Hostname: page-component-586b7cd67f-vdxz6 Total loading time: 0 Render date: 2024-11-26T12:11:56.437Z Has data issue: false hasContentIssue false
  • English
  • Français

Exploring the impact of adolescent exposure to cannabinoids and nicotine on psychiatric risk: insights from translational animal models

Published online by Cambridge University Press:  05 December 2019

Steven R. Laviolette Open the ORCID record for Steven R. Laviolette [Opens in a new window]
Steven R. Laviolette*
Affiliation:
Addiction Research Group, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, CanadaN6A3K7 Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, CanadaN6A3K7 Department of Psychiatry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, CanadaN6A3K7
*
Author for correspondence: Steven R. Laviolette, E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Adolescence represents a highly sensitive period of mammalian neurodevelopment wherein critical synaptic and structural changes are taking place in brain regions involved in cognition, self-regulation and emotional processing. Importantly, neural circuits such as the mesocorticolimbic pathway, comprising the prefrontal cortex, sub-cortical mesolimbic dopamine system and their associated input/output centres, are particularly vulnerable to drug-related insults. Human adolescence represents a life-period wherein many individuals first begin to experiment with recreational drugs such as nicotine and cannabis, both of which are known to profoundly modulate neurochemical signalling within the mesocorticolimbic pathway and to influence both long-term and acute neuropsychiatric symptoms. While a vast body of epidemiological clinical research has highlighted the effects of adolescent exposure to drugs such as nicotine and cannabis on the developing adolescent brain, many of these studies are limited to correlative analyses and rely on retrospective self-reports from subjects, making causal interpretations difficult to discern. The use of pre-clinical animal studies can avoid these issues by allowing for precise temporal and dose-related experimental control over drug exposure during adolescence. In addition, such animal-based research has the added advantage of allowing for in-depth molecular, pharmacological, genetic and neuronal analyses of how recreational drug exposure may set up the brain for neuropsychiatric risk. This review will explore some of the advantages and disadvantages of these models, with a focus on the common, divergent and synergistic effects of adolescent nicotine and cannabis exposure on neuropsychiatric risk.

Keywords

Anxietycannabisdelta-9-tetrahydrocannabinoldopaminemoodneurodevelopmentnicotineschizophrenia
Type
Invited Review
Information
Psychological Medicine , Volume 51 , Issue 6 , April 2021 , pp. 940 - 947
Check for updates
Copyright
Copyright © Cambridge University Press 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Agrawal, A., Budney, A. J., & Lynskey, M. T. (2012). The co-occurring use and misuse of cannabis and tobacco: a review. Addiction, 107, 1221–1233.CrossRefGoogle ScholarPubMed
Agrawal, A., Scherrer, J. F., Lynskey, M. T., Sartor, C. E., Grant, J. D., Haber, J. R. et al. (2011). Patterns of use, sequence of onsets and correlates of tobacco and cannabis. Addictive Behaviours, 36, 1141–1147.CrossRefGoogle ScholarPubMed
Andréasson, S., Allebeck, P., Engström, A., & Rydberg, U. (1987). Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet, 2, 1483–1486.CrossRefGoogle ScholarPubMed
Arseneault, L., Cannon, M., Poulton, R., Murray, R., Caspi, A., & Moffitt, T. E. (2002). Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. British Medical Journal, 325, 1212–1213. doi: 10.1136/bmj.325.7374.1212.CrossRefGoogle ScholarPubMed
Arseneault, L., Cannon, M., Witton, J., & Murray, R. M. (2004). Causal association between cannabis and psychosis: examination of the evidence. British Journal of Psychiatry, 184, 110–117.CrossRefGoogle Scholar
Audrain-McGovern, J., Stone, M. D., Barrington-Trimis, J., Unger, J. B., & Leventhal, A. M. (2018). Adolescent e-cigarette, hookah, and conventional cigarette use and subsequent marijuana use. Pediatrics, 142, e20173616.CrossRefGoogle ScholarPubMed
Bhavsar, V., Jauhar, S., Murray, R. M., Hotopf, M., Hatch, S. L., McNeill, A., … MacCabe, J. H. (2018). Tobacco smoking is associated with psychotic experiences in the general population of South London. Psychological Medicine, 48, 123–131.CrossRefGoogle ScholarPubMed
Bloomfield, M. A. P., Ashok, A. H., Volkow, N. D., & Howes, O. D. (2016). The effects of Δ9-tetrahydrocannabinol on the dopamine system. Nature, 539, 369–377.CrossRefGoogle ScholarPubMed
Breslau, N., Kilbey, M. M., & Andreski, P. (1993). Nicotine dependence and major depression. New evidence from a prospective investigation. Archives of General Psychiatry, 50, 31–35.CrossRefGoogle ScholarPubMed
Cannon, D. M., Klaver, J. M., Peck, S. A., Rallis-Voak, D., Erickson, K., & Drevets, W. C. (2009). Dopamine type-1 receptor binding in major depressive disorder assessed using positron emission tomography and [11C]NNC-112. Neuropsychopharmacology, 34, 1277–1287.CrossRefGoogle Scholar
Cass, D. K., Flores-Barrera, E., Thomases, D. R., Vital, W. F., Caballero, A., & Tseng, K. Y. (2014). CB1 cannabinoid receptor stimulation during adolescence impairs the maturation of GABA function in the adult rat prefrontal cortex. Molecular Psychiatry, 19, 536–543.CrossRefGoogle ScholarPubMed
Chye, Y., Lorenzetti, V., Suo, C., Batalla, A., Cousijn, J., Goudriaan, A. E., … Solowij, N. (2018). Alteration to hippocampal volume and shape confined to cannabis dependence: a multi-site study. Addiction Biology. doi: 10.1111/adb.12652, Epub ahead of print.Google ScholarPubMed
Curley, A. A., Arion, D., Volk, D. W., Asafu-Adjei, J. K., Sampson, A. R., Fish, K. N., & Lewis, D. A. (2011). Cortical deficits of glutamic acid decarboxylase 67 expression in schizophrenia: clinical, protein, and cell type-specific features. American Journal of Psychiatry, 168, 921–929.CrossRefGoogle ScholarPubMed
Colizzi, M., Iyegbe, C., Powell, J., Blasi, G., Bertolino, A., Murray, R. M., & Di Forti, M. (2015a). Interaction between DRD2 and AKT1 genetic variations on risk of psychosis in cannabis users: a case-control study. NPJ Schizophrenia, 1, 15025.CrossRefGoogle Scholar
Colizzi, M., Iyegbe, C., Powell, J., Ursini, G., Porcelli, A., Bonvino, A., … Di Forti, M. (2015b). Interaction between functional genetic variation of DRD2 and cannabis use on risk of psychosis. Schizophrenia Bulletin, 41, 1171–1182.CrossRefGoogle Scholar
Corongiu, S., Dessì, C., & Cadoni, C. (2019). Adolescence versus adulthood: differences in basal mesolimbic and nigrostriatal dopamine transmission and response to drugs of abuse. Addiction Biology. doi: 10.1111/adb.12721, Epub ahead of print.Google ScholarPubMed
Counotte, D. S., Goriounova, N. A., Li, K. W., Loos, M., van der Schors, R. C., Schetters, D., … Spijker, S. (2011). Lasting synaptic changes underlie attention deficits caused by nicotine exposure during adolescence. Nature Neuroscience, 14, 417–419.CrossRefGoogle ScholarPubMed
Counotte, D. S., Spijker, S., Van de Burgwal, L. H., Hogenboom, F., Schoffelmeer, A. N., De Vries, T. J., … Pattij, T. (2009). Long-lasting cognitive deficits resulting from adolescent nicotine exposure in rats. Neuropsychopharmacology, 34, 299–306.CrossRefGoogle ScholarPubMed
Dalack, G. W., & Meador-Woodruff, J. H. (1996). Smoking, smoking withdrawal and schizophrenia: case reports and a review of the literature. Schizophrenia Research, 22, 133–141.CrossRefGoogle Scholar
Dalton, V. S., Long, L. E., Weickert, C. S., & Zavitsanou, K. (2011). Paranoid schizophrenia is characterized by increased CB1 receptor binding in the dorsolateral prefrontal cortex. Neuropsychopharmacology, 36, 1620–1630.CrossRefGoogle ScholarPubMed
