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

THC 和 CBD 对记忆编码和检索过程的急性影响的 ERP 研究

• 批准号: 10459601
• 负责人: L. Cinnamon Bidwell
• 金额: $ 65.34万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10459601
• 关键词: Acute; Adverse effects; Blood; Brain; Cannabidiol; Cannabinoids; Cannabis; Climate; Cognitive; Data; Episodic memory; Event; Familiarity; Goals; Impairment; Intoxication; Learning; Legal; Measures; Medical; Medical Marijuana; Memory; Monitor; Participant; Performance; Pharmacology; Phase; Policies; Policy Maker; Process; Property; Randomized; Relative Risks; Research; Retrieval; Risk; Role; Self Administration; Stimulus; Testing; Tetrahydrocannabinol; Time; Variant; Work; base; cognitive function; design; endogenous cannabinoid system; experimental study; high risk; indexing; knowledge base; marijuana use; marijuana user; memory encoding; memory process; memory recognition; memory retrieval

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.

项目概要 先前的研究已经记录了大麻使用对言语情景记忆的严重有害影响，但之前 工作尚未充分考虑到大麻的记忆效应是不同物质的复合作用 大麻素作用于不同的记忆过程。具体来说，大麻二酚（CBD）是一种非拟精神病药 大麻的成分（不会产生“兴奋”），被认为具有认知保护特性，并且可能 减轻 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，之前很少有研究测试过高效力 常见的菌株。我们的总体假设是，大麻对记忆的影响因不同因素而异。 CBD 与 THC 的比例的函数，THC 具有可以被 CBD 抵消的副作用。这 这项研究的目的是测试三种现实世界中商业化大麻品种的效果，这三种大麻品种不同 CBD 与 THC 的比例尤为明显。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) 对识别记忆的影响为 以及先前发现与不同事件相关的脑电位（ERP） 底层的记忆过程。我们采用自然主义观察设计，每个参与者都会 一天喝醉时完成相同的记忆任务，另一天不喝醉时完成相同的记忆任务（顺序 平衡）。目标 1（实验 1）将评估识别记忆性能和记忆相关 大麻使用者自行服用三种随机分配的大麻之一后的 ERP 成分 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 将区分大麻对记忆编码和检索过程的影响。这 仅在记忆检索过程中，当使用者严重中毒时，才会测试这三种菌株的效果（目标 2，实验2）或当用户仅在记忆编码期间陶醉时（目标3，实验3）。我们 假设每个实验中应变的逐步影响，使得 + THC/-CBD 组将证明 与+THC/+CBD组相比，记忆准确度下降幅度最大，这将显示出更大的 记忆力比 -THC/+CBD 组减少。除了菌株分配外，CBD 和 THC 血液水平 还将测试与记忆准确性相关的测试，较高的 CBD/THC 水平与较高/较低的相关 记忆准确度。我们进一步预测，在编码和编码过程中记录的与记忆相关的 ERP 组件 检索将显示与准确性平行的应变和血液水平影响，这些影响的变化表明 对不同记忆子过程（编码、熟悉度、回忆、检索后）的相对影响 监控）。这项研究对于当今法律快速变化和大麻使用增加的环境至关重要 娱乐和药用目的。关于现实世界大麻对人的影响的及时、准确的数据 为了减少危害并确定广泛合法化的好处，记忆过程至关重要。