The Neurobiology of Methamphetamine Induced Psychosis

Overview

Journal Front Hum Neurosci

Specialty Neurology

Date 2014 Aug 8

PMID 25100979

Citations 62

Authors

Jennifer H Hsieh

Dan J Stein

Fleur M Howells

Affiliations

Soon will be listed here.

Abstract

Chronic methamphetamine abuse commonly leads to psychosis, with positive and cognitive symptoms that are similar to those of schizophrenia. Methamphetamine induced psychosis (MAP) can persist and diagnoses of MAP often change to a diagnosis of schizophrenia over time. Studies in schizophrenia have found much evidence of cortical GABAergic dysfunction. Methamphetamine psychosis is a well studied model for schizophrenia, however there is little research on the effects of methamphetamine on cortical GABAergic function in the model, and the neurobiology of MAP is unknown. This paper reviews the effects of methamphetamine on dopaminergic pathways, with focus on its ability to increase glutamate release in the cortex. Excess cortical glutamate would likely damage GABAergic interneurons, and evidence of this disturbance as a result of methamphetamine treatment will be discussed. We propose that cortical GABAergic interneurons are particularly vulnerable to glutamate overflow as a result of subcellular location of NMDA receptors on interneurons in the cortex. Damage to cortical GABAergic function would lead to dysregulation of cortical signals, resulting in psychosis, and further support MAP as a model for schizophrenia.

Citing Articles

Neurotoxicity mechanisms and clinical implications of six common recreational drugs.

Wang J, Hao Y, Ma D, Feng L, Yang F, An P Front Pharmacol. 2025; 16:1526270.

PMID: 40034818 PMC: 11873747. DOI: 10.3389/fphar.2025.1526270.

Practices and attitudes of adult psychiatrists regarding methamphetamine-associated psychotic disorder: an internet based survey conducted in Turkey.

Orum M, Kapici Y, Sonmez D, Tanrikulu A, Gumusay M, Kochan O BMC Health Serv Res. 2025; 25(1):20.

PMID: 39754117 PMC: 11699667. DOI: 10.1186/s12913-024-12134-1.

Psychotic symptoms associated increased CpG methylation of metabotropic glutamate receptor 8 gene in Chinese Han males with schizophrenia and methamphetamine induced psychotic disorder: a longitudinal study.

Dong H, Luo T, Yang C, Liu M, Shen Y, Hao W Schizophrenia (Heidelb). 2024; 10(1):91.

PMID: 39384625 PMC: 11464599. DOI: 10.1038/s41537-024-00506-9.

Real world clinical outcomes of treatment of cannabis-induced psychosis and prevalence of cannabis-related primary psychosis: a retrospective study.

Chuenchom O, Suansanae T, Lukanapichonchut L, Suwanmajo S, Suthisisang C BMC Psychiatry. 2024; 24(1):626.

PMID: 39334053 PMC: 11429432. DOI: 10.1186/s12888-024-06075-6.

Drug-induced change in transmitter identity is a shared mechanism generating cognitive deficits.

Pratelli M, Hakimi A, Thaker A, Jang H, Li H, Godavarthi S Nat Commun. 2024; 15(1):8260.

PMID: 39327428 PMC: 11427679. DOI: 10.1038/s41467-024-52451-x.

References

Papadia S, Hardingham G . The dichotomy of NMDA receptor signaling. Neuroscientist. 2007; 13(6):572-9. PMC: 2830536. DOI: 10.1177/10738584070130060401. View

Hardingham G, Fukunaga Y, Bading H . Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nat Neurosci. 2002; 5(5):405-14. DOI: 10.1038/nn835. View

Langford D, Adame A, Grigorian A, Grant I, McCutchan J, Ellis R . Patterns of selective neuronal damage in methamphetamine-user AIDS patients. J Acquir Immune Defic Syndr. 2003; 34(5):467-74. DOI: 10.1097/00126334-200312150-00004. View

Weich L, Pienaar W . Occurrence of comorbid substance use disorders among acute psychiatric inpatients at Stikland Hospital in the Western Cape, South Africa. Afr J Psychiatry (Johannesbg). 2009; 12(3):213-7. DOI: 10.4314/ajpsy.v12i3.48496. View

