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There is mounting evidence that positive allosteric modulation of metabotropic glutamate type 2 receptors (mGluR 2 ) is an efficacious approach to reduce the severity of L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia, psychosis-like behaviours (PLBs), while conferring additional anti-parkinsonian benefit. However, the mGluR 2 positive allosteric modulators (PAMs) tested so far, LY-487,379 and CBiPES, share a similar chemical scaffold. Here, we sought to assess whether similar benefits would be conferred by a structurally-distinct mGluR 2 PAM, biphenylindanone A (BINA). Six 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmosets exhibiting dyskinesia and PLBs were administered L-DOPA with either vehicle or BINA (0.1, 1, and 10 mg/kg) in a randomised within-subject design and recorded. Behaviour was analysed by a blinded rater who scored the severity of each of parkinsonism, dyskinesia and PLBs. When added to L-DOPA, BINA 0.1 mg/kg, 1 mg/kg, and 10 mg/kg all significantly reduced the severity of global dyskinesia, by 40%, 52% and 53%, (all P < 0.001) respectively. BINA similarly attenuated the severity of global PLBs by 35%, 48%, and 50%, (all P < 0.001) respectively. Meanwhile, BINA did not alter the effect of L-DOPA on parkinsonism exhibited by the marmosets. The results of this study provide incremental evidence of positive allosteric modulation of mGluR 2 as an effective therapeutic strategy for alleviating dyskinesia and PLBs, without hindering the anti-parkinsonian action of L-DOPA. Furthermore, this therapeutic benefit does not appear to be confined to a particular chemical scaffold., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: The psychopathological manifestations associated with substance use, including induced psychotic experiences, are increasingly relevant but not well-understood within the medical community. Novel psychoactive substances and potentiated old compounds like cannabis and cocaine have emerged as a global concern, especially among adolescents and young adults. Transition rates from substance-induced psychosis (SIP) to persistent psychosis are significant, particularly in cases of cannabis-induced psychosis. Scientific inquiry into induced psychotic phenomena has revealed differences between SIP and primary psychotic disorders, highlighting the risk factors associated with each. The concept of exogenous psychosis, including its toxic variant known as lysergic psychoma, provides valuable insights into the role of external factors in psychosis development. A phenomenological approach characterizes this disruption in perception as a shift in temporal and spatial dimensions, leading to auditory and visual hallucinations. The "twilight state" of consciousness plays a crucial role in the transition from substance use to psychosis, with implications for spatiality, intersubjectivity, and temporality. This complex path to psychosis challenges traditional diagnostic models and underscores the need for a more nuanced understanding of substance-induced psychopathological experiences., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: To determine whether the risk of psychotic symptoms during weeks of methamphetamine use was dependent on, increased by, or independent of having a family history of psychosis., Design: Secondary analysis of 13 contiguous 1-week periods of data (1370 weeks). A risk modification framework was used to test each scenario., Setting: Geelong, Wollongong and Melbourne, Australia., Participants: Participants in a randomized controlled trial of treatment for methamphetamine dependence (n = 148) who did not have a primary psychotic disorder on enrolment., Measurements: Psychotic symptoms in the previous week were defined as a score of 3+ on any of the Brief Psychiatric Rating Scale items of hallucinations, unusual thought content or suspiciousness. Any (vs no) methamphetamine use in the previous week was assessed using the Timeline Followback method. Self-reported family history of psychosis was assessed using the Diagnostic Interview for Psychosis., Findings: The risk of psychotic symptoms in the past week was independently associated with methamphetamine use in that week (relative risk [RR] = 2.3, 95% CI = 1.3-4.3) and with having a family history of psychosis (RR = 2.4, 95% CI = 0.9-7.0); the joint risk among participants with a family history of psychosis during weeks when they were using methamphetamine was large (RR = 4.0, 95% CI = 2.0-7.9). There was no significant interaction between a family history of psychosis and methamphetamine use in predicting psychotic symptoms (interaction RR = 0.7 95% CI = 0.3-1.8), but there was a small non-significant excess risk due to the interaction (0.20 95% CI = -1.63 to 2.03)., Conclusions: Among people dependent on methamphetamine, the relative risk of psychotic symptoms during weeks of methamphetamine use does not appear to be dependent on, or increased by, having a family history of psychosis. However, a family history of psychosis does appear to be an independent risk factor that contributes to the absolute risk of psychotic symptoms in this population., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Over the past decade, the number of individuals requiring medical care for amphetamine-related psychosis has increased., Objective: This study aims to examine the psychological characteristics of amphetamine psychosis in drug-addicted patients depending on the length of drug exposure and compared to patients diagnosed with paranoid schizophrenia., Methods: The study was carried out in psychiatric clinic No. 1 in Kyiv (Ukraine) in 2019, involving 107 patients. Of all the participants, 50 were included in Group 1 (methamphetamine psychosis) and 57 - in Group 2 (paranoid schizophrenia). All patients were treated with medication to relieve exacerbating symptoms. They underwent extensive testing to determine the impairment severity of cognitive function, attention, and task performance during remission., Results: In Group 1, the timing of onset for paranoid symptoms depends on the length of amphetamine exposure (Spearman correlation coefficient = 0.89). The efficacy and dynamics of drug treatment in Group 2 were similar to patients in Group 1. However, the effect of reduction in Group 2 was achieved only in 4 months. Delusions, emotional disturbances, hallucinations in patients of Group 1 occurred 2.3 times more frequently than in Group 2 (p ≤ 0.05). The patients of Group 1 are characterized by the presence of disorders related to the affective and behavioral components., Conclusion: All reported exacerbations are related to amphetamine use. Patients in Group 1 learned a smaller number of words compared to those in Group 2. Besides, a large number of errors and difficulties with shifting focus were recorded., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

