Methamphetamine-induced Psychosis Research Articles

Genetic polymorphism in DTNBP1 gene is associated with methamphetamine-induced panic disorder.

The dysbindin-1 (dystrobrevin-binding protein-1 [DTNBP-1]) gene has repeatedly been shown to be associated with psychotic disorder across diverse populations. In this study, we attempted to investigate the association of the rs3213207 (P1635) genetic polymorphism of the DTNBP1 gene with methamphetamine dependence and with methamphetamine-induced psychosis, manic episodes, and panic disorder in a male Malaysian population. This polymorphism was genotyped in 233 male methamphetamine-dependent subjects and in 301 male controls of the following 4 different ethnicities: Malay, Chinese, Kadazan-Dusun, and Bajau. Intergroup statistical analyses were performed by using the χ(2) test and the Fisher exact test where necessary. In cases of multiple comparisons, the Bonferroni correction was performed. Our results indicated that the DTNBP1 rs3213207 polymorphism did not show any significant association with risk of methamphetamine dependence, either in the pooled subjects or after stratification into the 4 different ethnic groups (P > 0.05). Furthermore, we did not find any association of this polymorphism with methamphetamine-induced psychosis and episodes of methamphetamine-induced mania. However, there was a strong association between this polymorphism and the occurrence of methamphetamine-induced panic disorder in the pooled subjects (odds ratio [OR] = 6.739, P < 0.001) and in the Malay (OR = 11.93, P = 0.022) and Kadazan-Dusun (OR = 115.0, P < 0.001) groups. Our findings suggest that the DTNBP1 rs3213207 polymorphism may contribute to methamphetamine-induced panic disorder in the pooled Malaysian male population, especially in the Malay and Kadazan-Dusun ethnic groups. However, no association was found with methamphetamine dependence, methamphetamine-induced psychosis, or methamphetamine-induced mania.

A study of the phenomenology of psychosis induced by methamphetamine: a preliminary research.

Psychotic disorder due to industrial drug, such as methamphetamine addiction, is one of the important causes for referral to psychiatric hospital. Psychotic symptoms in these patients are varied. A group of researchers believe that methamphetamine-induced psychosis is completely similar to schizophrenia. Others believe that at least some cases of permanent psychotic clinical manifestation due to methamphetamine abuse are different from schizophrenia. In the present study, the existence of differences between psychotic symptoms caused by methamphetamine addiction and schizophrenia is investigated. This study was a qualitative study. Patients with psychosis due to methamphetamine addiction were selected from among patients who were hospitalized in hospitals of the Kerman University of Medical Sciences, Iran. All patients were interviewed using unstructured interview based on self- reporting. Interviews were recorded and reviewed later. Based on clinical observations, some of the patients with psychotic disorder due to methamphetamine showed rare symptoms that had been mostly reported in psychosis due to organic disorders and some of them showed symptoms that had not been reported before. This study showed that in a group of patients with methamphetamine-induced psychosis, clinical manifestation is different from schizophrenia.

The neurobiology of methamphetamine induced psychosis.

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.

Prefrontal glutamate levels differentiate early phase schizophrenia and methamphetamine addiction: A 1H MRS study at 3 Tesla

Acute symptoms of methamphetamine-induced psychosis are similar to those of primary schizophrenia. Understanding similarities or differences in the biological substrate of these psychoses could lead to early differentiation of these two clinical conditions resulting in more efficient treatment strategies. Proton magnetic resonance spectroscopy was acquired from the medial prefrontal cortex in 29 unmedicated patients with first episode of psychosis (FEP), 29 abstinent methamphetamine-addicted people (METH) and 45 healthy controls (HCs) (age range 17.3 to 29.9years old). The METH group displayed robust reductions in concentration levels of glutamate (Glu) relative to FEP (Cohen's d=1.20) and HC (d=0.87). The METH group also displayed reduced levels of N-acetylaspartate (NAA) relative to FEP (d=0.53) and HC (d=0.76). The HC group displayed a positive association between levels of Glu and NAA, r(45)=0.52, p<0.001, while the two clinical groups failed to show this normal association. This suggests that the cellular metabolism is altered in both conditions. These data support the assumption that cellular abnormalities differ between primary schizophrenia and methamphetamine addiction despite the overlap in clinical presentation.

