Medical Cannabis and Behavior

NCT ID: NCT06808048

Last Updated: 2025-06-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-18
• Study Completion Date: 2029-07-31

Brief Summary

This study will assess cognition, neural function, and drug exposure in chronic pain patients who have been prescribed medical cannabis and will differentiate outcomes based on use of specific CBD-dominant versus THC-dominant treatment products. This longitudinal study will recruit medical cannabis users from local dispensaries. Each participant will complete a baseline assessment prior to the start of medical cannabis use, monthly phone calls to assess treatment adherence, and a four-month follow- up assessment. The aims of this project are: Aim 1. To assess impacts of medical cannabis compounds on executive functions, learning and memory in adults to determine whether cognitive impairments are evident after the onset of cannabis use; Aim 2. To assess the impacts of medical cannabis compounds on white matter microstructure, functional brain activity and functional connectivity; Aim 3. To differentiate change over four months in these outcomes as a function of (a) age and (b) pre-to-post-treatment changes in blood levels of cannabinoid compounds.

Detailed Description

This project was submitted to NIH in response to NOT-DA-22-003, Public Health Research on Cannabis. The overarching aim is to assess cognition, neural function, and SUD risk in a sample of patients treated with medical cannabis products in Minnesota (n=120) as compared to non-cannabis using controls (n=60) and to differentiate outcomes based on prescribed doses and blood concentrations of THC versus CBD as objective measures of drug exposure. Patients will be aged 35-65 and qualified for medicinal cannabis treatment in Minnesota due to diagnoses of chronic pain. While deficits in learning, memory and executive functions are reliably observed in young adult recreational cannabis users, it is unclear whether similar impairments characterize individuals who use cannabis for medical reasons, whether adults may be uniquely vulnerable to cannabis-related impairments or if, in fact, use in this age group might be neuroprotective. There are very few published studies of medical cannabis users that comprehensively focus on neurobehavioral outcomes even though at least 5 million people are registered for medical cannabis treatment in the United States. The current study will address this gap through a pre-post assessment of users as compared to matched controls (pain patients who do not use cannabis). Participants will be recruited through posted advertisements and through dispensaries via a collaboration with a local supplier of medical cannabis. They will complete a comprehensive pre-treatment behavioral assessment as well as multimodal brain MRI assessments. All measures will be repeated after four months of treatment. Participants will be interviewed monthly by phone in the interval between visits to assess treatment adherence, pain levels, quality of life, and substance use. Blood cannabinoid levels will be measured at baseline and after four months and will be correlated with behavioral and neural outcomes. The three aims are (1) To assess impacts of medical cannabis compounds on cognition and behavior in otherwise cannabis-naive adults to determine whether impairments that characterize younger users are evident after the onset of medical cannabis use; the investigation will also measure treatment-related changes in pain using well-validated measures. (2) To similarly assess the impacts of medical cannabis compounds on white matter microstructure, functional brain activity and functional connectivity using diffusion-weighted scans, task-based fMRI, and measures of resting state connectivity; (3) To differential change over time in these outcomes as a function of (a) exposure to distinct cannabinoids (THC vs. CBD) as assessed through blood concentrations and (b) age. Sex as a biological variable will be assessed as a covariate of interest. Thus, this proposal will yield a rich dataset through which medical cannabis effects on adults' neurobehavioral function can be assessed and contrasted with the literature on non-medical users.

Conditions

Chronic Pain Patients; Medical Cannabis Users

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Experimental cognitive and fMRI-based tasks

One primary aim of this study is to examine cognitive functioning in individuals who use medical cannabis. All participants in the study will complete cognitive measures that include measures of attention, learning, memory and executive function. All participants will complete task fMRI-based measures of learning and inhibitory control. NIH considers the cognitive and fMRI tasks to be interventions. The fMRI learning task measures face-name associative learning. The fMRI inhibitory control task is a go/no-go task whereby participants respond on some trials to "go" stimuli and withhold responses on other trials to "no-go" stimuli. Brain activations are measured in response to each task. Each participant will complete two cognitive testing sessions as well as two fMRI sessions during the course of the study.

