Cannabis Observations on Brain Waves, Retrieval, and Attention: Experiment 4 (COBRA 4)

Cannabis and Memory

This study investigates the impact of ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on recognition memory in healthy, regular cannabis users. Participants complete the same recognition memory task after self-administering one of two different strains of cannabis flower one day and while not intoxicated another day. Event-related potentials (ERPs) are measured via electroencephalogram (EEG) during the recognition memory task. Blood is collected to quantify THC and CBD exposure. Participants also complete self-report measures of medical history, sleep quality, subjective cognitive function, physical activity, psychological functioning, substance use, and acute drug effects.

Study Overview

• Status: Recruiting
• Conditions: Cannabis; Electroencephalography; Memory
• Intervention / Treatment: Drug: Cannabis (smoked flower)

Detailed Description

Previous research has established cannabis's harmful cognitive impact, with particularly robust and consistent effects in the domain of episodic memory. However, prior work has not sufficiently considered that the memory effects of cannabis are the compound action of different cannabinoids, which vary in their pharmacology and effects. Specifically, CBD, a non-psychotomimetic component of cannabis (doesn't produce a "high"), is thought to have cognitively protective properties and may mitigate some of the harmful effects of THC. Further, few prior studies have tested the effects of high potency strains that are commonly available.

This study tests the effects of commercially available cannabis flower strains on recognition memory performance and ERPs that are related to different underlying memory processes in healthy, regular cannabis users. An episodic memory task is used to assess recognition memory, which asks participants to discriminate between previously studied and non-studied items using pictures as stimuli. Participants complete the same memory task while intoxicated one day and not intoxicated another day. A THC-dominant strain and a strain containing both THC and CBD are included in the study. Participants self-administer one of the two cannabis strains prior to memory encoding and retrieval.

Blood is collected to determine THC and CBD exposure, as well as to explore how genetic variation in genes related to cannabinoid metabolism, cannabis-related behavior, and neurocognitive function associate with memory function before and after cannabis use. Participants also complete self-report measures of medical history, sleep quality, subjective cognitive function, physical activity, psychological functioning, substance use, and acute drug effects.

• Study Type: Observational
• Enrollment (Estimated): 64

Contacts and Locations

• Study Contact: Name: Katie N Paulich, Ph.D.; Phone Number: 303-492-9549; Email: cobra.custudy@gmail.com

Study Locations

• United States
  • Colorado
    • Boulder, Colorado, United States, 80301
      • Recruiting
      • Center for Innovation and Creativity (CINC)
      • Contact: Katie N Paulich, Ph.D.; Phone Number: 303-492-9549; Email: cobra.custudy@gmail.com
      • Principal Investigator: Timothy Curran, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Community sample of healthy, regular cannabis users in the Boulder/Denver areas.

Description

1. Must be between the ages of 21 and 40 and provide informed consent;
2. Must be right-handed (Laterality Quotient > 60 on Edinburgh Handedness Inventory - Short Form136);

3. Heavy users (HU) in Experiments 1, 2, 3, and 4:

   1. Must use cannabis at least 4 days during the month;
   2. Must be a cannabis user for at least a year;

4. Non-users (NU) in Experiment 2:

   1. Must not have used cannabis for prior 6 months;
   2. Must have at least one episode of lifetime cannabis use;
5. Must self-report not using other illicit recreational drugs (e.g., cocaine, benzodiazepines (non-prescription), opiates (non-prescription), MDMA, sedatives, or methamphetamine) in the past 30 days, during the Pre-Screening;
6. Must not test positive on a urine toxicology test for drugs of abuse at the Baseline Appointment (TDS);
7. Must not be using psychotropic medications, however anti-depressant, non-benzodiazepine anti-anxiety, and ADHD medications are ok. ADHD medication users must be willing to abstain from ADHD medication use on appointment days; ADHD medications, even extended-release forms, are short acting and medication" holidays" (e.g., on weekends and holidays) are routine in individuals prescribed ADHD medications, without adverse effects.
8. Must not be a regular nicotine user (≤4 days per week; cigarette, E-cigs, or smokeless);
9. Must not have used caffeine or nicotine (cigarette, E-cigs, or smokeless) for 4 hours;
10. Must have a breath alcohol level of 0 at screening (to sign consent form);
11. Must not be actively seeking or in treatment for any substance use disorder (drug use levels will be carefully monitored via Timeline Follow Back (TLFB) throughout the study to assess any confounding influences of drug or alcohol use;
12. Female subjects must not be or trying to become pregnant (as indicated by a pregnancy test & screening form administered at Baseline);
13. Must not be in treatment for psychotic disorder or bipolar disorder; or have a history with these disorders;
14. Must not have any physical characteristics (e.g., thick hair, head size exceeding the limit of the net, dyed hair) or experience any technical difficulties during testing that result in a poor-quality EEG recording.
15. Participants in Experiment 4 a. Must not have participated in Experiment 3

