ERP studies of acute influences of THC and CBD on memory encoding and retrieval processes

项目摘要 先前的研究已经记录了大麻使用对言语情景记忆的急性有害影响，但先前的研究表明， 工作没有充分考虑到大麻的记忆效应是不同的复合作用。 大麻素作用于不同的记忆过程具体来说，大麻二酚（CBD），一种非拟精神病药物， 大麻的一种成分（不产生“高”），被认为具有认知保护特性， 减轻1，9-四氢大麻酚（THC）的一些有害影响。初步数据，包括我们自己的数据，表明 THC和CBD对记忆的影响不同此外，很少有先前的研究已经测试了高效力 常见的菌株。我们的总体假设是，大麻对记忆的影响随着年龄的增长而变化。 CBD与THC的比率的函数，THC具有可以被CBD抵消的不利影响。的 这项研究的目的是测试三种真实世界的商用大麻品种的效果， CBD与THC的比例显著增加。为此，我们将测试-THC/+CBD（0%THC/16%CBD）的效果， +THC/-CBD（16%THC/0%CBD）和+THC/+CBD（16%THC/16%CBD）对识别记忆的应变， 事件相关脑电位（ERP），以前已经发现与不同的 潜在的记忆过程我们使用自然主义的观察设计，每个参与者都将 一天在醉酒状态下完成同样的记忆任务，另一天不醉酒（顺序 平衡）。目的1（实验1）将评估识别记忆性能和记忆相关的 大麻使用者自我施用三种随机分配的大麻之一后的ERP成分 在记忆编码（学习）和记忆过程中的菌株（+THC/-CBD vs. -THC/+CBD vs.+THC/+CBD） 检索目标2和3将分离大麻对记忆编码与检索过程的影响。的 当使用者仅在记忆提取期间急性中毒时，将测试三种菌株的效果（Aim 2，实验2）或当用户陶醉只在记忆编码（目标3，实验3）。我们 假设在每个实验中应变的逐步效应，使得+THC/-CBD组将证明 与+THC/+CBD组相比， 与-THC/+CBD组相比，记忆减退。除了菌株分配，CBD和THC血液水平 也将在记忆准确性方面进行测试，CBD/THC水平越高， 记忆准确度我们进一步预测，在编码过程中记录的与记忆相关的ERP成分， 检索将显示应变和血液水平的影响平行的准确性，在这些影响的变化表明， 对不同记忆子过程（编码、熟悉、回忆、后提取）的相对影响 监测）。这项研究在当今法律的迅速变化和大麻使用增加的气候下至关重要， 娱乐和医疗用途。关于真实世界大麻对人类健康影响的及时和准确的数据 为了减少危害和确定广泛合法化的好处，记忆过程至关重要。

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.