As an N-methyl-D-aspartate (NMDA) receptor inhibitor, ketamine has become a popular recreational substance and currently is used to address treatment-resistant depression. Since heavy ketamine use is associated with persisting psychosis, cognitive impairments, and neuronal damage, the safety of ketamine treatment for depression should be concerned. The nutrient supplement betaine has been shown to counteract the acute ketamine-induced psychotomimetic effects and cognitive dysfunction through modulating NMDA receptors. This study aimed to determine whether the adjunctive or subsequent betaine treatment would improve the enduring behavioral disturbances and hippocampal synaptic abnormality induced by repeated ketamine exposure. Mice received ketamine twice daily for 14 days, either combined with betaine co-treatment or subsequent betaine post-treatment for 7 days. Thereafter, three-chamber social approach test, reciprocal social interaction, novel location/object recognition test, forced swimming test, and head-twitch response induced by serotonergic hallucinogen were monitored. Data showed that the enduring behavioral abnormalities after repeated ketamine exposure, including disrupted social behaviors, recognition memory impairments, and increased depression-like and hallucinogen-induced head-twitch responses, were remarkably improved by betaine co-treatment or post-treatment. Consistently, betaine protected and reversed the reduced hippocampal synaptic activity, such as decreases in field excitatory post-synaptic potentiation (fEPSP), long-term potentiation (LTP), and PSD-95 levels, after repeated ketamine treatment. These results demonstrated that both co-treatment and post-treatment with betaine could effectively prevent and reverse the adverse behavioral manifestations and hippocampal synaptic plasticity after repeated ketamine use, suggesting that betaine can be used as a novel adjunct therapy with ketamine for treatment-resistant depression and provide benefits for ketamine use disorders., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Cannabis Withdrawal Syndrome (CWS) is a key feature of Cannabis Use Disorder (CUD). The CWS causes significant distress and disability. While the relationship between CUD and psychosis has been extensively studied, the potential connection between CWS and psychosis has not received as much attention., Case Presentation: The CARE guideline's methodology is followed in the presentation of this case report. During the national lockdown decreed by the Spanish government for the containment of the CoronaVirus Disease 19 (COVID-19) pandemic, a 29-year-old man suffers a CWS and a subsequent psychotic episode. He is admitted to a psychiatric unit, obtaining a rapid and complete response to treatment., Discussion: Clinical and pathophysiological data that support the hypothesis of CWS-induced psychosis are discussed. Due to the increasing use of cannabis worldwide, we believe that more research is needed on the mental disturbances associated with CUD, including CWS and psychosis. On the other hand, the confinement and social distancing measures adopted in the face of the current COVID-19 pandemic could have restricted the availability and consumption of certain drugs, precipitating the emergence of withdrawal syndromes such as CWS.

Rationale: Antipsychotics help alleviate the positive symptoms associated with schizophrenia; however, their debilitating side effects have spurred the search for better treatment options. Novel compounds can be screened for antipsychotic potential in neuronal cell cultures and following acute N-methyl-D-aspartate (NMDA) receptor blockade with non-competitive antagonists such as MK-801 in rodent behavioral models. Given the known interactions between NMDA receptors and type 1 cannabinoid receptors (CB1R), compounds that modulate CB1Rs may have therapeutic potential for schizophrenia., Objectives: This study assessed whether the CB1R positive allosteric modulator GAT211, when compared to ∆ 9 -tetrahydrocannabinol (THC), has potential to reduce psychiatric behavioral phenotypes following acute MK-801 treatment in rats, and block hyperdopaminergic signalling associated with those behaviors., Methods: The effects of GAT211 and THC on cellular signaling were compared in Neuro2a cells, and behavioral effects of GAT211 and THC on altered locomotor activity and prepulse inhibition of the acoustic startle response caused by acute MK-801 treatment were assessed in male, Long Evans rats., Results: GAT211 limited dopamine D2 receptor-mediated extracellular regulated kinase (ERK) phosphorylation in Neuro2a cells, whereas THC did not. As expected, acute MK-801 (0.15 mg/kg) produced a significant increase in locomotor activity and impaired PPI. GAT211 treatment alone (0.3-3.0 mg/kg) dose-dependently reduced locomotor activity and the acoustic startle response. GAT211 (3.0 mg/kg) also prevented hyperlocomotion caused by MK-801 but did not significantly affect PPI impairments., Conclusion: Taken together, these findings support continued preclinical research regarding the usefulness of CB1R positive allosteric modulators as antipsychotics.

Longitudinal studies of cannabis exposure during early adolescence in the general population frequently report an increased risk of subsequently developing psychotic symptoms or a psychotic illness. However, there is a dearth of knowledge about the effects of early cannabis exposure on psychosis in homeless and precariously housed adults, who represent a population afflicted with high rates of psychosis. The aim of the present study was to examine how early cannabis exposure (by age 15) compared to later first use (after age 15) affected the expression of adult psychosis in this population. Secondary measures of psychopathology, drug use, cognition and brain structure were also collected. 437 subjects were recruited from single room occupancy hotels in the urban setting of the Downtown Eastside of Vancouver, Canada. Psychiatric diagnoses were determined, and psychotic symptom severity was measured with the 5-factor PANSS. Participants completed a battery of neurocognitive tests, and brain structure was assessed using structural and diffusion tensor imaging MRI scans. Results indicated that early cannabis exposure was associated with an increased risk (OR = 1.09, p < .05) of developing substance induced psychosis, whereas later first use increased risk (OR = 2.19, p < .01) of developing schizophrenia or schizoaffective disorder. There was no group difference in neurocognitive function, although differences were observed in the lateral orbitofrontal cortex and white matter tract diffusivity. These findings indicate that early cannabis exposure in this population may increase the risk of developing drug associated psychoses, which could potentially be mediated in part through altered neurodevelopmental brain changes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The astrocytic glutamate transporter GLT-1 performs glutamate uptake thereby mediating NMDAr responses in neurons. Ceftriaxone (CEF) upregulates astrocytic GLT-1 expression/activity, which could counteract excessive glutamate levels and aggressive behavior induced by anabolic synthetic steroids such as nandrolone decanoate (ND). Here, adult male CF-1 mice were allocated to oil (VEH), ND, CEF, and ND/CEF groups. Mice were subcutaneously (s.c.) injected with ND (15 mg/kg) or VEH for 19 days, and received intraperitoneal (i.p.) injections of CEF (200 mg/kg) or saline for 5 days. The ND/CEF group received ND for 19 days plus coadministration of CEF in the last 5 days. On the 19th day, the aggressive phenotypes were evaluated through the resident-intruder test. After 24 h, cerebrospinal fluid was collected to measure glutamate levels, and the pre-frontal cortex was used to assess GLT-1, pGluN2B Tyr1472 , and pGluN2A Tyr1246 by Western blot. Synaptosomes from the left brain hemisphere was used to evaluate mitochondrial function including complex II-succinate dehydrogenase (SDH), Ca 2+ handling, membrane potential (ΔѰ m ), and H 2 O 2 production. ND decreased the latency for the first attack and increased the number of attacks by the resident mice against the intruder, mechanistically associated with an increase in glutamate levels and pGluN2B Tyr1472 but not pGluN2A Tyr1244 , and GLT-1 downregulation. The abnormalities in mitochondrial Ca 2+ influx, SDH, ΔѰ m , and H 2 O 2 implies in deficient energy support to the synaptic machinery. The ND/CEF group displayed a decreased aggressive behavior, normalization of glutamate and pGluN2B Tyr1472 levels, and mitochondrial function at synaptic terminals. In conclusion, the pharmacological modulation of GLT-1 highlights its relevance as an astrocytic target against highly impulsive and aggressive phenotypes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: First episode-psychosis (FEP) represents a stressful/traumatic event for patients. To our knowledge, no study to date has investigated thought suppression involved in FEP in a Romanian population. Our objective was to investigate thought suppression occurring during FEP within primary psychotic disorders (PPD) and substance/medication induced psychotic disorders (SMIPD). Further, we examined the relationship between thought suppression and negative automatic thoughts within PPD and SMIPD., Methods: The study included 30 participants (17 females) with PPD and 25 participants (10 females) with SMIPD. Psychological scales were administered to assess psychotic symptoms and negative automatic thoughts, along a psychiatric clinical interview and a biochemical drug test., Results: Participants in the PPD group reported higher thought suppression compared to SMIPD group. For the PPD group, results showed a positive correlation between thought suppression and automatic thoughts. For the SMIPD group, results also showed a positive correlation between thought suppression and automatic thoughts., Conclusions: Patients with PPD rely more on thought suppression, as opposed to SMIPD patients. Thought suppression may be viewed as an unhealthy reaction to FEP, which is associated with the experience of negative automatic thoughts and might be especially problematic in patients with PPD. Cognitive behavioral therapy is recommended to decrease thought suppression and improve patients' functioning.

