R01DA052431

ERP Studies of Acute Influences of THC and CBD on Memory Encoding and Retrieval Processes - Project Summary

Previous research has documented acute harmful effects of cannabis use on verbal episodic memory, but prior work has not sufficiently considered that the memory effects of cannabis are the compound action of different cannabinoids acting on different memory processes.

Specifically, cannabidiol (CBD), a non-psychotomimetic component of cannabis (doesn't produce a "high"), is thought to have cognitively protective properties and may mitigate some harmful effects of 9-tetrahydrocannabinol (THC). Preliminary data, including our own, suggest that THC and CBD render differential effects on memory. Further, few prior studies have tested high potency strains that are commonly available.

Our global hypothesis is that the effects of cannabis on memory vary as a function of the ratio of CBD to THC, with THC having adverse effects that may be counteracted by CBD. The goal of this study is to test the effects of three real-world commercially available cannabis strains that differ markedly in their ratio of CBD to THC.

To that end, we will test the effects of -THC/+CBD (0% THC/16% CBD), +THC/-CBD (16% THC/0% CBD), and +THC/+CBD (16% THC/16% CBD) strains on recognition memory as well as event-related brain potentials (ERPs) that have previously been found to be related to different underlying memory processes.

We use a naturalistic observational design in which each participant will complete the same memory task while intoxicated one day and not intoxicated another day (order counterbalanced).

Aim 1 (Experiment 1) will assess recognition memory performance and memory-related ERP components in cannabis users after self-administration of one of three randomly assigned cannabis strains (+THC/-CBD vs. -THC/+CBD vs. +THC/+CBD) during both memory encoding (learning) and memory retrieval.

Aims 2 and 3 will dissociate the effects of cannabis on memory encoding vs. retrieval processes. The effects of the three strains will be tested when users are acutely intoxicated only during memory retrieval (Aim 2, Experiment 2) or when users are intoxicated only during memory encoding (Aim 3, Experiment 3).

We hypothesize a stepwise effect of strain in each experiment such that the +THC/-CBD group will demonstrate the largest decrement in memory accuracy, as compared to the +THC/+CBD group, which will show a larger memory decrement than the -THC/+CBD group.

In addition to strain assignment, CBD and THC blood levels will also be tested in relation to memory accuracy, with greater CBD/THC levels associated with higher/lower memory accuracy. We further predict that memory-related ERP components recorded during encoding and retrieval will show strain and blood level effects paralleling accuracy, with variations in these effects indicating the relative influences on different memory sub-processes (encoding, familiarity, recollection, post-retrieval monitoring).

This study is critical in today's climate of rapid legal changes and increased cannabis use for both recreational and medicinal purposes. Timely and accurate data on the impact of real-world cannabis on memory processes is critical in order to reduce the harms and identify the benefits of widespread legalization.

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93.279 - Drug Abuse and Addiction Research Programs

National Institute on Drug Abuse (NIDA) [HHS - NIH]

Boulder, Colorado 803090001 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 419% from $611,542 to $3,173,683.