Phencyclidine-Like Abuse Liability and Psychosis-Like Neurocognitive Effects of Novel Arylcyclohexylamine Drugs of Abuse in Rodents.

Abuse of novel arylcyclohexylamines (ACX) poses risks for toxicities, including adverse neurocognitive effects. In vivo effects of ring-substituted analogs of phencyclidine (PCP), eticyclidine (PCE), and ketamine are understudied. Adult male National Institutes of Health Swiss mice were used to assess locomotor effects of PCP and its 3-OH, 3-MeO, 3-Cl, and 4-MeO analogs, PCE and its 3-OH and 3-MeO analogs, and ketamine and its deschloro and 2F-deschloro analogs, in comparison with those of methamphetamine (METH), 3,4-methylenedioxymethamphetamine (MDMA), and two benzofuran analogs of MDMA. PCP-like interoceptive effects for all of these ACXs were determined using a food-reinforced drug discrimination procedure in adult male Sprague Dawley rats. A novel operant assay of rule-governed behavior incorporating aspects of attentional set-shifting was used to profile psychosis-like neurocognitive effects of PCP and 3-Cl-PCP in rats, in comparison with cocaine and morphine. PCP-like ACXs were more effective locomotor stimulants than the amphetamines, PCE-like ACXs were as effective as the amphetamines, and ketamine-like ACXs were less effective than the amphetamines. Addition of -Cl, -OH, or -OMe at the 3-position on the aromatic ring did not impact locomotor effectiveness, but addition of -OMe at the 4-position reduced locomotor effectiveness. Lethal effects were induced by drugs with -OH at the 3-position or -OMe at the 3- or 4-position. All novel ACXs substituted at least partially for PCP, and PCP and 3-Cl-PCP elicited dose-dependent psychosis-like neurocognitive deficits in the rule-governed behavior task not observed with cocaine or morphine. Novel ACXs exhibit substantial abuse liability and toxicities not necessarily observed with their parent drugs. SIGNIFICANCE STATEMENT: Novel arylcyclohexylamine analogs of PCP, PCE, and ketamine are appearing on the illicit market, and abuse of these drugs poses risks for toxicities, including adverse neurocognitive effects. These studies demonstrate that the novel ACXs exhibit PCP-like abuse liability in the drug discrimination assay, elicit varied locomotor stimulant and lethal effects in mice, and induce psychosis-like neurocognitive effects in rats.

The Loss of Spatiality and Temporality in Twilight Consciousness: The Emergence of Exogenous Psychosis Induced by Novel Psychoactive Substances.

BACKGROUND: The state of twilight consciousness is marked by a focused narrowing of awareness, maintaining vigilance and attention while simultaneously experiencing perceptual shifts in the surrounding environment. It is crucial to recognize that this twilight state represents not just a contraction but also an expansion of conscious experience. SUMMARY: Substances of abuse, particularly new psychoactive substances, play a significant role in inducing this twilight state. They achieve this by deconstructing essential components of consciousness, such as the perception of time and space. KEY MESSAGE: This paper aimed to explore the phenomenon of the twilight state of consciousness and shed light on how new psychoactive substances can alter the perception of time and space during this twilight phase, potentially triggering exogenous psychosis. This comprehensive inquiry employs a phenomenological approach to the study of consciousness, recognizing it as the primary tool for ascribing significance to this intricate yet often overlooked aspect of psychopathology.

Methamphetamine use and psychotic symptoms: findings from a New Zealand longitudinal birth cohort.

