Skip to main content Accessibility help
×
Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-19T12:38:20.846Z Has data issue: false hasContentIssue false

Chapter 19 - The Endocannabinoid System in Schizophrenia

from Part VI - Cannabinoids and Schizophrenia: Aetiopathology and Treatment Implications

Published online by Cambridge University Press:  12 May 2023

Deepak Cyril D'Souza
Affiliation:
Staff Psychiatrist, VA Connecticut Healthcare System; Professor of Psychiatry, Yale University School of Medicine
David Castle
Affiliation:
University of Tasmania, Australia
Sir Robin Murray
Affiliation:
Honorary Consultant Psychiatrist, Psychosis Service at the South London and Maudsley NHS Trust; Professor of Psychiatric Research at the Institute of Psychiatry
Get access

Summary

An excess or deficit of specific neurotransmitters or receptors has been the dominant theme for explaining the pathology of major mental illness for many decades. The best known example is that hyperdopaminergia is the cause of psychosis. Similar proposals have been made for glutamate and the endocannabinoids, based on the ability of drugs acting on these systems to elicit psychotic mental states. In addition, cannabis is also a risk factor for the development of schizophrenia. On this background, researchers have measured several endocannabinoid components in people with psychotic illness compared to controls. These components include synthesizing and degrading enzymes for anandamide and 2-arochodonylglycerol, the amount of endocannabinoid transmitter in the bloodstream or CSF and the availability of cannabinoid receptors. There is inconsistency in the field as a whole, but a number of intriguing findings have emerged, particularly reports of increased anandamide level in psychosis. In this chapter, the major studies are reviewed and collated.

Type
Chapter
Information
Marijuana and Madness , pp. 189 - 199
Publisher: Cambridge University Press
Print publication year: 2023

