Evaluation of the efficacy, safety, and pharmacokinetics of nanodispersible cannabidiol oral solution (150 mg/mL) versus placebo in mild to moderate anxiety subjects: A double blind multicenter randomized clinical trial.

BACKGROUND: Anxiety disorders, an increasingly prevalent global mental health illness, affected approximately 301 million individuals worldwide in 2019. There is an unmet need for the treatment of anxiety disorders, as current therapies are associated with limited response rates, residual symptoms, and adverse effects. OBJECTIVES: To evaluate the efficacy, safety, and pharmacokinetics of nanodispersible cannabidiol (CBD) oral solution versus placebo for the treatment of mild to moderate anxiety disorders. METHODS: This phase 3 prospective, randomized, double blind, parallel group, placebo-controlled, 15-week cohort study took place at multiple sites across India. Eligible participants were randomly assigned to one of the two treatment arms (CBD or placebo) in a 1:1 ratio. RESULTS: 178 participants were randomized to receive CBD (n=89) or placebo (n=89). The study met both primary (GAD-7 and HAM-A scores) and secondary outcomes (CGI-I, CGI-S, PHQ-9 and PSQI scores). The GAD-7 score difference between the end of treatment and baseline for the CBD versus the placebo was -7.02 (S.E: 0.25, 95% CI -7.52; -6.52), p<0.0001. Similarly, the HAM-A score difference at the end of treatment compared to baseline for the CBD versus the placebo was -11.9 (S.E: 0.33, 95% CI -12.6; -11.3), p<0.0001. CONCLUSIONS: Nanodispersible CBD was therapeutically safe with no serious adverse events, well tolerated, and effective for the treatment of mild to moderate anxiety disorders, as well as associated depression and sleep quality disturbances. These results pave way for probable prospective use of nanodispersible CBD formulation for various psychiatry disorders alone or in conjunction with other drugs.

Association of Schizophrenia Risk With Disordered Niacin Metabolism in an Indian Genome-wide Association Study.

Importance: Genome-wide association studies (GWASs) in European populations have identified more than 100 schizophrenia-associated loci. A schizophrenia GWAS in a unique Indian population offers novel findings. Objective: To discover and functionally evaluate genetic loci for schizophrenia in a GWAS of a unique Indian population. Design, Setting, and Participants: This GWAS included a sample of affected individuals, family members, and unrelated cases and controls. Three thousand ninety-two individuals were recruited and diagnostically ascertained via medical records, hospitals, clinics, and clinical networks in Chennai and surrounding regions. Affected participants fulfilled DSM-IV diagnostic criteria for schizophrenia. Unrelated control participants had no personal or family history of psychotic disorder. Recruitment, genotyping, and analysis occurred in consecutive phases beginning January 1, 2001. Recruitment was completed on February 28, 2018, and genotyping and analysis are ongoing. Main Outcomes and Measures: Associations of single-nucleotide polymorphisms and gene expression with schizophrenia. Results: The study population included 1321 participants with schizophrenia, 885 family controls, and 886 unrelated controls. Among participants with schizophrenia, mean (SD) age was 39.1 (11.4) years, and 52.7% were male. This sample demonstrated uniform ethnicity, a degree of inbreeding, and negligible rates of substance abuse. A novel genome-wide significant association was observed between schizophrenia and a chromosome 8q24.3 locus (rs10866912, allele A; odds ratio [OR], 1.27 [95% CI, 1.17-1.38]; P = 4.35 × 10-8) that attracted support in the schizophrenia Psychiatric Genomics Consortium 2 data (rs10866912, allele A; OR, 1.04 [95% CI, 1.02-1.06]; P = 7.56 × 10-4). This locus has undergone natural selection, with the risk allele A declining in frequency from India (approximately 72%) to Europe (approximately 43%). rs10866912 directly modifies the abundance of the nicotinate phosphoribosyltransferase gene (NAPRT1) transcript in brain cortex (normalized effect size, 0.79; 95% CI, 0.6-1.0; P = 5.8 × 10-13). NAPRT1 encodes a key enzyme for niacin metabolism. In Indian lymphoblastoid cell lines, (risk) allele A of rs10866912 was associated with NAPRT1 downregulation (AA: 0.74, n = 21; CC: 1.56, n = 17; P = .004). Preliminary zebrafish data further suggest that partial loss of function of NAPRT1 leads to abnormal brain development. Conclusions and Relevance: Bioinformatic analyses and cellular and zebrafish gene expression studies implicate NAPRT1 as a novel susceptibility gene. Given this gene's role in niacin metabolism and the evidence for niacin deficiency provoking schizophrenialike symptoms in neuropsychiatric diseases such as pellagra and Hartnup disease, these results suggest that the rs10866912 genotype and niacin status may have implications for schizophrenia susceptibility and treatment.

