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Completed

NCT Number: NCT06669585

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

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.

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Key information

Age range

21 year–40 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Center for Innovation and Creativity (CINC)

Boulder, Colorado, 80301, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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, during the Pre-Screening;
  • Must not test positive on a urine toxicology test for drugs of abuse at the Baseline appointment;
  • 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 nicotine user (≤4 days per week; cigarette, E-cigs, or smokeless);
  • Must not have used caffeine or nicotine (cigarette, E-cigs, or smokeless) for 4 hours before each appointment;
  • Must have a breath alcohol level of 0 at Baseline appointment (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 (as indicated by a pregnancy test administered at Baseline appointment);
  • 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.

Treatment and study plan

Cannabis (smoked flower)

Drug

Self-Directed Use (ad-libitum)

Primary outcomes

  1. Difference in ERP amplitude (FN400)

    Time frame: Intoxicated session and not-intoxicated session (about 1 week)

    Electroencephalography is used to quantify FN400.

  2. Difference in ERP amplitude (parietal)

    Time frame: Intoxicated session and not-intoxicated session (about 1 week).

    Electroencephalography is used to quantify parietal ERP effects.

  3. Difference in retrieval memory accuracy

    Time frame: Intoxicated session and not-intoxicated session (about 1 week)

    Accuracy will be used to assess task performance.

  4. Difference in retrieval memory performance

    Time frame: Intoxicated session and not-intoxicated session (about 1 week)

    Reaction time will be used to assess task performance.

Secondary outcomes

  1. Change in Positive and Negative Affect Schedule (PANAS)

    Time frame: Before and after acute cannabis use during intoxicated session

    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.

  2. Change in Drug Effects Questionnaire (DEQ)

    Time frame: Before and after acute cannabis use during intoxicated session

    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.

  3. Change in Addiction Research Center Inventory (ARCI-M)

    Time frame: Before and after acute cannabis use during intoxicated session

    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.

  4. Change in Marijuana Craving Questionnaire

    Time frame: Before and after acute cannabis use during intoxicated session

    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.

  5. Change in Profile of Mood States (POMS)

    Time frame: Before and after acute cannabis use during intoxicated session

    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.

  6. Change in Alcohol Craving Questionnaire

    Time frame: Before and after acute cannabis use during intoxicated session

    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.

  7. Change in State Adapted Paranoia Checklist-Brief (SAPC-B)

    Time frame: Before and after acute cannabis use during intoxicated session

    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.

  8. Difference in circulating cannabinoid concentration

    Time frame: Baseline, intoxicated session, and not-intoxicated session (about 3 weeks total over all three sessions)

    Blood levels of THC and CBD will be quantified.

Other outcomes

  1. Exploratory: Correlations between genes related to cannabinoid metabolism, cannabis-related behavior, and neurocognitive function with ERPs and recognition memory performance

    Time frame: Baseline, intoxicated session, and not-intoxicated session (about 3 weeks total over all three sessions)

    DNA samples are collected from a baseline blood sample.

  2. Exploratory: Moderation of primary effects by baseline sleep quality using the Patient-Reported Outcomes Measurement Information Systems (PROMIS)

    Time frame: Baseline, intoxicated session, and not-intoxicated session (about 3 weeks total over all three sessions)

    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.

  3. Exploratory: Moderation of primary effects by baseline affective symptoms using the Depression Anxiety Stress Scale (DASS)

    Time frame: Baseline, intoxicated session, and not-intoxicated session (about 3 weeks total over all three sessions)

    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.

  4. Exploratory: Moderation of primary effects by baseline substance use history using the Timeline Followback (TLFB)

    Time frame: Baseline, intoxicated session, and not-intoxicated session (about 3 weeks total over all three sessions)

    This is a baseline measure of substance use history. Participants report their substance use over the last 30 days prior to the baseline appointment.

Sponsors and collaborators

Lead sponsor

L. Cinnamon Bidwell

Other

Collaborators

  • National Institute on Drug Abuse (NIDA)

Registry information

Official study title

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

Acronym: COBRA 3

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Nov 1, 2024
Registry last updated
May 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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