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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Cannabis
• Intervention / Treatment: Behavioral: Contingency management

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Jessica M Ross

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 31 years to 47 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Monozygotic (MZ) twin pair, in which both twins are willing to participate
2. MZ twin pair must be concordant in their frequency of cannabis use (+/- 2 days)
3. Cannabis use at least 1x per week on most weeks
4. Cannabis use in the past 7 days at the baseline visit
5. Positive qualitative urine toxicology at baseline for THC
6. Located within the state of Colorado

Exclusion Criteria:

1) Discordance in the twin pairs on a significant, adverse experience, like traumatic brain injury.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Contingency management; 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; Participants will be paid to abstain from cannabis use.
No Intervention: No intervention; Participants in this condition will be monitored and will not receive any compensation for cannabis abstinence.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: University of Colorado, Boulder
• Investigators: Principal Investigator: J. Megan Ross, Ph.D., University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2023
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: November 19, 2021
• First Submitted That Met QC Criteria: December 2, 2021
• First Posted (Actual): December 16, 2021

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Marijuana Abuse
• Other Study ID Numbers: 21-4899

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: In accordance with NIH data sharing policies, data produced from this project will be made available to ensure timely translation of research results to improve human health. The investigators believe there is a possibility of deductive disclosure of subjects with unusual characteristics, even though all identifiers would be removed prior to release for sharing. Thus, the investigators will make the data and associated documentation available to users only under a specific data-sharing agreement that requires: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No