BACKGROUND: This study examined the association between methamphetamine use and psychotic symptoms in a New Zealand general population birth cohort (n = 1265 at birth). METHODS: At age 18, 21, 25, 30, and 35, participants reported on their methamphetamine use and psychotic symptoms in the period since the previous interview. Generalized estimating equations modelled the association between methamphetamine use and psychotic symptoms (percentage reporting any symptom, and number of symptoms per participant). Confounding factors included childhood individual characteristics, family socioeconomic circumstances and family functioning. Long term effects of methamphetamine use on psychotic symptoms were assessed by comparing the incidence of psychotic symptoms at age 30-35 for those with and without a history of methamphetamine use prior to age 30. RESULTS: After adjusting for confounding factors and time-varying covariate factors including concurrent cannabis use, methamphetamine use was associated with a modest increase in psychosis risk over five waves of data (adjusted odds ratio (OR) 1.33, 95% confidence interval (CI) 1.03-1.72 for the percentage measure; and IRR 1.24, 95% CI 1.02-1.50 for the symptom count measure). The increased risk of psychotic symptoms was concentrated among participants who had used at least weekly at any point (adjusted OR 2.85, 95% CI 1.21-6.69). Use of methamphetamine less than weekly was not associated with increased psychosis risk. We found no evidence for a persistent vulnerability to psychosis in the absence of continuing methamphetamine use. CONCLUSION: Methamphetamine use is associated with increased risk of psychotic symptoms in the general population. Increased risk is chiefly confined to people who ever used regularly (at least weekly), and recently.

Differences between substance-induced psychotic disorders and non-substance-induced psychotic disorders and diagnostic stability. / Diferencias y estabilidad diagnóstica entre trastornos psicóticos inducidos por sustancias y trastornos psicóticos no inducidos.

Several hypotheses have been proposed to explain the comorbidity between psychotic disorders and substance use, one of them being the capacity of some to induce psychotic symptoms, although the transition from psychotic episodes induced by substances to schizophrenia has been less studied. In this study, differential variables between patients with induced and non-induced psychosis are determined, and the evolution and change of diagnosis of those induced to schizophrenia in the follow-up is analyzed. This is an observational case-control study with 238 patients admitted to the acute care unit for psychotic episodes between December 2003 and September 2011. The group of non-substance-induced psychotic disorders (NSIPD) included 127 patients, with 111 in the substance-induced (SIPD) group, according to the International Classification of Diseases. Sociodemographic and clinical characteristics, personal and family history, substance use, diagnostic stability and progression were compared. The NSIPD group showed higher scores in severity and in negative symptoms and more family history of psychosis. The SIPD group presented more personal history of personality disorder and family history of addictions and more positive symptoms At 6 years of follow-up, 40.9% of ISDP changed to a diagnosis of schizophrenia, presenting more family history of psychotic disorders and worse progression with more visits to the emergency department and readmissions, than subjects who maintained diagnostic stability. Therefore, special attention should be paid to this group of patients because of the potential severity and the increased risk of developing a chronic psychotic disorder.

Se han propuesto distintas hipótesis para explicar la comorbilidad entre trastornos psicóticos y por consumo de sustancias, siendo una de ellas la capacidad de algunas de inducir cuadros psicóticos, aunque la transición de episodios psicóticos inducidos por sustancias a esquizofrenia ha sido menos estudiada. En este trabajo se determinan variables diferenciales entre individuos con psicosis inducidas y no inducidas, y se analiza la evolución y el cambio de diagnóstico de las inducidas a esquizofrenia en el seguimiento. Es un estudio observacional de casos y controles con 238 pacientes ingresados en la unidad de agudos de un Hospital General de Madrid (España) por episodios psicóticos entre diciembre de 2003 y septiembre de 2011. Se incluyeron 127 en el grupo de trastornos psicóticos no inducidos por sustancias (TPNIS) y 111 en el de inducidos por sustancias (TPIS), según la Clasificación Internacional de Enfermedades. Se compararon características sociodemográficas, clínicas, antecedentes personales y familiares, de consumo de sustancias, estabilidad diagnóstica y evolución. El grupo de TPNIS presentó mayores puntuaciones en gravedad y sintomatología negativa mientras que el de TPIS tuvo más antecedentes personales de trastorno de personalidad y familiares de adicciones, y más sintomatología positiva. A los seis años un 40,9% de TPIS cambió a diagnóstico de esquizofrenia, presentando más antecedentes familiares de trastornos psicóticos y de adicciones, y una peor evolución con más visitas a urgencias y reingresos que los sujetos con estabilidad diagnóstica. Por tanto, habrá que prestar especial atención a este grupo de sujetos por su potencial gravedad y por el mayor riesgo de desarrollar un trastorno psicótico crónico.

