{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T04:37:31Z","timestamp":1789879051803,"version":"4.0.1"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T00:00:00Z","timestamp":1627948800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T00:00:00Z","timestamp":1627948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DA035680"],"award-info":[{"award-number":["R01 DA035680"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>High doses of the <jats:italic>Cannabis<\/jats:italic> constituent \u03949-tetrahydrocannabinol (THC) increase the risk of psychosis in humans. Highly accessible animal models are needed to address underlying mechanisms. Using zebrafish with a conserved endocannabinoid system, this study investigates the acute effects of THC on adult zebrafish behavior and the mechanisms involved. A concentration-dependent THC-induced behavioral stereotypy akin to THC\u2019s effect in rats and the psychotropics phencyclidine and ketamine in zebrafish was established. Distinctive circular swimming during THC-exposure was measured using a novel analytical method that we developed, which detected an elevated Repetition Index (RI) compared to vehicle controls. This was reduced upon co-administration of N-methyl-D-aspartate (NMDA) receptor agonist NMDA, suggesting that THC exerts its effects via biochemical or neurobiological mechanisms associated with NMDA receptor antagonism. Co-treatment of \u03b3\u2010aminobutyric acid receptor antagonist pentylenetetrazol also showed signs of reducing the RI. Since THC-induced repetitive behavior remained in co-administrations with cannabinoid receptor 1 inverse agonist AM251, the phenotype may be cannabinoid receptor 1-independent. Conversely, the inverse cannabinoid receptor 2 agonist AM630 significantly reduced THC-induced behavioral stereotypy, indicating cannabinoid receptor 2 as a possible mediator. A significant reduction of the THC-RI was also observed by the antipsychotic sulpiride. Together, these findings highlight this model\u2019s potential for elucidating the mechanistic relationship between <jats:italic>Cannabis<\/jats:italic> and psychosis.<\/jats:p>","DOI":"10.1038\/s41598-021-95016-4","type":"journal-article","created":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T10:03:01Z","timestamp":1627984981000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior"],"prefix":"10.1038","volume":"11","author":[{"given":"Amelia","family":"Dahl\u00e9n","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahdi","family":"Zarei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Melgoza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahendra","family":"Wagle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,3]]},"reference":[{"key":"95016_CR1","doi-asserted-by":"publisher","unstructured":"Goodman, S., Wadsworth, E., Leos-Toro, C., Hammond, D., & International Cannabis Policy Study team. Prevalence and forms of cannabis use in legal vs. illegal recreational cannabis markets. Int. J. Drug Policy 76, 102658. https:\/\/doi.org\/10.1016\/j.drugpo.2019.102658 (2020).","DOI":"10.1016\/j.drugpo.2019.102658"},{"key":"95016_CR2","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1016\/j.jpain.2007.12.010","volume":"9","author":"B Wilsey","year":"2008","unstructured":"Wilsey, B. et al. A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J. Pain. 9, 506\u2013521. https:\/\/doi.org\/10.1016\/j.jpain.2007.12.010 (2008).","journal-title":"J. Pain."},{"key":"95016_CR3","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1185\/030079907X167525","volume":"23","author":"E Meiri","year":"2007","unstructured":"Meiri, E. et al. Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Curr. Med. Res. Opin. 23, 533\u2013543. https:\/\/doi.org\/10.1185\/030079907X167525 (2007).","journal-title":"Curr. Med. Res. Opin."},{"key":"95016_CR4","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1097\/QAI.0b013e31811ed205","volume":"45","author":"M Haney","year":"2007","unstructured":"Haney, M. et al. Dronabinol and marijuana in HIV-positive marijuana smokers: caloric intake, mood, and sleep. J. Acquir. Immune Defic. Syndr. 