{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:23:19Z","timestamp":1792444999581,"version":"4.5.0"},"reference-count":58,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T00:00:00Z","timestamp":1670284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union\u2019s Horizon 2020 Research and Innovation Program","doi-asserted-by":"publisher","award":["952455"],"award-info":[{"award-number":["952455"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Recently, the potential use of phytocannabinoids (pCBs) to treat different pathological conditions has attracted great attention in the scientific community. Among the different pCBs, cannabidiol (CBD) has showed interesting biological properties, making it a promising molecule with a high security profile that has been approved for treatment as an add-on therapy in patients afflicted by severe pharmaco-resistant epilepsy, including Dravet syndrome (DS), Lennox\u2013Gastaut syndrome (LGS) and tuberous sclerosis complex (TSC). CBD is pharmacologically considered a \u201cdirty drug\u201d, since it has the capacity to bind different targets and to activate several cellular pathways. GABAergic impairment is one of the key processes during the epileptogenesis period able to induce a generalized hyperexcitability of the central nervous system (CNS), leading to epileptic seizures. Here, by using the microtransplantation of human brain membranes approach in Xenopus oocytes and electrophysiological recordings, we confirm the ability of CBD to modulate GABAergic neurotransmission in human cerebral tissues obtained from patients afflicted by different forms of pharmaco-resistant epilepsies, such as DS, TSC, focal cortical dysplasia (FCD) type IIb and temporal lobe epilepsy (TLE). Furthermore, using cDNAs encoding for human GABAA receptor subunits, we found that \u03b11\u03b22 receptors are still affected by CBD, while classical benzodiazepine lost its efficacy as expected.<\/jats:p>","DOI":"10.3390\/life12122042","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T02:49:35Z","timestamp":1670381375000},"page":"2042","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["GABAergic Neurotransmission in Human Tissues Is Modulated by Cannabidiol"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6554-5496","authenticated-orcid":false,"given":"Gabriele","family":"Ruffolo","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, 00185 Rome, Italy"},{"name":"IRCCS San Raffaele Roma, 00163 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Gaeta","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Cannata","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Pinzaglia","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3542-3770","authenticated-orcid":false,"given":"Eleonora","family":"Aronica","sequence":"additional","affiliation":[{"name":"Department of (Neuro)Pathology Amsterdam Neuroscience, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"Stichting Epilepsie Instellingen Nederland, 0397 Heemstede, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Morano","sequence":"additional","affiliation":[{"name":"Department of Human Neuroscience, University of Rome Sapienza, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierangelo","family":"Cifelli","sequence":"additional","affiliation":[{"name":"Department of Applied Clinical and Biotechnological Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6026-927X","authenticated-orcid":false,"given":"Eleonora","family":"Palma","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, 00185 Rome, Italy"},{"name":"IRCCS San Raffaele Roma, 00163 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/978-3-030-21737-2_8","article-title":"Pharmacology of Medical Cannabis","volume":"1162","author":"Amin","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.pharmthera.2011.09.002","article-title":"Phytocannabinoids as Novel Therapeutic Agents in CNS Disorders","volume":"133","author":"Hill","year":"2012","journal-title":"Pharmacol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3273","DOI":"10.1021\/ja01092a065","article-title":"A Total Synthesis of Dl-delta-1-tetrahydrocannabinol, the Active Constituent of Hashish","volume":"87","author":"Mechoulam","year":"1965","journal-title":"J. Am. Chem. Soc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.neures.2016.11.004","article-title":"Synapse Organization and Modulation via C1q Family Proteins and Their Receptors in the Central Nervous System","volume":"116","author":"Matsuda","year":"2017","journal-title":"Neurosci. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/365061a0","article-title":"Molecular Characterization of a Peripheral Receptor for Cannabinoids","volume":"365","author":"Munro","year":"1993","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/sj.bjp.0704327","article-title":"Molecular Targets for Cannabidiol and Its Synthetic Analogues: Effect on Vanilloid VR1 Receptors and on the Cellular Uptake and Enzymatic Hydrolysis of Anandamide","volume":"134","author":"Bisogno","year":"2001","journal-title":"Br. J. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1007\/s40265-019-01171-4","article-title":"Pharmacological and Therapeutic Properties of Cannabidiol for Epilepsy","volume":"79","author":"Franco","year":"2019","journal-title":"Drugs"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1038\/sj.bjp.0707460","article-title":"The Orphan Receptor GPR55 Is a Novel Cannabinoid Receptor","volume":"152","author":"Ryberg","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s13311-015-0377-3","article-title":"Molecular Targets of Cannabidiol in Neurological Disorders","volume":"12","author":"Chen","year":"2015","journal-title":"Neurotherapeutics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"16124","DOI":"10.1074\/jbc.M707104200","article-title":"Inhibition of Recombinant Human T-Type Calcium Channels by Delta9-Tetrahydrocannabinol and Cannabidiol","volume":"283","author":"Ross","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"381","DOI":"10.2147\/NDT.S203782","article-title":"Cannabinoids in the Treatment of Epilepsy: Current Status and Future Prospects","volume":"16","author":"Morano","year":"2020","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1084\/jem.20120242","article-title":"Cannabinoids Suppress Inflammatory and Neuropathic Pain by Targeting A3 Glycine Receptors","volume":"209","author":"Xiong","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1159\/000201556","article-title":"The Nonpsychotropic Cannabinoid Cannabidiol Modulates and Directly Activates Alpha-1 and Alpha-1-Beta Glycine Receptor Function","volume":"83","author":"Ahrens","year":"2009","journal-title":"Pharmacology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1007\/s11064-005-6978-1","article-title":"Agonistic Properties of Cannabidiol at 5-HT1a Receptors","volume":"30","author":"Russo","year":"2005","journal-title":"Neurochem. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/j.1476-5381.2008.00046.x","article-title":"5-HT1A Receptors Are Involved in the Cannabidiol-Induced Attenuation of Behavioural and Cardiovascular Responses to Acute Restraint Stress in Rats","volume":"156","author":"Resstel","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.ejphar.2013.10.011","article-title":"Effects of Cannabidiol on the Function of A7-Nicotinic Acetylcholine Receptors","volume":"720","author":"Mahgoub","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.phrs.2017.02.022","article-title":"The Direct Actions of Cannabidiol and 2-Arachidonoyl Glycerol at GABAA Receptors","volume":"119","author":"Bakas","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_18","unstructured":"U.S. Food and Drug Administration (2022, November 05). FDA Approves First Drug Comprised of an Active Ingredient Derived from Marijuana to Treat Rare, Severe Forms of Epilepsy, Available online: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-first-drug-comprised-active-ingredient-derived-marijuana-treat-rare-severe-forms."},{"key":"ref_19","unstructured":"(2022, November 05). GW Pharmaceuticals Receives European Commission Approval for Epidyolex. Available online: https:\/\/www.thepharmaletter.com\/article\/gw-pharmaceuticals-receives-european-commission-approval-for-epidyolex-for-seizures."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1111\/epi.17150","article-title":"Long-Term Cannabidiol Treatment for Seizures in Patients with Tuberous Sclerosis Complex: An Open-Label Extension Trial","volume":"63","author":"Thiele","year":"2022","journal-title":"Epilepsia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/978-1-59745-000-3_24","article-title":"Microtransplantation of Neurotransmitter Receptors from Cells to Xenopus Oocyte Membranes: New Procedure for Ion Channel Studies","volume":"322","author":"Miledi","year":"2006","journal-title":"Methods Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.pneurobio.2009.01.008","article-title":"Microtransplantation of Ligand-Gated Receptor-Channels from Fresh or Frozen Nervous Tissue into Xenopus Oocytes: A Potent Tool for Expanding Functional Information","volume":"88","author":"Eusebi","year":"2009","journal-title":"Prog. Neurobiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1111\/epi.12354","article-title":"Fractalkine\/CX3CL1 Modulates GABAA Currents in Human Temporal Lobe