Chronic Pain PatientsNCT06808048
Medical Cannabis and Behavior
A study testing Cognitive testing and Task-based fMRI measure of face-name and verbal learning in people with Chronic Pain Patients and Medical Cannabis Users, run by University of Minnesota at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 75 years
- Conditions the study is for
- Chronic Pain Patients, Medical Cannabis Users
- What is being tested?
- Cognitive testing and Task-based fMRI measure of face-name and verbal learning
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jun 2025to 31 Jul 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Medical cannabis users (n=120) will be required to
- Be ages 30-75;
- 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.
- Have normal or corrected-to-normal vision and hearing;
- Be free of current and past DSM-V-defined substance use disorders; have < 5 lifetime recreational uses of illicit drugs.
- Have limited daily exposure to nicotine (e.g., no daily smokers/vapers; use of nicotine products fewer than 5 occasions weekly);
Show all 25Show fewer
- 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);
- Must be right handed as assessed by the Edinburgh Handedness Inventory;
- No history of daily cannabis use; limited cannabis product use (recreational or therapeutic) within the past three months;
- Able to schedule and complete a multi-hour single session protocol;
- Have sufficient manual mobility to be able to complete computerized neurocognitive assessments;
- 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:
- Be ages 30-75;
- Suffer from a chronic pain condition that could qualify them for medical cannabis; People with orthopedic pain will be prioritized.
- Have normal or corrected-to-normal vision and hearing;
- Be free of current and past DSM-V-defined substance use disorders; have < 5 lifetime recreational uses of illicit drugs.
- Have limited daily exposure to nicotine (e.g., no daily smokers/vapers; use of nicotine products fewer than 5 occasions weekly);
- 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);
- Must be right handed as assessed by the Edinburgh Handedness Inventory;
- No history of daily cannabis use; cannabis use within the past three months limited to a few times.
- Able to schedule and complete a multi-hour single session protocol;
- Have sufficient manual mobility to be able to complete computerized neurocognitive assessments;
- 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).
Who cannot join
- Cannot have a degenerative neurological condition or a neurological condition that impacts brain function (e.g., epilepsy);
- No contraindications to MRI scanning;
- No lifetime history of severe DSM-V psychopathology (psychotic disorders, bipolar disorder); if currently treated mood for anxiety disorders, must be stable;
- No current pregnancy or pregnancy within the prior 3 months; cannot be lactating;
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Angela Birnbaum, Ph.D., MLS(ASCP), FAES contact
United States1 site, 1 recruiting
- Recruiting
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: Neurobehavioral Impacts of Medical Cannabis Use: An Observational Study
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.
Read the 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
- Being tested
- Cognitive testing, Task-based fMRI measure of face-name and verbal learning
- Keywords
- cannabis, medical cannabis, brain MRI, pharmacokinetics
- Medical subject headings
- Marijuana Abuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive testingBehavioural
Participants will complete a cognitive testing battery that includes measures of attention, learning, memory, problem-solving and executive function.
Task-based fMRI measure of face-name and verbal learningBehavioural
Cognitive testing Participants will complete a cognitive battery that includes measures of attention, learning, memory, and executive function. Behavioral: Task-based fMRI measure of face-name and verbal learning. These tasks will assess cannabis effects on explicit associative learning and memory mediated by frontohippocampal networks. Participants memorize face-name or word pairs (encoding), then recall the names and word pairs after a delay. The first encoding block begins with a "MEMORIZE" cue followed by 5 face-name or word pairs; participants press a button when each pair is encoded. A distractor block follows. Next, a retrieval block begins with a "RECALL" cue, followed by the same faces or words paired with a recall prompt, with a 4-second stimulus duration. On recall trials, participants indicate recall of the name for the displayed face or word stem and engage in silent uncued recall of learned pairs. After the scan, participants are tested for retrieval accuracy.
| Study group | Role | What they receive |
|---|---|---|
| Experimental cognitive and fMRI-based tasks | Experimental | 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 memory. NIH considers the cognitive and fMRI tasks to be interventions. The fMRI learning and memory tasks measures face-name associative learning and verbal associative learning. 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. Receives: Behavioral: Cognitive testing; Behavioral: Task-based fMRI measure of face-name and verbal learning |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rey Auditory Verbal Learning Test
All participants will complete a cognitive task battery measuring processes such as learning and memory. The Rey Auditory Verbal Learning Test requires individuals to learn a list of words across five learning trials followed by a distractor list then immediate recall of the initial word list then a 30-minute delayed recall. The minimum score on each trial is 0 and the maximum score on each trial is 15. Scores are tabulated for each of the eight trials. Scores on trials 1-5 reflect learning. Scores on trials 7 and 8 reflect immediate and delayed recall.