45, 545\u2013554. https:\/\/doi.org\/10.1097\/QAI.0b013e31811ed205 (2007).","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"95016_CR5","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1177\/0269881110379283","volume":"25","author":"JAS Crippa","year":"2011","unstructured":"Crippa, J. A. S. et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: A preliminary report. J. Psychopharmacol. 25, 121\u2013130. https:\/\/doi.org\/10.1177\/0269881110379283 (2011).","journal-title":"J. Psychopharmacol."},{"key":"95016_CR6","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1177\/0269881112460109","volume":"27","author":"A Englund","year":"2013","unstructured":"Englund, A. et al. Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. J. Psychopharmacol. 27, 19\u201327. https:\/\/doi.org\/10.1177\/0269881112460109 (2013).","journal-title":"J. Psychopharmacol."},{"key":"95016_CR7","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1017\/S0033291709005522","volume":"39","author":"PD Morrison","year":"2009","unstructured":"Morrison, P. D. et al. The acute effects of synthetic intravenous \u0394 9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychol. Med. 39, 1607\u20131616. https:\/\/doi.org\/10.1017\/S0033291709005522 (2009).","journal-title":"Psychol. Med."},{"key":"95016_CR8","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1016\/S0140-6736(87)92620-1","volume":"330","author":"S Andr\u00e9asson","year":"1987","unstructured":"Andr\u00e9asson, S., Engstr\u00f6m, A., Allebeck, P. & Rydberg, U. Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet 330, 1483\u20131486. https:\/\/doi.org\/10.1016\/S0140-6736(87)92620-1 (1987).","journal-title":"Lancet"},{"key":"95016_CR9","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1192\/bjp.bp.109.064220","volume":"195","author":"M Di Forti","year":"2009","unstructured":"Di Forti, M. et al. High-potency cannabis and the risk of psychosis. Br. J. Psychiatry 195, 488\u2013491. https:\/\/doi.org\/10.1192\/bjp.bp.109.064220 (2009).","journal-title":"Br. J. Psychiatry"},{"key":"95016_CR10","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1093\/schbul\/sby058","volume":"44","author":"FJ Charlson","year":"2018","unstructured":"Charlson, F. J. et al. Global epidemiology and burden of schizophrenia: findings from the global burden of disease study 2016. Schizophr. Bull. 44, 1195\u20131203. https:\/\/doi.org\/10.1093\/schbul\/sby058 (2018).","journal-title":"Schizophr. Bull."},{"key":"95016_CR11","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. (5th ed.). Arlington, VA, American Psychiatric Association. (2013).","DOI":"10.1176\/appi.books.9780890425596"},{"key":"95016_CR12","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1001\/archpsyc.62.2.137","volume":"62","author":"CL Caton","year":"2005","unstructured":"Caton, C. L. et al. Differences between early-phase primary psychotic disorders with concurrent substance use and substance-induced psychoses. Arch. Gen. Psychiatry. 62, 137\u2013145. https:\/\/doi.org\/10.1001\/archpsyc.62.2.137 (2005).","journal-title":"Arch. Gen. Psychiatry."},{"key":"95016_CR13","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1093\/schbul\/sbn101","volume":"34","author":"R Van Winkel","year":"2008","unstructured":"Van Winkel, R., Stefanis, N. C. & Myin-Germeys, I. Psychosocial stress and psychosis. A review of the neurobiological mechanisms and the evidence for gene-stress interaction. Schizophr. Bull. 34, 1095\u20131105. https:\/\/doi.org\/10.1093\/schbul\/sbn101 (2008).","journal-title":"Schizophr. Bull."},{"key":"95016_CR14","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1176\/ajp.135.9.1081","volume":"135","author":"RM Allen","year":"1978","unstructured":"Allen, R. M. & Young, S. J. Phencyclidine-induced psychosis. Am. J. Psychiatry. 135, 1081\u20131084. https:\/\/doi.org\/10.1176\/ajp.135.9.1081 (1978).","journal-title":"Am. J. Psychiatry."},{"key":"95016_CR15","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/S0893-133X(01)00243-3","volume":"25","author":"AC Lahti","year":"2001","unstructured":"Lahti, A. C., Weiler, M. A., Michaelidis, B. T., Parwani, A. & Tamminga, C. A. Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology 25, 455\u2013467. https:\/\/doi.org\/10.1016\/S0893-133X(01)00243-3 (2001).","journal-title":"Neuropsychopharmacology"},{"key":"95016_CR16","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.pnpbp.2012.01.003","volume":"37","author":"E Kyzar","year":"2012","unstructured":"Kyzar, E. et al. Effects of hallucinogenic agents mescaline and phencyclidine on zebrafish behavior and physiology. Prog. Neuropsychopharmacol. Biol. Psychiatry. 37, 194\u2013202. https:\/\/doi.org\/10.1016\/j.pnpbp.2012.01.003 (2012).","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry."},{"key":"95016_CR17","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.ntt.2011.05.011","volume":"33","author":"R Riehl","year":"2011","unstructured":"Riehl, R. et al. Behavioral and physiological effects of acute ketamine exposure in adult zebrafish. Neurotoxicol. Teratol. 33, 658\u2013667. https:\/\/doi.org\/10.1016\/j.ntt.2011.05.011 (2011).","journal-title":"Neurotoxicol. Teratol."},{"key":"95016_CR18","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.bbr.2010.05.039","volume":"214","author":"L Grossman","year":"2010","unstructured":"Grossman, L. et al. Characterization of behavioral and endocrine effects of LSD on zebrafish. Behav. Brain Res. 214, 277\u2013284. https:\/\/doi.org\/10.1016\/j.bbr.2010.05.039 (2010).","journal-title":"Behav. Brain Res."},{"key":"95016_CR19","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1097\/FBP.0b013e328345f758","volume":"22","author":"A Stewart","year":"2011","unstructured":"Stewart, A. et al. Behavioral effects of MDMA (\u2018ecstasy\u2019) on adult zebrafish. Behav. Pharmacol. 22, 275\u2013280. https:\/\/doi.org\/10.1097\/FBP.0b013e328345f758 (2011).","journal-title":"Behav. Pharmacol."},{"key":"95016_CR20","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1111\/j.1476-5381.1983.tb11031.x","volume":"79","author":"NA Anis","year":"1983","unstructured":"Anis, N. A., Berry, S. C., Burton, N. R. & Lodge, D. The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Br. J. Pharmacol. 79, 565\u2013575. https:\/\/doi.org\/10.1111\/j.1476-5381.1983.tb11031.x (1983).","journal-title":"Br. J. Pharmacol."},{"key":"95016_CR21","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1111\/j.1471-4159.2006.03913.x","volume":"98","author":"LK Bak","year":"2006","unstructured":"Bak, L. K., Schousboe, A. & Waagepetersen, H. S. The glutamate\/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer. J. Neurochem. 98, 641\u2013653. https:\/\/doi.org\/10.1111\/j.1471-4159.2006.03913.x (2006).","journal-title":"J. Neurochem."},{"key":"95016_CR22","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/nrn3504","volume":"14","author":"P Paoletti","year":"2013","unstructured":"Paoletti, P., Bellone, C. & Zhou, Q. NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease. Nat. Rev. Neurosci. 14, 383\u2013400. https:\/\/doi.org\/10.1038\/nrn3504 (2013).","journal-title":"Nat. Rev. Neurosci."},{"key":"95016_CR23","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1177\/0269881114563634","volume":"29","author":"O Howes","year":"2015","unstructured":"Howes, O., McCutcheon, R. & Stone, J. Glutamate and dopamine in schizophrenia: An update for the 21st century. J. Psychopharmacol. 29, 97\u2013115. https:\/\/doi.org\/10.1177\/0269881114563634 (2015).","journal-title":"J. Psychopharmacol."},{"key":"95016_CR24","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1016\/s0091-3057(02)00938-3","volume":"73","author":"TU J\u00e4rbe","year":"2002","unstructured":"J\u00e4rbe, T. U., Andrzejewski, M. E. & DiPatrizio, N. V. Interactions between the CB1 receptor agonist \u03949-THC and the CB1 receptor antagonist SR-141716 in rats: open-field revisited. Pharmacol. Biochem. Behav. 73, 911\u2013919. https:\/\/doi.org\/10.1016\/s0091-3057(02)00938-3 (2002).","journal-title":"Pharmacol. Biochem. Behav."