ArticleMolecular psychiatry2025
Cannabidiol abrogates cue-induced anxiety associated with normalization of mitochondria-specific transcripts and linoleic acid in the nucleus accumbens shell.
Article in Molecular psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Cannabidiol in Anorexia Nervosa: A Double-Blind Randomized Placebo Controlled Pilot Study to Test Safety, Pharmacokinetics, and Symptom Change.The International journal of eating disorders · 2026Trial
- Cannabidiol Attenuates Heroin Seeking in Male Rats Associated With Normalization of Discrete Neurobiological Signatures Within the Nucleus Accumbens With Subregional Specificity.Biological psychiatry · 2026Article
- The genetics of fibromyalgia and its relationships to psychiatric and medical traits.Nature communications · 2026Article
- SU-Eohyeol Pharmacopuncture Ameliorates Parkinson's Disease-Associated Pain via the CB1 and PPARγ Pathways in an MPTP-Induced Mouse Model.Pain research & management · 2026Article
- Cannabidiol Reduces D1 and D2 Medium Spiny Neuron Excitability in the Nucleus Accumbens Core.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
7 authors.
Funding
Abstract
Anxiety disorders are one of the top contributors to psychiatric burden worldwide. Recent years have seen a dramatic rise in the potential anxiolytic properties ascribed to cannabidiol (CBD), a non-intoxicating constituent of the Cannabis Sativa plant. This has led to several clinical trials underway to examine the therapeutic potential of CBD for anxiety disorders. Yet, CBD's anxiolytic effects are mixed with some studies reporting little to no impact on trait anxiety but significant reductions in pathological anxiety with suggestions that CBD's effect may relate to triggered or cue-induced behavior. Here, we studied the effects of CBD on cued and non-cued behaviors and related neurobiological underpinnings. To investigate the effect of CBD on cue-induced anxiety, male rats underwent a fear conditioning protocol (odor associated with shock) followed by assessments of avoidance behavior. CBD (10 mg/kg) was administered 1 h prior to anxiety assessments. To understand molecular mechanisms associated with behavior, we investigated the transcriptome and lipid profile of the nucleus accumbens shell (NAcSh), a structure implicated in cue-mediated behaviors and aversion. Administration of CBD significantly reduced avoidance behavior, but only in animals repeatedly exposed to a shock-paired cue. CBD did not affect behavior in animals exposed to neutral cue or encoding of the cue behavioral response. RNA sequencing revealed substantial impact of the shock-paired cue in control animals, recruiting mechanisms ranging from cytoskeletal dynamics to mitochondria dysfunction. The shock-paired cue also resulted in elevated linoleic acid in vehicle animals which correlated with anxiety-like behavior. CBD either reversed or normalized these cue-induced molecular phenotypes. CBD also recruited lipid networks which correlated with transcripts involved in synaptic plasticity, signaling, and epigenetic mechanisms. These results suggest that CBD may specifically alleviate salient, conditioned anxiety and normalize related biological mechanisms in the NAcSh which may guide therapeutic interventions for anxiety disorders.
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