Measured: Administered at baseline and after four months
Digit Span Task
The digit span task is a measure of working memory and has a forward and a backward condition. On the forward condition, participants are presented with sequences of digits that are read aloud, beginning with two digits, which the participant must repeat in order. The sequence increases by one digit for each correct level of performance up to a maximum of 9 digits. On the backward condition, the presentation of digits is the same but participants must recall the digit sequences in backward order. The maximum forward and backward span that was correctly recalled is tabulated (min = 0; max = 9).
Measured: Administered at baseline and after four months
Verbal Fluency Task
Participants are told that they will hear a letter (e.g. F) and must generate as many words as they can that begin with that letter in a one-minute period while adhering to certain task rules. Three letters are presented in total, and the total number of words generated without errors is recorded for each letter (min = 0; max = unspecified).
Measured: Administered at baseline and after four months
Spatial Span Task
The spatial span task is a measure of working memory for locations and has a forward and a backward condition. On the forward condition, participants are presented with sequences of targeted locations, beginning with two, which the participant must repeat in order by touching those locations on a computer screen. The sequence increases by one location for each correct level of performance up to a maximum of 9 locations. On the backward condition, the presentation of locations is the same but participants must recall the spatial sequences in backward order. The maximum forward and backward spatial span that was correctly recalled is tabulated (min = 0; max = 9).
Measured: Administered at baseline and after four months
Grooved Pegboard Task
This task is a measure of fine motor coordination. Participants are provided with a board upon which 25 small holes are inserted. They are provided with small pegs to be inserted into the holes. They must place pegs one-by-one into the holes using first the dominant hand and then the non-dominant hand. Dropped pegs are recorded as errors (0 to 25). Completion time (in seconds; min = unspecified; max = 300) is recorded for each hand and is the primary metric that is examined to assess fine motor function and the presence of lateralized motor difficulties.
Measured: Administered at baseline and after four months
CANTAB Spatial Paired Associates Learning Task
Participants view a computer screen on which some number of boxes is displayed in a circular pattern. Boxes are "opened" in a randomized order, one by one. One or more of them will contain a pattern. Participants must learn which patterns go in which boxes. After all box-pattern pairs are shown, the patterns are then displayed in the middle of the screen, one at a time and the participant must select the box in which the pattern was originally located. If the participant makes an error, the boxes are opened in sequence again to remind the participant of the locations of the patterns. Increased difficulty levels (arrays with a greater number of boxes) can be used. Specifically, participants complete up to 5 stages, which involve learning one, two, three, six or eight pattern-location pairings. Outcome measures include the errors made by the participant (max score is unspecified), the number of trials required to locate the pattern(s) correctly, and the number of stages completed.
Measured: Administered at baseline and after four months
CANTAB Stockings of Cambridge Task
This task is a computerized measure of planning ability. On each trial, the participant is shown two displays. In each of these displays, three columns - each containing three colored balls - are suspended from a beam. The two displays appear at the top and bottom of the screen. The balls are arranged in different patterns in each display.The participant must move the balls in the bottom display to match the pattern shown in the top display. The balls are moved one at a time by selecting the required ball, then selecting the position to which it should be moved. The participant is instructed to make as few moves as possible to match the two patterns and is told how many moves are optimal.
Trials increase in difficulty from 2-move to 5-move problems. Outcomes include the number of problems perfectly solved (max = 12), the number of moves used to execute each problem, and planning time (in milliseconds; how much time the participant waited before beginning to execute each problem).
Measured: Administered at baseline and after four months
CANTAB Self-Ordered Search Task
On each trial of this working memory task, participants view an array of boxes on a computer screen. Participants search for tokens hidden inside of the boxes. Touching a box reveals whether a token is present. The array size varies from 2 to 8 boxes. When a token is found, it is placed at the side of the screen, and participants are instructed not to return to a location that was previously targeted. Returning to a previously targeted location is a forgetting error. Thus, they must remember where they have searched and found tokens on each trial. For each difficulty level (trials of 3, 4, 6 and 8 boxes), the number of forgetting errors is recorded (high scores = more error). Across 6 and 8-item searches, a strategy score is computed to reflect the extent to which the participant used an organized search strategy. High scores reflect decreased strategy use. Both scores are normed, yielding age-scaled percentiles. CANTAB documentation does not provide max values for the raw scores.
