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 step wise 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 subprocesses (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.