Whereas monoamine oxidase (MAO) type B inhibitors are used as adjunct to L-3,4-dihydroxyphenylalanine (L-DOPA) in the treatment of Parkinson's disease (PD), the enzyme MAO type A (MAO-A) also participates in the metabolism of dopamine in the human and primate striatum. Here, we sought to assess the effect of the selective reversible MAO-A inhibitor moclobemide on L-DOPA anti-parkinsonian in the gold standard animal model of PD, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate. We also assessed the effect of moclobemide on L-DOPA-induced dyskinesia and psychosis-like behaviours (PLBs). Experiments were performed in six MPTP-lesioned marmosets chronically treated with L-DOPA and exhibiting stable dyskinesia and PLBs upon each administration. In a randomised within-subject design, animals were administered a therapeutic dose of L-DOPA in combination with moclobemide (0.1, 1 and 10 mg/kg) or its vehicle, after which the severity of parkinsonism, dyskinesia, and PLBs was rated by an experienced blinded rater. Moclobemide significantly reduced the global parkinsonian disability (- 36% with 0.1 mg/kg, P < 0.05; - 38% with 1 mg/kg, P < 0.01; - 47% with 10 mg/kg, P < 0.01), when compared with its vehicle. This reduction of parkinsonism was not accompanied by an exacerbation of dyskinesia or PLBs. Reversible MAO-A inhibition with moclobemide appears as an effective way to increase the anti-parkinsonian action of L-DOPA, without negatively affecting dyskinesia or dopaminergic psychosis.

The study by Moran et al. on the risk of psychosis among adolescents in the US who are treated with a stimulant for ADHD is important. This is because ADHD is a common disorder (3-5%), because psychosis often emerges in adolescence, because ADHD and psychosis share increased comorbidity and because ADHD is treated with stimulant medication that may increase the risk of psychosis. This means there is a multifactorial relationship between ADHD and psychosis.The outcome of the study is that stimulants increase the risk of psychosis to a limited extent, i.e. 0.10% for methylphenidate and 0.21% for dexamphetamine. It is recommended to opt for methylphenidate in adolescents with ADHD. This is confirmed by a Swedish registry study that controlled for a history of psychosis and showed that methylphenidate did not increase the incidence of psychosis after one year, regardless of a history of psychosis.

Psychosis and dyskinesia significantly diminish the quality of life of patients with advanced Parkinson's disease (PD). Available treatment options are unfortunately few and their use is limited by adverse effects. We have recently shown that activation of metabotropic glutamate 2 and 3 (mGlu2/3) receptors produced significant relief of L-3,4-dihydroxyphenylalanine (L-DOPA)-induced psychosis-like behaviours (PLBs) and dyskinesia in experimental models of PD. Here, using the highly-selective mGlu2 positive allosteric modulator (PAM) LY-487,379, we seek to determine the contribution of selective mGlu2 activation on both L-DOPA-induced PLBs and dyskinesia, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate. We first determined the pharmacokinetic (PK) profile of LY-487,379 in the common marmoset, following which we administered it (0.1, 1 and 10 mg/kg) or its vehicle to 6 MPTP-lesioned marmosets previously exposed to L-DOPA to elicit stable PLBs and dyskinesia. We found that LY-487,379 provided a ≈45% reduction of the global PLBs observed and reduced global dyskinesia score by ≈ 55%. Moreover, LY-487,379 enhanced the anti-parkinsonian effect of L-DOPA, by reducing global parkinsonian score by ≈ 15%. Our data suggest that selective mGlu2 positive allosteric modulation with LY-487,379 may represent a potential therapeutic approach to alleviate both L-DOPA-induced PLBs and dyskinesia in PD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Drug induced sleep endoscopy (DISE) has emerged as a promising tool for customizing the adequate surgical approach to relieve airway obstruction in sleep apnea patients. We aimed to compare propofol, dexmedetomidine or ketofol with regards their efficacy and safety for sedation in patients with obstructive sleep apnea (OSA) undergoing DISE procedure., Methods: Sixty adult OSA patients scheduled for DISE procedure were randomly allocated into three equal groups to receive either propofol (group P), dexmedetomidine (group D), or ketofol (group K). Incidence of oxygen desaturation <90%, hemodynamic variables, time to achieve sufficient sedation level, recovery time, patients' and endoscopists' satisfaction, and incidence of adverse effects were recorded., Results: Higher incidence of oxygen desaturation <90% was observed in group P as compared to groups D and K (70%, 35%, and 30% respectively, P=0.021*). Group D showed a significantly longer time to reach target sedation level, prolonged recovery time with more consumption of rescue propofol as compared to group P and group K (P=0.000*, 0.000*, 0.000* respectively). Heart rate values were lower in group D after the loading dose till 30 min postoperative as compared to the other two groups, while blood pressure was lower in both P and D groups at five, 10, 15 min, and on reaching recovery room compared to K group. Two patients in the K group had psychomimetic symptoms with no difference between groups as regards other adverse events or patients' and endoscopist's satisfactions., Conclusions: Dexmedetomidine and ketofol provided a safe respiratory profile compared to propofol during DISE without significant hemodynamic adverse events.