},{"key":"95016_CR25","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1007\/BF00431466","volume":"84","author":"I Nir","year":"1984","unstructured":"Nir, I., Veldhuis, H. & van Ree, J. \u0394 1-tetrahydrocannabinol-induced circling behavior in rats: A possible measure of psychotomimetic activity?. Psychopharmacology 84, 556\u2013560. https:\/\/doi.org\/10.1007\/BF00431466 (1984).","journal-title":"Psychopharmacology"},{"key":"95016_CR26","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1124\/pr.54.2.161","volume":"54","author":"AC Howlett","year":"2002","unstructured":"Howlett, A. C. et al. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol. Rev. 54, 161\u2013202. https:\/\/doi.org\/10.1124\/pr.54.2.161 (2002).","journal-title":"Pharmacol. Rev."},{"key":"95016_CR27","doi-asserted-by":"publisher","first-page":"E5007","DOI":"10.1073\/pnas.1413210111","volume":"111","author":"HY Zhang","year":"2014","unstructured":"Zhang, H. Y. et al. Cannabinoid CB2 receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice. Proc. Natl. Acad. Sci. USA 111, E5007\u2013E5015. https:\/\/doi.org\/10.1073\/pnas.1413210111 (2014).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"95016_CR28","doi-asserted-by":"publisher","unstructured":"Rodr\u00edguez-Mu\u00f1oz, M., S\u00e1nchez-Bl\u00e1zquez, P., Merlos, M. & Garz\u00f3n-Ni\u00f1o, J. Endocannabinoid control of glutamate NMDA receptors: The therapeutic potential and consequences of dysfunction. Oncotarget 7, 55840\u201355862. https:\/\/doi.org\/10.18632\/oncotarget.10095 (2016).","DOI":"10.18632\/oncotarget.10095"},{"key":"95016_CR29","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/sj.bjp.0705931","volume":"143","author":"C Lupica","year":"2004","unstructured":"Lupica, C., Riegel, A. & Hoffman, A. Marijuana and cannabinoid regulation of brain reward circuits. Br. J. Pharmacol. 143, 227\u2013234. https:\/\/doi.org\/10.1038\/sj.bjp.0705931 (2004).","journal-title":"Br. J. Pharmacol."},{"key":"95016_CR30","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1111\/dgd.12351","volume":"59","author":"F Oltrabella","year":"2017","unstructured":"Oltrabella, F., Melgoza, A., Nguyen, B. & Guo, S. Role of the endocannabinoid system in vertebrates: Emphasis on the zebrafish model. Dev. Growth Differ. 59, 194\u2013210. https:\/\/doi.org\/10.1111\/dgd.12351 (2017).","journal-title":"Dev. Growth Differ."},{"key":"95016_CR31","doi-asserted-by":"crossref","first-page":"82","DOI":"10.46867\/IJCP.2010.23.01.03","volume":"23","author":"J Chen","year":"2010","unstructured":"Chen, J., Patel, R., Friedman, T. C. & Jones, K. S. The behavioral and pharmacological actions of NMDA receptor antagonism are conserved in zebrafish larvae. Int. J. Comp. Psychol. 23, 82\u201390 (2010).","journal-title":"Int. J. Comp. Psychol."},{"key":"95016_CR32","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1111\/j.1601-183X.2005.00185.x","volume":"5","author":"B Lau","year":"2006","unstructured":"Lau, B., Bretaud, S., Huang, Y., Lin, E. & Guo, S. Dissociation of food and opiate preference by a genetic mutation in zebrafish. Genes Brain Behav. 5, 497\u2013505. https:\/\/doi.org\/10.1111\/j.1601-183X.2005.00185.x (2006).","journal-title":"Genes Brain Behav."},{"issue":"2609\u20132622","key":"95016_CR33","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.3390\/molecules15042609","volume":"15","author":"R Gerlai","year":"2010","unstructured":"Gerlai, R. High-throughput behavioral screens: the first step towards finding genes involved in vertebrate brain function using zebrafish. Molecules 15(2609\u20132622), 2010. https:\/\/doi.org\/10.3390\/molecules15042609 (2010).","journal-title":"Molecules"},{"key":"95016_CR34","doi-asserted-by":"publisher","first-page":"e51295","DOI":"10.7554\/eLife.51295","volume":"9","author":"J Garc\u00eda-Gonz\u00e1lez","year":"2020","unstructured":"Garc\u00eda-Gonz\u00e1lez, J. et al. Identification of slit3 as a locus affecting nicotine preference in zebrafish and human smoking behaviour. Elife 9, e51295. https:\/\/doi.org\/10.7554\/eLife.51295 (2020).","journal-title":"Elife"},{"key":"95016_CR35","doi-asserted-by":"publisher","first-page":"33822","DOI":"10.1038\/srep33822","volume":"6","author":"S Pei","year":"2016","unstructured":"Pei, S. et al. Risk of prenatal depression and stress treatment: alteration on serotonin system of offspring through exposure to Fluoxetine. Sci. Rep. 6, 33822. https:\/\/doi.org\/10.1038\/srep33822 (2016).","journal-title":"Sci. Rep."