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in ERP amplitude (FN400)	The FN400 event-related potential (ERP) old/new effect will be measured using electroencephalography (EEG) during a recognition memory test. The FN400 reflects familiarity-based memory retrieval and is defined as the mean ERP amplitude difference between correctly recognized previously presented items ("hits") and correctly rejected novel items ("correct rejections") at mid-frontal electrode sites during the 300-500ms post-stimulus interval.	Intoxicated session and not-intoxicated session (about 1 week)
Difference in ERP amplitude (parietal)	The parietal ERP old/new effect will be measured using EEG during a recognition memory test. The parietal old/new effect reflects recollection-based memory retrieval and is defined as the mean ERP amplitude difference between hits and correct rejections at parietal electrode sites during the 500-800ms post-stimulus interval.	Intoxicated session and not-intoxicated session (about 1 week)
Difference in retrieval memory accuracy	Behavioral accuracy during recognition memory test will be assessed by the number of hits and correct rejections made during memory recall. Retrieval memory accuracy will be compared between intoxicated and not-intoxicated sessions.	Intoxicated session and not-intoxicated session (about 1 week)
Difference in retrieval memory performance	Memory performance will be assessed via reaction time, measured by a photocell during recognition memory testing and concurrent EEG. During the recall phase, a light indicator will appear in the bottom-right corner of the stimulus screen when a prompted image is presented, activating the photocell. This indicator disappears once the participant responds. The interval between stimulus onset and the participant's "new" or "old" response is used as the reaction time measure for both intoxicated and non-intoxicated sessions. Retrieval memory performance will be compared between intoxicated and not-intoxicated sessions.	Intoxicated session and not-intoxicated session (about 1 week)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Positive and Negative Affect Schedule (PANAS)	The PANAS is a Self-report measurement of positive and negative affect that will be administered at all times of the Mobile sessions: the pre-use and post-use timepoints of the intoxicated session, well as the not-intoxicated session. The PANAS will be used twice at the intoxicated session to measure changes in mood before and after cannabis use. The survey presents a 20-item scale from 1 (very slightly or not at all) to 5 (extremely), with a higher score on the positive affect scale indicating higher positive affect and a higher score on the negative affect scale indicating higher negative affect.	During a single non-intoxicated laboratory session and immediately before and immediately after acute cannabis use during a single intoxicated laboratory session
Change in Drug Effects Questionnaire (DEQ)	The DEQ is a 5-item visual analogue scale that measures acute drug effects, with prevalent use across numerous drug studies. Specifically, the questionnaire measures strength of the effects of cannabis as well as the desirability of the effects. Participants answer questions on a range from 0 - 100, with higher values for each item indicating greater drug effect or desire. The specific items related to drug "liking" and "wanting more" have been associated with harmful drug use. Participants will be administered the DEQ at all time points of the Mobile sessions to assess differences following intoxication.	During a single non-intoxicated laboratory session and immediately before and immediately after acute cannabis use during a single intoxicated laboratory session
Change in Addiction Research Center Inventory (ARCI-M)	The ARCI-M is a self-report measure of subjective effects of marijuana in addition to drug-induced euphoria, stimulant-like effects, intellectual efficiency and energy, sedation, dysphoria, and other somatic effects. This is a 12 item true-false task, in which higher (true) scores indicate greater intoxication. Participants will be administered the ARCI-M at all time points of the Mobile sessions to assess differences following intoxication.	During a single non-intoxicated laboratory session and immediately before and immediately after acute cannabis use during a single intoxicated laboratory session
Change in Marijuana Craving Questionnaire (MCQ)	The Marijuana Craving Questionnaire is a self-report measure of marijuana craving that will be administered at all time points during the Mobile sessions. Participants complete 8 questions ranging from 0 - 10, with a higher score indicating greater cannabis craving and somatic symptoms. The primary focus of this questionnaire will be the effect of intoxication on reporting.	During a single non-intoxicated laboratory session and immediately before and immediately after acute cannabis use during a single intoxicated laboratory session
Change in Profile of Mood States (POMS)	The POMS is a self-report measure of mood. Participants complete 27 mood-related items ranging from 0 - 4, with higher scores indicating greater levels of specific mood states. The POMS will be administered at all time points of the Mobile sessions, in order to measure changes in mood before and after intoxication.	During a single non-intoxicated laboratory session and immediately before and immediately after acute cannabis use during a single intoxicated laboratory session