Measured: Assessed at baseline and after four months
Iowa Gambling Task (IGT)
The IGT measures reward-related decision-making. On each of 100 trials, participants select from one of four cards presented on a computer screen. After the selection, feedback is provided. Participants are told that they have won points and, possibly, that they have lost points. Over the course of 100 trials, participants must use this feedback to determine which of the four decks are advantageous (yielding net gains) or disadvantageous (yielding net losses). There are two of each. Outcome measures include the total number of advantageous minus disadvantageous choices across all 100 trials (min = 0; max = 100) as well as for each of five blocks of 20 trials (min score on each block = 0; max = 20). High scores indicate better performance, and the slope of scores across the five blocks indicates rate of learning. Scores will be examined as a function of cannabis use.
Measured: Assessed at baseline and after four months
Face-Name Learning Task.
The Face-Name Learning Task will be administered while neural activity is measured. During the task, participants will be presented with ten faces, each of which will be paired with a name. They are asked to memorize the face-name pairings. After all 10 pairs are presented, there is a short delay after which each face is presented alone without the name. Participants are asked to silently recall the name that was associated with the face. Neural activation throughout the brain is measured during the encoding (memorization) phase as well as the recall phase to determine which neural networks are active during these cognitive processes. Activation patterns are then analyzed and contrasted between individuals.
Measured: Administered at baseline and after four months
Verbal Paired Associates Learning Task.
The Verbal Paired Associates Learning Task will be administered while neural activity is measured. During the task, participants will be presented with ten word pairs. They are asked to memorize the pairings. After all 10 pairs are presented, there is a short delay after which each word is presented alone without its pair. Participants are asked to silently recall the word that was associated with the presented word. Neural activation throughout the brain is measured during the encoding (memorization) phase as well as the recall phase to determine which neural networks are active during these cognitive processes. Activation patterns are then analyzed and contrasted between individuals.
Measured: Administered at baseline and after four months
Intrinsic functional brain activity
Participants will complete a resting state MRI scan to yield brainwide measures of neural activity at rest. These neural signals form patterns that can be analyzed to differentiate patterns of activation within and between distinct functional networks. These activations will be associated with other behaviors measured in the study, including cannabis use. For this project, activations within the brain's executive control, salience, and reward networks are of maximal interest and will be quantified
Measured: Administered at baseline and after four months
MRI measurement of cortical thickness and white matter volume
Participants will complete structural MRI scans to yield measures of neural structure (gray and white matter volumes and cortical thickness). Images will be acquired for the entire brain and processed to yield cortical thickness (mm), gray matter (volume mm) and white matter (volume mm) for 138 cortical parcels (regions) and 40 subcortical regions.
Measured: Administered at baseline and after four months
Frontostriatal structural and functional neural connectivity
To assess frontostriatal structure and function, FreeSurfer's segmentation of striatal nuclei (dorsal striatum/caudate; ventral striatum/nucleus accumbens) will be registered to EPI scans to generate seed regions for analyses of frontostriatal structural (diffusion) and functional (fMRI) connectivity. Connections between the dorsal and ventral striatum and discrete regions of the frontal cortex will be quantified and analyzed in relation to performance on the Go No-Go inhibitory control task and as a function of cannabis use over time.
Measured: Assessed at baseline and after four months
Frontohippocampal structural and functional connectivity
Brain MRI T1 and T2 scans will be processed using FreeSurfer, yielding brain-wide cortical parcellations (available across several standard atlases) and subcortical segmentation, which in turn can be employed as ROIs for quantification of diffusion and functional scans following structural-to-EPI registrations. To assess hippocampal structure and function, FreeSurfer's segmentation of hippocampal subfields (based on the high- resolution T2-weighted hippocampal anatomical scan) will be registered to EPI scans to generate seed regions for analyses of frontohippocampal structural (diffusion) and functional (fMRI) connectivity. Anterior-to-posterior (head to tail) hippocampal gradients in structural and functional connectivity will be analyzed with regard to performance on tests of verbal and Face-Name learning as a function of cannabis exposure.