Treatment of methamphetamine-induced psychosis: a double-blind randomized controlled trial comparing haloperidol and quetiapine

To our knowledge, only a few double-blind randomized controlled trials with antipsychotic drugs have been conducted to examine the treatment of methamphetamine-induced psychosis (MAP). The aims of this study are to compare the antipsychotic and adverse events of quetiapine, an atypical antipsychotic drug, to haloperidol, a standard treatment for primary psychotic disorder, in individuals with MAP. Eighty individuals with MAP were randomly assigned into two groups, i.e. treatment with quetiapine (n = 36) and haloperidol (n = 44). Sixty-eight patients (85 %) completed the study protocol, i.e. treatment with quetiapine at least 100 mg per day or haloperidol at least 2 mg per day orally once a day for 4 weeks. The doses were increased every 5 days until no psychotic symptom was observed from the Positive and Negative Syndrome Scale (PANSS). Data were analysed by survival analysis with Cox's proportional regression analysis, general estimating equations and log-rank tests. Thirty-two (89 %) subjects from the quetiapine group and 37 subjects (84 %) from the haloperidol group met the remission criteria at the end of the study. Baseline PANSS total scores of quetiapine and haloperidol groups were 82.4 ± 16.6 and 90.0 ± 18.4, respectively (mean ± SD; p = 0.06). The change-from-baseline scores were -47.8 for the quetiapine group and -53.2 for the haloperidol group. There were no significant differences between the antipsychotic effects (coefficient value = -2.6, p = 0.32, 95%CI = -7.6, 2.5) and the adverse effects of quetiapine and haloperidol. Quetiapine may be used as an antipsychotic treatment for MAP with comparable therapeutic effects and adverse events to treatment with classical antipsychotic drugs.

Treating methamphetamine-induced resistant psychosis with clozapine.

Background. Methamphetamine-induced psychosis (MIP) in Iran has turned into a serious issue in terms of health and treatment, lacking any obvious treatment methods for its resistant cases. Aims of Case Report. In the present study, a number of two cases of treatment of MIP with clozapine, which were resistant to the treatment with other antipsychotics, have been reported. Both cases completely responded to the treatment in only 2 weeks and no signs of psychosis relapse were seen in an 8-9 follow-up. Conclusion. Because of its particular pharmacologic features, clozapine may be effective in treating MIP.

Improvement of Methamphetamine-Induced Psychosis, Retardation and Craving after Few Sessions of ECT

Background: Methamphetamine abuse is now a significant problem in Iran. Objective: To present usefulness of ECT in the improvement of methamphetamine induced psychosis, methamphetamine withdrawal retardation and methamphetamine withdrawal craving, in a single case. Results/Conclusion: ECT can be beneficial in the treatment of these serious conditions.

SASOP Biological Psychiatry Congress 2013 Abstracts

SASOP Biological Psychiatry Congress 2013 Abstracts

Could cognitive deficits help distinguish methamphetamine-induced psychosis from a psychotic disorder with substance abuse?

Dissociating a primary psychotic disorder (PPD) with concurrent substance use from substance-induced psychosis (SID) can be a difficult task. This study explored the possibility of distinguishing subgroups using cognitive functioning in order to potentially help diagnose individuals with a PPD co-occurring with substance-use and a methamphetamine (MA) induced psychosis. The hypothesis stipulates that individuals with a PPD should present with different cognitive deficits compared to individuals with SID. The study used the data collected as part of a longitudinal study (the MAPS project) that took place in Vancouver BC, Canada. One hundred and seventy-two individuals presenting with psychosis and MA abuse were recruited. Substance use, symptoms severity and cognitive deficits were assessed. A cluster analyses revealed two profiles: individuals in Cluster 1 had a poorer performance on the Gambling task net score (M = −28.1) and on the Hopkins Verbal Learning Test – Revised (HVLT-R; M = 63) % of retention s...