Psychosis with Methylphenidate or Amphetamine in Patients with ADHD.

BACKGROUND: The prescription use of the stimulants methylphenidate and amphetamine for the treatment of attention deficit-hyperactivity disorder (ADHD) has been increasing. In 2007, the Food and Drug Administration mandated changes to drug labels for stimulants on the basis of findings of new-onset psychosis. Whether the risk of psychosis in adolescents and young adults with ADHD differs among various stimulants has not been extensively studied. METHODS: We used data from two commercial insurance claims databases to assess patients 13 to 25 years of age who had received a diagnosis of ADHD and who started taking methylphenidate or amphetamine between January 1, 2004, and September 30, 2015. The outcome was a new diagnosis of psychosis for which an antipsychotic medication was prescribed during the first 60 days after the date of the onset of psychosis. To estimate hazard ratios for psychosis, we used propensity scores to match patients who received methylphenidate with patients who received amphetamine in each database, compared the incidence of psychosis between the two stimulant groups, and then pooled the results across the two databases. RESULTS: We assessed 337,919 adolescents and young adults who received a prescription for a stimulant for ADHD. The study population consisted of 221,846 patients with 143,286 person-years of follow up; 110,923 patients taking methylphenidate were matched with 110,923 patients taking amphetamines. There were 343 episodes of psychosis (with an episode defined as a new diagnosis code for psychosis and a prescription for an antipsychotic medication) in the matched populations (2.4 per 1000 person-years): 106 episodes (0.10%) in the methylphenidate group and 237 episodes (0.21%) in the amphetamine group (hazard ratio with amphetamine use, 1.65; 95% confidence interval, 1.31 to 2.09). CONCLUSIONS: Among adolescents and young adults with ADHD who were receiving prescription stimulants, new-onset psychosis occurred in approximately 1 in 660 patients. Amphetamine use was associated with a greater risk of psychosis than methylphenidate. (Funded by the National Institute of Mental Health and others.).

Reassessment of amphetamine- and phencyclidine-induced locomotor hyperactivity as a model of psychosis-like behavior in rats.

Locomotor hyperactivity induced by psychotomimetic drugs, such as amphetamine and phencyclidine, is widely used as an animal model of psychosis-like behaviour and is commonly attributed to an interaction with dopamine release and N-methyl-D-aspartate (NMDA) receptors, respectively. However, what is often not sufficiently taken into account is that the pharmacological profile of these drugs is complex and may involve other neurotransmitter/receptor systems. Therefore, this study aimed to assess the effect of three antagonists targeting different monoamine pathways on amphetamine- and phencyclidine-induced locomotor hyperactivity. A total of 32 rats were pre-treated with antagonists affecting dopaminergic, noradrenergic and serotonergic transmission: haloperidol (0.05 mg/kg), prazosin (2 mg/kg) and ritanserin (1 mg/kg), respectively. After 30 min of spontaneous activity, rats were injected with amphetamine (0.5 mg/kg) or phencyclidine (2.5 mg/kg) and distance travelled, stereotypy and rearing recorded in photocell cages over 90 min. Pre-treatment with haloperidol or prazosin both reduced amphetamine-induced hyperactivity although pre-treatment with ritanserin had only a partial effect. None of the pre-treatments significantly altered the hyperlocomotion effects of phencyclidine. These findings suggest that noradrenergic as well as dopaminergic neurotransmission is critical for amphetamine-induced locomotor hyperactivity. Hyperlocomotion effects of phencyclidine are dependent on other factors, most likely NMDA receptor antagonism. These results help to interpret psychotomimetic drug-induced locomotor hyperactivity as an experimental model of psychosis.

Application Prospect of Integrative Omics in Forensic Identification of Methamphetamine-Associated Psychosis.