Rationale: Schizophrenia and stimulant-induced psychosis (SIP) represent two different forms of psychotic disorder, with different etiologies. While many of the symptoms of psychosis are common to both disorders, there have been few direct comparisons between these conditions, especially when controlling for stimulant use in individuals with schizophrenia., Objectives: We directly compared both psychotic disorders with a comprehensive battery of clinical, neurocognitive and neuroanatomical measures. This included one group with SIP (and concurrent stimulant dependence) and two groups with schizophrenia (either with or without concurrent stimulant dependence)., Methods: Ninety-six participants were recruited from a marginalized urban population, which included 39 with SIP (and concurrent stimulant dependence), 18 with schizophrenia (without stimulant dependence), and 39 with schizophrenia (with concurrent stimulant dependence). All subjects had extensive clinical and neurocognitive evaluations, complemented with structural MRI including diffusion tensor imaging (DTI) sequences to determine regional brain volumes and white matter connectivity., Results: Both positive and negative symptoms were greater in the SZ-dependent group than the other two. Neurocognitive function was broadly similar. The structural brain imaging revealed lateralized changes to the left parietal/temporal lobe, in which regional volumes were smaller in the SZ-dependent than the SZ-non-dependent group. DTI analysis indicated extensive decreases in fractional anisotropy, with parallel increases in radial diffusivity, in the SIP group compared to the SZ-dependent group., Conclusions: These findings reveal both similarities and differences between SIP and schizophrenia. Furthermore, schizophrenia with concurrent stimulant dependence may be associated with a different clinical and neuroanatomical profile as compared to schizophrenia alone.

Methamphetamine is a highly addictive psychostimulant. A subset of methamphetamine users develops methamphetamine-associated psychosis (MAP), which causes poorer prognoses and cognitive function than those with no psychosis (MNP). Comprehensive and integrative summaries of studies utilizing various neuroimaging modalities (structural, functional, and neurochemical) are limited. We conducted a systematic review of literature regarding clinical neuroimaging research published between January 1988 and July 2018 using the PubMed, Web of Science, Scopus, and ScienceDirect databases. Studies comparing the neuroimaging of patients with MAP with healthy controls or patients with MNP or schizophrenia were included to understand the distinct profiles associated with MAP. A total of six structural, three functional, and three neurochemical studies were reviewed. A general trend was identified that showed MAP-related brain alterations were mainly in the frontal lobe (especially the orbitofrontal cortex), striatum, and limbic systems (amygdala and hippocampus). Furthermore, some clinical manifestations, such as the severity of psychotic symptoms and cognitive performance, were correlated with neuroimaging abnormalities. In summary, distinct structural, functional, and neurochemical changes, especially in the frontostriatal circuit and network dynamic systems, play critical roles in the pathophysiology of MAP. Future studies using longitudinal study designs and including individuals with MNP and schizophrenia as controls are warranted., (Copyright © 2019. Published by Elsevier B.V.)

A BDNF rs6265 [A/A] by gender by cannabis use interaction has been associated with age of onset of psychosis (AoP). We examined the gender and cannabis use-adjusted association between BDNF rs6265 [G>A] and AKT1 rs2494732 [T>C] and AoP. Data from 167 Caucasians on AoP and age at first regular cannabis use were collected. Kaplan-Meier and Cox regression analyses were conducted. A trend level gene-gender interaction effect was observed for the BDNF rs6265 A/A genotype, controlling for age at first regular cannabis use. Larger collaborative research projects are required to further investigate this effect., (Copyright © 2019. Published by Elsevier B.V.)

Background: Positive psychotic symptoms have consistently been associated with methamphetamine use but the presence of a negative symptom cluster remains unclear. We used exploratory factor analysis to examine whether a discrete negative syndrome could be delineated among methamphetamine users, and to examine the clinical correlates of this syndrome., Method: Participants (N = 154) were people who used methamphetamine at least monthly and did not meet DSM-IV diagnostic criteria for lifetime schizophrenia. Scores on the Brief Psychiatric Rating Scale for the past month were subject to exploratory factor analysis. Latent class analysis was applied to resultant factor scores to determine whether negative and positive factors were experienced by the same participants. Past-month substance use measures were days of use for each drug type and methamphetamine dependence assessed using the Severity of Dependence Scale., Results: We articulated a three-factor model including 'positive/activation symptoms' (e.g. suspiciousness, hallucinations, conceptual disorganisation, tension), 'affective symptoms' (e.g. depression, anxiety) and 'negative symptoms' (e.g. blunted affect, motor retardation). Positive-activation and affective symptoms (but not negative symptoms) were positively correlated with past month days of methamphetamine use (r = 0.16; r = 0.25) and severity of dependence (r = 0.24; r = 0.41). Negative symptoms were correlated with heroin (r = 0.24) and benzodiazepine use (r = 0.21). Latent class analysis revealed a three-class model comprising a positive-symptom class (44%, high positive-activation, low negative symptoms), a negative-symptom class (31%, low positive-activation, high negative symptoms), and a low-symptom class (38%, low on all factors)., Conclusions: A negative symptom syndrome exists among people who use methamphetamine, but this appears related to polysubstance use rather than forming a part of the psychotic syndrome associated with methamphetamine use. Overlooking the role of polysubstance use on negative symptoms may conflate the profiles of methamphetamine-associated psychosis and schizophrenia., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Methamphetamine-associated psychotic symptoms are common among regular users, and can overlap with the emergence of a primary psychotic disorder. In contrast to previous research, this retrospective observational study aims to describe the characteristics of young people experiencing early psychosis who use methamphetamine regularly. We also aimed to investigate associations between regular methamphetamine use and markers of psychosocial functioning, psychosis outcomes and substance use., Method: This study involved 116 young people (19 using methamphetamine regularly) referred to the Camperdown Early Intervention in Psychosis Service from January 2015 to January 2016. Variables including demographic information, psychosocial functioning and psychosis outcomes were collected on referral to the service, updated throughout treatment and at discharge., Results: There were significant associations found between regular methamphetamine use and a criminal history (p<0.001), regular cannabis use ( p =0.002) and regular nicotine use ( p <0.001)., Conclusion: This study suggests that in early psychosis, regular methamphetamine use could signify a subgroup of young people who use multiple substances and may engage in criminal activity. Addressing substance use in early psychosis may be an important treatment target for this vulnerable group of young people.

Background: Current evidence suggests that women are more sensitive to the effects of cannabinoids. The aim of this study was to investigate the relevance of sex in the association of synthetic cannabinoid (SC) use with psychosis and agitation., Methods: A retrospective chart review was conducted for patients admitted to a psychiatric unit (2014-2016) to extract information on demographic factors, use of substances, clinical symptoms, and pharmacologic treatments. Study groups were defined as SC users (anyone who reported use of SCs over the past 3 months), cannabis users (positive toxicology screen for Δ⁹-tetrahydrocannabinol [THC]), and controls (those who denied use of SCs over the past 3 months and had negative toxicology for THC)., Results: Digital charts of 983 patients were reviewed. A total of 162 subjects reported use of SCs over the past 3 months (76% male), and 292 subjects had positive toxicology screen for THC (67% male). A total of 38.9% of SC users (n = 63) had positive urine toxicology screen for THC. SC users had higher risks of psychotic presentations (adjusted odds ratio [AOR] = 3.390; 95% CI, 1.390-8.267) and agitation (AOR = 4.643; 95% CI, 1.974-10.918) compared to the controls. While women had lower rates of psychosis than men in the cannabis and control groups, the rates were markedly potentiated with SC use to high levels (79%) approximately equal to that seen in men (80%). There was also a significant interaction between SC use and sex for agitation (AOR = 0.308; 95% CI, 0.117-0.808). Female SC users were significantly more agitated than male SC users (73.7% vs 47.6%, respectively, P = .005)., Conclusions: SC users are more likely than nonusers to be psychotic or agitated in an inpatient setting. The potentiated rates of psychosis and agitation with SC use in women suggest that they may have a greater sensitivity to these synthetic compounds.​., (© Copyright 2019 Physicians Postgraduate Press, Inc.)

Background: Khat is an amphetamine like psychostimulant chewed by over 10 million people globally. Khat use is thought to increase the risk of psychosis among its chewers. The evidence around this however remains inconclusive stemming from the scanty number of studies in this area and small study sample sizes. We undertook a large household survey to determine the association between psychotic symptoms and khat chewing in a rural khat growing and chewing population in Kenya., Methods: For this cross-sectional household survey, we randomly selected 831 participants aged 10 years and above residing in the Eastern region of Kenya. We used the psychosis screening questionnaire (PSQ) to collect information on psychotic symptoms and a researcher designed sociodemographic and clinical questionnaire to collect information on its risk factors. We used descriptive analysis to describe the burden of khat chewing and other substance use as well as rates and types of psychotic symptoms. Using a univariate and multivariate analyses with 95% confidence interval, we estimated the association between khat chewing and specific psychotic symptoms., Results: The prevalence of current khat chewing in the region was at 36.8% (n = 306) with a male gender predominance (54.8%). At least one psychotic symptom was reported by 16.8% (n = 168) of the study population. Interestingly, psychotic symptoms in general were significantly prevalent in women (19.5%) compared to men (13.6%) (p = 0.023). Khat chewing was significantly associated with reported strange experiences (p = 0.024) and hallucinations (p = 0.0017), the two predominantly reported psychotic symptoms. In multivariate analysis controlling for age, gender, alcohol use and cigarette smoking, there was a positive association of strange experiences (OR, 2.45; 95%CI, 1.13-5.34) and hallucination (OR, 2.08; 95% C.I, 1.06-4.08) with khat chewing. Of note was the high concurrent polysubstance use among khat chewers specifically alcohol use (78.4%) and cigarette smoking (64.5%)., Conclusions: Psychotic symptoms were significantly elevated in khat users in this population. Future prospective studies examining dose effect and age of first use may establish causality.

Objectives: The psychiatric symptom profile of methamphetamine-associated psychosis (MAP) has varied considerably across studies of different research designs. We performed a systematic review to examine the available evidence for specific psychotic symptoms associated with MAP, including the clinical course and longitudinal changes in this symptom profile., Methods: Five key electronic databases were searched to identify studies that examined the symptom profile or clinical course of MAP in individuals identified as having MAP. The reporting of specific psychiatric symptoms, and duration of symptoms where available, was recorded for each study., Results: Ninety-four articles were identified (n = 7387), including case-control (k = 29), cross-sectional (k = 20), experimental (k = 6), case report (k = 29), and longitudinal (k = 20) studies. Persecutory delusions, auditory and visual auditory hallucinations were by far the most commonly reported symptoms (reported in 65-84% of studies). Hostility, conceptual disorganization, and depression were reported in a large proportion of studies (31-53%). Negative symptoms were mostly absent (<20%). The median percentage of participants with persistent psychotic symptoms (>1 month duration) across studies was 25% (excluding case reports)., Conclusion: Persecutory delusions, auditory and visual hallucinations, hostility, depression and conceptual disorganization are central to MAP, whereas negative psychotic symptoms are typically absent. An overrepresentation of institutionalized or male participants may have overemphasized negative symptoms and underreported affective symptoms in past research. Symptoms of MAP may persist beyond one month after drug cessation in some individuals. Clinicians are encouraged to manage affective symptoms in MAP individuals, and monitor for the development of chronic psychotic symptoms.

Synthetic cannabinoid (SC) products have gained popularity as abused drugs over the past decade in many countries. The SCs broadly impact psychological state (e.g., mood, suicidal thoughts and psychosis) and physiological functions (e.g., cardiovascular, gastrointestinal and urinary). This review is about the effects of SCs on psychotic symptoms in clinical settings and the potentially relevant chemistry and mechanisms of action for SCs. Induction of psychotic symptoms after consuming SC products were reported, including new-onset psychosis and psychotic relapses. The role of SCs in psychosis is more complex than any single chemical component might explain, and these effects may not be a simple extension of the typical effects of cannabis or natural cannabinoids., (Copyright © 2018. Published by Elsevier B.V.)

Antipsychotic drugs, including both typical such as haloperidol and atypical such as clozapine, remain the current standard for schizophrenia treatment. These agents are relatively effective in treating hallucinations and delusions. However, cognitive deficits are at present essentially either persistent or exacerbated following chronic antipsychotic drug exposure. This underlines the need of new therapeutic approaches to improve cognition in treated schizophrenia patients. Our previous findings suggested that upregulation of histone deacetylase 2 (HDAC2) expression upon chronic antipsychotic treatment may lead to negative effects on cognition and cortical synaptic structure. Here we tested different phenotypes of psychosis, synaptic plasticity, cognition and antipsychotic drug action in HDAC2 conditional knockout (HDAC2-cKO) mice and controls. Conditional depletion of HDAC2 function in glutamatergic pyramidal neurons led to a protective phenotype against behavior models induced by psychedelic and dissociative drugs, such as DOI and MK801, respectively. Immunoreactivity toward synaptophysin, which labels presynaptic terminals of functional synapses, was decreased in the frontal cortex of control mice chronically treated with clozapine - an opposite effect occurred in HDAC2-cKO mice. Chronic treatment with the class I and class II HDAC inhibitor SAHA prevented via HDAC2 the disruptive effects of MK801 on recognition memory. Additionally, chronic SAHA treatment affected transcription of numerous plasticity-related genes in the frontal cortex of control mice, an effect that was not observed in HDAC2-cKO animals. Together, these findings suggest that HDAC2 may represent a novel target to improve synaptic plasticity and cognition in treated schizophrenia patients., (Published by Elsevier Ltd.)

