Cannabis Observations on Brain Waves, Retrieval, and Attention: Experiment 1 (COBRA)

ERP Studies of Acute Influences of THC and CBD on Memory Encoding and Retrieval Processes: Experiment 1

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 three 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 verbal 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 words as stimuli. Participants complete the same memory task while intoxicated one day and not intoxicated another day. A THC-dominant, a CBD-dominant, and a strain containing both THC and CBD are included in the study. Participants self-administer one of the three 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

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Community Sample

Description

Inclusion Criteria:

• Must be between the ages of 21 and 40 and provide informed consent.
• Must be right-handed (Laterality Quotient > 60 on Edinburgh Handedness Inventory - Short Form).
• Must use cannabis at least 4 days during the month.
• Must be a cannabis user for at least a year.
• 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.
• Must not test positive on a urine toxicology test for drugs of abuse.
• 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.
• Must not be a regular tobacco user (≤4 days per week; cigarette, E-cigs, or smokeless).
• Must not have used caffeine or tobacco (cigarette, E-cigs, or smokeless) for 4 hours prior to appointments.
• Must have a breath alcohol level of 0 to sign consent form.
• Must not be actively seeking or in treatment for any substance use disorder.
• Female subjects must not be or trying to become pregnant.
• Must not be in treatment for psychotic disorder or bipolar disorder; or have a history with these disorders.
• 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	Electroencephalography is used to quantify FN400 and parietal ERP effects.	intoxicated session and not-intoxicated session
Difference in recognition memory performance	Accuracy and 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
Difference in Flanker Task performance	Accuracy and reaction time will be used to assess task performance.	intoxicated session and not-intoxicated session (about 1 week)
Difference in Flanker Task ERPs	Electroencephalography is used to quantify ERN effects.	intoxicated session and not-intoxicated session (about 1 week)
Change in Positive and Negative Affect Schedule (PANAS)	The PANAS is Self-report measurement of positive and negative affect.	before and after acute cannabis use (about 30 minutes)
Change in Drug Effects Questionnaire (DEQ)	The DEQ is a visual analogue scale of measure of acute drug effects.	before and after acute cannabis use (about 30 minutes)
Change in Addiction Research Center Inventory (ARCI-M)	The ARCI-M is a self-report measure of subjective effects of marijuana.	before and after acute cannabis use (about 30 minutes)
Change in Marijuana Craving Questionnaire	The Marijuana Craving Questionnaire is a self-report measure of marijuana craving.	before and after acute cannabis use (about 30 minutes)
Change in Profile of Mood States (POMS)	The POMS is a self-report measure of mood.	before and after acute cannabis use (about 30 minutes)
Change in Alcohol Craving Questionnaire	The Alcohol Craving Questionnaire is a self-report measure of alcohol craving.	before and after acute cannabis use (about 30 minutes)
Change in State Adapted Paranoia Checklist-Brief (SAPC-B)	The SAPC-B is a self-report measure of paranoia.	before and after acute cannabis use (about 30 minutes)
Difference in circulating cannabinoids	Blood levels of THC and CBD will be quantified.	baseline, intoxicated session, and not-intoxicated session (about 3 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory: Associations 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)
Exploratory: Moderation of primary effects by baseline health and psychological functioning	Baseline health and psychological function include measures of sleep quality, affective symptoms, and substance use history.	baseline, intoxicated session, and not-intoxicated session (about 3 weeks)

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• More information

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2022
• Primary Completion (Actual): December 15, 2024
• Study Completion (Actual): December 15, 2024

Study Registration Dates

• First Submitted: April 11, 2023
• First Submitted That Met QC Criteria: May 11, 2023
• First Posted (Actual): May 22, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Memory; CBD; Cannabis; THC; Electroencephalography; Marijuana; Event-related potential; Episodic memory; Verbal learning
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Marijuana Abuse
• Other Study ID Numbers: 20-0309: Experiment 1; 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