Evidence for Shared Genetic Risk Between Methamphetamine-Induced Psychosis and Schizophrenia

Methamphetamine (METH) use can provoke psychotic reactions requiring immediate treatment, namely METH-induced psychosis. Although the distinction between METH-induced and primary psychosis is important for understanding their clinical courses, we do not have clear diagnostic procedure by their symptoms. Not only are there similarities between the clinical features of METH-induced psychosis and schizophrenia (SCZ), but there is also epidemiological evidence of a shared genetic risk between 'METH-related' disorders and SCZ, which makes the differentiation of these two conditions difficult. In this study, we conducted a genome-wide association study (GWAS) targeting METH-dependent patients. The METH sample group, used in the METH-dependence GWAS, included 236 METH-dependent patients and 864 healthy controls. We also included a 'within-case' comparison between 194 METH-induced psychosis patients and 42 METH-dependent patients without psychosis in a METH-induced psychosis GWAS. To investigate the shared genetic components between METH dependence, METH-induced psychosis, and SCZ, data from our previous SCZ GWAS (total N=1108) were re-analyzed. In the SNP-based analysis, none of the SNPs showed genome-wide significance in either data set. By performing a polygenic component analysis, however, we found that a large number of 'risk' alleles for METH-induced psychosis are over-represented in individuals with SCZ (Pbest=0.0090). Conversely, we did not detect enrichment either between METH dependence and METH-induced psychosis or between METH dependence and SCZ. The results support previous epidemiological and neurobiological evidence for a relationship between METH-induced psychosis and SCZ. These also suggest that the overlap between genes scored as positive in these data sets can have higher probability as susceptibility genes for psychosis.

Association of a Functional FAAH Polymorphism with Methamphetamine-Induced Symptoms and Dependence in a Malaysian Population

FAAH is a membrane enzyme that terminates the activity of a large class of endogenous signaling lipids. Recent studies suggest that the FAAH Pro129Thr polymorphism is a common mutation in the FAAH gene that is significantly associated with drug-addictive traits. This study investigated the association of the Pro129Thr polymorphism of the FAAH gene with methamphetamine dependence, methamphetamine-induced psychosis, manic episodes and panic disorder in a Malaysian population. This polymorphism was genotyped in 232 male methamphetamine-dependent subjects and in 241 male controls of four different ethnicities: Malay, Chinese, Kadazan-Dusun and Bajau. Intergroup statistical analyses were performed by using the χ(2)-square test and Fisher's exact test, where necessary. In cases of multiple comparisons, the Bonferroni correction was performed. Our results indicated that the FAAH Pro129Thr polymorphism showed a significant association with risk of methamphetamine dependence in the pooled subjects (odds ratio [OR]: 2.017; p < 0.001) and in the Malay (OR: 2.829; p < 0.001) and Chinese (OR: 3.685; p < 0.001) groups. We also found an association of this polymorphism with episodes of methamphetamine-induced mania in the Malay group (OR: 2.836; p = 0.035). However, there was no association between this polymorphism and age of onset of drug use or the occurrence of methamphetamine-induced psychosis or of panic disorder. Our findings suggest that the FAAH Pro129Thr polymorphism may contribute to methamphetamine dependence in the Malay and Chinese ethnic groups.

A Sex- and Region-Specific Role of Akt1 in the Modulation of Methamphetamine-Induced Hyperlocomotion and Striatal Neuronal Activity: Implications in Schizophrenia and Methamphetamine-Induced Psychosis

AKT1 (also known as protein kinase B, α), a serine/threonine kinase of AKT family, has been implicated in both schizophrenia and methamphetamine (Meth) use disorders. AKT1 or its protein also has epistatic effects on the regulation of dopamine-dependent behaviors or drug effects, especially in the striatum. The aim of this study is to investigate the sex-specific role of Akt1 in the regulation of Meth-induced behavioral sensitization and the alterations of striatal neurons using Akt1(-/-) mice and wild-type littermates as a model. A series of 4 Experiments were conducted. Meth-induced hyperlocomotion and Meth-related alterations of brain activity were measured. The neural properties of striatal medium spiny neurons (MSNs) were also characterized. Further, 17β-estradiol was applied to examine its protective effect in Meth-sensitized male mice. Our findings indicate that (1) Akt1(-/-) males were less sensitive to Meth-induced hyperlocomotion during Meth challenge compared with wild-type controls and Akt1(-/-) females, (2) further sex differences were revealed by coinjection of Meth with raclopride but not SCH23390 in Meth-sensitized Akt1(-/-) males, (3) Meth-induced alterations of striatal activity were confirmed in Akt1(-/-) males using microPET scan with (18)F-flurodeoxyglucose, (4) Akt1 deficiency had a significant impact on the electrophysiological and neuromorphological properties of striatal MSNs in male mice, and (5) subchronic injections of 17β-estradiol prevented the reduction of Meth-induced hyperactivity in Meth-sensitized Akt1(-/-) male mice. This study highlights a sex- and region-specific effect of Akt1 in the regulation of dopamine-dependent behaviors and implies the importance of AKT1 in the modulation of sex differences in Meth sensitivity and schizophrenia.