Epilepsy","volume":"54","author":"Roseti","year":"2013","journal-title":"Epilepsia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.nbd.2015.07.003","article-title":"GABAA Currents Are Decreased by IL-1\u03b2 in Epileptogenic Tissue of Patients with Temporal Lobe Epilepsy: Implications for Ictogenesis","volume":"82","author":"Roseti","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15078","DOI":"10.1073\/pnas.232574499","article-title":"Expression of Human Epileptic Temporal Lobe Neurotransmitter Receptors in Xenopus Oocytes: An Innovative Approach to Study Epilepsy","volume":"99","author":"Palma","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13238","DOI":"10.1073\/pnas.192445299","article-title":"Expression of Functional Neurotransmitter Receptors in Xenopus Oocytes after Injection of Human Brain Membranes","volume":"99","author":"Miledi","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11229","DOI":"10.1073\/pnas.1711351114","article-title":"Cannabidiol Attenuates Seizures and Social Deficits in a Mouse Model of Dravet Syndrome","volume":"114","author":"Kaplan","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1056\/NEJMc1708349","article-title":"Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome","volume":"377","author":"Tang","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1056\/NEJMoa1611618","article-title":"Cannabidiol in Dravet Syndrome Study Group Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome","volume":"376","author":"Devinsky","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/S1474-4422(22)00213-7","article-title":"Advances in the Genetics and Neuropathology of Tuberous Sclerosis Complex: Edging Closer to Targeted Therapy","volume":"21","author":"Curatolo","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.nbd.2016.07.014","article-title":"Functional Aspects of Early Brain Development Are Preserved in Tuberous Sclerosis Complex (TSC) Epileptogenic Lesions","volume":"95","author":"Ruffolo","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1146\/annurev-pathol-052016-100138","article-title":"Focal Cortical Dysplasia: Gene Mutations, Cell Signaling, and Therapeutic Implications","volume":"12","author":"Iffland","year":"2017","journal-title":"Annu. Rev. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1111\/epi.17301","article-title":"The ILAE Consensus Classification of Focal Cortical Dysplasia: An Update Proposed by an Ad Hoc Task Force of the ILAE Diagnostic Methods Commission","volume":"63","author":"Najm","year":"2022","journal-title":"Epilepsia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1056\/NEJMoa1703784","article-title":"Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery","volume":"377","author":"Blumcke","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1002\/ana.25403","article-title":"Gamma-Aminobutyric Acidergic Transmission Underlies Interictal Epileptogenicity in Pediatric Focal Cortical Dysplasia","volume":"85","author":"Blauwblomme","year":"2019","journal-title":"Ann. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.nbd.2013.10.001","article-title":"Pacemaker GABA Synaptic Activity May Contribute to Network Synchronization in Pediatric Cortical Dysplasia","volume":"62","author":"Cepeda","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S1474-4422(10)70310-0","article-title":"Mechanisms of Epileptogenesis and Potential Treatment Targets","volume":"10","author":"Lukasiuk","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/B978-0-12-823493-8.00027-4","article-title":"Neuropathology of the Temporal Lobe","volume":"187","author":"Boluda","year":"2022","journal-title":"Handb. Clin. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.phrs.2016.09.019","article-title":"Pharmacological Modulation in Mesial Temporal Lobe Epilepsy: Current Status and Future Perspectives","volume":"113","author":"Gambardella","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10183","DOI":"10.1073\/pnas.0403683101","article-title":"Phosphatase Inhibitors Remove the Run-down of Gamma-Aminobutyric Acid Type A Receptors in the Human Epileptic Brain","volume":"101","author":"Palma","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"15219","DOI":"10.1073\/pnas.0507339102","article-title":"Rundown of GABA Type A Receptors Is a Dysfunction Associated with Human Drug-Resistant Mesial Temporal Lobe Epilepsy","volume":"102","author":"Ragozzino","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3180","DOI":"10.1073\/pnas.0914710107","article-title":"Enhancement of GABA(A)-Current Run-down in the Hippocampus Occurs at the First Spontaneous Seizure in a Model of Temporal Lobe Epilepsy","volume":"107","author":"Mazzuferi","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"20944","DOI":"10.1073\/pnas.0710522105","article-title":"GABA(A)-Current Rundown of Temporal Lobe Epilepsy Is Associated with Repetitive Activation of GABA(A) \u201cPhasic\u201d Receptors","volume":"104","author":"Palma","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/nrd3502","article-title":"Beyond Classical Benzodiazepines: Novel Therapeutic Potential of GABAA Receptor Subtypes","volume":"10","author":"Rudolph","year":"2011","journal-title":"Nat Rev. Drug Discov."