The clinical symptoms and signs of methamphetamine-associated psychosis (MAP) and schizophrenia are highly similar, but the situation is completely different when MAP and schizophrenia patients need to be assessed for criminal responsibility after they comitted a harmful behavior. Therefore, the distinction between the two psychoses is very important in forensic psychiatry. At present, the identification of these two psychoses is mainly dependent on the corresponding criteria such as the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the Chinese Classification of Mental Disorders Version 3 (CCMD-3). It's challenging to diagnose and distinguish between the two in practical cases due to their similar clinical symptoms and the lack of effective objective indexes. Different from the limitations of single omics, integrative omics intergrates data from multiple dimensions and has been extensively studied in the field of schizophrenia and has achieved some preliminary results. In view of the correlation between MAP and schizophrenia and the potential application value of integrative omics, this paper proposes an integrative omics strategy for MAP pathogenesis and forensic identification, aiming to improve the further understanding of the relationship between the two psychoses and the corresponding pathogenesis. It also provides references for the future exploration of integrative omics in forensic precise identification and effective monitoring and early warning methods.

Risk of depression, suicide and psychosis with hydroxychloroquine treatment for rheumatoid arthritis: a multinational network cohort study.

OBJECTIVES: Concern has been raised in the rheumatology community regarding recent regulatory warnings that HCQ used in the coronavirus disease 2019 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation or psychosis associated with HCQ as used for RA. METHODS: We performed a new-user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and USA). RA patients ≥18 years of age and initiating HCQ were compared with those initiating SSZ (active comparator) and followed up in the short (30 days) and long term (on treatment). Study outcomes included depression, suicide/suicidal ideation and hospitalization for psychosis. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate database-specific calibrated hazard ratios (HRs), with estimates pooled where I2 <40%. RESULTS: A total of 918 144 and 290 383 users of HCQ and SSZ, respectively, were included. No consistent risk of psychiatric events was observed with short-term HCQ (compared with SSZ) use, with meta-analytic HRs of 0.96 (95% CI 0.79, 1.16) for depression, 0.94 (95% CI 0.49, 1.77) for suicide/suicidal ideation and 1.03 (95% CI 0.66, 1.60) for psychosis. No consistent long-term risk was seen, with meta-analytic HRs of 0.94 (95% CI 0.71, 1.26) for depression, 0.77 (95% CI 0.56, 1.07) for suicide/suicidal ideation and 0.99 (95% CI 0.72, 1.35) for psychosis. CONCLUSION: HCQ as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation or psychosis compared with SSZ. No effects were seen in the short or long term. Use at a higher dose or for different indications needs further investigation. TRIAL REGISTRATION: Registered with EU PAS (reference no. EUPAS34497; http://www.encepp.eu/encepp/viewResource.htm? id=34498). The full study protocol and analysis source code can be found at https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine2.

Direction of the relationship between methamphetamine use and positive psychotic symptoms in regular methamphetamine users: evidence from a prospective cohort study.

BACKGROUND: Methamphetamine has been consistently associated with positive psychotic symptoms, but little is known about whether the reverse also occurs. AIMS: This study determined whether the relationship between methamphetamine use and positive psychotic symptoms is bidirectional over 12 months. The impact of lifetime psychotic disorders and methamphetamine dependence on these relationships was also examined. METHOD: A total of 201 regular (at least monthly) primary methamphetamine users were recruited from free needle and syringe programmes in three Australian cities. Data on the frequency of methamphetamine and other drug use (from Timeline Followback inteviews) and the severity of positive psychotic symptoms (using the Brief Psychiatric Rating Scale) in the past 2 weeks were collected in 12 contiguous monthly face-to-face interviews (mean of 9.14/11 (s.d. = 3.16) follow-ups completed). Diagnoses were derived using the Psychiatric Research Interview for DSM-IV Substance and Mental Disorders. RESULTS: The mean age of participants was 31.71 years (s.d. = 8.19) and 39% (n = 77) were women. At baseline 55% (n = 110) were dependent on methamphetamine and 51% (n = 102) had a lifetime psychotic disorder. Cross-lagged dynamic panel models found a significant bidirectional relationship between psychotic symptoms and methamphetamine use (Comparative Fit Index (CFI) = 0.94, standardised root mean square residual (SRMR) = 0.05, root mean square error of approximation (RMSEA) = 0.05, 95% CI 0.04-0.06). The magnitude of the relationship in each direction was similar, and the presence of methamphetamine dependence or a lifetime psychotic disorder did not have an impact on results. CONCLUSIONS: A dynamic, bidirectional relationship between methamphetamine and psychotic symptoms of similar magnitude in each direction was found over 1 year. This suggests integrated treatments that target methamphetamine, psychotic symptoms and their interrelationship may be of most benefit.