Measured: Assessed at baseline and after four months
Cannabis Use Disorder Identification Test (CUDIT)
Participants will complete an 8-item questionnaire that asked about problems associated with their use of medical cannabis. Each question is rated on a five-point scale (0-4) where high scores indicate increasing frequencies of use or more problematic patterns of use. Scores are summed across the 8 questions to yield a total score, ranging from 0 to 40. Scores of 8 or more indicate hazardous cannabis use, while scores of 12 or more indicate a possible cannabis use disorder.
Measured: Baseline and monthly for four months thereafter
Blood levels of cannabinoid compounds
Participants will provide blood samples at the study baseline and four months post-baseline for the measurement of blood cannabinoid levels.
Measured: Collected at baseline and after four months
Structured Clinical Interview for DSM-V Substance Use Module
The SCID-V Substance Use Module is a semi-structured interview that queries the use of substances of abuse (alcohol, cannabis, stimulants, sedatives, opioids, hypnotics) and the extent to which 11 symptoms of substance use disorder, as defined by the Diagnostic and Statistical Manual of Mental Disorders V, are present for each substance currently and in the past. For each substance, answers to the 11 symptom questions are scored on a three-point scale (0 = absent; 2 = present at subthreshhold level; 3 = present). The full endorsement of two or more symptoms (scores of 3) for each substance class indicates the presence of a substance use disorder (SUD). Three outcome measures that will be analyzed include (1) presence/absence of a SUD for each class of substance, (2) total symptom scores (number of symptoms positively endorsed with ratings of 3) and (3) total symptom scores (summed scores on the 1-3 scale across 11 items for each substance class; min score = 11; max score = 33).
Measured: Assessed at baseline and after four months
Daily Medication Diary
Participants will complete daily diaries across a four-month period to indicate prescription and non-prescription medications that they are ingesting and in what doses. Average daily doses of each medication type, including medical cannabis products, will be quantified and used as outcome measures in data analyses. Minimum possible values = 0; maximum = unspecified.
Measured: Daily for the four month duration of the study
Secondary outcomes (4)
Alcohol Use Disorders Identification Test (AUDIT)
Participant alcohol use will be measured over time using the AUDIT, a 10-item screening tool developed by the World Health Organization (WHO) to assess alcohol consumption, drinking behaviors, and alcohol-related problems. Participants rate each item on a five point scale (0 to 4), and scores are summed across all 10 items to yield an index of problematic alcohol use (min score = 0; max score = 40). A score of 8 or more is considered to indicate hazardous or harmful alcohol use.
Measured: Baseline and monthly for four months thereafter
Brief Pain Inventory
Participants will complete the Brief Pain Inventory to assess their current pain levels and pain-related quality of life. This self report questionnaire asks patients to rate (a) four pain items (worst pain in 24 hours; average pain; least pain in 24 hours; pain right now) and (b) Extent to which pain interferes with general activity, mood, walking ability, sleep, normal work, relations with other people, and enjoyment of life. Each item is rated on a 10-point scale with 1 reflecting low/less pain scores and 10 reflecting high/high pain/high interference with life scores. In addition to scores on individual items, three scores are derived, one that sums responses to the four pain items (max score = 40) and one that sums responses to the interference items (max score = 70) and a total score (sum of all items; max score = 120). High scores reflect worse pain-related impairment.
Measured: Baseline and monthly for four months thereafter
Beck Depression Inventory (BDI)
The BDI is a 21-item self report questionnaire that assesses symptoms of clinical depression and their severity, each rated on a four point scale (0 = symptom is absent; 3 = full presence of the symptom). The questions assess mood and motivation, cognitive symptoms, suicidality, and vegetative symptoms (sleep; libido; eating/weight). Scores are summed across all 21 items to yield a depression severity score (range from 0 to 63). Scores above 21 indicate moderate to severe depression.
Measured: Assessed at baseline and monthly for four months
UPPS-P Impulsive Behavior Scale
The UPPS-P is a 59-item self-report questionnaire that measures five facets of impulsivity (sensation seeking (12 items; scores range from 12 to 48); positive urgency (14 items; scores range from 14 to 56 ); negative urgency (12 items; scores range from 12 to 48); lack of premeditation (11 items; scores range from 11 to 44); lack of perseverance (10 items; scores range from 10 to 40)). Each question is endorsed on a four point scale (1 = strongly agree; 4 = strongly disagree), and the five metrics are derived after implementing reverse-scoring on some items. These five facets of impulsivity will be examined before versus after use of medical cannabis.
