polygenic scores will be more strongly associated with cognitive outcomes in the control group compared to the abstinent group.

Official Title
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Changes in Cognition and Psychiatric Disorder Symptoms During Cannabis Abstinence Using a Novel Discordant Twin Design

Conditions
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Cannabis

Intervention / Treatment
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* Behavioral: Contingency management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Monozygotic (MZ) twin pair, in which both twins are willing to participate MZ twin pair must be concordant in their frequency of cannabis use (+/- 2 days) Cannabis use at least 1x per week on most weeks Cannabis use in the past 7 days at the baseline visit Positive qualitative urine toxicology at baseline for THC Located within the state of Colorado Exclusion Criteria: 1) Discordance in the twin pairs on a significant, adverse experience, like traumatic brain injury.

Ages Eligible for Study
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Minimum Age: 31 Years
Maximum Age: 47 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Contingency management<br>Contingency management (CM) is an incentive-based intervention providing patients with tangible rewards as reinforcement for positive behaviors like abstinence from drug use. Incentives are provided with each urine sample that is drug-free and are increased with each subsequent drug-free urine sample. Participants in the CM condition will receive increasing payments for abstinence: $30 on day 3, $45 on day 5, $60 on day 7, $75 on day 14, $90 on day 21, $105 on day 28, and $120 on day 42. Participants in both conditions also receive increasing payment for visit attendance: $10 on day 1, $15 on day 3, $20 on day 5, $25 on day 7, $30 on day 14, $35 on day 21, $45 on day 28, and $55 on day 42. At the end of the baseline visit, participants in the CM condition will sign a behavioral contract with study staff that clearly outlines expectations as well as the payment schedule. | Behavioral: Contingency management<br>* Participants will be paid to abstain from cannabis use.<br>|
| No Intervention: No intervention<br>Participants in this condition will be monitored and will not receive any compensation for cannabis abstinence. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in attention performance | Flanker Inhibitory Control and Attention Test on NIH Toolbox: Composite score of accuracy and reaction time | Change from baseline to day 42 | 
| Change in episodic memory | Picture Sequence Memory Test on NIH Toolbox: Cumulative number of correct adjacent pairs | Change from baseline to day 42 | 
| Change in working memory | List Sorting Working Memory Test on NIH Toolbox: Total items correct across all trials | Change from baseline to day 42 | 
| Change in receptive vocabulary | Picture Vocabulary Test on NIH Toolbox: Computer adaptive testing | Change from baseline to day 42 | 
| Change in reading decoding | Oral Reading Recognition Test: Number of letters and words read correctly | Change from baseline to day 42 | 
| Change in immediate memory/verbal learning | Auditory Verbal Learning Test on NIH Toolbox: Total number of words recalled | Change from baseline to day 4 | 
| Change in pattern comparison processing speed | Pattern Comparison Processing Speed Test: Total number of correct responses | Change from baseline to day 42 | 
| Change in oral symbol digit test processing speed | Oral Symbol Digit Test on NIH Toolbox: Total number of correctly identified symbols | Change from baseline to day 42 | 
| Change in attention and executive function | Dimensional Change Card Sort Test on NIH Toolbox: Composite score of accuracy and correct answers | Change from baseline to day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in anxiety symptoms | Beck Anxiety Inventory: Total score. Scores range from 0-63 and higher scores indicate higher levels of anxiety. | Change from baseline to day 42 | 
| Change in depressive symptoms | Beck Depression Inventory: Total score. Scores range from 0-63 and higher scores indicate greater levels of depression. | Change from baseline to day 42 | 
| Change in attention deficit/hyperactivity disorder symptoms | Adult Self-Report Scale: Total score. Scores range from 0-72 and higher scores indicate greater level of symptoms of attention deficit/hyperactivity disorder. | Change from baseline to day 42 |