},{"key":"95016_CR36","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/j.neuroscience.2004.11.031","volume":"131","author":"SC Baraban","year":"2005","unstructured":"Baraban, S. C., Taylor, M. R., Castro, P. A. & Baier, H. Pentylenetetrazole induced changes in zebrafish behavior, neural activity and c-fos expression. Neuroscience 131, 759\u2013768. https:\/\/doi.org\/10.1016\/j.neuroscience.2004.11.031 (2005).","journal-title":"Neuroscience"},{"key":"95016_CR37","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1089\/can.2018.0025","volume":"4","author":"A Acevedo-Canabal","year":"2019","unstructured":"Acevedo-Canabal, A. et al. Altered swimming behaviors in zebrafish larvae lacking cannabinoid receptor 2. Cannabis Cannabinoid Res. 4, 88\u2013101. https:\/\/doi.org\/10.1089\/can.2018.0025 (2019).","journal-title":"Cannabis Cannabinoid Res."},{"issue":"331\u2013337","key":"95016_CR38","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1016\/j.bbr.2011.02.019","volume":"220","author":"M Sison","year":"2011","unstructured":"Sison, M. & Gerlai, R. Behavioral performance altering effects of MK-801 in zebrafish (Danio rerio). Behav. Brain Res. 220(331\u2013337), 2011. https:\/\/doi.org\/10.1016\/j.bbr.2011.02.019 (2011).","journal-title":"Behav. Brain Res."},{"key":"95016_CR39","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1080\/02791072.1981.10471447","volume":"13","author":"M Touw","year":"1981","unstructured":"Touw, M. The religious and medicinal uses of Cannabis in China, India and Tibet. J. Psychoactive Drugs 13, 23\u201334. https:\/\/doi.org\/10.1080\/02791072.1981.10471447 (1981).","journal-title":"J. Psychoactive Drugs"},{"key":"95016_CR40","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.drugalcdep.2010.11.004","volume":"115","author":"C Lopez-Quintero","year":"2011","unstructured":"Lopez-Quintero, C. et al. Probability and predictors of transition from first use to dependence on nicotine, alcohol, cannabis, and cocaine: Results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Drug Alcohol Depend. 115, 120\u2013130. https:\/\/doi.org\/10.1016\/j.drugalcdep.2010.11.004 (2011).","journal-title":"Drug Alcohol Depend."},{"key":"95016_CR41","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/S0140-6736(07)61162-3","volume":"370","author":"TH Moore","year":"2007","unstructured":"Moore, T. H. et al. Cannabis use and risk of psychotic or affective mental health outcomes: A systematic review. Lancet 370, 319\u2013328. https:\/\/doi.org\/10.1016\/S0140-6736(07)61162-3 (2007).","journal-title":"Lancet"},{"key":"95016_CR42","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.1038\/sj.npp.1300496","volume":"29","author":"DC D'Souza","year":"2004","unstructured":"D\u2019Souza, D. C. et al. The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: Implications for psychosis. Neuropsychopharmacology 29, 1558\u20131572. https:\/\/doi.org\/10.1038\/sj.npp.1300496 (2004).","journal-title":"Neuropsychopharmacology"},{"key":"95016_CR43","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1192\/bjp.187.6.510","volume":"187","author":"M Arendt","year":"2005","unstructured":"Arendt, M., Rosenberg, R., Foldager, L., Perto, G. & Munk-J\u00f8rgensen, P. Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: Follow-up study of 535 incident cases. Br. J. Psychiatry. 187, 510\u2013515. https:\/\/doi.org\/10.1192\/bjp.187.6.510 (2005).","journal-title":"Br. J. Psychiatry."},{"key":"95016_CR44","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1016\/j.biopsych.2016.01.011","volume":"79","author":"M Sherif","year":"2016","unstructured":"Sherif, M., Radhakrishnan, R., D\u2019Souza, D. & Ranganathan, M. Human laboratory studies on cannabinoids and psychosis. Biol. Psychiatry. 