Chang L, Alicata D, Ernst T, Volkow N . Structural and metabolic brain changes in the striatum associated with methamphetamine abuse. Addiction. 2007; 102 Suppl 1:16-32. DOI: 10.1111/j.1360-0443.2006.01782.x. View

Aoki C, Venkatesan C, Go C, Mong J, Dawson T . Cellular and subcellular localization of NMDA-R1 subunit immunoreactivity in the visual cortex of adult and neonatal rats. J Neurosci. 1994; 14(9):5202-22. PMC: 6577065. View

Hardingham G, Bading H . Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nat Rev Neurosci. 2010; 11(10):682-96. PMC: 2948541. DOI: 10.1038/nrn2911. View

Haber S, Knutson B . The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology. 2009; 35(1):4-26. PMC: 3055449. DOI: 10.1038/npp.2009.129. View

Petralia R, Wang Y, Wenthold R . The NMDA receptor subunits NR2A and NR2B show histological and ultrastructural localization patterns similar to those of NR1. J Neurosci. 1994; 14(10):6102-20. PMC: 6576991. View

10.

Bu Q, Lv L, Yan G, Deng P, Wang Y, Zhou J . NMR-based metabonomic in hippocampus, nucleus accumbens and prefrontal cortex of methamphetamine-sensitized rats. Neurotoxicology. 2013; 36:17-23. DOI: 10.1016/j.neuro.2013.02.007. View

11.

Rymar V, Sasseville R, Luk K, Sadikot A . Neurogenesis and stereological morphometry of calretinin-immunoreactive GABAergic interneurons of the neostriatum. J Comp Neurol. 2004; 469(3):325-39. DOI: 10.1002/cne.11008. View

12.

Chen C, Lin S, Sham P, Ball D, Loh E, Hsiao C . Pre-morbid characteristics and co-morbidity of methamphetamine users with and without psychosis. Psychol Med. 2003; 33(8):1407-14. DOI: 10.1017/s0033291703008353. View

13.

Nagai T, Yamada K . [Molecular mechanism for methamphetamine-induced memory impairment]. Nihon Arukoru Yakubutsu Igakkai Zasshi. 2010; 45(2):81-91. View

14.

Castner S, Goldman-Rakic P . Long-lasting psychotomimetic consequences of repeated low-dose amphetamine exposure in rhesus monkeys. Neuropsychopharmacology. 1999; 20(1):10-28. DOI: 10.1016/S0893-133X(98)00050-5. View

15.

Batki S, Harris D . Quantitative drug levels in stimulant psychosis: relationship to symptom severity, catecholamines and hyperkinesia. Am J Addict. 2005; 13(5):461-70. DOI: 10.1080/10550490490512834. View

16.

Kittirattanapaiboon P, Mahatnirunkul S, Booncharoen H, Thummawomg P, Dumrongchai U, Chutha W . Long-term outcomes in methamphetamine psychosis patients after first hospitalisation. Drug Alcohol Rev. 2010; 29(4):456-61. DOI: 10.1111/j.1465-3362.2010.00196.x. View

17.

Sora I, Li B, Fumushima S, Fukui A, Arime Y, Kasahara Y . Monoamine transporter as a target molecule for psychostimulants. Int Rev Neurobiol. 2009; 85:29-33. DOI: 10.1016/S0074-7742(09)85003-4. View

18.

Robinson T, Kolb B . Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine. Eur J Neurosci. 1999; 11(5):1598-604. DOI: 10.1046/j.1460-9568.1999.00576.x. View

19.

Fowler J, Volkow N, Logan J, Alexoff D, Telang F, Wang G . Fast uptake and long-lasting binding of methamphetamine in the human brain: comparison with cocaine. Neuroimage. 2008; 43(4):756-63. PMC: 2606665. DOI: 10.1016/j.neuroimage.2008.07.020. View

20.

Silber B, Croft R, Papafotiou K, Stough C . The acute effects of d-amphetamine and methamphetamine on attention and psychomotor performance. Psychopharmacology (Berl). 2006; 187(2):154-69. DOI: 10.1007/s00213-006-0410-7. View