Background and Aims: To review early case reports and experimental inductions of amphetamine and methamphetamine psychosis, prior to the prohibition of these drugs, to gain a better understanding of the nature and aetiology of methamphetamine psychosis., Methods: Papers considered were historical case reports and case series of psychosis relating to the use and misuse of prescription amphetamine, focusing upon papers by Young & Scoville (1938), Connell (1958), and three subsequent experimental studies published in the early 1970s (Griffith 1972, Angrist & Gershon 1970 and Bell 1973), where psychosis was induced in volunteers using high-dose amphetamine and methamphetamine., Results: High-dose methamphetamine and amphetamine can result in a paranoid psychosis which remits rapidly (within days) of discontinuing use. The central feature is paranoia occurring in a clear state of consciousness. This may be accompanied by other psychotic symptoms (e.g. hallucinations). Pre-existing schizophrenia is not necessary, and the syndrome is not due to sleep deprivation., Conclusions: Research findings from the 1930s to the 1970s suggest that paranoid psychosis should be considered a probable consequence of high-dose methamphetamine use. Individuals who experience psychotic symptoms for any substantive period after intoxication has ended should be suspected of having a functional non-organic psychosis, or a latent vulnerability thereto., (© 2018 Society for the Study of Addiction.)

Background: Methamphetamine use is associated with a variety of negative health outcomes, including psychosis. The frontal cortex serotonin receptors are thought to contribute to psychosis-like behaviors. This study investigated changes in serotonergic markers in the frontal cortex following methamphetamine self-administration and hallucinogenic drug-induced behavior., Methods: Consistent with previously published studies, freely cycling male and female rats were allowed to self-administer methamphetamine (males: 0.12 mg/infusion; females: 0.09 mg/infusion) or saline (10 µL) for 7 days. On the day following self-administration or following 10 days of extinction training, animals were given the serotonin 2A/2C agonist, 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (2 mg/kg, i.p.), and head twitches were analyzed. Autoradiography was also used to assess serotonin receptors and transporters in the frontal cortex following self-administration., Results: Methamphetamine self-administration led to an increase in DOI-induced head-twitch behavior compared to saline only on the day following self-administration. Increases in serotonin receptors in the orbitofrontal cortex and decreases in serotonin transporters in the orbitofrontal cortex and infralimbic cortex were observed following methamphetamine self-administration as assessed by autoradiography., Conclusions: Methamphetamine self-administration was associated with serotonergic alterations in the frontal cortex, which may underlie behavioral changes related to methamphetamine-associated psychosis., (© The Author(s) 2018. Published by Oxford University Press on behalf of CINP.)

Background: It aimed to observe the effect of electro-acupuncture on the improvement of psychiatric symptoms, as well as anxiety and depression in methamphetamine (MA) addicts during abstinence using randomized controlled trials., Methods: All patients in the present study received compulsory drug detoxification in Shanghai Drug Rehabilitation Center. All patients were enrolled consecutively from June 2014 to February 2015; data collection was completed in March 2015. According to the randomized, single-blind and control principle, 68 men MA addicts were randomly divided into 2 groups: electro-acupuncture (EA) and sham electro-acupuncture (sham-EA) groups. Patients were given 20 minutes EA or sham-EA treatment every Monday, Wednesday, and Friday, with a total of 4 weeks. Positive and Negative Syndrome Scale (PANSS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD) were used to evaluate the patients' psychotic symptoms, anxiety and depression before treatment and after receiving treatment with 1 to 4 weeks, respectively., Results: EA could effectively improve the symptoms of psychosis, anxiety, and depression during abstinence in patients with MA addiction. In terms of PANSS score, the scores for positive symptoms and general psychopathological symptoms in patients after receiving 1 to 4 weeks of treatment were significantly decreased compared with the control group, while the score for negative symptoms was significantly decreased after receiving 2 and 4 weeks of treatment. For the HAMA score, the psychotic anxiety scores in patients receiving 1 to 4 weeks of treatment were significant lower than the control group. In terms of HAMD score, there was a significant reduction in anxiety/somatization and sleep disturbance scores after the 4 weeks of EA treatment., Conclusion: Electroacupuncture helps to improve psychiatric symptoms and anxiety and depression in MA addicts during abstinence, and promote rehabilitation of patients.

Cannabis use has been associated with psychosis and cognitive dysfunction. Some evidence suggests that the acute behavioral and neurocognitive effects of the main active ingredient in cannabis, (-)-trans-Δ9-tetrahydrocannabinol (∆9-THC), might be modulated by previous cannabis exposure. However, this has not been investigated either using a control group of non-users, or following abstinence in modest cannabis users, who represent the majority of recreational users. Twenty-four healthy men participated in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject, ∆9-THC challenge study. Compared to non-users (N=12; <5 lifetime cannabis joints smoked), abstinent modest cannabis users (N=12; 24.5±9 lifetime cannabis joints smoked) showed worse performance and stronger right hemispheric activation during cognitive processing, independent of the acute challenge (all P≤0.047). Acute ∆9-THC administration produced transient anxiety and psychotomimetic symptoms (all P≤0.02), the latter being greater in non-users compared to users (P=0.040). Non-users under placebo (control group) activated specific brain areas to perform the tasks, while deactivating others. An opposite pattern was found under acute (∆9-THC challenge in non-users) as well as residual (cannabis users under placebo) effect of ∆9-THC. Under ∆9-THC, cannabis users showed brain activity patterns intermediate between those in non-users under placebo (control group), and non-users under ∆9-THC (acute effect) and cannabis users under placebo (residual effect). In non-users, the more severe the ∆9-THC-induced psychotomimetic symptoms and cognitive impairments, the more pronounced was the neurophysiological alteration (all P≤0.036). Previous modest cannabis use blunts the acute behavioral and neurophysiological effects of ∆9-THC, which are more marked in people who have never used cannabis., (Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.)

This study examines whether illicit amphetamine use is associated with differences in the prevalence of specific psychiatric symptoms in a community sample of individuals diagnosed with schizophrenia or affective psychotic disorders. Data was drawn from the Australian Survey of High Impact Psychosis. The Diagnostic Interview for Psychosis was used to measure substance use and psychiatric symptoms. Participants had used amphetamine within their lifetime and had an ICD-10 diagnosis of schizophrenia (n = 347) or an affective psychotic disorder (n = 289). The past year prevalence of psychiatric symptoms was compared among those who had used amphetamine in the past year (past-year use, 32%) with those who had not (former use, 68%). Univariate logistic regression analysis indicated that past-year users with schizophrenia had a significantly higher past year prevalence of hallucinations, persecutory delusions, racing thoughts, dysphoria, and anhedonia relative to former amphetamine users with schizophrenia. There were no significant differences in symptoms between past-year and former users with affective psychotic disorders. The relationship between amphetamine use and specific psychiatric symptoms varies across different psychotic disorders. Amphetamine use may hinder prognosis by exacerbating symptoms of schizophrenia through dopaminergic dysfunctions or depressive vulnerabilities, however, this needs to be confirmed by prospective longitudinal research., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Structural and functional changes in the lateral temporal language areas have been related to formal thought disorder (FTD) in schizophrenia. Continuous, natural speech production activates the right lateral temporal lobe in schizophrenia, as opposed to the left in healthy subjects. Positive and negative FTD can be elicited in healthy subjects by glutamatergic NMDA blockade with ketamine. It is unclear whether the glutamate system is related to the reversed hemispheric lateralization during speaking in patients. In a double-blind, crossover, placebo-controlled study, 15 healthy, male, right-handed volunteers overtly described 7 pictures for 3 min each while BOLD signal changes were acquired with fMRI. As a measure of linguistic demand, the number of words within 20 s epochs was correlated with BOLD responses. Participants developed S-ketamine-induced psychotic symptoms, particularly positive FTD. Ketamine vs placebo was associated with enhanced neural responses in the right middle and inferior temporal gyri. Similar to a previous fMRI study in schizophrenia patients vs healthy controls applying the same design, S-ketamine reversed functional lateralization during speech production in healthy subjects. Results demonstrate an association between glutamatergic imbalance, dysactivations in lateral temporal brain areas, and FTD symptom formation.