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

Bailey, C. H., Giustetto, M., Huang, Y. Y., et al. (2000). Is heterosynaptic modulation essential for stabilizing Hebbian plasticity and memory? Nat Rev Neurosci, 1, 1120.Google Scholar
Borgan, F., Laurikainen, H., Veronese, M., et al. (2019). In vivo availability of cannabinoid 1 receptor levels in patients with first-episode psychosis. JAMA Psychiatry, 76, 10741084.CrossRefGoogle ScholarPubMed
Buzsáki, G., and Draguhn, A. (2004). Neuronal oscillations in cortical Networks. Science, 304, 19261929.Google Scholar
Carlsson, A. (2001). A half-century of neurotransmitter research: Impact on neurology and psychiatry. Nobel lecture. Biosci Rep, 21, 691710.Google Scholar
Ceccarini, J., De Hert, M., Van Winkel, R., et al. (2013). Increased ventral striatal CB1 receptor binding is related to negative symptoms in drug-free patients with schizophrenia. Neuroimage, 79, 304312.CrossRefGoogle ScholarPubMed
Ceccarini, J., Kuepper, R., Kemels, D., et al. (2015). [18F]MK-9470 PET measurement of cannabinoid CB1 receptor availability in chronic cannabis users. Addict Biol, 20, 357367.CrossRefGoogle ScholarPubMed
Chevaleyre, V., Takahashi, K. A., and Castillo, P. E. (2006). Endocannabinoid-mediated synaptic plasticity in the CNS. Annu Rev Neurosci, 29, 3776.CrossRefGoogle ScholarPubMed
Collingridge, G. L., and Bliss, T. V. P. (1995). Memories of NMDA receptors and LTP. Trends Neurosci, 18, 5456.Google Scholar
Cortes-Briones, J., Skosnik, P. D., Mathalon, D., et al. (2015). Δ9-THC disrupts gamma (γ)-band neural oscillations in humans. Neuropsychopharmacology, 40, 21242134.CrossRefGoogle ScholarPubMed
D’Souza, D. C., Cortes-Briones, J. A., Ranganathan, M., et al. (2016). Rapid changes in CB1 receptor availability in cannabis dependent males after abstinence from cannabis. Biol Psychiatry Cogn Neurosci Neuroimaging, 1, 6067.Google Scholar
D’Souza, D. C., Perry, E., MacDougall, L., et al. (2004). The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: Implications for psychosis. Neuropsychopharmacology, 29, 15581572.Google Scholar
Dalton, V. S., Long, L. E., Weickert, C. S., et al. (2011). Paranoid schizophrenia is characterized by increased CB1 receptor binding in the dorsolateral prefrontal cortex. Neuropsychopharmacology, 36, 16201630.Google Scholar
De Marchi, N., De Petrocellis, L., Orlando, P., et al. (2003). Endocannabinoid signalling in the blood of patients with schizophrenia. Lipids Health Dis, 2, 5.Google Scholar
Dean, B., Sundram, S., Bradbury, R., et al. (2001). Studies on [3H]CP-55940 binding in the human central nervous system: regional specific changes in density of cannabinoid-1 receptors associated with schizophrenia and cannabis use. Neuroscience, 103, 915.CrossRefGoogle ScholarPubMed
DeFelipe, J. (2006). Brain plasticity and mental processes: Cajal again. Nat Rev Neurosci, 7, 811817.CrossRefGoogle Scholar
Deng, C., Han, M., and Huang, X.-F. (2007). No changes in densities of cannabinoid receptors in the superior temporal gyrus in schizophrenia. Neurosci Bull, 23, 341347.CrossRefGoogle ScholarPubMed
Desfossés, J., Stip, E., Bentaleb, L. A., et al. (2012). Plasma endocannabinoid alterations in individuals with substance use disorder are dependent on the ‘mirror effect’ of schizophrenia. Front Psychiatry, 3, 85.CrossRefGoogle ScholarPubMed
Eggan, S. M., Hashimoto, T., and Lewis, D. A. (2008). Reduced cortical cannabinoid 1 receptor messenger RNA and protein expression in schizophrenia. Arch Gen Psychiatry, 65, 772784.Google Scholar
Eggan, S. M., Stoyak, S. R., Verrico, C. D., et al. (2010). Cannabinoid CB1 receptor immunoreactivity in the prefrontal cortex: Comparison of schizophrenia and major depressive disorder. Neuropsychopharmacology, 35, 20602071.Google Scholar
Engel, A. K., and Singer, W. (2001). Temporal binding and the neural correlates of sensory awareness. Trends Cogn Sci, 5, 1625.Google Scholar
Giuffrida, A., Leweke, F. M., Gerth, C. W., et al. (2004). Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology, 29, 21082114.Google Scholar
Hillard, C. J. (2018). Circulating endocannabinoids: From whence do they come and where are they going? Neuropsychopharmacology, 43, 155172.Google Scholar
Hirvonen, J., Goodwin, R. S., Li, C.-T., et al. (2012). Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers. Mol Psychiatry, 17, 642649.CrossRefGoogle ScholarPubMed
Ibarra-Lecue, I., Pilar-Cuéllar, F., Muguruza, C., et al. (2018). The endocannabinoid system in mental disorders: Evidence from human brain studies. Biochem Pharmacol, 157, 97107.Google Scholar
Jenko, K. J., Hirvonen, J., Henter, I. D., et al. (2012). Binding of a tritiated inverse agonist to cannabinoid CB1 receptors is increased in patients with schizophrenia. Schizophr Res, 141, 185188.Google Scholar
Kandel, E. R. (1998). A new intellectual framework for psychiatry. Am J Psychiatry, 155, 457469.CrossRefGoogle ScholarPubMed
Katona, I., and Freund, T. F. (2012). Multiple functions of endocannabinoid signaling in the brain. Annu Rev Neurosci, 35, 529558.Google Scholar
Katz, B., and Miledi, R. (1970). Membrane noise produced by acetylcholine. Nature, 226, 962963.Google Scholar
Koethe, D., Giuffrida, A., Schreiber, D., et al. (2009). Anandamide elevation in cerebrospinal fluid in initial prodromal states of psychosis. Br J Psychiatry, 194, 371372.Google Scholar
Koethe, D., Llenos, I. C., Dulay, J. R., et al. (2007). Expression of CB1 cannabinoid receptor in the anterior cingulate cortex in schizophrenia, bipolar disorder, and major depression. J Neural Transm (Vienna), 114, 10551063.Google Scholar
Koethe, D., Pahlisch, F., Hellmich, M., et al. (2019). Familial abnormalities of endocannabinoid signaling in schizophrenia. World J Biol Psychiatry, 20, 117125.Google Scholar
Kreitzer, A. C., and Malenka, R. C. (2007). Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson’s disease models. Nature, 445, 643647.Google Scholar
