Clinical trial NCT04855526: THC + CBD and Memory Study
Official title: Effects of Marijuana on Memory-Related Neurochemistry and Neural Response
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Marijuana Use
Cannabis Use
Cannabis Intoxication
Keywords: marijuana
cannabidiol
memory
THC
cannabis
intoxication
MRI
glutamate
MRS
Lead sponsor: Hartford Hospital
Sponsor class: OTHER
Collaborators: name: Yale University
First posted: 2021-04-22
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: Memory deficits are one of the most consistently observed cognitive effects of marijuana use. There is evidence that some decrements attributable to the primary psychoactive ingredient, delta-9-tetrahydrocannabinol (THC), may be attenuated by cannabidiol (CBD). This study will help us learn more about the relationship between THC and CBD consumption with memory processes. A combination of MRI and neuropsychological tests (which are computer and paper/pencil tasks) will be used to measure the neurocognitive and behavioral impacts of THC and CBD use.

Detailed description: With increased legalization and medicalization of marijuana (MJ), there is an urgent need to understand the acute effects of use. One of the most consistently observed cognitive outcomes associated with MJ use is memory dysfunction, which may have a substantial impact on daily life in individuals using MJ for recreational or medicinal purposes. Notably, there are numerous preparations of MJ with varying proportions of cannabinoids, which may differ in behavioral and cognitive effects. For instance, there is emerging evidence that acute administration of delta-9-tetrahydrocannabinol (THC), the main psychoactive constituent of MJ, hinders memory and reduces prefrontal and hippocampal functional magnetic resonance imaging (fMRI) activation, but cannabidiol (CBD) may mitigate some of these impairments. Given the role of glutamate in learning and memory, the investigators suggest that these effects may be subserved, in part, by glutamatergic mechanisms. The investigators will use magnetic resonance spectroscopy (MRS) to non-invasively measure glutamate in order to explore the neurochemical underpinnings of memory-related fMRI response changes following acute administration of THC and CBD in a randomized, double-blind, placebo-controlled, cross-over design. A total of 9 healthy participants ages 18-40 will be enrolled. Participants will first undergo one screening visit (\~4 hours), comprising informed consent, assessment of health history, psychiatric diagnoses, cognitive function, and substance use history, and a structural MRI session. This will be followed by 3 separate MJ dose visits (\~4 hours each), at which participants will complete neuroimaging after administration of one of 3 preparations of vaporized MJ in a randomized, counterbalanced, double-blinded fashion: 1) high THC and no CBD (THC), 2) high THC and high CBD (THC+CBD), and 3) no THC and no CBD (placebo MJ). As in the investigator's ongoing studies, bulk MJ plant material will be provided by the National Institute on Drug Abuse. MJ dose visits will comprise MJ administration, blood collection, MRS/fMRI scan, subjective reports, and a brief cognitive assessment.

Eligibility criteria: Inclusion Criteria:

* Right-handed
* Prior MJ users (has used MJ at least once in the past year, but no more than 1x/month in the past 12 months)
* Medically healthy (as determined by medical history and treatment)
* Adequate comprehension of English in order to complete study materials
* Acceptable birth control method for women (i.e., no copper IUD or any device that is not MRI safe)

Exclusion Criteria:

* Participant currently uses psychoactive medications or substances
* Psychiatric diagnoses (determined by DSM-V)
* Participant heavily or regularly uses MJ (more than 1x/month in the past year)
* Current or past substance dependence (including MJ)
* Positive urine toxicology screens
* Positive pregnancy screens
* MRI contraindications (e.g., heart pacemaker)

Primary outcomes:
measure: fMRI response
timeFrame: approximately 1 hour following drug administration
measure: Glutamate
timeFrame: approximately 1 hour following drug administration
Secondary outcomes:
measure: HVLT-R performance
timeFrame: Approximately 2.50 hours after drug administration
measure: Performance on CHARLIE cognitive task
timeFrame: Approximately 3.00 hours after drug administration
measure: Blood THC and CBD concentration testing
timeFrame: Immediately after drug administration (~0.25 hours after drug administration)
measure: Subjective effects on drug effects questionnaire
timeFrame: Post drug administration at: 0.00 hours (immediately after); 1.0 hours; 2.0 hours; 3.0 hours
Other outcomes:
Locations:
Study officials:
affiliation: Hartford Hospital - Olin Neuropsychiatry Research Center; Yale University
name: Godfrey Pearlson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hartford Hospital - Olin Neuropsychiatry Research Center; Yale University
name: Alecia Dager, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hartford Hospital - Olin Neuropsychiatry Research Center
name: Michael Stevens, PhD
role: PRINCIPAL_INVESTIGATOR
References: