Clinical trial NCT06808048: Medical Cannabis and Behavior
Official title: Neurobehavioral Impacts of Medical Cannabis Use: An Observational Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Chronic Pain Patients
Medical Cannabis Users
Keywords: cannabis
medical cannabis
brain MRI
pharmacokinetics
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2025-02-05
Enrollment: 180
Sex: ALL
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: BASIC_SCIENCE

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.

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;

Primary outcomes:
measure: Rey Auditory Verbal Learning Test
timeFrame: Administered at baseline and after four months
measure: Digit Span Task
timeFrame: Administered at baseline and after four months
measure: Verbal Fluency Task
timeFrame: Administered at baseline and after four months
measure: Spatial Span Task
timeFrame: Administered at baseline and after four months
measure: Grooved Pegboard Task
timeFrame: Administered at baseline and after four months
measure: CANTAB Spatial Paired Associates Learning Task
timeFrame: Administered at baseline and after four months
measure: CANTAB Stockings of Cambridge Task
timeFrame: Administered at baseline and after four months
measure: CANTAB Self-Ordered Search Task
timeFrame: Assessed at baseline and after four months
measure: Iowa Gambling Task (IGT)
timeFrame: Assessed at baseline and after four months
measure: Face-Name Learning Task.
timeFrame: Administered at baseline and after four months
measure: Go No-Go Task of Inhibitory Control
timeFrame: Administered at baseline and after four months
measure: Intrinsic functional brain activity
timeFrame: Administered at baseline and after four months
measure: MRI measurement of cortical thickness and white matter volume
timeFrame: Administered at baseline and after four months
measure: Frontostriatal structural and functional neural connectivity
timeFrame: Assessed at baseline and after four months
measure: Frontohippocampal structural and functional connectivity
timeFrame: Assessed at baseline and after four months
measure: Cannabis Use Disorder Identification Test (CUDIT)
timeFrame: Baseline and monthly for four months thereafter
measure: Blood levels of cannabinoid compounds
timeFrame: Collected at baseline and after four months
measure: Structured Clinical Interview for DSM-V Substance Use Module
timeFrame: Assessed at baseline and after four months
measure: Daily Medication Diary
timeFrame: Daily for the four month duration of the study
Secondary outcomes:
measure: Alcohol Use Disorders Identification Test (AUDIT)
timeFrame: Baseline and monthly for four months thereafter
measure: Brief Pain Inventory
timeFrame: Baseline and monthly for four months thereafter
measure: Beck Depression Inventory (BDI)
timeFrame: Assessed at baseline and monthly for four months
measure: UPPS-P Impulsive Behavior Scale
timeFrame: Assessed at baseline and after four months
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
References: