Rajiv Radhakrishnan

Gone to pot - a review of the association between cannabis and psychosis

Cannabis is the most commonly used illicit drug worldwide, with ~5 million daily users worldwide. Emerging evidence supports a number of associations between cannabis and psychosis/psychotic disorders, including schizophrenia. These associations-based on case-studies, surveys, epidemiological studies, and experimental studies indicate that cannabinoids can produce acute, transient effects; acute, persistent effects; and delayed, persistent effects that recapitulate the psychopathology and psychophysiology seen in schizophrenia. Acute exposure to both cannabis and synthetic cannabinoids (Spice/K2) can produce a full range of transient psychotomimetic symptoms, cognitive deficits, and psychophysiological abnormalities that bear a striking resemblance to symptoms of schizophrenia. In individuals with an established psychotic disorder, cannabinoids can exacerbate symptoms, trigger relapse, and have negative consequences on the course of the illness. Several factors appear to moderate these associations, including family history, genetic factors, history of childhood abuse, and the age at onset of cannabis use. Exposure to cannabinoids in adolescence confers a higher risk for psychosis outcomes in later life and the risk is dose-related. Individuals with polymorphisms of COMT and AKT1 genes may be at increased risk for psychotic disorders in association with cannabinoids, as are individuals with a family history of psychotic disorders or a history of childhood trauma. The relationship between cannabis and schizophrenia fulfills many but not all of the standard criteria for causality, including temporality, biological gradient, biological plausibility, experimental evidence, consistency, and coherence. At the present time, the evidence indicates that cannabis may be a component cause in the emergence of psychosis, and this warrants serious consideration from the point of view of public health policy.

Suicide: An Indian perspective

Suicide is the third leading cause of death among young adults worldwide. There is a growing recognition that prevention strategies need to be tailored to the region-specific demographics of a country and to be implemented in a culturally-sensitive manner. This review explores the historical, epidemiological and demographic factors of suicide in India and examines the strategies aimed at the prevention of suicide. There has been an increase in the rates of suicide in India over the years, although trends of both increases and decline in suicide rates have been present. Distinct from global demographic risk factors, In India, marital status is not necessarily protective and the female: male ratio in the rate of suicide is higher. The motives and modes of suicide are also distinct from western countries. Preventive strategies implemented at a community level and identifying vulnerable individuals maybe more effective than global strategies.

Marijuana Legalization: Impact on Physicians and Public Health

Marijuana is becoming legal in an increasing number of states for both medical and recreational use. Considerable controversy exists regarding the public health impact of these changes. The evidence for the legitimate medical use of marijuana or cannabinoids is limited to a few indications, notably HIV/AIDS cachexia, nausea/vomiting related to chemotherapy, neuropathic pain, and spasticity in multiple sclerosis. Although cannabinoids show therapeutic promise in other areas, robust clinical evidence is still lacking. The relationship between legalization and prevalence is still unknown. Although states where marijuana use is legal have higher rates of use than nonlegal states, these higher rates were generally found even prior to legalization. As states continue to proceed with legalization for both medical and recreational use, certain public health issues have become increasingly relevant, including the effects of acute marijuana intoxication on driving abilities, unintentional ingestion of marijuana products by children, the relationship between marijuana and opioid use, and whether there will be an increase in health problems related to marijuana use, such as dependence/addiction, psychosis, and pulmonary disorders. In light of this rapidly shifting legal landscape, more research is urgently needed to better understand the impact of legalization on public health.

Feasibility, Safety, and Efficacy of the Combination of D -Serine and Computerized Cognitive Retraining in Schizophrenia: An International Collaborative Pilot Study