Di Forti, M., Iyegbe, C., Sallis, H., Kolliakou, A., Falcone, M. A., Paparelli, A., … Murray, R. M. (2012). Confirmation that the AKT1 (rs2494732) genotype influences the risk of psychosis in cannabis users. Biological Psychiatry, 72, 811–816.CrossRefGoogle ScholarPubMed
Dougherty, D. D., Bonab, A. A., Ottowitz, W. E., Livni, E., Alpert, N. M., Rauch, S. L., … Fischman, A. J. (2006). Decreased striatal D1 binding as measured using PET and [11C]SCH 23,390 in patients with major depression with anger attacks. Depression and Anxiety, 23, 175–177.CrossRefGoogle Scholar
Draycott, B., Loureiro, M., Ahmad, T., Tan, H., Zunder, J., & Laviolette, S. R. (2014). Cannabinoid transmission in the prefrontal cortex bi-phasically controls emotional memory formation via functional interactions with the ventral tegmental area. Journal of Neuroscience, 34, 13096–13109.CrossRefGoogle ScholarPubMed
Filbey, F. M., Gohel, S., Prashad, S., & Biswal, B. B. (2018). Differential associations of combined vs. isolated cannabis and nicotine on brain resting state networks. Brain Structure and Function, 223, 3317–3326.CrossRefGoogle ScholarPubMed
Fitoussi, A., Zunder, J., Tan, H., & Laviolette, S. R. (2018). Delta-9-tetrahydrocannabinol potentiates fear memory salience through functional modulation of mesolimbic dopaminergic activity states. European Journal of Neuroscience, 47, 1385–1400.CrossRefGoogle ScholarPubMed
Fleming, J. E., & Offord, D. R. (1990). Epidemiology of childhood depressive disorders: a critical review. Journal of the American Academy of Child and Adolescent Psychiatry, 29, 571–580.CrossRefGoogle ScholarPubMed
Fornito, A., Yung, A. R., Wood, S. J., Phillips, L. J., Nelson, B., Cotton, S., … Yücel, M. (2008). Anatomic abnormalities of the anterior cingulate cortex before psychosis onset: an MRI study of ultra-high-risk individuals. Biological Psychiatry, 64, 758–765.CrossRefGoogle ScholarPubMed
Freels, T. G., Baxter-Potter, L. N., Lugo, J. M., Glodosky, N. C., Wright, H. R., Baglot, S. L., … McLaughlin, R. J. (2019). Vaporized cannabis extracts have reinforcing properties and support conditioned drug-seeking behavior in rats. bioRxiv 791319. doi: https://doi.org/10.1101/791319.Google Scholar
Friend, L., Weed, J., Sandoval, P., Nufer, T., Ostlund, I., & Edwards, J. G. (2017). CB1-dependent long-term depression in ventral tegmental area GABA neurons: a novel target for marijuana. Journal of Neuroscience, 37, 10943–10954.CrossRefGoogle ScholarPubMed
Gobbi, G., Atkin, T., Zytynski, T., Wang, S., Askari, S., Boruff, J., … Mayo, N. (2019). Association of cannabis use in adolescence and risk of depression, anxiety, and suicidality in young adulthood: a systematic review and meta-analysis. JAMA Psychiatry. Feb 13. [Epub ahead of print].CrossRefGoogle ScholarPubMed
Goodwin, R. D., Zvolensky, M. J., Keyes, K. M., & Hasin, D. S. (2012). Mental disorders and cigarette use among adults in the United States. American Journal of Addiction, 21, 416–423.CrossRefGoogle ScholarPubMed
Grieder, T. E., George, O., Tan, H., George, S. R., Le Foll, B., Laviolette, S. R., & van der Kooy, D. (2012). Phasic D1 and tonic D2 dopamine receptor signaling double dissociate the motivational effects of acute nicotine and chronic nicotine withdrawal. Proceedings of the National Academy of Sciences, 109, 3101–3106.CrossRefGoogle ScholarPubMed
Gueye, A. B., Pryslawsky, Y., Trigo, J. M., Poulia, N., Delis, F., Antoniou, K., … Le Foll, B. (2016). The CB1 neutral antagonist AM4113 retains the therapeutic efficacy of the inverse agonist rimonabant for nicotine dependence and weight loss with better psychiatric tolerability. International Journal of Neuropsychopharmacology, 19(12).CrossRefGoogle ScholarPubMed