The risk and associated factors of methamphetamine psychosis in methamphetamine-dependent patients in Malaysia

ObjectiveThe objective of this study was to determine the risk of lifetime and current methamphetamine-induced psychosis in patients with methamphetamine dependence. The association between psychiatric co-morbidity and methamphetamine-induced psychosis was also studied. MethodsThis was a cross-sectional study conducted concurrently at a teaching hospital and a drug rehabilitation center in Malaysia. Patients with the diagnosis of methamphetamine based on DSM-IV were interviewed using the Mini International Neuropsychiatric Interview (M.I.N.I.) for methamphetamine-induced psychosis and other Axis I psychiatric disorders. The information on sociodemographic background and drug use history was obtained from interview or medical records. ResultsOf 292 subjects, 47.9% of the subjects had a past history of psychotic symptoms and 13.0% of the patients were having current psychotic symptoms. Co-morbid major depressive disorder (OR=7.18, 95 CI=2.612–19.708), bipolar disorder (OR=13.807, 95 CI=5.194–36.706), antisocial personality disorder (OR=12.619, 95 CI=6.702–23.759) and heavy methamphetamine uses were significantly associated with lifetime methamphetamine-induced psychosis after adjusted for other factors. Major depressive disorder (OR=2.870, CI=1.154–7.142) and antisocial personality disorder (OR=3.299, 95 CI=1.375–7.914) were the only factors associated with current psychosis. ConclusionThere was a high risk of psychosis in patients with methamphetamine dependence. It was associated with co-morbid affective disorder, antisocial personality, and heavy methamphetamine use. It is recommended that all cases of methamphetamine dependence should be screened for psychotic symptoms.

Clinical features of inpatients with methamphetamine-induced psychosis

Background: An epidemic of methamphetamine use has begun in Iran in recent years and psychiatric emergency services are overloaded with patients with methamphetamine-induced psychosis (MIP).Aims: To define the clinical features of inpatients with MIP in a psychiatric hospital.Method: The files of all MIP patients admitted to Iran Psychiatric Hospital located in Tehran from April 2008 to April 2010 were assessed. Data related to psychotic episode, substance use, previous psychiatric history and demographic data of 111 MIP patients were extracted and analyzed using descriptive statistical methods.Results: The most prevalent psychotic symptoms were persecutory delusion (82%), auditory hallucination (70.3%), reference delusion (57.7%), visual hallucination (44.1%), grandiosity delusion (39.6%) and jealousy delusion (26.1%). The mean duration of admission and psychotic episode was 21.43 and 17.37 days, respectively. In seven cases (8.75%), symptoms continued for more than one month.Conclusion: Frequency of psychotic symptoms in this study is relatively similar to previous studies. However, some clinical determinants such as latency of psychosis from first use and the course of psychosis are more similar to the first epidemic of methamphetamine in Japan than to more recent epidemics; which could be due to the short history of methamphetamine use in Iran.

Orengedoku-to augmentation in cases showing partial response to yokukan-san treatment: a case report and literature review of the evidence for use of these Kampo herbal formulae