The combination of pharmacotherapy and cognitive retraining (CRT) for the cognitive deficits of schizophrenia may be more efficacious than either approach alone, but this has not yet been tested. This study evaluated the feasibility, safety, tolerability, and efficacy of 12 weeks of D-serine, combined with CRT in the treatment of cognitive deficits in schizophrenia at two academic sites in parallel, in India and the United States. In a randomized, partial double-blind, placebo-controlled, parallel-group design, 104 schizophrenia subjects (US site=22, Indian site=82) were randomized to: (1) D-serine (30 mg/kg)+CRT (5 h/week), (2) D-serine+control CRT, (3) CRT+placebo D-serine, and (4) placebo+control CRT. Completion rates were 84 and 100% in the Indian and US samples, respectively. On various outcome measures of safety and tolerability, the interventions were well tolerated. D-Serine and CRT did not show any significant effect on the Global Cognitive Index, although both interventions showed differential site effects on individual test performance. CRT resulted in a significant improvement in Verbal Working Memory, and a trend toward improvement in Attention/Vigilance. This is the first study to demonstrating the feasibility, safety, and tolerability of combination pharmacotherapy and CRT in a multicenter international clinical trial. These preliminary findings provide support for future studies using higher doses of D-serine that have been shown to be efficacious or other pharmacotherapies, along with the newer cognitive remediation strategies that are individualized and that target basic information processing.

Impact of Cannabis Use on the Development of Psychotic Disorders

The link between cannabis use and psychosis comprises three distinct relationships: acute psychosis associated with cannabis intoxication; acute psychosis that lasts beyond the period of acute intoxication; and persistent psychosis not time-locked to exposure. Experimental studies reveal that cannabis, delta-9-tetrahydrocannabinol (THC) and synthetic cannabinoids reliably produce transient positive, negative, and cognitive symptoms in healthy volunteers. Case studies indicate that cannabinoids can induce acute psychosis that lasts beyond the period of acute intoxication but resolves within a month. Exposure to cannabis in adolescence is associated with a risk for later psychotic disorder in adulthood; this association is consistent, temporally related, shows a dose response, and is biologically plausible. However, cannabis is neither necessary nor sufficient to cause a persistent psychotic disorder. More likely, it is a component cause that interacts with other factors to result in psychosis. The link between cannabis and psychosis is moderated by age at onset of cannabis use, childhood abuse, and genetic vulnerability. While more research is needed to better characterize the relationship between cannabinoid use and the onset and persistence of psychosis, clinicians should be mindful of the potential risk of psychosis, especially in vulnerable populations, including adolescents and those with a psychosis diathesis.

Association between unconjugated bilirubin and schizophrenia

The evidence regarding the association between schizophrenia and the fractions of bilirubin is mixed. In a retrospective case-control design we examined the association between total bilirubin, conjugated bilirubin, unconjugated bilirubin and schizophrenia. The relevance of our findings and that of the association of unconjugated bilirubin to schizophrenia is discussed.

A Systematic Review of the Evidence for Medical Marijuana in Psychiatric Indications.

OBJECTIVE Marijuana has been approved for a number of psychiatric conditions in many states in the US including posttraumatic stress disorder (PTSD), agitation in Alzheimers disease, and Tourettes disorder. In this systematic review, we examine the strength of evidence for the efficacy of marijuana and other cannabinoids for these psychiatric indications. DATA SOURCES The literature (MEDLINE) was searched for studies published between January 1980 and March 2015 using search terms related to marijuana and other cannabinoids and the specific diagnosis. STUDY SELECTION The best quality of evidence, namely placebo-controlled, randomized clinical trials (RCTs) and meta-analyses, was sought per PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. In the absence of RCTs, the next best available evidence (eg, observational studies, case reports) was reviewed. Of 170 publications that were screened, 40 were related to the topic, 29 were included in the qualitative synthesis, and 13 studies examined the efficacy of cannabinoids in humans. DATA EXTRACTION The evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) method. RESULTS No RCTs have thus far examined the efficacy of marijuana for Tourettes disorder, PTSD, or Alzheimers disease. Lower-quality studies examined the efficacy of marijuana, Δ⁹-tetrahydrocannabinol, and nabilone; the strength of evidence for the use of cannabinoids for these conditions is very low at the present time. The consequences of chronic cannabinoid exposure includes tolerance, dependence, and withdrawal. Early and persistent marijuana use has been associated with the emergence of psychosis. Marijuana impairs attention, memory, IQ, and driving ability. CONCLUSIONS Given its rapidly changing legal status, there is an urgent need to conduct double-blind, randomized, placebo- or active-controlled studies on the efficacy and safety of marijuana or its constituent cannabinoids for psychiatric conditions. Physicians and policy-makers should take into account the limited existing evidence and balance that with side effects before approving medical marijuana for psychiatric indications.