A Cross-sectional Study to Estimate Cardiovascular Risk Factors in Patients with Bipolar Disorder.

BACKGROUND: There is increasing recognition of cardiovascular mortality and comorbidity in bipolar disorder (BD) in the recent times. Framingham 10 years risk of coronary heart disease (CHD) has been a widely accepted as a reliable estimate of cardiovascular risk in the general population. A few studies have estimated the relative risk of developing CHD in BDs, in India. We attempt to present a cross-sectional data from a prospective study to estimate the 10 years cardiovascular risk in BD population. SUBJECTS AND METHODS: A total of 50 patients with BD aged between 20 and 60 years fulfilling the inclusion and exclusion criteria were enrolled into this study. Demographic variables and clinical evaluations including smoking history, medical and pharmacologic treatment history, physical examination, anthropometric measurements, and clinical laboratories for metabolic profiles were assessed. Using the Framingham 10-year risk questionnaire, the risk for each patient was calculated and compared with that of normal healthy control group. RESULTS: The risk of developing a future cardiovascular event was 3.26% in BD and 2.02% in controls. We identified that a higher age at onset of illness, waist-hip ratio, total cholesterol, and unemployment showed a strong positive correlation with future CHD risk whereas administration of valproate, lithium for management of BD, higher socioeconomic status and educational status, and nonsmokers was associated negatively with the future CHD risk. CONCLUSIONS: It appears that there is a significant association between BD and metabolic factors, CHD, sociodemographic variables, and underscores the predictive ability of Framingham risk score in detecting cardiovascular diseases.

Effects of oral versus long-acting antipsychotics on social functioning: A psychiatrists' survey in India.

BACKGROUND: Schizophrenia is associated with functional challenges for patients; relapses in schizophrenia may lead to increased treatment costs and poor quality of life. OBJECTIVE: This SUSTAIN-I study was conducted to establish psychiatrists' perspective on impact of long-acting injectables (LAIs) antipsychotics on the socio-economic and functional burden of schizophrenia. METHODS: This cross-sectional, survey-based study was conducted in 5 cities in India. Psychiatrists (≥5years of experience) working in clinics, psychiatric, government hospitals and rehabilitation centers were included and administered a specially designed questionnaire to elicit information on their clinical practice and prescription patterns. Perceived treatment costs for LAI versus oral antipsychotic treatments (OATs) and relapse rates were assessed. Descriptive statistics were used to summarize results. RESULTS: Total 31 physicians completed this survey. In acute phase, OAT prescription was higher whereas chronic patients were treated with either OATs or LAIs. Treatment with LAIs was the preferred treatment in 9% of chronic cases. Reduced relapse rates were observed with LAI treatment: 12% patients on LAIs relapsed as compared with 60% patients on OATs. Monthly medication cost for oral medications was lower ($8-$17) than short-acting injectables ($22-$50). For chronic cases, atypical antipsychotics cost (oral: $11.7-25, LAI: $150-167) was higher than typical antipsychotics (oral: $4-5, LAI: $5-25). Of the total expenses incurred, cost for hospital admissions was the largest component (78%). CONCLUSION: Despite enhanced treatment adherence and potential to lower risk of rehospitalizations from relapse, LAIs are not the preferred treatment choice for patients with schizophrenia in India, owing to their perceived high costs.