Kucewicz, M. T., Tricklebank, M. D., Bogacz, R., et al. (2011). Dysfunctional prefrontal cortical network activity and interactions following cannabinoid receptor activation. J Neurosci, 31, 1556015568.CrossRefGoogle ScholarPubMed
Leweke, F. M., Giuffrida, A., Koethe, D., et al. (2007). Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: Impact of cannabis use. Schizophr Res, 94, 2936.Google Scholar
Leweke, F. M., Giuffrida, A., Wurster, U., et al. (1999). Elevated endogenous cannabinoids in schizophrenia. NeuroReport, 10, 16651669.Google Scholar
Lewis, D. A., Hashimoto, T., and Volk, D. W. (2005). Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci, 6, 312324.Google Scholar
Lisman, J. (2017). Glutamatergic synapses are structurally and biochemically complex because of multiple plasticity processes: Long-term potentiation, long-term depression, short-term potentiation and scaling. Phil Trans R Soc Lond B Biol Sci, 372, 20160260.CrossRefGoogle ScholarPubMed
Mihov, Y. (2016). Positron emission tomography studies on cannabinoid receptor type 1 in schizophrenia. Biol Psychiatry, 79, e97e99.Google Scholar
Minichino, A., Senior, M., Brondino, N., et al. (2019). Measuring disturbance of the endocannabinoid system in psychosis: A systematic review and meta-analysis. JAMA Psychiatry, 76, 914923.Google Scholar
Morrison, P. D., Nottage, J., Stone, J. M., et al. (2011). Disruption of frontal θ coherence by Δ9-tetrahydrocannabinol is associated with positive psychotic symptoms. Neuropsychopharmacology, 36, 827836.Google Scholar
Morrison, P. D., Taylor, D., and McGuire, P. (2019). The Maudsley Guidelines on Advanced Prescribing in Psychosis. Hoboken, NJ: Wiley.Google Scholar
Muguruza, C., Lehtonen, M., Aaltonen, N., et al. (2013). Quantification of endocannabinoids in postmortem brain of schizophrenic subjects. Schizophr Res, 148, 145150.Google Scholar
Newell, K. A., Deng, C., and Huang, X.-F. (2006). Increased cannabinoid receptor density in the posterior cingulate cortex in schizophrenia. Exp Brain Res, 172, 556560.CrossRefGoogle ScholarPubMed
Nottage, J. F., Stone, J., Murray, R. M., et al. (2015). Delta-9-tetrahydrocannabinol, neural oscillations above 20 Hz and induced acute psychosis. Psychopharmacology (Berl), 232, 519528.CrossRefGoogle ScholarPubMed
Pittman-Polletta, B. R., Kocsis, B., Vijayan, S., et al. (2015). Brain rhythms connect impaired inhibition to altered cognition in schizophrenia. Biol Psychiatry, 77, 10201030.Google Scholar
Potvin, S., Kouassi, E., Lipp, O., et al. (2008). Endogenous cannabinoids in patients with schizophrenia and substance use disorder during quetiapine therapy. J Psychopharmacol, 22, 262269.Google Scholar
Potvin, S., Mahrouche, L., Assaf, R., et al. (2020). Peripheral endogenous cannabinoid levels are increased in schizophrenia patients evaluated in a psychiatric emergency setting. Front Psychiatry, 11, 628.Google Scholar
Ranganathan, M., Cortes-Briones, J., Radhakrishnan, R., et al. (2016). Reduced brain cannabinoid receptor availability in schizophrenia. Biol Psychiatry, 79, 9971005.Google Scholar
Robbe, D., and Buzsáki, G. (2009). Alteration of theta timescale dynamics of hippocampal place cells by a cannabinoid is associated with memory impairment. J Neurosci, 29, 1259712605.CrossRefGoogle ScholarPubMed
Robbe, D., Montgomery, S. M., Thome, A., et al. (2006). Cannabinoids reveal importance of spike timing coordination in hippocampal function. Nat Neurosci, 9, 15261533.Google Scholar
Shen, W., Flajolet, M., Greengard, P., et al. (2008). Dichotomous dopaminergic control of striatal synaptic plasticity. Science, 321, 848851.CrossRefGoogle ScholarPubMed
Sloan, M. E., Grant, C. W., Gowin, J. L., et al. (2019). Endocannabinoid signaling in psychiatric disorders: A review of positron emission tomography studies. Acta Pharmacol Sin, 40, 342350.Google Scholar
Stone, J. M., Morrison, P. D., Brugger, S., et al. (2012). Communication breakdown: Delta-9 tetrahydrocannabinol effects on pre-speech neural coherence. Mol Psychiatry, 17, 568569.Google Scholar
Uhlhaas, P. J., and Singer, W. (2015). Oscillations and neuronal dynamics in schizophrenia: The search for basic symptoms and translational opportunities. Biol Psychiatry, 77, 10011009.Google Scholar
Urigüen, L., García-Fuster, M. J., Callado, L. F., et al. (2009). Immunodensity and mRNA expression of A2A adenosine, D2 dopamine, and CB1 cannabinoid receptors in postmortem frontal cortex of subjects with schizophrenia: Effect of antipsychotic treatment. Psychopharmacology (Berl), 206, 313324.Google Scholar
Volk, D. W., Eggan, S. M., and Lewis, D. A. (2010). Alterations in metabotropic glutamate receptor 1α and regulator of G protein signaling 4 in the prefrontal cortex in schizophrenia. Am J Psychiatry, 167, 14891498.Google Scholar
Wang, D., Sun, X., Yan, J., et al. (2018). Alterations of eicosanoids and related mediators in patients with schizophrenia. J Psychiatr Res, 102, 168178.Google Scholar
Wilson, R. I., and Nicoll, R. A. (2001). Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature, 410, 588592.CrossRefGoogle ScholarPubMed
Wong, D. F., Kuwabara, H., Horti, A. G., et al. (2010). Quantification of cerebral cannabinoid receptors subtype 1 (CB1) in healthy subjects and schizophrenia by the novel PET radioligand [11C]OMAR. Neuroimage, 52, 15051513.Google Scholar
Xu, H., Perez, S., Cornil, A., et al. (2018). Dopamine-endocannabinoid interactions mediate spike-timing-dependent potentiation in the striatum. Nat Commun, 9, 4118.CrossRefGoogle ScholarPubMed
Zavitsanou, K., Garrick, T., and Huang, X. F. (2004). Selective antagonist [3H]SR141716A binding to cannabinoid CB1 receptors is increased in the anterior cingulate cortex in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry, 28, 355360.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

