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

Official title

Cannabis and Memory

Overview

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.

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.

Interventions

• Drug Cannabis (smoked flower)
  Self directed use (ad libitum)

Primary outcome measures

• Difference in ERP amplitude (FN400) [Time frame: Intoxicated session and not-intoxicated session (about 1 week)]
• Difference in ERP amplitude (parietal) [Time frame: Intoxicated session and not-intoxicated session (about 1 week)]
• Difference in retrieval memory accuracy [Time frame: Intoxicated session and not-intoxicated session (about 1 week)]
• Difference in retrieval memory performance [Time frame: Intoxicated session and not-intoxicated session (about 1 week)]

Secondary outcome measures (8)

• Change in Positive and Negative Affect Schedule (PANAS) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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 [Time frame: Baseline, intoxicated session, and not-intoxicated session (about 3 weeks total over all three sessions)]

Eligibility 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 Form136);
• Heavy users (HU) in Experiments 1, 2, 3, and 4:

• Must use cannabis at least 4 days during the month;
• Must be a cannabis user for at least a year;
• Non-users (NU) in Experiment 2:

• Must not have used cannabis for prior 6 months;
• Must have at least one episode of lifetime cannabis use;
• 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 (TDS);
• 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.
• 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;
• Must have a breath alcohol level of 0 at screening (to sign consent form);
• 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;
• Female subjects must not be or trying to become pregnant (as indicated by a pregnancy test \& screening form administered at Baseline);
• 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.
• Participants in Experiment 4 a. Must not have participated in Experiment 3

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

United States · 1 center

• Center for Innovation and Creativity (CINC) — Boulder

Identifiers

NCT: NCT07679581 · 20-0309: Experiment 4 · R01DA052431

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