79, 526\u2013538. https:\/\/doi.org\/10.1016\/j.biopsych.2016.01.011 (2016).","journal-title":"Biol. Psychiatry."},{"key":"95016_CR45","doi-asserted-by":"publisher","first-page":"2748","DOI":"10.1038\/sj.npp.1301197","volume":"31","author":"C Henquet","year":"2006","unstructured":"Henquet, C. et al. An experimental study of catechol-o-methyltransferase Val 158 Met moderation of \u0394-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology 31, 2748\u20132757. https:\/\/doi.org\/10.1038\/sj.npp.1301197 (2006).","journal-title":"Neuropsychopharmacology"},{"key":"95016_CR46","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1016\/j.biopsych.2005.01.026","volume":"57","author":"A Caspi","year":"2005","unstructured":"Caspi, A. et al. Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: Longitudinal evidence of a gene X environment interaction. Biol. Psychiatry 57, 1117\u20131127. https:\/\/doi.org\/10.1016\/j.biopsych.2005.01.026 (2005).","journal-title":"Biol. Psychiatry"},{"key":"95016_CR47","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1038\/mp.2011.187","volume":"17","author":"S Bhattacharyya","year":"2012","unstructured":"Bhattacharyya, S. et al. Preliminary report of biological basis of sensitivity to the effects of cannabis on psychosis: AKT1 and DAT1 genotype modulates the effects of \u03b4-9-tetrahydrocannabinol on midbrain and striatal function. Mol. Psychiatry 17, 1152\u20131155. https:\/\/doi.org\/10.1038\/mp.2011.187 (2012).","journal-title":"Mol. Psychiatry"},{"key":"95016_CR48","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.brainres.2013.11.002","volume":"1543","author":"AM Stewart","year":"2014","unstructured":"Stewart, A. M. & Kalueff, A. V. The behavioral effects of acute \u03949-tetrahydrocannabinol and heroin (diacetylmorphine) exposure in adult zebrafish. Brain Res. 1543, 109\u2013119. https:\/\/doi.org\/10.1016\/j.brainres.2013.11.002 (2014).","journal-title":"Brain Res."},{"key":"95016_CR49","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1089\/zeb.2012.0785","volume":"10","author":"MT Akhtar","year":"2013","unstructured":"Akhtar, M. T. et al. Developmental effects of cannabinoids on zebrafish larvae. Zebrafish 10, 283\u2013293. https:\/\/doi.org\/10.1089\/zeb.2012.0785 (2013).","journal-title":"Zebrafish"},{"key":"95016_CR50","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/j.ntt.2004.06.009","volume":"26","author":"HA Swain","year":"2004","unstructured":"Swain, H. A., Sigstad, C. & Scalzo, F. M. Effects of dizocilpine (MK-801) on circling behavior, swimming activity, and place preference in zebrafish (Danio rerio). Neurotoxicol. Teratol. 26, 725\u2013729. https:\/\/doi.org\/10.1016\/j.ntt.2004.06.009 (2004).","journal-title":"Neurotoxicol. Teratol."},{"key":"95016_CR51","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.bbr.2015.12.023","volume":"301","author":"M Kruk-Slomka","year":"2016","unstructured":"Kruk-Slomka, M. & Biala, G. CB1 receptors in the formation of the different phases of memory-related processes in the inhibitory avoidance test in mice. Behav. Brain Res. 301, 84\u201395. https:\/\/doi.org\/10.1016\/j.bbr.2015.12.023 (2016).","journal-title":"Behav. Brain Res."},{"key":"95016_CR52","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.pbb.2013.04.011","volume":"109","author":"PJ McLaughlin","year":"2013","unstructured":"McLaughlin, P. J. et al. Behavioral effects of the novel potent cannabinoid CB1 agonist AM 4054. Pharmacol. Biochem. Behav. 109, 16\u201322. https:\/\/doi.org\/10.1016\/j.pbb.2013.04.011 (2013).","journal-title":"Pharmacol. Biochem. Behav."