Measured: Assessed at baseline and after four months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2025
- Study start18 Jun 2025
- Primary completion15 Jul 2029 (estimated)
- Study completion31 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Pain PatientsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This study is classified by NIH as a basic experimental study of humans (BESH) clinical trial. Enrolled participants are chronic pain patients, some of whom have been prescribed medical cannabis. The study team is not involved in the prescribing of medical cannabis. The interventions to be used in the study are laboratory-based cognitive tests as well as cognitive tasks administered while functional brain activity is recorded. All participants will be administered these measures at a baseline assessment and again after four months.
- Masking
- None (open label)
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06808048
- Sponsor's protocol ID
- STUDY00011239
- Other IDs
- R01DA059961
- Status last verified
- Jul 2026
- First submitted
- 14 Jan 2025
- Last updated
- 14 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Per NIH regulations, data from this project will be shared in a repository. The following types of data will be collected from 180 research participants (chronic pain sufferers who do and do not use medical cannabis): demographic information, lab measures of cognitive performance, self-reported health history and medication use, substance use assessments, multimodal MRI assessments, and biological specimens for the quantification of blood cannabinoid concentrations. Each participant will complete two study visits, during which these measures will be collected, and three interim monthly phone calls during which data on medication use, affect, sleep and pain will be collected. Participants will consent to sharing of their de-identified data. Data will be de- identified prior to receipt by the repository. This study's de-identified data will be shared within the Open Science Framework (OSF), an open platform that facilitates resource sharing and collaboration among registered users.
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurobehavioral Impacts of Medical Cannabis Use: An Observational Study
- ClinicalTrials.gov ID
- NCT06808048
- Acronym / sponsor ID
- STUDY00011239
- Conditions
- Chronic Pain Patients, Medical Cannabis Users
- Keywords
- cannabis, medical cannabis, brain MRI, pharmacokinetics
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 18 Jun 2025 (actual)
- Primary completion
- 15 Jul 2029 (estimated)
- Study completion
- 31 Jul 2029 (estimated)
- First posted
- 5 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This study is classified by NIH as a basic experimental study of humans (BESH) clinical trial. Enrolled participants are chronic pain patients, some of whom have been prescribed medical cannabis. The study team is not involved in the prescribing of medical cannabis. The interventions to be used in the study are laboratory-based cognitive tests as well as cognitive tasks administered while functional brain activity is recorded. All participants will be administered these measures at a baseline assessment and again after four months.
| Arm | Type | Receives |
|---|---|---|
| Experimental cognitive and fMRI-based tasks | Experimental | Behavioral: Cognitive testing, Behavioral: Task-based fMRI measure of face-name and verbal learningOne 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 memory. NIH considers the cognitive and fMRI tasks to be interventions. The fMRI learning and memory tasks measures face-name associative learning and verbal associative learning. 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. |
Who may qualify
- Ages
- 30 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Medical cannabis users (n=120) will be required to
- Be ages 30-75;
- Suffer from a chronic pain condition that could qualify them for medical cannabis; People with orthopedic pain will be prioritized.
- Have normal or corrected-to-normal vision and hearing;
- Be free of current and past DSM-V-defined substance use disorders; have < 5 lifetime recreational uses of illicit drugs.
