{
  "abstract": "To date, no pharmacotherapy has been approved for cocaine use disorder. Endocannabinoid signaling is closely related to dopamine-dependent reinforcement and may regulate cocaine-related behaviors. In this study, we used common marmosets (Callithrix jacchus) to investigate whether 2-arachidonoylglycerol (2-AG), an endogenous cannabinoid lipid, reduces cocaine reinforcement in a non-restraint oral self-administration model. Marmosets performed oral cocaine self-administration under a fixed-ratio 1 schedule, and cocaine intake was confirmed using plasma benzoylecgonine detection. Dopamine transporter (DAT)-related positron emission tomography (PET) signal, DAT and G protein-coupled receptor 55 (GPR55)-associated fluorescent signals, GPR55/DAT immunofluorescence, and synaptosomal dopamine responses were assessed using 18F-N-(3-fluoropropyl)-2{beta}-carboxymethoxy-3{beta}-(4-iodophenyl) nortropane (18F-FP-CIT) PET imaging, ex vivo fluorescent ligand imaging, confocal microscopy, and dopamine quantification. Marmosets acquired oral cocaine self-administration with preferential active lever responding. Repeated cocaine self-administration reduced striatal DAT-related 18F-FP-CIT PET signal in vivo. In striatal slices, cocaine decreased fluorescent false neurotransmitter (FFN102)-associated DAT signal and increased T1117-associated GPR55 signal. Systemic 2-AG pretreatment reduced cocaine self-administration while restoring diminished circulating 2-AG levels. GPR55 and DAT immunofluorescent signals were colocalized in marmoset brain sections, and 2-AG enhanced cocaine-induced dopamine elevation in synaptosomal preparations. Taken together, these findings suggest that 2-AG attenuates cocaine-taking behavior and may be associated with GPR55/DAT-related dopaminergic responses in common marmosets.",
  "abstract_shown": true,
  "affiliations": [
    "Chungbuk National University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "C. K. Lee"
    },
    {
      "name": "H. Eom"
    },
    {
      "name": "T. Yoo"
    },
    {
      "name": "S. M. Gu"
    },
    {
      "name": "J. J. Lee"
    },
    {
      "name": "H. Kwon"
    },
    {
      "name": "S.-B. Na"
    },
    {
      "name": "E. Kim"
    },
    {
      "name": "T. H. Kim"
    },
    {
      "name": "C.-W. Park"
    },
    {
      "name": "B. Y. Hwang"
    },
    {
      "name": "S. S. Yoon"
    },
    {
      "name": "D. Lee"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Yun"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/421k986cdaktr.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.01.748459",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748459v1.full",
  "id": "421k986cdaktr",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748459v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "pharmacology and toxicology"
    ],
    [
      "openalex",
      "2736|Cannabis and Cannabinoid Research"
    ]
  ],
  "openalex": "W7208823701",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748459v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/421k986cdaktr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:33Z",
      "native_id": "10.64898/2026.09.01.748459",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748459v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:pharmacology and toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Restoration of circulating 2-arachidonoylglycerol levels attenuates cocaine self-administration through endocannabinoid-dopamine interactions in common marmosets",
  "title_text": "Restoration of circulating 2-arachidonoylglycerol levels attenuates cocaine self-administration through endocannabinoid-dopamine interactions in common marmosets",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:33Z",
  "url": "https://research.draconitic.com/paper/421k986cdaktr",
  "venue": "bioRxiv",
  "versions": []
}