},{"key":"95016_CR53","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/1756-6606-6-42","volume":"6","author":"A Vicente-S\u00e1nchez","year":"2013","unstructured":"Vicente-S\u00e1nchez, A., S\u00e1nchez-Bl\u00e1zquez, P., Rodr\u00edguez-Mu\u00f1oz, M. & Garz\u00f3n, J. HINT1 protein cooperates with cannabinoid 1 receptor to negatively regulate glutamate NMDA receptor activity. Mol. Brain 6, 42. https:\/\/doi.org\/10.1186\/1756-6606-6-42 (2013).","journal-title":"Mol. Brain"},{"key":"95016_CR54","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1016\/j.neuroscience.2010.06.011","volume":"169","author":"SM Eggan","year":"2010","unstructured":"Eggan, S. M., Melchitzky, D. S., Sesack, S. R., Fish, K. N. & Lewis, D. A. Relationship of cannabinoid CB1 receptor and cholecystokinin immunoreactivity in monkey dorsolateral prefrontal cortex. Neuroscience 169, 1651\u20131661. https:\/\/doi.org\/10.1016\/j.neuroscience.2010.06.011 (2010).","journal-title":"Neuroscience"},{"key":"95016_CR55","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.brainres.2010.04.029","volume":"1342","author":"Q Li","year":"2010","unstructured":"Li, Q., Yan, H., Wilson, W. A. & Swartzwelder, H. S. Modulation of NMDA and AMPA-mediated synaptic transmission by CB1 receptors in frontal cortical pyramidal cells. Brain Res. 1342, 127\u2013137. https:\/\/doi.org\/10.1016\/j.brainres.2010.04.029 (2010).","journal-title":"Brain Res."},{"key":"95016_CR56","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1152\/jn.2002.88.1.534","volume":"88","author":"J Trettel","year":"2002","unstructured":"Trettel, J. & Levine, E. S. Cannabinoids depress inhibitory synaptic inputs received by layer 2\/3 pyramidal neurons of the neocortex. J. Neurophysiol. 88, 534\u2013539. https:\/\/doi.org\/10.1152\/jn.2002.88.1.534 (2002).","journal-title":"J. Neurophysiol."},{"key":"95016_CR57","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/npp.2009.111","volume":"35","author":"DP Eisenberg","year":"2010","unstructured":"Eisenberg, D. P. & Berman, K. F. Executive function, neural circuitry, and genetic mechanisms in schizophrenia. Neuropsychopharmacol. 35, 258. https:\/\/doi.org\/10.1038\/npp.2009.111 (2010).","journal-title":"Neuropsychopharmacol."},{"key":"95016_CR58","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/978-3-319-45541-9_4","volume":"103","author":"P Morales","year":"2017","unstructured":"Morales, P., Hurst, D. P. & Reggio, P. H. Molecular targets of the phytocannabinoids: A complex picture. Prog. Chem. Org. Nat. Prod. 103, 103\u2013131. https:\/\/doi.org\/10.1007\/978-3-319-45541-9_4 (2017).","journal-title":"Prog. Chem. Org. Nat. Prod."},{"key":"95016_CR59","doi-asserted-by":"publisher","unstructured":"Rodriguez-Martin, I., Herrero-Turrion, M.J., Marron Fdez de Velasco, E., Gonzalez-Sarmiento, R., & Rodriguez R.E. Characterization of two duplicate zebrafish Cb2-like cannabinoid receptors. Gene. 389, 36\u201344. https:\/\/doi.org\/10.1016\/j.gene.2006.09.016 (2007).","DOI":"10.1016\/j.gene.2006.09.016"},{"key":"95016_CR60","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1016\/j.biopsych.2009.09.024","volume":"67","author":"H Ishiguro","year":"2010","unstructured":"Ishiguro, H. et al. Brain cannabinoid CB2 receptor in schizophrenia. Biol. Psychiatry. 67, 974\u2013982. https:\/\/doi.org\/10.1016\/j.biopsych.2009.09.024 (2010).","journal-title":"Biol. Psychiatry."},{"key":"95016_CR61","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1001\/archpsyc.63.12.1325","volume":"63","author":"NR Swerdlow","year":"2006","unstructured":"Swerdlow, N. R. et al. Startle gating deficits in a large cohort of patients with schizophrenia: Relationship to medications, symptoms, neurocognition, and level of function. Arch. Gen. Psychiatry. 63, 1325\u20131335. https:\/\/doi.org\/10.1001\/archpsyc.63.12.1325 (2006).","journal-title":"Arch. Gen. Psychiatry."},{"key":"95016_CR62","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1038\/npp.2011.34","volume":"36","author":"A Ortega-Alvaro","year":"2011","unstructured":"Ortega-Alvaro, A., Aracil-Fern\u00e1ndez, A., Garc\u00eda-Guti\u00e9rrez, M. S., Navarrete, F. & Manzanares, J. Deletion of CB 2 cannabinoid receptor induces schizophrenia-related behaviors in mice. Neuropsychopharmacol. 36, 1489\u20131504. https:\/\/doi.org\/10.1038\/npp.2011.34 (2011).","journal-title":"Neuropsychopharmacol."},{"key":"95016_CR63","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.bbr.2011.05.034","volume":"224","author":"KJ Seibt","year":"2011","unstructured":"Seibt, K. J. et al. Antipsychotic drugs reverse MK-801-induced cognitive and social interaction deficits in zebrafish (Danio rerio). Behav. Brain Res. 224, 135\u2013139. https:\/\/doi.org\/10.1016\/j.bbr.2011.05.034 (2011).","journal-title":"Behav. Brain Res."