Faculty Bibliography

Ayahuasca is a psychedelic brew originally used for magico-religious purposes by Amerindian populations of the western Amazon Basin. Throughout the last four decades, the use of ayahuasca spread towards major cities in all regions of Brazil and abroad. This trend has raised concerns that regular use of this N,N-dimethyltryptamine- and harmala-alkaloid-containing tea may lead to mental and physical health problems associated typically with drug abuse. To further elucidate the mental and physical health of ayahuasca users, we conducted a literature search in the international medical PubMed database. Inclusion criteria were evaluation of any related effect of ayahuasca use that occurred after the resolution of acute effects of the brew. Fifteen publications were related to emotional, cognitive, and physical health of ayahuasca users. The accumulated data suggest that ayahuasca use is safe and may even be, under certain conditions, beneficial. However, methodological bias of the reviewed studies might have contributed to the preponderance of beneficial effects and to the few adverse effects reported. The data up to now do not appear to allow for definitive conclusions to be drawn on the effects of ayahuasca use on mental and physical health, but some studies point in the direction of beneficial effects. Additional studies are suggested to provide further clarification.

BACKGROUND: Screening, brief intervention, and referral to treatment (SBIRT) approaches to reducing hazardous alcohol and illicit drug use have been assessed in a variety of health care settings, including primary care, trauma centers, and emergency departments. A major methodological concern in these trials, however, is "assessment reactivity," the hypothesized impact of intensive research assessments to reduce alcohol and drug use and thus mask the purported efficacy of the interventions under scrutiny. Thus, it has been recommended that prospective research designs take assessment reactivity into account. The present article describes the design of the National Institute on Drug Abuse Clinical Trials Network protocol, Screening, Motivational Assessment, Referral, and Treatment in Emergency Departments (SMART-ED), which addresses the potential bias of assessment reactivity. METHODS/DESIGN: The protocol employs a 3-arm design. Following an initial brief screening, individuals identified as positive cases are consented, asked to provide demographic and locator information, and randomly assigned to one of the three conditions: minimal screening only, screening + assessment, or screening + assessment + brief intervention. In a two-stage process, the randomization procedure first reveals whether or not the participant will be in the minimal-screening-only condition. Participants in the other two groups receive a more extensive baseline assessment before it is revealed whether they have been randomized to also receive a brief intervention. Comparing the screening only and screening + assessment conditions will allow determination of the incremental effect of assessment reactivity. DISCUSSION: Assessment reactivity is a potential source of bias that may reduce and/or lead to an underestimation of the purported effectiveness of brief interventions. From a methodological perspective, it needs to be accounted for in research designs. The SMART-ED design offers an approach to minimize assessment reactivity as a potential source of bias. Elucidating the role of assessment reactivity may offer insights into the mechanisms underlying SBIRT as well as suggest clinical options incorporating assessment reactivity as a treatment adjunct. CLINICALTRIALS.GOV IDENTIFIER: NCT01207791.

ABSTRACT: Psychosis and substance abuse are intimately related. Psychotic spectrum illnesses commonly co-occur with substance use disorders (SUDs), and many substances of abuse can cause or exacerbate psychotic symptoms along a temporal spectrum from acute to chronic presentations. Despite the common co-occurrence between psychotic spectrum illnesses and SUDs, they are often under-recognized and undertreated, leading to poor treatment outcomes. Accurate detection and diagnosis of individuals with psychotic illness co-occurring with addictive disorders is key to properly treat such disorders. This article will review the nature of the relationship between psychosis and substance abuse by examining prevalence rates of each disorder alone and their rates of co-occurrence, the neurobiological basis for substance abuse comorbidity in schizophrenia spectrum disorders, key and salient aspects related to accurate diagnosis along a continuum from acute to subacute to chronic conditions, and pitfalls associated with diagnostic dilemmas. A case example will be used to highlight key points related to diagnostic challenges.

A mood stabilizing and antidepressant response to lithium is only found in a subgroup of patients with bipolar disorder and depression. Identifying strains of mice that manifest differential behavioral responses to lithium may assist in the identification of genomic and other biologic factors that play a role in lithium responsiveness. Mouse strains were tested in the forced swim test (FST), tail suspension test (TST) and open-field test after acute and chronic systemic and intracerebroventricular (ICV) lithium treatments. Serum and brain lithium levels were measured. Three (129S6/SvEvTac, C3H/HeNHsd and C57BL/6J) of the eight inbred strains tested, and one (CD-1) of the three outbred strains, showed an antidepressant-like response in the FST following acute systemic administration of lithium. The three responsive inbred strains, as well as the DBA/2J strain, displayed antidepressant-like responses to lithium in the FST after chronic administration of lithium. However, in the TST, acute lithium resulted in an antidepressant-like effect only in C3H/HeNHsd mice. Only C57BL/6J and DBA/2J showed an antidepressant-like response to lithium in the TST after chronic administration. ICV lithium administration resulted in a similar response profile in BALB/cJ (non-responsive) and C57BL/6J (responsive) strains. Serum and brain lithium concentrations showed that behavioral results were not because of differential pharmacokinetics of lithium in individual strains, suggesting that genetic factors likely regulate these behavioral responses to lithium. Our results indicate that antidepressant-like responses to lithium in tests of antidepressant efficacy varies among genetically diverse mouse strains. These results will assist in identifying genomic factors associated with lithium responsiveness and the mechanisms of lithium action.

