THC + CBD and Memory Study

Cannabis Use Clinical Trial

Official title:

Effects of Marijuana on Memory-Related Neurochemistry and Neural Response

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04855526
• Other study ID #: R-HHC-2019-0137
• Secondary ID: 126663
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: April 1, 2022
• Est. completion date: June 30, 2022

Study information

• Verified date: January 2022
• Source: Hartford Hospital
• Contact: Chelsea N Meagher, BA
• Phone: 860-545-7106
• Email: chelsea.meagher[@]hhchealth.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 9
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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)

Related Conditions & MeSH terms

• Cannabis Intoxication
• Cannabis Use
• Marijuana Abuse
• Marijuana Use

Intervention

Drug:
• High THC/No CBD Marihuana
high THC (65 mg THC) and no CBD (0 mg CBD)
• High THC/High CBD Marihuana
high THC (65 mg THC) and high CBD (50 mg CBD)
• No THC/No CBD Marihuana
no THC (0 mg THC) and no CBD (0 mg CBD); placebo drug

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Hartford Hospital	Yale University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	fMRI response	Blood oxygen level dependent functional magnetic resonance imaging (fMRI) response during the relational and item specific encoding task. fMRI response will be evaluated during the encoding phase (relational vs. item encoding), item recognition phase (hits vs. misses for item-specific encoding, and hits vs. misses for relational encoding), and associative recognition phase (hits vs. misses).	approximately 1 hour following drug administration
Primary	Glutamate	Magnetic resonance spectroscopy (MRS)-acquired glutamate containing compounds (Glx).	approximately 1 hour following drug administration
Secondary	HVLT-R performance	The Hopkins Verbal Learning Test-Revised will ascertain verbal list learning and immediate and delayed recall (~15min); alternate forms have been validated, and the order of versions participants receive will be randomized	Approximately 2.50 hours after drug administration
Secondary	Performance on CHARLIE cognitive task	This is a computer-based cognitive battery that administers the Digit Span and Letter/Number Sequencing Test (working memory) and the Digit Symbol Coding test (processing speed). It should take about 10 minutes to complete.	Approximately 3.00 hours after drug administration
Secondary	Blood THC and CBD concentration testing	A blood sample will be taken once per dose visit to assess the concentration of the following metabolites in ng/mL: delta-9-tetrahydrocannabinol, 11-hydroxy-tetrahydrocannabinol, 11-Nor-9-Carboxy-tetrahydrocannabinol (THCCOOH), tetrahydrocannabinol-Glucuronide, THCCOOH-Glucuronide, cannabinol (CBN), and cannabidiol (CBD).	Immediately after drug administration (~0.25 hours after drug administration)
Secondary	Subjective effects on drug effects questionnaire	This self-report will be used to assess subjective reports every 60 minutes throughout the dose visit days. These subjective ratings will be obtained using rapidly completed Visual Analog Scales (VASs) scored on a 0-100 scale. Items include: Do you feel a drug effect right now?, Are you high right now?, Do you dislike any of the effects you are feeling right now?, Do you like any of the effects you are feeling right now? and Would you like more of the drug you took, right now?	Post drug administration at: 0.00 hours (immediately after); 1.0 hours; 2.0 hours; 3.0 hours