Key exclusion criteria (4 listed)
- Cannot have a degenerative neurological condition or a neurological condition that impacts brain function (e.g., epilepsy);
- No contraindications to MRI scanning;
- No lifetime history of severe DSM-V psychopathology (psychotic disorders, bipolar disorder); if currently treated mood for anxiety disorders, must be stable;
- No current pregnancy or pregnancy within the prior 3 months; cannot be lactating;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cognitive testingParticipants will complete a cognitive testing battery that includes measures of attention, learning, memory, problem-solving and executive function. | Behavioural | Experimental cognitive and fMRI-based tasks |
| Task-based fMRI measure of face-name and verbal learningCognitive testing Participants will complete a cognitive battery that includes measures of attention, learning, memory, and executive function. Behavioral: Task-based fMRI measure of face-name and verbal learning. These tasks will assess cannabis effects on explicit associative learning and memory mediated by frontohippocampal networks. Participants memorize face-name or word pairs (encoding), then recall the names and word pairs after a delay. The first encoding block begins with a "MEMORIZE" cue followed by 5 face-name or word pairs; participants press a button when each pair is encoded. A distractor block follows. Next, a retrieval block begins with a "RECALL" cue, followed by the same faces or words paired with a recall prompt, with a 4-second stimulus duration. On recall trials, participants indicate recall of the name for the displayed face or word stem and engage in silent uncued recall of learned pairs. After the scan, participants are tested for retrieval accuracy. | Behavioural | Experimental cognitive and fMRI-based tasks |
Primary outcome
Rey Auditory Verbal Learning Test
Time frame: Administered at baseline and after four months
All participants will complete a cognitive task battery measuring processes such as learning and memory. The Rey Auditory Verbal Learning Test requires individuals to learn a list of words across five learning trials followed by a distractor list then immediate recall of the initial word list then a 30-minute delayed recall. The minimum score on each trial is 0 and the maximum score on each trial is 15. Scores are tabulated for each of the eight trials. Scores on trials 1-5 reflect learning. Scores on trials 7 and 8 reflect immediate and delayed recall.
Digit Span Task
Time frame: Administered at baseline and after four months
The digit span task is a measure of working memory and has a forward and a backward condition. On the forward condition, participants are presented with sequences of digits that are read aloud, beginning with two digits, which the participant must repeat in order. The sequence increases by one digit for each correct level of performance up to a maximum of 9 digits. On the backward condition, the presentation of digits is the same but participants must recall the digit sequences in backward order. The maximum forward and backward span that was correctly recalled is tabulated (min = 0; max = 9).
Verbal Fluency Task
Time frame: Administered at baseline and after four months
Participants are told that they will hear a letter (e.g. F) and must generate as many words as they can that begin with that letter in a one-minute period while adhering to certain task rules. Three letters are presented in total, and the total number of words generated without errors is recorded for each letter (min = 0; max = unspecified).
Spatial Span Task
Time frame: Administered at baseline and after four months
The spatial span task is a measure of working memory for locations and has a forward and a backward condition. On the forward condition, participants are presented with sequences of targeted locations, beginning with two, which the participant must repeat in order by touching those locations on a computer screen. The sequence increases by one location for each correct level of performance up to a maximum of 9 locations. On the backward condition, the presentation of locations is the same but participants must recall the spatial sequences in backward order. The maximum forward and backward spatial span that was correctly recalled is tabulated (min = 0; max = 9).
Grooved Pegboard Task
Time frame: Administered at baseline and after four months
This task is a measure of fine motor coordination. Participants are provided with a board upon which 25 small holes are inserted. They are provided with small pegs to be inserted into the holes. They must place pegs one-by-one into the holes using first the dominant hand and then the non-dominant hand. Dropped pegs are recorded as errors (0 to 25). Completion time (in seconds; min = unspecified; max = 300) is recorded for each hand and is the primary metric that is examined to assess fine motor function and the presence of lateralized motor difficulties.
CANTAB Spatial Paired Associates Learning Task
Time frame: Administered at baseline and after four months
Participants view a computer screen on which some number of boxes is displayed in a circular pattern. Boxes are "opened" in a randomized order, one by one. One or more of them will contain a pattern. Participants must learn which patterns go in which boxes. After all box-pattern pairs are shown, the patterns are then displayed in the middle of the screen, one at a time and the participant must select the box in which the pattern was originally located. If the participant makes an error, the boxes are opened in sequence again to remind the participant of the locations of the patterns. Increased difficulty levels (arrays with a greater number of boxes) can be used. Specifically, participants complete up to 5 stages, which involve learning one, two, three, six or eight pattern-location pairings. Outcome measures include the errors made by the participant (max score is unspecified), the number of trials required to locate the pattern(s) correctly, and the number of stages completed.
CANTAB Stockings of Cambridge Task
Time frame: Administered at baseline and after four months
This task is a computerized measure of planning ability. On each trial, the participant is shown two displays. In each of these displays, three columns - each containing three colored balls - are suspended from a beam. The two displays appear at the top and bottom of the screen. The balls are arranged in different patterns in each display.The participant must move the balls in the bottom display to match the pattern shown in the top display. The balls are moved one at a time by selecting the required ball, then selecting the position to which it should be moved. The participant is instructed to make as few moves as possible to match the two patterns and is told how many moves are optimal. Trials increase in difficulty from 2-move to 5-move problems. Outcomes include the number of problems perfectly solved (max = 12), the number of moves used to execute each problem, and planning time (in milliseconds; how much time the participant waited before beginning to execute each problem).