Change in Alcohol Craving Questionnaire (ACQ)	The Alcohol Craving Questionnaire is a self-report measure of alcohol craving. This is a 2-item scale with each item ranging 0 - 10, with higher scores indicating greater alcohol craving. The ACQ is used at all time points of the Mobile sessions.	During a single non-intoxicated laboratory session and immediately before and immediately after acute cannabis use during a single intoxicated laboratory session
Change in State Adapted Paranoia Checklist-Brief (SAPC-B)	The SAPC-B is a self-report measure of paranoia. Participants complete 5 items each ranging from 0 - 10, with higher scores indicating greater feelings of paranoia. The SAPC-B is administered at all time points of the Mobile sessions to assess changes in paranoia after intoxication.	During a single non-intoxicated laboratory session and immediately before and immediately after acute cannabis use during a single intoxicated laboratory session
Difference in circulating cannabinoid concentration	Participants use cannabis ad-libitum. Therefore, blood levels of THC and CBD will be used to quantify dosage and compared across the not-intoxicated, pre-use and post-use time points of the Mobile sessions. This further allows for a direct test of whether any differences in outcomes for participants randomly assigned to the -THC/+CBD strain are due to an increase in CBD or a decrease in THC as compared to their baseline.	Baseline, intoxicated session, and not-intoxicated session (about 3 weeks total over all three sessions)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory: Correlations between genes related to cannabinoid metabolism, cannabis-related behavior, and neurocognitive function with ERPs and recognition memory performance	DNA will be extracted from 3.0 ml of blood from the baseline session. After extraction, DNA will be quantified and stored at -80° for analysis. DNA will be collected to look at differences in epigenetic and single nucleotide polymorphisms (SNPs) in participants. Due to the rapidly changing landscape of genetic science, the DNA samples collected in this study are primarily for bio-banking purposes. The analysis of these genetic samples is expected to be performed at a future date to contribute to the current study and/or future studies. Participants will be allowed to opt out of storage of genetic samples for future research.	Baseline, intoxicated session, and not-intoxicated session (about 3 weeks total over all three sessions)
Exploratory: Moderation of primary effects by baseline sleep quality using the Patient-Reported Outcomes Measurement Information Systems (PROMIS)	Baseline measurement of sleep disturbance, assessing participant's quality and patterns of sleep over the last seven days. Participants complete 4 items, for a total scale score from 4 - 20, with higher scores indicating more sleep disturbance.	Baseline, intoxicated session, and not-intoxicated session (about 3 weeks total over all three sessions)
Exploratory: Moderation of primary effects by baseline affective symptoms using the Depression Anxiety Stress Scale (DASS)	Baseline assessment of affective symptoms. Participants complete the Depression, Anxiety, and Stress Scale-21 (DASS-21), a 21-item measure consisting of three 7-item subscales assessing depression, anxiety, and stress/tension. Higher scores indicate greater symptom severity within each domain. Acute drug-effect measures will be collected at each study session, including before and after participants self-administer their assigned cannabis strain during mobile laboratory sessions.	Baseline, intoxicated session, and not-intoxicated session (about 3 weeks total over all three sessions)
Exploratory: Moderation of primary effects by baseline substance use history using the Timeline Followback (TLFB)	The TLFB is used to assess daily substance use for 30 days prior to the Baseline Appointment and 3-7 days prior to the later sessions. Our modified TLFB procedure will estimate both frequency of marijuana use and amount used per day, using visual stimuli as well as the method of administration.	Baseline, intoxicated session, and not-intoxicated session (about 3 weeks total over all three sessions)

Collaborators and Investigators

• Sponsor: L. Cinnamon Bidwell
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Timothy Curran, Ph.D., University of Colorado, Boulder

Publications and helpful links

Helpful Links

• CU Change Study Website

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: June 18, 2026
• First Submitted That Met QC Criteria: June 29, 2026
• First Posted (Actual): July 1, 2026

Study Record Updates

• Last Update Posted (Actual): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 29, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Memory; Cannabis; Electroencephalography
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Marijuana Abuse; nabiximols
• Other Study ID Numbers: 20-0309: Experiment 4; R01DA052431 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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