Guidotti, A., Auta, J., Davis, J. M., Gerevini, V. D., Dwivedi, Y., Grayson, D. R., … Costa, E. (2000). Decrease in reelin and glutamic acid decarboxylase 67 (GAD 67) expression in schizophrenia and bipolar disorder. Archives of General Psychiatry, 57, 1061–1069.CrossRefGoogle ScholarPubMed
Gurillo, P., Jauhar, S., Murray, R. M., & MacCabe, J. H. (2015). Does tobacco use cause psychosis? Systematic review and meta-analysis. The Lancet. Psychiatry, 2, 718–725.CrossRefGoogle ScholarPubMed
Hashimoto, T., Volk, D. W., Eggan, S. M., Mirnics, K., Pierri, J. N., Sun, Z., … Lewis, D. A. (2003). Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia. Journal of Neuroscience, 23, 6315–6326.CrossRefGoogle Scholar
Harvey, P. D. (2019). Smoking cannabis and acquired impairments in cognition: starting early seems like a really bad idea. American Journal of Psychiatry, 176, 90–91.CrossRefGoogle Scholar
Hughes, J. R., Hatsukami, D. K., Mitchell, J. E., & Dahlgren, L. A. (1986). Prevalence of smoking among psychiatric outpatients. American Journal of Psychiatry, 143, 993–997.Google ScholarPubMed
Huntsman, M. M., Tran, B. V., Potkin, S. G., Bunney, W. E. Jr., & Jones, E. G. (1998). Altered ratios of alternatively spliced long and short gamma-2 subunit mRNAs of the g-amino butyrate type A receptor in prefrontal cortex of schizophrenics. Proceedings of the National Academy of Sciences, 95, 15066–15071.CrossRefGoogle Scholar
Iñiguez, S. D., Warren, B. L., Parise, E. M., Alcantara, L. F., Schuh, B., Maffeo, M. L., … Bolaños-Guzmán, C. A. (2009). Nicotine exposure during adolescence induces a depression-like state in adulthood. Neuropsychopharmacology, 34, 1609–1624.CrossRefGoogle ScholarPubMed
Jernigan, C. S., Goswami, D. B., Austin, M. C., Iyo, A. H., Chandran, A., Stockmeier, C. A., & Karolewicz, B. (2011). The mTOR signaling pathway in the prefrontal cortex is compromised in major depressive disorder. Progress in Neuropsychopharmacology and Biological Psychiatry, 35, 1774–1779.CrossRefGoogle ScholarPubMed
Jobson, C. L. M., Renard, J., Szkudlarek, H., Rosen, L. G., Pereira, B., Wright, D. J., Rushlow, W. & Laviolette, S. R. (2019). Adolescent Nicotine Exposure Induces Dysregulation of Mesocorticolimbic Activity States and Depressive and Anxiety-like Prefrontal Cortical Molecular Phenotypes Persisting into Adulthood. Cereb Cortex, 29, 3140–3153.CrossRefGoogle ScholarPubMed
Johnson, J. G., Cohen, P., Pine, D. S., Klein, D. F., Kasen, S., & Brook, J. S. (2000). Association between cigarette smoking and anxiety disorders during adolescence and early adulthood. JAMA, 284, 2348–2351.CrossRefGoogle ScholarPubMed
Kiran, C., & Chaudhury, S. (2016). Prevalence of comorbid anxiety disorders in schizophrenia. Indian Psychiatry Journal, 25, 35–40.Google Scholar
Koenders, L., Machielsen, M. W., van der Meer, F. J., van Gasselt, A. C., Meijer, C. J., van den Brink, W., … de Haan, L. (2015). Brain volume in male patients with recent onset schizophrenia with and without cannabis use disorders. Journal of Psychiatry and Neuroscience, 40, 197–206.CrossRefGoogle ScholarPubMed
Kozlovsky, N., Belmaker, R. H., & Agam, G. (2001). Low GSK-3 activity in frontal cortex of schizophrenic patients. Schizophrenia Research, 52, 101–105.CrossRefGoogle ScholarPubMed
Kruse, L. C., Cao, J. K., Viray, K., Stella, N., & Clark, J. J. (2019). Voluntary oral consumption of Δ9-tetrahydrocannabinol by adolescent rats impairs reward-predictive cue behaviors in adulthood. Neuropsychopharmacology, 44, 1406–1414.CrossRefGoogle ScholarPubMed
Laviolette, S. R., & Grace, A. A. (2006). Cannabinoids potentiate emotional learning plasticity in neurons of the medial prefrontal cortex through basolateral amygdala inputs. Journal of Neuroscience, 26, 6458–6468.CrossRefGoogle ScholarPubMed
Laviolette, S. R., Lauzon, N. M., Bishop, S. F., Sun, N., & Tan, H. (2008). Dopamine signaling through D1-like versus D2-like receptors in the nucleus accumbens core versus shell differentially modulates nicotine reward sensitivity. Journal of Neuroscience, 28, 8025–8033.CrossRefGoogle ScholarPubMed