CANTAB Self-Ordered Search Task
Time frame: Assessed at baseline and after four months
On each trial of this working memory task, participants view an array of boxes on a computer screen. Participants search for tokens hidden inside of the boxes. Touching a box reveals whether a token is present. The array size varies from 2 to 8 boxes. When a token is found, it is placed at the side of the screen, and participants are instructed not to return to a location that was previously targeted. Returning to a previously targeted location is a forgetting error. Thus, they must remember where they have searched and found tokens on each trial. For each difficulty level (trials of 3, 4, 6 and 8 boxes), the number of forgetting errors is recorded (high scores = more error). Across 6 and 8-item searches, a strategy score is computed to reflect the extent to which the participant used an organized search strategy. High scores reflect decreased strategy use. Both scores are normed, yielding age-scaled percentiles. CANTAB documentation does not provide max values for the raw scores.
Iowa Gambling Task (IGT)
Time frame: Assessed at baseline and after four months
The IGT measures reward-related decision-making. On each of 100 trials, participants select from one of four cards presented on a computer screen. After the selection, feedback is provided. Participants are told that they have won points and, possibly, that they have lost points. Over the course of 100 trials, participants must use this feedback to determine which of the four decks are advantageous (yielding net gains) or disadvantageous (yielding net losses). There are two of each. Outcome measures include the total number of advantageous minus disadvantageous choices across all 100 trials (min = 0; max = 100) as well as for each of five blocks of 20 trials (min score on each block = 0; max = 20). High scores indicate better performance, and the slope of scores across the five blocks indicates rate of learning. Scores will be examined as a function of cannabis use.
Face-Name Learning Task.
Time frame: Administered at baseline and after four months
The Face-Name Learning Task will be administered while neural activity is measured. During the task, participants will be presented with ten faces, each of which will be paired with a name. They are asked to memorize the face-name pairings. After all 10 pairs are presented, there is a short delay after which each face is presented alone without the name. Participants are asked to silently recall the name that was associated with the face. Neural activation throughout the brain is measured during the encoding (memorization) phase as well as the recall phase to determine which neural networks are active during these cognitive processes. Activation patterns are then analyzed and contrasted between individuals.
Verbal Paired Associates Learning Task.
Time frame: Administered at baseline and after four months
The Verbal Paired Associates Learning Task will be administered while neural activity is measured. During the task, participants will be presented with ten word pairs. They are asked to memorize the pairings. After all 10 pairs are presented, there is a short delay after which each word is presented alone without its pair. Participants are asked to silently recall the word that was associated with the presented word. Neural activation throughout the brain is measured during the encoding (memorization) phase as well as the recall phase to determine which neural networks are active during these cognitive processes. Activation patterns are then analyzed and contrasted between individuals.
Intrinsic functional brain activity
Time frame: Administered at baseline and after four months
Participants will complete a resting state MRI scan to yield brainwide measures of neural activity at rest. These neural signals form patterns that can be analyzed to differentiate patterns of activation within and between distinct functional networks. These activations will be associated with other behaviors measured in the study, including cannabis use. For this project, activations within the brain's executive control, salience, and reward networks are of maximal interest and will be quantified
MRI measurement of cortical thickness and white matter volume
Time frame: Administered at baseline and after four months
Participants will complete structural MRI scans to yield measures of neural structure (gray and white matter volumes and cortical thickness). Images will be acquired for the entire brain and processed to yield cortical thickness (mm), gray matter (volume mm) and white matter (volume mm) for 138 cortical parcels (regions) and 40 subcortical regions.
Frontostriatal structural and functional neural connectivity
Time frame: Assessed at baseline and after four months
To assess frontostriatal structure and function, FreeSurfer's segmentation of striatal nuclei (dorsal striatum/caudate; ventral striatum/nucleus accumbens) will be registered to EPI scans to generate seed regions for analyses of frontostriatal structural (diffusion) and functional (fMRI) connectivity. Connections between the dorsal and ventral striatum and discrete regions of the frontal cortex will be quantified and analyzed in relation to performance on the Go No-Go inhibitory control task and as a function of cannabis use over time.