BackgroundYokukan-san, a Japanese traditional herbal (Kampo) prescription, has recently gathered increasing attention due to accumulating reports showing its remarkable efficacy in treating a wide variety of diseases refractory to conventional medicine as well as the behavioral and psychological symptoms of dementia. As yokukan-san has become broadly integrated with conventional medicine, augmentation therapy with other Kampo prescriptions has become necessary when the yokukan-san has been only partially efficacious. In this paper, we report three cases in which the addition of orengedoku-to, another Kampo formula, to yokukan-san was remarkably effective.CasesCase 1 was an 85-year-old man with Alzheimer-type dementia who had become aggressive during the past 2 years. Three milligrams of aripiprazole completely suppressed his problematic behaviors but had to be stopped because of extrapyramidal symptoms. In the second case, a 44-year-old man with methamphetamine-induced psychosis had suffered from serious tardive dystonia for 2 years. No conventional approach had improved his tardive dystonia. The third case was a 29-year-old engineer who often failed to resist aggressive impulses and was diagnosed with intermittent explosive disorder. He was prescribed 5 mg of olanzapine, which did not suppress his extraordinary anger and caused somnolence even though the dose was low.Interventions and outcomesYokukan-san was complementarily added to the patients’ regular medication and exerted a definitive but partial effect in all cases. The addition of orengedoku-to to yokukan-san exerted the same efficacy as aripiprazole in controlling aggressiveness in Case 1, improved the tardive dystonia by 80% in Case 2, and was completely effective in controlling the patient’s aggressive impulses in Case 3.ConclusionTogether with empirical evidence demonstrating the effectiveness of both yokukansan and orengedoku-to in reducing irritability, impulsivity, and aggression, these three cases suggest that orengedoku-to augmentation can be an effective option in cases that are partially responsive to yokukan-san treatment.

15:00 SHINING LIGHT ON SLEEP-WAKE AND CORTICAL GAMMA OSCILLATIONS IN SCHIZOPHRENIA: THE ROLE OF PARVALBUMIN GABA NEURONS

Phencyclidine (PCP) is a psychotomimetic drug that induces schizophrenia-like symptoms in healthy individuals and exacerbates pre-existing symptoms in patients with schizophrenia. PCP also induces behavioral and cognitive abnormalities in non-human animals, and PCP-treated animals are considered a reliable pharmacological model of schizophrenia. However, the exact neural mechanisms by which PCP modulates behavior are not known. During the last decade several studies have indicated that disturbed activity of the prefrontal cortex (PFC) may be closely related to PCP-induced psychosis. Systemic administration of PCP produces long-lasting activation of medial PFC (mPFC) neurons in rats, almost in parallel with augmentation of locomotor activity and behavioral stereotypies. Later studies have showed that such PCP-induced behavioral abnormalities are ameliorated by prior administration of drugs that normalize or inhibit excess excitability of PFC neurons. Similar activation of mPFC neurons is not induced by systemic injection of a typical psychostimulant such as methamphetamine, even though behavioral hyperactivity is induced to almost the same level. This suggests that the neural circuits mediating PCP-induced psychosis are different to those mediating methamphetamine-induced psychosis. Locally applied PCP does not induce excitation of mPFC neurons, indicating that PCP-induced tonic excitation of mPFC neurons is mediated by inputs from regions outside the mPFC. This hypothesis is strongly supported by experimental results showing that local perfusion of PCP in the ventral hippocampus, which has dense fiber projections to the mPFC, induces tonic activation of mPFC neurons with accompanying augmentation of behavioral abnormalities. In this review we summarize current knowledge on the neural mechanisms underlying PCP-induced psychosis and highlight a possible involvement of the PFC and the hippocampus in PCP-induced psychosis.

No significant association between SIRT1 gene and methamphetamine‐induced psychosis in the Japanese population

We previously showed that the sirtuin 1 gene (SIRT1 gene), one of the clock genes, was associated with schizophrenia in a Japanese patient population. Because the symptoms of methamphetamine (METH)-induced psychosis are similar to those of paranoid type schizophrenia and because not every METH user develops psychosis, it is conceivable that METH-induced psychosis and schizophrenia have common susceptibility genes. Therefore, we conducted an analysis of the association of SIRT1 gene with METH-induced psychosis, hypothesizing a significant relationship. This paper presents a case-control study of the SIRT1 gene in 515 Japanese individuals (197 with METH-induced psychosis and 318 age-matched and sex-matched controls) with four tagging single nucleotide polymorphisms (rs12778366, rs2273773, rs4746720, and rs10997875), selected a priori using the HapMap database. rs10997875 (located in the 3' flanking region) was associated with METH-induced psychosis (unadjusted p(genotype) = 0.0203). However, these results became non-significant after Bonferroni correction (corrected p(genotype) = 0.0812). In the all-marker haplotype analysis, the SIRT1 gene was not associated with METH-induced psychosis (p = 0.146). Our findings suggest that SIRT1 gene does not contribute to the development of METH-induced psychosis in the Japanese population. However, a replication study using larger samples should be conducted to obtain conclusive results.