Psychosis-Relevant Effects of Intravenous Delta-9-Tetrahydrocannabinol: A Mega Analysis of Individual Participant-Data from Human Laboratory Studies.

INTRODUCTION: There is increasing interest in the relationship between cannabinoids and psychosis. While individual human laboratory studies have been critical in demonstrating that cannabinoids (e.g., delta-9-tetrahydrocannabinol [THC]) can induce acute transient psychosis-like effects in healthy human volunteers, combining data from multiple studies offers a fine-grained view of these effects. METHODS: THC-induced psychosis-relevant effects were examined using a data repository of 10 double-blind, randomized, placebo-controlled, crossover studies with 400 i.v. THC infusions in healthy human volunteers. The Positive and Negative Syndrome scale was used to measure psychotomimetic effects. The profile of symptoms, frequency of a response, its relationship to THC dose and substance use, latent structure in Positive and Negative Syndrome scale response, and the relationships between psychotomimetic and perceptual alteration symptoms were evaluated. RESULTS: Clinically meaningful increases in positive symptoms were noted in 44.75% infusions; conceptual disorganization, hallucinations, blunted affect, somatic concern, motor retardation, and poor attention were the items most frequently altered by THC. The increase in Positive and Negative Syndrome scale positive symptoms was positively associated with THC dose (beta = 11.13, SE = 4.94, Wald χ 2 = 19.88, P < .001) and negatively associated with frequent cannabis use (beta = -0.575, SE = 0.14, Wald χ 2 = 18.13, P < .001). Furthermore, positive symptoms were strongly correlated with Clinician Administered Dissociative States Scale perceptual alterations score (rs = 0.514, P < .001). CONCLUSION: Intravenous administration of THC consistently induces psychotomimetic effects that include symptoms across Positive and Negative Syndrome scale domains. Moreover, healthy individuals who frequently use cannabis have a blunted psychotomimetic response.

Association of Megestrol Use With the Development of New Psychiatric Diagnoses.

OBJECTIVE: To analyze the risk of megestrol, a glucocorticoid and progesterone receptor agonist used to enhance appetite, on the development of a new psychiatric diagnosis. DESIGN AND PARTICIPANTS: Deidentified data of megestrol (n = 706) and propensity score-matched comparison (age, gender, and body mass index) patients (n = 2,118) from January 1, 2001 to June 30, 2018 were obtained from the UT Southwestern patient database. Data were analyzed using a series of conditional binary logistic regressions controlling for comorbidities, pre-existing psychiatric disorders, and number of patient encounters. SETTING: A large academic medical center database of megestrol-treated patients and matched comparison patients was used. MEASUREMENTS AND RESULTS: The regression model showed that megestrol was significantly associated with developing a new psychiatric diagnosis (B = 1.28, Wald χ21 = 83.12, odds ratio [OR] = 3.60, p <0.001). In subgroup analyses, development of cognitive (B = 2.42, Wald χ21 = 16.09, OR = 11.30, p <0.001), mood (B = 1.31, Wald χ21 = 40.38, OR = 3.70, p <0.001), and anxiety (B = 1.72, Wald χ21 = 45.28, OR = 5.60, p <0.001) disorders were also associated with megestrol use. CONCLUSIONS: Patients taking megestrol were significantly more likely to develop a new psychiatric diagnosis than comparison patients. Highest risks were associated with the development of cognitive diagnoses. The findings suggest that megestrol, like other glucocorticoid agonists, is associated with an increased risk of developing a psychiatric disorder. This risk should be considered when determining the risk-to-benefit ratio of megestrol use in patients.

Comparisons of Voxel-Based Morphometric Brain Volumes of Individuals with Methamphetamine-Induced Psychotic Disorder and Schizophrenia Spectrum Disorder and Healthy Controls.