Frontohippocampal structural and functional connectivity
Time frame: Assessed at baseline and after four months
Brain MRI T1 and T2 scans will be processed using FreeSurfer, yielding brain-wide cortical parcellations (available across several standard atlases) and subcortical segmentation, which in turn can be employed as ROIs for quantification of diffusion and functional scans following structural-to-EPI registrations. To assess hippocampal structure and function, FreeSurfer's segmentation of hippocampal subfields (based on the high- resolution T2-weighted hippocampal anatomical scan) will be registered to EPI scans to generate seed regions for analyses of frontohippocampal structural (diffusion) and functional (fMRI) connectivity. Anterior-to-posterior (head to tail) hippocampal gradients in structural and functional connectivity will be analyzed with regard to performance on tests of verbal and Face-Name learning as a function of cannabis exposure.
Cannabis Use Disorder Identification Test (CUDIT)
Time frame: Baseline and monthly for four months thereafter
Participants will complete an 8-item questionnaire that asked about problems associated with their use of medical cannabis. Each question is rated on a five-point scale (0-4) where high scores indicate increasing frequencies of use or more problematic patterns of use. Scores are summed across the 8 questions to yield a total score, ranging from 0 to 40. Scores of 8 or more indicate hazardous cannabis use, while scores of 12 or more indicate a possible cannabis use disorder.
Blood levels of cannabinoid compounds
Time frame: Collected at baseline and after four months
Participants will provide blood samples at the study baseline and four months post-baseline for the measurement of blood cannabinoid levels.
Structured Clinical Interview for DSM-V Substance Use Module
Time frame: Assessed at baseline and after four months
The SCID-V Substance Use Module is a semi-structured interview that queries the use of substances of abuse (alcohol, cannabis, stimulants, sedatives, opioids, hypnotics) and the extent to which 11 symptoms of substance use disorder, as defined by the Diagnostic and Statistical Manual of Mental Disorders V, are present for each substance currently and in the past. For each substance, answers to the 11 symptom questions are scored on a three-point scale (0 = absent; 2 = present at subthreshhold level; 3 = present). The full endorsement of two or more symptoms (scores of 3) for each substance class indicates the presence of a substance use disorder (SUD). Three outcome measures that will be analyzed include (1) presence/absence of a SUD for each class of substance, (2) total symptom scores (number of symptoms positively endorsed with ratings of 3) and (3) total symptom scores (summed scores on the 1-3 scale across 11 items for each substance class; min score = 11; max score = 33).
Daily Medication Diary
Time frame: Daily for the four month duration of the study
Participants will complete daily diaries across a four-month period to indicate prescription and non-prescription medications that they are ingesting and in what doses. Average daily doses of each medication type, including medical cannabis products, will be quantified and used as outcome measures in data analyses. Minimum possible values = 0; maximum = unspecified.
4 secondary outcomes
Alcohol Use Disorders Identification Test (AUDIT)
Time frame: Baseline and monthly for four months thereafter
Brief Pain Inventory
Time frame: Baseline and monthly for four months thereafter
Beck Depression Inventory (BDI)
Time frame: Assessed at baseline and monthly for four months
UPPS-P Impulsive Behavior Scale
Time frame: Assessed at baseline and after four months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2026.
- Individual participant dataSharing planned: Yes. Per NIH regulations, data from this project will be shared in a repository. The following types of data will be collected from 180 research participants (chronic pain sufferers who do and do not use medical cannabis): demographic information, lab measures of cognitive performance, self-reported health history and medication use, substance use assessments, multimodal MRI assessments, and biological specimens for the quantification of blood cannabinoid concentrations. Each participant will complete two study visits, during which these measures will be collected, and three interim monthly phone calls during which data on medication use, affect, sleep and pain will be collected. Participants will consent to sharing of their de-identified data. Data will be de- identified prior to receipt by the repository. This study's de-identified data will be shared within the Open Science Framework (OSF), an open platform that facilitates resource sharing and collaboration among registered users.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Angela Birnbaum, Ph.D., MLS(ASCP), FAES contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cognitive testing and Task-based fMRI measure of face-name and verbal learning in people with Chronic Pain Patients and Medical Cannabis Users, run by University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Monica Luciana, Ph.D. (612-626-0757, lucia003@umn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rey Auditory Verbal Learning Test (time frame: Administered at baseline and after four months). The study lists 19 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2026.