Group Type: EXPERIMENTAL

Cognitive testing

Intervention Type: BEHAVIORAL

Participants will complete a cognitive testing battery that includes measures of attention, learning, memory, problem-solving and executive function.

Task-based fMRI measure of inhibitory control

Intervention Type: BEHAVIORAL

All participants will complete a task-based fMRI measure of inhibitory control. This Go/No-Go task provides a contrast of BOLD signals when response conflict is low (execution of motor responses on frequent Go trials) vs high (inhibiting the prepotent response on infrequent NoGo trials). It will provide an assessment of the effects of cannabis use on the frontostriatal implicit motor learning and cognitive control systems. Participants view shapes and press a button quickly (Go trials) to every shape except circles and squares (NoGo Trials). To increase response prepotency, Go trials are frequent (75%). Button presses must be rapid to be considered correct. The task uses an event-related design with each stimulus presented for 600 ms, followed by a 1.0-4.5 second jittered ISI during which a white fixation crosshair is displayed. Trial type is pseudo-randomized with the constraint of equal frequencies of consecutive Go trials (2, 3, or 4) between NoGo trials.

Task-based fMRI measure of face-name learning

Intervention Type: BEHAVIORAL

This task is ideally suited to assess cannabis effects on explicit associative learning and memory as mediated by frontohippocampal networks. Participants memorize names corresponding to faces (encoding phase), and then recall the names after a short delay. The first encoding block begins with a 2-second cue ("MEMORIZE") followed by 5 face-name pairs, each shown for 4 seconds; participants press a button when they encode each face-name pair. A distractor block follows. Next, a retrieval block begins with a cue to "RECALL" followed by presentations of each of the same 5 faces, now paired with "???" (i.e., prompting recall of previously paired names), with a 4 second stimulus duration and no ISI. On recall trials, participants press a button to indicate that they have recalled the name for the displayed face. Participants engage in silent uncued recall of face-name pairs. Immediately following the scan, participants are tested for accuracy of name retrieval.

Interventions

Cognitive testing

Participants will complete a cognitive testing battery that includes measures of attention, learning, memory, problem-solving and executive function.

Intervention Type: BEHAVIORAL

Task-based fMRI measure of inhibitory control

All participants will complete a task-based fMRI measure of inhibitory control. This Go/No-Go task provides a contrast of BOLD signals when response conflict is low (execution of motor responses on frequent Go trials) vs high (inhibiting the prepotent response on infrequent NoGo trials). It will provide an assessment of the effects of cannabis use on the frontostriatal implicit motor learning and cognitive control systems. Participants view shapes and press a button quickly (Go trials) to every shape except circles and squares (NoGo Trials). To increase response prepotency, Go trials are frequent (75%). Button presses must be rapid to be considered correct. The task uses an event-related design with each stimulus presented for 600 ms, followed by a 1.0-4.5 second jittered ISI during which a white fixation crosshair is displayed. Trial type is pseudo-randomized with the constraint of equal frequencies of consecutive Go trials (2, 3, or 4) between NoGo trials.

Intervention Type: BEHAVIORAL

Task-based fMRI measure of face-name learning

This task is ideally suited to assess cannabis effects on explicit associative learning and memory as mediated by frontohippocampal networks. Participants memorize names corresponding to faces (encoding phase), and then recall the names after a short delay. The first encoding block begins with a 2-second cue ("MEMORIZE") followed by 5 face-name pairs, each shown for 4 seconds; participants press a button when they encode each face-name pair. A distractor block follows. Next, a retrieval block begins with a cue to "RECALL" followed by presentations of each of the same 5 faces, now paired with "???" (i.e., prompting recall of previously paired names), with a 4 second stimulus duration and no ISI. On recall trials, participants press a button to indicate that they have recalled the name for the displayed face. Participants engage in silent uncued recall of face-name pairs. Immediately following the scan, participants are tested for accuracy of name retrieval.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Medical cannabis users (n=120) will be required to

1. Be ages 35-65;

2. Be qualified for a medical cannabis prescription based only on a diagnosis of chronic pain; note that individuals can, in theory, utilize medical cannabis for more than one qualifying condition. People with orthopedic pain will be prioritized.