Naltrexone does not attenuate the effects of intravenous Δ9-tetrahydrocannabinol in healthy humans.

Although a wealth of preclinical evidence indicates an interplay between the μ-opioid (MOR) and cannabinoid 1 receptor (CB1R) systems, the precise nature of the cross modulation in humans is unclear. The objective of this study was to evaluate the effects of pretreatment with the MOR antagonist, naltrexone, on the subjective, behavioural and cognitive effects of the CB1R agonist, Δ9-tetrahydrocannabinol (THC), in healthy human subjects. Healthy human subjects, screened carefully for any medical or psychiatric illness, were administered either placebo or active naltrexone (25 mg) orally on each test day, followed 45 min later by placebo and 165 min later by active i.v. THC (0.025 mg/kg) in a randomized, fixed-order, double-blind manner. Subjective, behavioural and cognitive effects were assessed before and at several points after each drug administration. THC produced expected effects, including euphoria, anxiety, transient perceptual alterations, transient psychotomimetic effects and cognitive impairments. However, naltrexone did not produce any effects alone, nor did it attenuate any of THCs effects. Thus, in healthy human subjects who use cannabis intermittently, MOR antagonism does not modulate the common acute subjective, behavioural and cognitive effects of THC.

Body mass index identified as an independent predictor of psychiatric readmission.

BACKGROUND Psychiatric hospital readmissions correlate with illness severity, drug selection, and compliance with treatment in the outpatient setting. The risk factors for psychiatric rehospitalization have been mainly assessed in databases lacking information regarding somatic comorbidity and anthropometric variables, such as body mass index (BMI), which are known to predict readmissions in nonpsychiatric settings. OBJECTIVE To determine independent predictors of 1-year readmission occurring among unselected adults consecutively admitted for treatment of severe mental illness to an academic, freestanding psychiatric hospital in New York City from August 2010 through January 2011. METHOD After identifying univariate correlates of readmission, we used logistic regression with backward elimination to identify independent predictors of readmissions within 1 year after the index psychiatric hospitalization. RESULTS Among 224 (23.7%) of 945 readmitted patients, psychiatric readmission was significantly associated with age (P = .0029), length of stay (P = .036), schizophrenia/schizoaffective disorder (P < . 0001), dementia (P = .027), major depressive disorder (P = .0006), treatment with atypical antipsychotic drugs (P = .0054), electroconvulsive therapy (P < .0001), and BMI (P = .0079), but not with physical comorbidities and routine laboratory data.The independent predictors of readmission were higher BMI (median = 28.5 kg/ m2; odds ratio [OR] = 3.6; Cl, 1.2-10.6), a diagnosis of schizophrenia/schizoaffective disorder (OR = 2.2; Cl, 1.5-3.4), clozapine treatment (OR = 2.8; CI, 1.1-6.9), no electroconvulsive therapy (OR = 0.13; Cl, 0.02-0.45), and shorter length of stay (median = 18 days; OR = 0.08; Cl, 0.01-0.42). CONCLUSIONS Body mass index was identified, for the first time, as an independent predictor of psychiatric rehospitalization. Enhanced outpatient treatment programs for overweight and obese psychiatric patients might influence readmission rates and should be explored in prospective studies.

Asian Indians in America: The influence of values and culture on mental health

Asian Indians represent a significant portion of the largest growing race of Asians in the past decade in the United States. This selective review examines major cultural themes related to first- and second-generation Asian Indians living in the United States as they impact psychological and psychiatric dysfunction in this population. Specifically, we review the impact of Asian Indian culture on mental health, discuss the impact of acculturation and ethnic identity development on the mental health of Indian-Americans, and focus on typical mental health problems of Asian Indian adolescents, women and elderly in America. Finally, we provide a brief overview of empirically-supported treatment approaches and cultural considerations for additional treatments relevant to this population. This review is intended to provide an important foundation for more systematic empirically-driven investigation into better understanding how Asian Indian cultural themes impact mental health for Indian-Americans, and how to develop effective treatments for these issues in this cultural group.