Background and Objective: Recreational use of salvia divinorum (salvia), a potent, naturally occurring hallucinogen, is on the rise internationally. Despite the paucity of information about its long-term health effects, salvia is readily available and generally portrayed as a safe non-addictive substance., Methods and Results: We report on two patients who presented with an enduring and pervasive pattern of salvia use., Discussion and Conclusions: Evaluating patients for salvia use during clinical assessment is strongly encouraged, especially among young polysubstance users., Scientific Significance: Clinicians should be mindful of the multifaceted psychiatric effects of salvia, including the potential for a use disorder. (Am J Addict 2018;27:163-165)., (© 2018 American Academy of Addiction Psychiatry.)

Accumulating evidence suggests that neuroinflammation is one of the important etiologic factors of abusive and neuropsychiatric disorders. Platelet-activating factor (PAF) is potent proinflammatory lipid mediat1or and plays a pivotal role in neuroinflammatory disorders through the specific PAF receptor (PAF-R). Phencyclidine (PCP) induces a psychotomimetic state that closely resembles schizophrenia. Here, we investigated the role of PAF-R in the abnormal behaviors induced by PCP in mice. Repeated treatment with PCP resulted in a significant increase in PAF-R gene expression in the prefrontal cortex (PFC) and in the hippocampus. This increase was more pronounced in the PFC than hippocampus. Treatment with PCP resulted in a significant increase in nuclear translocation of the nuclear factor kappa beta (NF-κB) p65 and DNA binding activity, indicating that the proinflammatory molecule NF-κB was increased through up-regulation of PAF-R. Consistently, NF-κB activation was significantly protected by the PAF-R antagonist, ginkgolide B (Gink B), in PAF-R knockout mice and by the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC). In addition, PCP-induced abnormal behaviors (i.e., reduced sociability, depression, cognitive impairment, and behavioral sensitization) were significantly attenuated by Gink B, in PAF-R knockout mice, and by PDTC. Importantly, PDTC did not significantly alter the attenuations observed in Gink B-treated mice or PAF-R knockout mice, indicating that NF-κB is a critical target for neuropsychotoxic modulation of PAF-R. Therefore, the results suggest that PAF-R mediates PCP-induced neuropsychotoxicity via a NF-κB-dependent mechanism, and that up-regulation of PAF-R may be associated with schizophrenia-like behavior in animal models., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of experimental psychopathology is to delineate overlapping functional disorders of psychoneurobiologically-defined systems where a set of common symptoms may correspond to a variety of nosological entities. According to the vulnerability model of psychosis, experimental research needs to go beyond categories such as "schizophrenia". Prospective studies of the effects of psychoactive substances in normal control subjects offer several methodological advantages over routine clinical reviews of schizophrenic patients, especially in terms of standardization. Carefully designed studies utilizing a model psychosis paradigm are a step toward symptom-oriented research. Combining psychological and neurobiological techniques, the experimental psychopathological approach can provide us with a valuable tool for psychiatric research.

Rationale: Recent studies have shown that cannabis may disrupt glutamate (Glu) signaling depressing Glu tone in frequent users. Current evidence have also consistently reported lower Glu-levels in various brain regions, particularly in the medial prefrontal cortex (mPFC) of chronic schizophrenia patients, while findings in early psychosis (EP) are not conclusive. Since cannabis may alter Glu synaptic plasticity and its use is a known risk factor for psychosis, studies focusing on Glu signaling in EP with or without a concomitant cannabis-usage seem crucial., Objective: We investigate the effect of cannabis use on prefrontal Glu-levels in EP users vs. both EP non-users and healthy controls (HC)., Methods: Magnetic resonance spectroscopy was used to measure [Glu mPFC ] of 35 EP subjects (18 of whom were cannabis users) and 33 HC. For correlative analysis, neuropsychological performances were scored by the MATRICS-consensus cognitive battery., Results: [Glu mPFC ] was lower in EP users comparing to both HC and EP non-users (p < 0.001 and p = 0.01, respectively), while no differences were observed between EP non-users and HC. A greater [Glu mPFC ]-decline with age was observed in EP users (r = -.46; p = 0.04), but not in EP non-users or HC. Among neuropsychological outcomes, working memory was the only domain that differentiates patients depending on their cannabis use, with users having poorer performances., Conclusions: Cannabis use is associated with reduced prefrontal [Glu mPFC ] and with a stronger Glu-levels decline with age. Glutamatergic abnormalities might influence the cognitive impairment observed in users and have some relevance for the progression of the disease.

Rationale: Decreased GABA B receptor function is proposed to mediate some symptoms of schizophrenia., Objectives: In this study, we tested the effect of CGP7930, a GABA B receptor positive allosteric modulator, on ketamine-induced psychosis-relevant behaviors and hippocampal electrical activity in behaving rats., Methods: Electrodes were bilaterally implanted into the hippocampus, and cannulae were placed into the lateral ventricles of Long-Evans rats. CGP7930 or vehicle was injected intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.), alone or 15 min prior to ketamine (3 mg/kg, subcutaneous) injection. Paired click auditory evoked potentials in the hippocampus (AEP), prepulse inhibition (PPI), and locomotor activity were recorded before and after drug injection., Results: CGP7930 at doses of 1 mg/kg (i.p.) prevented ketamine-induced deficit of PPI. CGP7930 (1 mg/kg i.p.) also prevented the decrease in gating of hippocampal AEP and the increase in hippocampal gamma (65-100 Hz) waves induced by ketamine. Unilateral i.c.v. infusion of CGP7930 (0.3 mM/1 μL) also prevented the decrease in gating of hippocampal AEP induced by ketamine. Ketamine-induced behavioral hyperlocomotion was suppressed by 5 mg/kg i.p. CGP7930. CGP7930 alone, without ketamine, did not significantly affect integrated PPI, locomotion, gating of hippocampal AEP, or gamma waves. CGP7930 (1 mg/kg i.p.) increased heterosynaptically mediated paired pulse depression in the hippocampus, a measure of GABA B receptor function in vivo., Conclusions: CGP7930 reduces the behavioral and electrophysiological disruptions induced by ketamine in animals, and the hippocampus may be one of the neural targets where CGP7930 exerts its actions.