3. Have normal or corrected-to-normal vision and hearing;

4. Be free of current and past DSM-V-defined substance use disorders; have < 5 lifetime recreational uses of illicit drugs.

5. Have limited daily exposure to nicotine (e.g., no daily smokers/vapers; use of nicotine products fewer than 5 occasions weekly);

6. Willing to abstain from alcohol, nicotine, and other (non-treatment) drugs for 24 hours prior to study. Abstinence will be verified by breathalyzer and urine drug screening; must not test positive on breathalyzer and urine drug screenings for any nonprescribed psychoactive substance or for cannabis (at baseline);

7. Must be right handed as assessed by the Edinburgh Handedness Inventory;

8. Lifetime use of cannabis < 15 times; no cannabis product use (recreational or therapeutic) within the past six months;

9. Able to schedule and complete a multi-hour single session protocol;

10. Have sufficient manual mobility to be able to complete computerized neurocognitive assessments;

11. Able to communicate with the researchers by phone during the four month pre-post assessment interval

Pain patients who are not using medical cannabis (n=60) will be required to:

1. Be ages 35-65;

2. Suffer from a chronic pain condition that could qualify them for medical cannabis; People with orthopedic pain will be prioritized.

3. Have normal or corrected-to-normal vision and hearing;

4. Be free of current and past DSM-V-defined substance use disorders; have < 5 lifetime recreational uses of illicit drugs.

5. Have limited daily exposure to nicotine (e.g., no daily smokers/vapers; use of nicotine products fewer than 5 occasions weekly);

6. Willing to abstain from alcohol, nicotine, and other (non-treatment) drugs for 24 hours prior to study. Abstinence will be verified by breathalyzer and urine drug screening; must not test positive on breathalyzer and urine drug screenings for any non- prescribed psychoactive substance or for cannabis (at baseline);

7. Must be right handed as assessed by the Edinburgh Handedness Inventory;

8. Lifetime use of cannabis < 15 times; no cannabis product use (recreational or therapeutic) within the past six months;

9. Able to schedule and complete a multi-hour single session protocol;

10. Have sufficient manual mobility to be able to complete computerized neurocognitive assessments;

11. Able to communicate with the researchers by phone during the four month pre-post assessment interval Within both groups, concomitant opioid use will be allowed as will other prescribed treatments. Controls will be matched to the cannabis group on age, sex, socioeconomic status (SES), type of pain condition (orthopedic pain will be targeted) and comorbid opioid use.

All potential participants must indicate at the baseline enrollment that they have no immediate plans to relocate from the Twin Cities metro area (e.g., must be willing and able to participate in longitudinal assessment for a four-month period).

Exclusion Criteria

1. Cannot have a degenerative neurological condition or a neurological condition that impacts brain function (e.g., epilepsy);

2. No contraindications to MRI scanning;

3. No lifetime history of severe DSM-V psychopathology (psychotic disorders, bipolar disorder); if currently treated mood for anxiety disorders, must be stable;

4. No current pregnancy or pregnancy within the prior 3 months; cannot be lactating;

5. No cannabis product use (recreational or therapeutic) within the past six months;

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Minnesota

Minneapolis, Minnesota, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Monica Luciana, Ph.D.

Role: CONTACT

lucia003@umn.edu

612-626-0757

Angela Birnbaum, Ph.D., MLS(ASCP), FAES

Role: CONTACT

birnb002@umn.edu

Other Identifiers

R01DA059961

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00011239

Identifier Type: -

Identifier Source: org_study_id