{
  "abstract": "Background\n\nHyperlocomotion induced by psychotomimetic agents is considered a proxy for positive psychotic-like symptoms and is used in antipsychotic drug screenings with rodents. Cannabinoids are psychotomimetic drugs in humans, and low doses of cannabinoid CB₁ receptor (CB1R) agonists induce hyperlocomotion in rodents. However, the cellular and molecular mechanisms underlying this effect remain unexplored so far.Methods\n\nWe used a combination of pharmacological and genetic manipulations in cultured cells and adult male mouse models, together with an intracellular signaling detection method. Our multidisciplinary approach included locomotor activity (n = 10-12 mice/group), alphaLISA technology (n = 4-12 mice/group), transfection of the β-arrestin 1 protein in STHdh Q7/Q7 cells (n = 4-6/group) and a viral strategy in transgenic lines to selectively block GSK-3β (glycogen synthase kinase-3β) phosphorylation (n = 8-10 mice/group). We also used fluorescence in situ hybridization, real-time quantitative and droplet digital polymerase chain reaction, and tandem mass spectrometry.Results\n\nWe showed that the hyperlocomotion induced by a low dose (0.3 mg/kg) of cannabinoid Δ⁹-tetrahydrocannabinol depends on the activation of plasma membrane CB1R located on dopamine D₂ receptor-positive striatopallidal projecting neurons. This activation regulates the β-arrestin 1/Akt/GSK-3β signaling pathway, which is required for the hyperlocomotor effect. The signaling-specific CB1R inhibitors, pregnenolone and its clinically developed analog, AEF0117, prevent GSK-3β-dependent psychomotor stimulation induced by THC.Conclusions\n\nThis work highlights an intracellular mechanism of CB1R expressed by a selective key neuronal pathway mediating the psychotomimetic effect of THC and, by extension, low-dose cannabis consumption. This discovery will likely aid the development of unprecedented therapeutic modalities for the treatment of psychotic conditions.",
  "abstract_shown": true,
  "affiliations": [
    "University of Bordeaux, French National Institute of Health and Medical Research, Neurocentre Magendie, U1215, Bordeaux, France.",
    "Aelis Farma, Bordeaux, France."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Giovanni Tomaselli"
    },
    {
      "affs": [
        0
      ],
      "name": "Luigi Bellocchio"
    },
    {
      "affs": [
        0
      ],
      "name": "Pierre-Louis Raux"
    },
    {
      "affs": [
        0
      ],
      "name": "Valérie Roullot-Lacarrière"
    },
    {
      "affs": [
        0
      ],
      "name": "Arnau Busquets-Garcia"
    },
    {
      "affs": [
        0
      ],
      "name": "Valérie Lalanne"
    },
    {
      "affs": [
        0
      ],
      "name": "Yamuna Mariani"
    },
    {
      "affs": [
        0
      ],
      "name": "Adeline Cathala"
    },
    {
      "affs": [
        1
      ],
      "name": "Marion Zanese"
    },
    {
      "affs": [
        0
      ],
      "name": "Astrid Cannich"
    },
    {
      "affs": [
        0
      ],
      "name": "Agnès Grel"
    },
    {
      "affs": [
        0
      ],
      "name": "Doriane Gisquet"
    },
    {
      "affs": [
        0
      ],
      "name": "Miguel Mondesir"
    },
    {
      "affs": [
        1
      ],
      "name": "Mathilde Metna-Laurent"
    },
    {
      "affs": [
        0
      ],
      "name": "Guillaume Drutel"
    },
    {
      "affs": [
        0
      ],
      "name": "Giovanni Marsicano"
    },
    {
      "affs": [
        1
      ],
      "name": "Pier Vincenzo Piazza"
    },
    {
      "affs": [
        0
      ],
      "name": "Jean-Michel Revest"
    },
    {
      "affs": [
        0
      ],
      "name": "Monique Vallée",
      "orcid": "0000-0002-3642-4257"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4mf6jrv8byy6m.bib",
  "cited_by": 0,
  "doi": "10.1016/j.bpsgos.2026.100816",
  "fulltext_url": "https://europepmc.org/articles/PMC13685958",
  "id": "4mf6jrv8byy6m",
  "issns": [
    "2667-1743"
  ],
  "landing_url": "https://europepmc.org/article/MED/42909990",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2736|Cannabis and Cannabinoid Research"
    ]
  ],
  "openalex": "W7204525679",
  "pdf_url": "https://europepmc.org/articles/PMC13685958?pdf=render",
  "pmcid": "PMC13685958",
  "pmid": "42909990",
  "published": "2026-08-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4mf6jrv8byy6m.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:14Z",
      "native_id": "MED:42909990",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42909990"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Cannabis and Cannabinoid Research",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Psychotomimetic Cannabinoid Hyperlocomotion Involves GSK-3β Signaling at Striatopallidal Neurons in Male Mice.",
  "title_text": "Psychotomimetic Cannabinoid Hyperlocomotion Involves GSK-3β Signaling at Striatopallidal Neurons in Male Mice.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:14Z",
  "url": "https://research.draconitic.com/paper/4mf6jrv8byy6m",
  "venue": "Biological psychiatry global open science",
  "versions": []
}