Laviolette, S. R., & van der Kooy, D. (2003). Blockade of mesolimbic dopamine transmission dramatically increases sensitivity to the rewarding effects of nicotine in the ventral tegmental area. Molecular Psychiatry, 8, 50–59.CrossRefGoogle Scholar
Lewinshohn, P. M., Hops, H., Roberts, R. E., Seeley, J. R., & Andrews, J. A. (1993). Adolescent psychopathology: I. Prevalence and incidence of depression and other DSMIII-R disorders in high school students. Journal of Abnormal Psychology, 102, 133–144.CrossRefGoogle Scholar
Maldonado-Avilés, J. G., Curley, A. A., Hashimoto, T., Morrow, A. L., Ramsey, A. J., O'Donnell, P., … Lewis, D. A. (2009). Altered markers of tonic inhibition in the dorsolateral prefrontal cortex of subjects with schizophrenia. American Journal of Psychiatry, 166, 450–459.CrossRefGoogle ScholarPubMed
Maple, K. E., Thomas, A. M., Kangiser, M. M., & Lisdahl, K. M. (2019). Anterior cingulate volume reductions in abstinent adolescent and young adult cannabis users: association with affective processing deficits. Psychiatry Research and Neuroimaging, 288, 51–59.CrossRefGoogle Scholar
Mustonen, A., Ahokas, T., Nordström, T., Murray, G. K., Mäki, P., Jääskeläinen, E., … Niemelä, S. (2018). Smokin’ hot: adolescent smoking and the risk of psychosis. Acta Psychiatrica Scandinivica, 138, 5–14.CrossRefGoogle ScholarPubMed
Moylan, S., Gustavson, K., Karevold, E., Øverland, S., Jacka, F. N., et al. (2013). The impact of smoking in adolescence on early adult anxiety symptoms and the relationship between infant vulnerability factors for anxiety and early adult anxiety symptoms: the TOPP study. PLoS ONE, 8, e63252.CrossRefGoogle Scholar
Myles, N., Newall, H. D., Curtis, J., Nielssen, O., Shiers, D., & Large, M. (2012). Tobacco use before, at, and after first-episode psychosis: a systematic meta-analysis. Journal of Clinical Psychiatry, 73, 468–475.CrossRefGoogle ScholarPubMed
Orr, C., Spechler, P., Cao, Z., Albaugh, M., Chaarani, B., Mackey, S., … Garavan, H. (2019). Grey matter volume differences associated with extremely low levels of cannabis use in adolescence. Journal of Neuroscience, 39, 1817–1827.CrossRefGoogle ScholarPubMed
Osuch, E. A., Manning, K., Hegele, R. A., Théberge, J., Neufeld, R., Mitchell, D., … Gardner, R. C. (2016). Depression, marijuana use and early-onset marijuana use conferred unique effects on neural connectivity and cognition. Acta Psychiatrica Scandinivica, 134, 399–409.CrossRefGoogle ScholarPubMed
Peters, E. N., Budney, A. J., & Carroll, K. M. (2012). Clinical correlates of co-occurring cannabis and tobacco use: a systematic review. Addiction, 107, 1404–1417.CrossRefGoogle ScholarPubMed
Renard, J., Rushlow, W. J., & Laviolette, S. R. (2016). What Can Rats Tell Us about Adolescent Cannabis Exposure? Insights from Preclinical Research. Canadian Journal of Psychiatry, 61, 328–34.CrossRefGoogle ScholarPubMed
Renard, J., Rushlow, W. J., & Laviolette, S. R. (2018). Effects of adolescent THC exposure on the prefrontal GABAergic system: implications for schizophrenia-related psychopathology. Frontiers in Psychiatry, 9, 281.CrossRefGoogle ScholarPubMed
Renard, J., Szkudlarek, H. J., Kramar, C. P., Jobson, C. E. L., Moura, K., Rushlow, W. J., & Laviolette, S. R. (2017). Adolescent THC Adolescent THC Exposure Causes Enduring Prefrontal Cortical Disruption of GABAergic Inhibition and Dysregulation of Sub-Cortical Dopamine Function. Scientific Reports, 7, 11420.CrossRefGoogle ScholarPubMed
Saddleson, M. L., Kozlowski, L. T., Giovino, G. A., et al. (2016). Assessing 30-day quantity-frequency of U.S. Adolescent cigarette smoking as a predictor of adult smoking 14 years later. Drug and Alcohol Dependence, 162, 92–98.CrossRefGoogle ScholarPubMed