BACKGROUND: Several psychological and neurological pathways are described to explain the emergence and maintenance of psychiatric disorders, and changes in brain volumes and brain activity are observed as correlates of psychiatric disorders. In the present study, we investigated if and to what extent specific voxel-based morphometric brain volume differences could be observed among individuals with methamphetamine-induced psychosis (MAIP) and schizophrenia spectrum disorder (SSD) compared to healthy controls. METHODS: A total of 69 individuals took part in the present study. Of those, 26 were diagnosed with MAIP, 23 with SSD, and 20 were healthy controls. After a thorough psychiatric assessment, participants underwent brain volume measurement. RESULTS: Compared to healthy controls, participants with MAIP had smaller volumes for left caudate and left and right parahippocampal gyrus. Compared to healthy controls, participants with SSD had smaller volumes for the gray and white matter, left amygdala, left hippocampus, left parahippocampal gyrus, left putamen, and the total volume. Compared to individuals with MAIP, individuals with SSD had a lower white matter brain volume. CONCLUSIONS: The pattern of results suggests that individuals with MAIP and SSD showed specific and regional brain atrophies on the left hemisphere, always compared to healthy controls. Given the cross-sectional design, it remains undisclosed if specific and regional brain atrophies were the cause or the consequence of the psychiatric issues.

Psychiatric Aspects of Chloroquine and Hydroxychloroquine Treatment in the Wake of Coronavirus Disease-2019: Psychopharmacological Interactions and Neuropsychiatric Sequelae.

BACKGROUND: Chloroquine and hydroxychloroquine are among several experimental treatments being investigated in the urgent response to the coronavirus disease-2019. With increased use of these medications, physicians need to become knowledgeable of these drugs' neuropsychiatric side effects and interactions with psychiatric medications. OBJECTIVE: Clarify evidence base regarding the psychiatric side effects and psychiatric drug interactions of chloroquine and hydroxychloroquine. METHODS: A literature review was performed in PubMed from 1950 to 2020 regarding psychiatric topics and targeted pharmacological properties of chloroquine and hydroxychloroquine. RESULTS: First, chloroquine and hydroxychloroquine may mildly inhibit CYP2D6 metabolism of psychiatric medications, and psychiatric medications that interfere with CYP2D6 or CYP3A4 activity could alter chloroquine and hydroxychloroquine levels. Second, they may prolong the QT interval, warranting caution with concomitant prescription of other QT prolonging agents. Finally, neuropsychiatric side effects are very uncommon but possible and include a potentially prolonged phenomenon of "psychosis after chloroquine." Hydroxychloroquine has less information available about its neuropsychiatric side effects than chloroquine, with psychosis literature limited to several case reports. Weak evidence suggests a possible association of hydroxychloroquine exposure and increased suicidal ideation. It is not clear whether patients with psychiatric illness are more vulnerable to neuropsychiatric sequela of these medications; however, overdose of these medications by suicidal patients has high risk of mortality. CONCLUSION: The risk of neuropsychiatric side effects of chloroquine and hydroxychloroquine when used for coronavirus disease-2019 treatment is not known. Best practice may include suicide risk assessment for patients treated with hydroxychloroquine. However, delirium is expected to be a more likely etiology of neuropsychiatric symptoms in critically ill patients treated for coronavirus disease-2019, and adjustment disorder is a much more likely etiology of anxiety and depression symptoms than the side effects of chloroquine or hydroxychloroquine.

Nitrous Oxide Inhalant Use Disorder Preceding Symptoms Concerning for Primary Psychotic Illness.

BACKGROUND AND OBJECTIVE: Nitrous oxide has long been used recreationally for its ability to induce euphoria and other deliriant effects. In modern times, it remains a popular, legal, and widely available option for those seeking altered states. Though substance-induced psychotic symptoms have been mentioned in the literature, the potential long-term negative neuropsychiatric effects related to its use have not been well established. METHODS AND RESULTS: This is a patient case report of a young man (N = 1) who initially presented with acute neurological symptoms requiring hospitalization due to heavy nitrous oxide inhalant use, and went on to present with symptoms concerning for a primary psychotic illness over multiple inpatient admissions. He provided both verbal and written consent to share his story for this case report. DISCUSSION AND CONCLUSIONS: It is important to consider nitrous oxide use as a possible contributing factor to the development of primary psychotic illness. SCIENTIFIC SIGNIFICANCE: Current literature suggests that psychosis associated with nitrous oxide use is transient and resolves upon cessation and treatment of vitamin B12 deficiency. Here, we present a patient with risk factors for psychotic illness developing psychotic illness following extensive nitrous oxide use. This report offers a unique perspective of longitudinal follow-up (often not provided with reports on this topic), and illustrates the importance of healthcare providers inquiring about nitrous oxide abuse in patients presenting with early psychotic symptoms. (Am J Addict 2020;29:525-527).

