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Δ⁹-Tetrahydrocannabinol (THC) impairs visual working memory performance: a randomized crossover trial.

ABSTRACT: With the increasing prevalence of legal cannabis use and availability, there is an urgent need to identify cognitive impairments related to its use. It is widely believed that cannabis, or its main psychoactive component Δ⁹-tetrahydrocannabinol (THC), impairs working memory, i.e., the ability to temporarily hold information in mind. However, our review of the literature yielded surprisingly little empirical support for an effect of THC or cannabis on working memory. We thus conducted a study with three main goals: (1) quantify the effect of THC on visual working memory in a well-powered sample, (2) test the potential role of cognitive effects (mind wandering and metacognition) in disrupting working memory, and (3) demonstrate how insufficient sample size and task duration reduce the likelihood of detecting a drug effect. We conducted two double-blind, randomized crossover experiments in which healthy adults (N = 23, 23) performed a reliable and validated visual working memory task (the "Discrete Whole Report task", 90 trials) after administration of THC (7.5 and/or 15 mg oral) or placebo. We also assessed self-reported "mind wandering" (Exp 1) and metacognitive accuracy about ongoing task performance (Exp 2). THC impaired working memory performance (d = 0.65), increased mind wandering (Exp 1), and decreased metacognitive accuracy about task performance (Exp 2). Thus, our findings indicate that THC does impair visual working memory, and that this impairment may be related to both increased mind wandering and decreased monitoring of task performance. Finally, we used a down-sampling procedure to illustrate the effects of task length and sample size on power to detect the acute effect of THC on working memory.

SUBMITTER: Adam KCS

PROVIDER: S-EPMC7608353 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:CD8+ T cells can contribute to neuroinflammation by secretion of inflammatory cytokines like interferon γ (IFNγ) and tumor necrosis factor α (TNFα). Astrocytes, a glial cell in the brain, can be stimulated by IFNγ and TNFα to secrete the inflammatory cytokines, monocyte chemotactic protein 1 (MCP-1), interleukin 6 (IL-6), and interferon-γ inducible protein 10 (IP-10). Δ9-Tetrahydrocannabinol (THC), the primary psychoactive cannabinoid in Cannabis sativa, possesses potent anti-inflammatory activity. The objective of this investigation was to assess the effects of THC treatment on CD8+ T cell-mediated activation of astrocytes. CD3/CD28/IFNα- stimulated CD8+ T cells were treated with vehicle (0.03% EtOH) or THC and cocultured with U251 astrocytes. IP-10+, MCP-1+, and IL-6+ astrocytes were quantified by flow cytometry. LegendPlex™ was used to measure cytokine secretion by CD8+ T cells and flow cytometry was employed to quantify IFNγ, TNFα, and lysosomal-associated membrane protein 1 (LAMP-1) expression. Recombinant TNFα and IFNγ were used to stimulate MCP-1, IP-10, IL-6 responses in U251 astrocytes, which were measured by flow cytometry. Treatment with THC reduced CD8+ T cell-mediated induction of IP-10 and IL-6 responses in U251 astrocytes but had no effect on MCP-1. THC treatment differentially affected T cell effector functions such that IFNγ and degranulation responses were sensitive to THC-mediated ablation while TNFα was not. Lastly, THC treatment reduced the IFNγ-induced IP-10 response but had no effect on TNFα-induced MCP-1 response in U251 astrocytes. The results suggest that cannabinoid treatment can selectively reduce certain CD8+ T cell responses that contribute to stimulation of astrocytes. Graphical Abstract Treatment with THC can abate CD8+ T cell-dependent neuroinflammatory processes by inhibiting CD8+ cell differentiation into effector cells, suppressing CD8+ effector cell function, and reducing activation of astrocytes by CD8+ T cell-derived inflammatory cytokines.

Project description:Alpha band (8-12 Hz) phase dynamics in the visual cortex are thought to reflect fluctuations in cortical excitability that influences perceptual processing. As such, visual stimuli are better detected when their onset is concurrent with specific phases of the alpha cycle. However, it is unclear whether alpha phase differentially influences cognitive performance at specific times relative to stimulus onset (i.e., is the influence of phase maximal before, at, or after stimulus onset?). To address this, participants performed a delayed-recognition, working memory (WM) task for visual motion direction during two separate visits. The first visit utilized functional magnetic resonance (fMRI) imaging to identify neural regions associated with task performance. Replicating previous studies, fMRI data showed engagement of visual cortical area V5, as well as a prefrontal cortical region, the inferior frontal junction (IFJ). During the second visit, transcranial magnetic stimulation (TMS) was applied separately to both the right IFJ and right V5 (with the vertex as a control region) while electroencephalography (EEG) was simultaneously recorded. During each trial, a single pulse of TMS (spTMS) was applied at one of six time points (-200, -100, -50, 0, 80, 160 ms) relative to the encoded stimulus onset. Results demonstrated a relationship between the phase of the posterior alpha signal prior to stimulus encoding and subsequent response times to the memory probe two seconds later. Specifically, spTMS to V5, and not the IFJ or vertex, yielded faster response times, indicating improved WM performance, when delivered during the peak, compared to the trough, of the alpha cycle, but only when spTMS was applied 100 ms prior to stimulus onset. These faster responses to the probe correlated with decreased early event related potential (ERP) amplitudes (i.e., P1) to the probe stimuli. Moreover, participants that were least affected by spTMS exhibited greater functional connectivity between V5 and fronto-parietal regions. These results suggest that posterior alpha phase indexes a critical time period for motion processing in the context of WM encoding goals, which occurs in anticipation of stimulus onset.

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Δ⁹-Tetrahydrocannabinol (THC) impairs visual working memory performance: a randomized crossover trial.

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Dataset Information

Δ9-Tetrahydrocannabinol (THC) impairs visual working memory performance: a randomized crossover trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Δ⁹-Tetrahydrocannabinol (THC) impairs visual working memory performance: a randomized crossover trial.