Samsom, J. N., & Wong, A. H. (2015). Schizophrenia and depression co-morbidity: what we have learned from animal models. Frontiers in Psychiatry, 6, 13.CrossRefGoogle ScholarPubMed
Stefanis, N. C., Delespaul, P., Henquet, C., Bakoula, C., Stefanis, C. N., & Van Os, J. (2004). Early adolescent cannabis exposure and positive and negative dimensions of psychosis. Addiction, 99, 1333–1341.CrossRefGoogle ScholarPubMed
Sun, N., & Laviolette, S. R. (2014). Dopamine receptor blockade modulates the rewarding and aversive properties of nicotine via dissociable neuronal activity patterns in the nucleus accumbens. Neuropsychopharmacology, 39, 2799–2815.CrossRefGoogle ScholarPubMed
Sutton, L. P., & Rushlow, W. J. (2012). The dopamine D2 receptor regulates Akt and GSK-3 via Dvl-3. International Journal of Neuropsychopharmacology, 15, 965–979.CrossRefGoogle ScholarPubMed
Tan, H., Bishop, S. F., Lauzon, N. M., Sun, N., & Laviolette, S. R. (2009). Chronic nicotine exposure switches the functional role of mesolimbic dopamine transmission in the processing of nicotine's rewarding and aversive effects. Neuropharmacology, 56, 741–751.CrossRefGoogle ScholarPubMed
Tucker, J. S., Pedersen, E. R., Seelam, R., Dunbar, M. S., Shih, R. A., & D'Amico, E. J. (2019). Types of cannabis and tobacco/nicotine co-use and associated outcomes in young adulthood. Psychology of Addictive Behaviour. doi: 10.1037/adb0000464, Epub ahead of print.CrossRefGoogle ScholarPubMed
Urban, N. B., Slifstein, M., Thompson, J. L., Xu, X., Girgis, R. R., Raheja, S., … Abi-Dargham, A. (2012). Dopamine release in chronic cannabis users: a [11c]raclopride positron emission tomography study. Biological Psychiatry, 71, 677–683.CrossRefGoogle Scholar
van de Giessen, E., Weinstein, J. J., Cassidy, C. M., Haney, H., Dong, Z., Ghazzaoui, R., … Abi-Dargham, A. (2017). Deficits in striatal dopamine release in cannabis dependence. Molecular Psychiatry, 22, 68–75.CrossRefGoogle ScholarPubMed
Velakoulis, D, Wood, S. J., Wong, M. T., McGorry, P. D., Yung, A., Phillips, L., … Pantelis, C. (2006). Hippocampal and amygdala volumes according to psychosis stage and diagnosis: a magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra-high-risk individuals. Archives of General Psychiatry, 63, 139–149.CrossRefGoogle ScholarPubMed
Volk, D. W., Austin, M. C., Pierri, J. N., Sampson, A. R., & Lewis, D. A. (2000). Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical gamma-aminobutyric acid neurons in subjects with schizophrenia. Archives of General Psychiatry, 57, 237–245.CrossRefGoogle Scholar
Wetherill, R. R., Fang, Z., Jagannathan, K., Childress, A. R., Rao, H., & Franklin, T. R. (2015a). Cannabis, cigarettes, and their co-occurring use: disentangling differences in default mode network functional connectivity. Drug and Alcohol Dependence, 153, 116–123.CrossRefGoogle Scholar
Wetherill, R. R., Jagannathan, K., Hager, N., Childress, A. R., Rao, H., & Franklin, T. R. (2015b). Cannabis, cigarettes, and their co-occurring use: disentangling differences in gray matter volume. International Journal of Neuropsychopharmacology, 18(10).CrossRefGoogle Scholar
Wood, S. J., Kennedy, D., Phillips, L. J., Seal, M. L., Yücel, M., Nelson, B., … Pantelis, C. (2010). Hippocampal pathology in individuals at ultra-high risk for psychosis: a multi-modal magnetic resonance study. Neuroimage, 52, 62–68.CrossRefGoogle ScholarPubMed
Yücel, M., Solowij, N., Respondek, C., Whittle, S., Fornito, A., Pantelis, C., & Lubman, D. I. (2008). Regional brain abnormalities associated with long-term heavy cannabis use. Archives of General Psychiatry, 65, 694–701.CrossRefGoogle ScholarPubMed
Zavitsanou, K., Garrick, T., & Huang, X. F. (2004). Selective antagonist [3H]SR141716A binding to cannabinoid CB1 receptors is increased in the anterior cingulate cortex in schizophrenia. Progress in Neuropsychopharmacology and Biological Psychiatry, 28, 355–360.CrossRefGoogle Scholar