Background and Objective: Bupropion is generally considered safe and is widely used both as a monotherapy and as an augmentation agent for the treatment of major depression. Concerns have been raised about bupropion's propensity to precipitate new psychosis and worsen existing psychotic symptoms, although the mechanism is poorly understood. Three cases are reported in which bupropion use was associated with psychosis. The aim of the study was to explore the risk factors and possible mechanisms of psychosis in each case., Case Reports: Case 1 describes the interaction of cocaine abuse sensitization in a patient who developed psychosis with a lower dosage of bupropion. Cases 2 and 3 discuss the role of traumatic brain injury and structural brain lesions in increasing the risk of psychosis when using bupropion., Conclusions: Cocaine abuse, traumatic brain injury, and preexisting brain lesions appear to be risk factors for developing psychosis in persons taking bupropion. In such cases, clinicians should carefully assess the risks and benefits and closely monitor patients for symptoms of psychosis.

Background: Cannabis-induced psychotic disorder (CIPD) is a psychiatric disorder induced by cannabis consumption. The psychological and psychophysiological features of this disorder are still unknown. We aimed to examine the psychological, personality and psychophysiological features of patients with CIPD. This study is an analytical extension of our previously published data, which previously found prepulse inhibition (PPI) deficits in the CIPD group used in this current paper., Methods: We used a sample of 45 patients with CIPD. After 9 months of follow up, these patients were assessed with a Symptom Checklist-90-R (SCL-90-R) questionnaire of psychopathology, with the Eysenck Personality Questionnaire, and with a psychophysiological paradigm of inhibition of the startle reflex (PPI). These results were compared with a group of patients with schizophrenia and cannabis abuse (SCHZ) ( n = 54); patients with cannabis dependence (CD) ( n = 21); and healthy controls ( n = 50)., Results: CIPD patients obtained significant higher scores in the SCL-90-R subscale of neuroticism. These patients showed PPI percentages similar to SCHZ patients within early attentional levels (30 ms). The variables with greater correlation, and that appeared in the CIPD group were interpersonal sensitivity, depression and phobia., Conclusions: Neurotic symptomatology and difficulties in inhibition of the startle reflex might be risk factors for developing CIPD.

Rationale: The psychostimulant drugs cocaine and methamphetamine are potent indirect dopamine receptor agonists which act through similar but not identical mechanisms. Studies in humans have observed that a large proportion of those who chronically use these drugs experience psychotic symptoms. However, direct comparisons of psychotic symptom severity between cocaine and methamphetamine users are lacking., Objectives: The goal of the present study was to directly compare severity of psychotic symptoms between cocaine- and methamphetamine-dependent individuals. Additionally, we sought to determine how concurrent cocaine + methamphetamine dependence would influence psychotic symptoms., Methods: We recruited 153 polysubstance-using subjects meeting DSM-IV-TR criteria for cocaine dependence, 38 with methamphetamine dependence, and 32 with cocaine + methamphetamine dependence. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) and analyzed using a five-factor model. All participants were also assessed for physical and mental illnesses as well as recent substance use. Most subjects completed a comprehensive neurocognitive battery., Results: While all three groups exhibited high total PANSS scores, the positive symptom subscale was significantly higher in the methamphetamine-dependent (17.03 ± 6.3) than the cocaine-dependent group (13.51 ± 4.12) and non-significantly higher (p = 0.08) than the cocaine + methamphetamine group (14.44 ± 5.50). Groups also differed on demographic variables, viral infection, and other indices of substance use, which were unlikely to account for the difference in positive symptoms. There were only modest differences between groups in neurocognitive function., Conclusions: Methamphetamine dependence was associated with more severe positive symptoms of psychosis than cocaine dependence. Concurrent cocaine + methamphetamine dependence did not increase psychosis severity.

We examined the lifetime experience of hallucinations and delusions associated with transient methamphetamine-related psychosis (MAP), persistent MAP and primary psychosis among a cohort of dependent methamphetamine users. Participants were classified as having (a) no current psychotic symptoms, (n=110); (b) psychotic symptoms only when using methamphetamine (transient MAP, n=85); (c) psychotic symptoms both when using methamphetamine and when abstaining from methamphetamine (persistent MAP, n=37), or (d) meeting DSM-IV criteria for lifetime schizophrenia or mania (primary psychosis, n=52). Current psychotic symptoms were classified as a score of 4 or more on any of the Brief Psychiatric Rating Scale items of suspiciousness, hallucinations or unusual thought content in the past month. Lifetime psychotic diagnoses and symptoms were assessed using the Composite International Diagnostic Interview. Transient MAP was associated with persecutory delusions and tactile hallucinations (compared to the no symptom group). Persistent MAP was additionally associated with delusions of reference, thought interference and complex auditory, visual, olfactory and tactile hallucinations, while primary psychosis was also associated with delusions of thought projection, erotomania and passivity. The presence of non-persecutory delusions and hallucinations across various modalities is a marker for persistent MAP or primary psychosis in people who use methamphetamine., (Copyright © 2017. Published by Elsevier B.V.)

Background: Parkinson's disease (PD) psychosis is encountered in as many as 50% of patients with advanced disease. Treatment options for PD psychosis are few. In fact, only clozapine and pimavanserin have shown efficacy in randomised controlled trials. Clinicians are often reluctant to prescribe the former, due to the risk of agranulocytosis, while the latter is not widely available yet. Because it is already clinically available and exhibits high affinity for serotonin 2A receptors, a target with which both clozapine and pimavanserin interact, we hypothesised that the anti-depressant mirtazapine might be effective to alleviate PD psychosis., Methods: Here, we tested the anti-psychotic potential of mirtazapine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned common marmoset. Five MPTP-lesioned marmosets exhibiting psychosis-like behaviours were administered L-3,4-dihydroxyphenylalanine (L-DOPA) in combination with mirtazapine (0.1, 1 and 10 mg/kg) or vehicle. We also tested the effect of mirtazapine on L-DOPA-induced dyskinesia., Results: The addition of mirtazapine 10 mg/kg to L-DOPA reduced psychosis-like behaviours by 50% (P < 0.05) and dyskinesia by 29% (P < 0.01), when compared to L-DOPA/vehicle. Importantly, the antipsychotic and antidyskinetic effects of mirtazapine were achieved without hindering L-DOPA anti-parkinsonian action., Conclusions: Our results suggest that mirtazapine may be effective to alleviate PD psychosis and, because the drug is clinically available, clinical trials that would assess its anti-psychotic efficacy in PD could be rapidly undertaken, hopefully leading to a new treatment option for this debilitating condition.