NCT04855526

THC + CBD and Memory Study

Effects of Marijuana on Memory-Related Neurochemistry and Neural Response

• Status: Not Yet Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Sponsor: Hartford Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 40 Years
• Healthy volunteers: Accepted

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.

Conditions

• Marijuana Use
• Cannabis Use
• Cannabis Intoxication

Interventions

Type	Name	Description
DRUG	High THC/No CBD Marihuana	high THC (65 mg THC) and no CBD (0 mg CBD)
DRUG	High THC/High CBD Marihuana	high THC (65 mg THC) and high CBD (50 mg CBD)
DRUG	No THC/No CBD Marihuana	no THC (0 mg THC) and no CBD (0 mg CBD); placebo drug

Timeline

• Start date: 2025-12-01
• Primary completion: 2026-12-30
• Completion: 2026-12-30
• First posted: 2021-04-22
• Last updated: 2025-03-17

Regulatory

• FDA-regulated drug study