},{"key":"95016_CR64","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1097\/FBP.0000000000000178","volume":"26","author":"S Deiana","year":"2015","unstructured":"Deiana, S. et al. MK-801-induced deficits in social recognition in rats: reversal by aripiprazole, but not olanzapine, risperidone, or cannabidiol. Behav. Pharmacol. 26, 748\u2013765. https:\/\/doi.org\/10.1097\/FBP.0000000000000178 (2015).","journal-title":"Behav. Pharmacol."},{"key":"95016_CR65","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.pharmthera.2018.06.012","volume":"192","author":"S Aringhieri","year":"2018","unstructured":"Aringhieri, S. et al. Molecular targets of atypical antipsychotics: From mechanism of action to clinical differences. Pharmacol. Ther. 192, 20\u201341. https:\/\/doi.org\/10.1016\/j.pharmthera.2018.06.012 (2018).","journal-title":"Pharmacol. Ther."},{"key":"95016_CR66","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1111\/j.1476-5381.2011.01638.x","volume":"165","author":"S Tanahashi","year":"2012","unstructured":"Tanahashi, S., Yamamura, S., Nakagawa, M., Motomura, E. & Okada, M. Clozapine, but not haloperidol, enhances glial d-serine and L-glutamate release in rat frontal cortex and primary cultured astrocytes. Br. J. Pharmacol. 165, 1543\u20131555. https:\/\/doi.org\/10.1111\/j.1476-5381.2011.01638.x (2012).","journal-title":"Br. J. Pharmacol."},{"key":"95016_CR67","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.bbr.2019.03.044","volume":"367","author":"KN Zabegalov","year":"2019","unstructured":"Zabegalov, K. N. et al. Abnormal repetitive behaviors in zebrafish and their relevance to human brain disorders. Behav. Brain Res. 367, 101\u2013110. https:\/\/doi.org\/10.1016\/j.bbr.2019.03.044 (2019).","journal-title":"Behav. Brain Res."},{"issue":"113\u2013119","key":"95016_CR68","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1111\/j.1601-183X.2005.00186.x","volume":"5","author":"TD Gould","year":"2006","unstructured":"Gould, T. D. & Gottesman, I. I. Psychiatric endophenotypes and the development of valid animal models. Genes Brain Behav. 5(113\u2013119), 2006. https:\/\/doi.org\/10.1111\/j.1601-183X.2005.00186.x (2006).","journal-title":"Genes Brain Behav."},{"key":"95016_CR69","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1534\/genetics.105.045658","volume":"171","author":"TL Petryshen","year":"2005","unstructured":"Petryshen, T. L. et al. Two quantitative trait loci for prepulse inhibition of startle identified on mouse chromosome 16 using chromosome substitution strains. Genetics 171, 1895\u20131904. https:\/\/doi.org\/10.1534\/genetics.105.045658 (2005).","journal-title":"Genetics"},{"key":"95016_CR70","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1038\/ng.3894","volume":"49","author":"S Steinberg","year":"2017","unstructured":"Steinberg, S. et al. Truncating mutations in RBM12 are associated with psychosis. Nat. Genet. 49, 1251\u20131254. https:\/\/doi.org\/10.1038\/ng.3894 (2017).","journal-title":"Nat. Genet."},{"key":"95016_CR71","doi-asserted-by":"publisher","unstructured":"Percie du Sert, N. et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol 18, e3000410. https:\/\/doi.org\/10.1371\/journal.pbio.3000410 (2020).","DOI":"10.1371\/journal.pbio.3000410"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-95016-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-95016-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-95016-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T12:08:39Z","timestamp":1670069319000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-95016-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,3]]},"references-count":71,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["95016"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-95016-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,3]]},"assertion":[{"value":"11 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15693"}}