  • The Endocannabinoid System in Schizophrenia
  • Edited by Deepak Cyril D'Souza, Staff Psychiatrist, VA Connecticut Healthcare System; Professor of Psychiatry, Yale University School of Medicine, David Castle, University of Tasmania, Australia, Sir Robin Murray, Honorary Consultant Psychiatrist, Psychosis Service at the South London and Maudsley NHS Trust; Professor of Psychiatric Research at the Institute of Psychiatry
  • Book: Marijuana and Madness
  • Online publication: 12 May 2023
  • Chapter DOI: https://doi.org/10.1017/9781108943246.020
Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

  • The Endocannabinoid System in Schizophrenia
  • Edited by Deepak Cyril D'Souza, Staff Psychiatrist, VA Connecticut Healthcare System; Professor of Psychiatry, Yale University School of Medicine, David Castle, University of Tasmania, Australia, Sir Robin Murray, Honorary Consultant Psychiatrist, Psychosis Service at the South London and Maudsley NHS Trust; Professor of Psychiatric Research at the Institute of Psychiatry
  • Book: Marijuana and Madness
  • Online publication: 12 May 2023
  • Chapter DOI: https://doi.org/10.1017/9781108943246.020
Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

  • The Endocannabinoid System in Schizophrenia
  • Edited by Deepak Cyril D'Souza, Staff Psychiatrist, VA Connecticut Healthcare System; Professor of Psychiatry, Yale University School of Medicine, David Castle, University of Tasmania, Australia, Sir Robin Murray, Honorary Consultant Psychiatrist, Psychosis Service at the South London and Maudsley NHS Trust; Professor of Psychiatric Research at the Institute of Psychiatry
  • Book: Marijuana and Madness
  • Online publication: 12 May 2023
  • Chapter DOI: https://doi.org/10.1017/9781108943246.020
Available formats
×