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1111\/epi.14574","article-title":"A Novel GABAergic Dysfunction in Human Dravet Syndrome","volume":"59","author":"Ruffolo","year":"2018","journal-title":"Epilepsia"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5563","DOI":"10.2174\/1381612823666170809100230","article-title":"Modulation of GABAA Receptors in the Treatment of Epilepsy","volume":"23","author":"Palma","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Noebels, J.L., Avoli, M., Rogawski, M.A., Olsen, R.W., and Delgado-Escueta, A.V. (2012). Regulation of GABAA Receptor Gene Expression and Epilepsy, Jasper\u2019s Basic Mechanisms of the Epilepsies.","DOI":"10.1093\/med\/9780199746545.001.0001"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1021\/cn5000524","article-title":"Nonpsychotropic Plant Cannabinoids, Cannabidivarin (CBDV) and Cannabidiol (CBD), Activate and Desensitize Transient Receptor Potential Vanilloid 1 (TRPV1) Channels in Vitro: Potential for the Treatment of Neuronal Hyperexcitability","volume":"5","author":"Iannotti","year":"2014","journal-title":"ACS Chem. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1111\/j.1528-1167.2007.01131.x","article-title":"The Antiepileptic Drug Levetiracetam Stabilizes the Human Epileptic GABAA Receptors upon Repetitive Activation","volume":"48","author":"Palma","year":"2007","journal-title":"Epilepsia"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Cifelli, P., Ruffolo, G., De Felice, E., Alfano, V., van Vliet, E.A., Aronica, E., and Palma, E. (2020). Phytocannabinoids in Neurological Diseases: Could They Restore a Physiological GABAergic Transmission?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030723"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"S34","DOI":"10.1002\/epi4.12537","article-title":"Transporter Hypothesis in Pharmacoresistant Epilepsies. Is It at the Central or Peripheral Level?","volume":"7","author":"Czornyj","year":"2022","journal-title":"Epilepsia Open"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/s41582-022-00664-3","article-title":"Why Won\u2019t It Stop? The Dynamics of Benzodiazepine Resistance in Status Epilepticus","volume":"18","author":"Burman","year":"2022","journal-title":"Nat. Rev. Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1038\/nm.2058","article-title":"Enhanced Tonic GABAA Inhibition in Typical Absence Epilepsy","volume":"15","author":"Cope","year":"2009","journal-title":"Nat. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1111\/epi.17036","article-title":"Add-on Cannabidiol in Patients with Dravet Syndrome: Results of a Long-Term Open-Label Extension Trial","volume":"62","author":"Scheffer","year":"2021","journal-title":"Epilepsia"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.pnpbp.2018.08.030","article-title":"Cannabidiol as a Suggested Candidate for Treatment of Autism Spectrum Disorder","volume":"89","author":"Poleg","year":"2019","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.3233\/JAD-140921","article-title":"Long-Term Cannabidiol Treatment Prevents the Development of Social Recognition Memory Deficits in Alzheimer\u2019s Disease Transgenic Mice","volume":"42","author":"Cheng","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1089\/can.2017.0002","article-title":"Cannabinoids in Parkinson\u2019s Disease","volume":"2","author":"Sancesario","year":"2017","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1212\/WNL.57.11.2108","article-title":"Cannabinoids Reduce Levodopa-Induced Dyskinesia in Parkinson\u2019s Disease: A Pilot Study","volume":"57","author":"Sieradzan","year":"2001","journal-title":"Neurology"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/12\/2042\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:35:19Z","timestamp":1760146519000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/12\/2042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,6]]},"references-count":58,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["life12122042"],"URL":"https:\/\/doi.org\/10.3390\/life12122042","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,6]]}}}