THC
Conditions
Keywords
Memory Impairment, Learning Impairment
Brief summary
The purpose of this study is to begin investigating acute impairment of various forms of memory and learning by Tetrahydrocannabinol (THC) in cannabis (CNB) compared to placebo, in a 2-session per subject double-blind, random assignment, placebo-controlled counterbalanced design in young to middle-aged adults.
Detailed description
Tasks tapping each of the major cognitive memory-related domains will be performed in the MRI scanner, to reveal the relevant underlying circuitry and its disruption by drug using functional MRI. On an initial Screening Visit, regular or novice cannabis (CNB) users will undergo informed consent, clinical assessment (to fully evaluate inclusion/exclusion criteria), cognitive/personality assessment, and a structural MRI scan. At each assessment, subjects will provide subjectively-rated CNB intoxication using a verbal analog scale, complete 2 fMRI paradigms within \ 1.5 hours: a) Card Guessing task and b) Complex Working Memory Span, and complete the computer-based Effort Expenditure for Reward Task within \ 2 hours. These tests will be counterbalanced across subjects and sessions to minimize order and fatigue effects. Breaks will be standardized in a private environment and snacks/meals provided. Bathroom visits given as needed. Subjects will be supervised at all times by study staff and vital signs monitored. On assessment days, participants will remain at the Olin NRC until they report no subjective intoxication, and are observed by study staff to be no longer objectively intoxicated, then use taxi or Uber transportation home.
Interventions
DRUGTHC
Participants will be administered 0.5g of vaporized THC cannabis (12% THC cannabis)
DRUGPlacebo
Participants will be administered identical plant material from which all THC has been removed by solvent extraction.
Sponsors
Biopharmaceutical Research Company
Bloom Labs Cannabis Solutions
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
The dose will be portioned by the unblinded co-investigator to assure each participant receives the correct dose.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* CNB use within past 2 years and felt high when used. * Able to read, speak, and understand English. * Able and willing to provide written informed consent, and willing to commit to the study protocol.
Exclusion criteria
* Current marijuana tolerance, desire to cut down, or cravings to use during periods of abstinence. * Positive screen for drug or alcohol (except CNB) on test day will result in rescheduling the appointment * History of adverse effects with CNB * CNB users who are abstaining * IQ \<80 on the Wechsler Abbreviated Scale of Intelligence * Inability to comprehend written instructions using the WRAT 4 reading achievement test * Pregnant, breastfeeding, and ineffective birth control methods * Unable or unsafe to have an MRI * Serious medical, neuro-ophthalmological, or neurological illness (e.g. cancer, seizure disorders, encephalopathy * History of head trauma with loss of consciousness \> 30 minutes or concussion lasting 30 days * Focal brain lesion seen on structural MRI * Any medical/neurological condition that could compromise neurocognitive performance (e.g. epilepsy, multiple sclerosis, fetal alcohol syndrome) * Anyone deemed unsafe to study personnel for any reason * Hearing loss such that subject cannot hear sounds at the levels (dB) or pitches (Hz) to be used in the study * Significant pain and/or reduced mobility in the arms
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Complex Working Memory Span (CWMS) Task- Items Recalled | At sessions 1 and 2 while under fMRI, immediately post drug administration | CWMS Task assesses immediate plus delayed recall and working memory by assessing working memory capacity by presenting a list of stimuli to be recalled while simultaneously performing a secondary task. This task uses a fully crossed design which includes both same-domain CWMS conditions (e.g. verbal storage combined with verbal processing) as well as cross-domain CWMS conditions (e.g., verbal storage combined with spatial processing). Mean number of total items recalled. |
| The Complex Working Memory Span (CWMS) Task- fMRI measure | At sessions 1 and 2 while under fMRI, immediately post drug administration | CWMS Task assesses immediate plus delayed recall and working memory by assessing working memory capacity by presenting a list of stimuli to be recalled while simultaneously performing a secondary task. This task uses a fully crossed design which includes both same-domain CWMS conditions (e.g. verbal storage combined with verbal processing) as well as cross-domain CWMS conditions (e.g., verbal storage combined with spatial processing). BOLD signal Infrontal lobe. |
| The Effort Expenditure for Reward Task (EEfRT) | At sessions 1 and 2 immediately post drug administration | (EEfRT) is an out-of-scanner measure of effort-based decision-making that utilizes a choice model (easy-task or hard-task) in response to varying monetary rewards. This task assesses motivation in relation to reward magnitude, implicating the activation or suppression of dopaminergic pathways in the nucleus accumbens (NAcc). Percentage of hard-task choices across all levels of probability is calculated from all hard choices. Lower percentages of hard task choices indicate decreased motivation. |
| The Card-Guessing fMRI task | At sessions 1 and 2 while under fMRI, immediately post drug administration | The Card-Guessing fMRI task (28) will be used to investigate the effects of acute THC intoxication on decision-making, risk-taking, and reward processing. This task involves various trial types including win, loss, disappointment, and relief, to assess how THC affects reward expectancy and prediction error processing during decision-making presented as the fMRI blood-oxygen-level-dependent (BOLD) signal in response to card-guessing task. |
| The Zibrio SmartScale | At sessions 1 and 2 while under fMRI, immediately post drug administration | The Zibrio SmartScale aggregates balance data to create a Balance Score, which assesses postural sway with respect to balance ability and fall risk. Total score range 1 and 10. A lower score indicates a higher risk of falling. |
Countries
United States
Contacts
Primary ContactGodfrey Pearlson, MD
Backup ContactAriana Caruso
Outcome results
None listed