Features of psychological reactions induced by perampanel: A case report.

WHAT IS KNOWN AND OBJECTIVE: Perampanel, an anticonvulsant, might induce psychological reactions. CASE DESCRIPTION: A 70-year-old woman, who had been taking 2500 mg/day levetiracetam, complained of right-hand minor-convulsion. Perampanel of 2 mg/day was additionally prescribed, and the dosage was increased to 4 mg/day. Two weeks after taking 4 mg/day perampanel, she changed her personality and kept insulting her husband; however, the patient herself was aware of her strange behaviour. She regained her normal personality after quitting the perampanel medication. WHAT IS NEW AND CONCLUSION: This self-awareness is crucial to distinguish the perampanel-induced reaction from psychosis.

Acute Illness Associated With Cannabis Use, by Route of Exposure: An Observational Study.

Background: Little is known about the relative harms of edible and inhalable cannabis products. Objective: To describe and compare adult emergency department (ED) visits related to edible and inhaled cannabis exposure. Design: Chart review of ED visits between 1 January 2012 and 31 December 2016. Setting: A large urban academic hospital in Colorado. Participants: Adults with ED visits with a cannabis-related International Classification of Diseases, Ninth or 10th Revision, Clinical Modification (ICD-9-CM or ICD-10-CM), code. Measurements: Patient demographic characteristics, route of exposure, dose, symptoms, length of stay, disposition, discharge diagnoses, and attribution of visit to cannabis. Results: There were 9973 visits with an ICD-9-CM or ICD-10-CM code for cannabis use. Of these, 2567 (25.7%) visits were at least partially attributable to cannabis, and 238 of those (9.3%) were related to edible cannabis. Visits attributable to inhaled cannabis were more likely to be for cannabinoid hyperemesis syndrome (18.0% vs. 8.4%), and visits attributable to edible cannabis were more likely to be due to acute psychiatric symptoms (18.0% vs. 10.9%), intoxication (48% vs. 28%), and cardiovascular symptoms (8.0% vs. 3.1%). Edible products accounted for 10.7% of cannabis-attributable visits between 2014 and 2016 but represented only 0.32% of total cannabis sales in Colorado (in kilograms of tetrahydrocannabinol) during that period. Limitation: Retrospective study design, single academic center, self-reported exposure data, and limited availability of dose data. Conclusion: Visits attributable to inhaled cannabis are more frequent than those attributable to edible cannabis, although the latter is associated with more acute psychiatric visits and more ED visits than expected. Primary Funding Source: Colorado Department of Public Health and Environment.

Cannabis Use and the Risk for Psychosis and Affective Disorders.

Objective: This review discusses the relationship between cannabis use and psychotic, bipolar, depressive, and anxiety disorders, as well as suicide. It summarizes epidemiological evidence from cross-sectional and long-term prospective studies and considers possible etiological mechanisms. Methods: Systematic reviews and methodologically robust studies in the field (from inception to February 2019) were identified using a comprehensive search of Medline, PsychINFO, and Embase and summarized using a narrative synthesis. Results: Consistent evidence, both from observational and experimental studies, has confirmed the important role of cannabis use in the initiation and persistence of psychotic disorders. The size of the effect is related to the extent of cannabis use, with greater risk for early cannabis use and use of high-potency varieties and synthetic cannabinoids. Accumulating evidence suggests that frequent cannabis use also increases the risk for mania as well as for suicide. However, the effect on depression is less clear and findings on anxiety are contradictory with only a few methodologically robust studies. Furthermore, the relationship with common mental disorders may involve reverse causality, as depression and anxiety are reported to lead to greater cannabis consumption in some studies. Pathogenetic mechanisms focus on the effect of tetrahydrocannabinol (THC, the main psychoactive ingredient of cannabis) interacting with genetic predisposition and perhaps other environmental risk factors. Cannabidiol (CBD), the other important ingredient of traditional cannabis, ameliorates the psychotogenic effects of THC but is absent from the high-potency varieties that are increasingly available. Conclusions: The evidence that heavy use of high-THC/low-CBD types of cannabis increases the risk of psychosis is sufficiently strong to merit public health education. Evidence of similar but smaller effects in mania and suicide is growing, but is not convincing for depression and anxiety. There is much current interest in the possibility that CBD may be therapeutically useful.