Effects of repeated electroconvulsive shock on methamphetamine-induced behavioral abnormalities in mice

Methamphetamine abuse and addiction can lead to impaired cognition and psychosis, and there is no effective treatment for methamphetamine-induced mental illnesses. The aim of this study was to test whether repeated electroconvulsive shock (ECS) treatment has a therapeutic effect on methamphetamine-induced abnormal behavior in mice. To test the effects of ECS on methamphetamine-induced psychosis, ICR mice were randomly assigned to administration with either chronic methamphetamine or saline injection, and then both groups underwent post-treatment with either six once-daily ECS treatments or parallel sham controls. Prepulse inhibition (PPI), the novel object recognition test (NORT) and behavioral sensitization were performed for behavioral evaluation between the groups. To test the effects of ECS on methamphetamine addiction, methamphetamine-induced conditioned place preference (CPP) was examined after ECS and drug-primed reinstatement in the other set of experiments. The animals receiving repeated ECS following pretreatment with methamphetamine showed significant improvement in PPI and NORT, but not in behavioral sensitization. In the CPP study, the ECS-treated animals achieved extinction of place preference, but relapsed after a low-dose reinstatement of methamphetamine. The results indicated that repeated ECS treatments can ameliorate impairment to the sensorimotor gating and recognition memory elicited by methamphetamine, and temporarily suppress the reinforcement induced by methamphetamine in mice. Our findings suggest electroconvulsive therapy (ECT) may have potential applications with regard to the treatment of methamphetamine psychosis and addiction.

No Association Between GRM3 and Japanese Methamphetamine- Induced Psychosis

Several investigations have suggested that abnormalities in glutamate neural transmission play a role in the pathophysiology of psychiatric disorders, including schizophrenia. The metabotropic glutamate 3 receptor (mGluR3) gene was reported to be associated with schizophrenia, and paranoid type schizophrenia has symptoms that are similar to those of methamphetamine-induced psychosis. This suggests that mGluR3 gene (GRM3) is a good candidate gene for the pathogenesis of methamphetamine-induced psychosis. To evaluate the association between GRM3 and methamphetamine-induced psychosis, we conducted a case-control study of Japanese samples (181 methamphetamine-induced psychosis and 232 controls). Methods:We selected one functional SNP (rs6465084), reported to be associated with prefrontal brain functioning, for an association analysis. Written informed consent was obtained from each subject. This study was approved by the ethics committees at Fujita Health University, Nagoya University Graduate School of Medicine and each participating member of the Institute of the Japanese Genetics Initiative for Drug Abuse (JGIDA).Results:We did not detect an association between rs6465084 in GRM3 and Japanese methamphetamine-induced psychosis.Conclusion:Our findings suggest that rs6465084 in GRM3 does not play a major role in the pathophysiology of methamphetamine-induced psychosis in the Japanese population. However, because we did not perform an association analysis based on linkage disequilibrium (LD) or a mutation scan of GRM3, a replication study using a larger sample and based on LD may be required for conclusive results.

Genetic Association Analysis of NOS3 and Methamphetamine-Induced Psychosis Among Japanese

Endothelial nitric oxide synthase (NOS3) is one of the enzymes influencing nitric oxide (NO) function in the human brain. NO is a gaseous neurotransmitter that is involved in a variety of mechanisms in the central nervous system, such as N-methyl-D-aspartate receptor activation and oxidative stress. The evidence from animal pharmacological studies and postmortem studies supports an association between NO and psychotic disorders. Methamphetamine (METH) use disorder is a known psychotic disorder, and we therefore conducted a gene-based case-control study between tagging single nucleotide polymorphisms (SNPs) (rs2070744, rs1799983) in NOS3 and METH-induced psychosis in Japanese subjects (183 with METH-induced psychosis and 267 controls). Written informed consent was obtained from each subject. No significant association was found between any tagging SNP in NOS3 and METH-induced psychosis in the allele/genotype-wise or haplotype-wise analyses. In conclusion, we suggest that NOS3 might not contribute to the risk of METH-induced psychosis in the Japanese population.