Cannabis Observations on Brain Waves, Retrieval, and Attention: Experiment 3 (COBRA 3)

Cannabis Observations on Brain Waves, Retrieval, and Attention: Experiment 3 (COBRA)

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: Completed
• 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 (Actual): 96

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Boulder, Colorado, United States, 80301
      • Center for Innovation and Creativity (CINC)

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 and Denver areas

Description

Inclusion Criteria:

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 Form);
3. Must use cannabis at least 4 days during the month;
4. Must be a cannabis user for at least a year;
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;
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;
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 before each appointment;
10. Must have a breath alcohol level of 0 at Baseline appointment (to sign consent form);
11. Must not be actively seeking or in treatment for any substance use disorder;
12. Female subjects must not be or trying to become pregnant (as indicated by a pregnancy test administered at Baseline appointment);
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.

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)	Electroencephalography is used to quantify FN400.	Intoxicated session and not-intoxicated session (about 1 week)
Difference in ERP amplitude (parietal)	Electroencephalography is used to quantify parietal ERP effects.	Intoxicated session and not-intoxicated session (about 1 week).
Difference in retrieval memory accuracy	Accuracy will be used to assess task performance.	Intoxicated session and not-intoxicated session (about 1 week)
Difference in retrieval memory performance	Reaction time will be used to assess task performance.	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 Self-report measurement of positive and negative affect. Both subscales range from 1 - 50, 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.	Before and after acute cannabis use during intoxicated session
Change in Drug Effects Questionnaire (DEQ)	The DEQ is a visual analogue scale of measure of acute drug effects. Participants are asked 5 questions on the DEQ, each of which range from 0 - 100, with higher values for each item indicating greater drug effect.	Before and after acute cannabis use during intoxicated session
Change in Addiction Research Center Inventory (ARCI-M)	The ARCI-M is a self-report measure of subjective effects of marijuana. This is a 12-item true-false task, in which higher (true) scores indicate greater intoxication.	Before and after acute cannabis use during intoxicated session
Change in Marijuana Craving Questionnaire	The Marijuana Craving Questionnaire is a self-report measure of marijuana craving. Participants complete 8 questions ranging from 0 - 10, with a higher score indicating greater cannabis craving and somatic symptoms.	Before and after acute cannabis use during intoxicated 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.	Before and after acute cannabis use during intoxicated session
Change in Alcohol Craving Questionnaire	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.	Before and after acute cannabis use during intoxicated 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.	Before and after acute cannabis use during intoxicated session
Difference in circulating cannabinoid concentration	Blood levels of THC and CBD will be quantified.	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 samples are collected from a baseline blood sample.	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)	This is a baseline measure of participant sleep disturbance. 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)	This is a baseline measure of affective symptoms. Participants complete three separate subscales assessing depression, anxiety, and stress, each with 7 items and with higher scores indicating greater levels of depression, anxiety, and stress.	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)	This is a baseline measure of substance use history. Participants report their substance use over the last 30 days prior to the baseline appointment.	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, PhD, University of Colorado, Boulder

Publications and helpful links

Helpful Links

• CUChange Study Website

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2024
• Primary Completion (Actual): December 10, 2025
• Study Completion (Actual): December 10, 2025

Study Registration Dates

• First Submitted: October 23, 2024
• First Submitted That Met QC Criteria: October 30, 2024
• First Posted (Actual): November 1, 2024

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 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 3; 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
• product manufactured in and exported from the U.S.: No