Methamphetamine-associated psychosis: links to drug use characteristics and similarity to primary psychosis.

Objectives: Despite the prevalence of methamphetamine-associated psychosis, how characteristics of drug use affect the severity and clinical course, and its optimal treatments have not been established. We addressed these questions, assessing clinical features of methamphetamine-associated psychosis, and compared it with primary psychosis.Methods: Hospitalised patients with methamphetamine-associated (n = 70) or primary schizophrenic psychosis (n = 70) were matched on sex, age and duration of psychosis. Association of drug use variables (age at initiation, duration of methamphetamine use) with the Brief Psychiatric Rating Scale (BPRS) scores and psychosis duration were examined for patients with methamphetamine-associated psychosis, and the groups were compared on the BPRS scores.Results: Methamphetamine use initiation age correlated negatively with the BPRS total score and the Activation subscale score; methamphetamine use duration correlated positively with psychosis duration. Methamphetamine-associated psychosis group scored lower on the Hostility-Suspiciousness and Anergia subscales of the BPRS (adjusted p values < .05).Conclusions: Association of early initiation of methamphetamine with psychosis severity may suggest a lasting effect on brain development. Correlation of drug use and psychosis durations may suggest a cumulative effect of methamphetamine exposure. Less severe paranoia and negative symptoms in the methamphetamine-using group could implicate better social functioning of these patients. Further mechanistic studies are warranted.Key pointsEarly initiation of methamphetamine use is associated with psychosis severity.Methamphetamine use duration associates with psychosis duration.Methamphetamine-associated and primary schizophrenic psychoses were similar in symptoms.Methamphetamine psychosis patients were less severe in paranoia and negative symptoms.

Emergencies and critical issues in Parkinson's disease.

Complications from Parkinson's disease may develop over the disease course, sometimes unexpectedly, and require prompt or even urgent medical intervention. The most common are associated with aggravation of motor symptoms; serious non-motor complications, such as psychosis, orthostatic hypotension or sleep attacks, also occur. Here we review such complications, their clinical presentation, precipitating factors and management, including those related to using device-aided therapies. Early recognition and prompt attention to these critical situations is challenging, even for the Parkinson's disease specialist, but is essential to prevent serious problems.

Quinolone-induced psychosis: an updated review.

Quinolones are an antibiotic group widely used due to their antimicrobial action and security profile, however, it has been described neuropsychiatric adverse effects, being induced-psychotic episodes one of the most clinically relevant. Nevertheless, this secondary effect has been scarcely studied. A literature search using PRISMA guidelines was performed between 01/01/1962 and 01/31/2019 on PubMed and ScienceDirect, including manuscripts which described substance-induced psychotic disorder according to DSM-5 and in which the symptomatology was not attributable to an acute confusional state (delirium) or to other induced psychiatric disorders. 459 articles were found, but only 27 manuscripts fulfilled inclusion criteria (n=27 patients, median age of 36.15±16.96 years). Ciprofloxacin, levofloxacin and ofloxacin were the main antibiotics implicated. Quinolone- induced psychosis is a clinical relevant issue due to the high prescription of these antibiotics and the severity of this clinical syndrome. In general, this syndrome can remit in a few days with the withdrawal of the quinolone and performing symptomatic support if it is necessary. Finally, it is important to perform further research on this issue. Keywords: Quinolones, Psychosis, Ciprofloxacin, Levofloxacinn, Psychotic Induced.