BACKGROUND: Inhalants are among the most common and dangerous forms of substance use, but very little research on inhalant use disorders exist. Unlike other substances, the Diagnostic and Statistical Manual, 4th edition (DSM-IV) indicates that inhalants do not have an associated withdrawal syndrome among persons who meet criteria for inhalant dependence. METHODS: Using data from the National Epidemiologic Survey on Alcohol and Related Conditions, this study examines the prevalence of withdrawal symptoms among inhalant users. Prevalence of inhalant withdrawal symptoms for inhalants was also compared with the prevalence of cocaine withdrawal symptoms to help determine the presence of an inhalant withdrawal syndrome. RESULTS: Approximately 47.8% of persons who met criteria for inhalant dependence reported experiencing three or more inhalant-related withdrawal symptoms that were clinically significant. Among those with inhalant dependence, almost half of the withdrawal symptoms were as common as the corresponding withdrawal symptoms experienced by persons with cocaine dependence. Furthermore, the percentage of persons with inhalant dependence reporting clinically significant inhalant withdrawal symptoms was almost equal to the percentage of persons with cocaine dependence reporting clinically significant cocaine withdrawal symptoms. CONCLUSIONS: These data provide evidence for an inhalant-related withdrawal syndrome among persons with inhalant dependence. Revisions to DSM-IV should consider including inhalant withdrawal as a diagnostic criterion for this disorder.

BACKGROUND: Adolescence is a period in which cognition and brain undergo dramatic parallel development. Whereas chronic use of alcohol and marijuana is known to cause cognitive impairments in adults, far less is known about the effect of these substances of abuse on adolescent cognition, including possible interactions with developmental processes. METHODS: Neuropsychological performance, alcohol use, and marijuana use were assessed in 48 adolescents (ages 12 to 18), recruited in 3 groups: a healthy control group (HC, n = 15), a group diagnosed with substance abuse or dependence (SUD, n = 19), and a group with a family history positive for alcohol use disorder (AUD) but no personal substance use disorder (FHP, n = 14). Age, drinks per drinking day (DPDD), percentage days drinking, and percentage days using marijuana were considered as covariates in a MANCOVA in which 6 neuropsychological composites (Verbal Reasoning, Visuospatial Ability, Executive Function, Memory, Attention, and Processing Speed) served as dependent variables. RESULTS: More DPDD predicted poorer performance on Attention and Executive Function composites, and more frequent use of marijuana was associated with poorer Memory performance. In separate analyses, adolescents in the SUD group had lower scores on Attention, Memory, and Processing Speed composites, and FHP adolescents had poorer Visuospatial Ability. CONCLUSIONS: In combination, these analyses suggest that heavy alcohol use in adolescence leads to reduction in attention and executive functioning and that marijuana use exerts an independent deleterious effect on memory. At the same time, premorbid deficits associated with family history of AUD appeared to be specific to visuospatial ability.

As acute ethanol exposure inhibits N-methyl-D-aspartate glutamate (Glu) receptors, sudden withdrawal from chronic alcohol use may lead to an increased activation of these receptors with excitotoxic effects. In the longer term, brain levels of Glu and its metabolites, such as glutamine (Gln), are likely to be chronically altered by alcohol, possibly providing a measure of overall abnormal Glu-Gln cycling. However, few studies have assessed concentrations of these metabolites in clinical populations of individuals with alcohol use disorders. Glu and Gln levels were compared in groups of 17 healthy controls and in 13 participants with alcohol dependence. Within the alcohol-dependent group, seven participants had current alcohol use disorder (AUD), and six had AUD in remission for at least 1 year (AUD-R). Neurometabolite concentrations were measured with proton magnetic resonance spectroscopy ((1)H-MRS) in a predominantly gray matter voxel that included the bilateral anterior cingulate gyri. Tissue segmentation provided an assessment of the proportion of gray matter in the (1)H-MRS voxel. The Drinker Inventory of Consequences (DrInC) and Form-90 were administered to all participants to quantify alcohol consequences and use. Glu level was lower and Gln level was higher in the AUD and AUD-R groups relative to the control group; creatine, choline, myo-inositol, and total N-acetyl groups, primarily N-acetylaspartate did not differ across groups. These results were not confounded by age, sex, or proportion of gray matter in the (1)H-MRS voxel. Neurometabolite concentrations did not differ between AUD and AUD-R groups. Subsequent regressions in the combined clinical group, treating voxel gray matter proportion as a covariate, revealed that total score on the DrInC was positively correlated with Gln but negatively correlated with both Glu and gray matter proportion. Regression analyses, including DrInC scores and smoking variables, identified a marginal independent effect of smoking on Gln. The current findings of higher Gln and lower Glu in the combined AUD and AUD-R groups might indicate a perturbation of the Glu-Gln cycle in alcohol use disorders. The absence of differences in mean Glu and Gln between the AUD and AUD-R groups suggests that altered Glu-Gln metabolism may either predate the onset of abuse or persist during prolonged abstinence.

BACKGROUND: Medical settings such as emergency departments (EDs) present an opportunity to identify and provide services for individuals with substance use problems who might otherwise never receive any form of assessment, referral, or intervention. Although screening, brief intervention, and referral to treatment models have been extensively studied and are considered effective for individuals with alcohol problems presenting in EDs and other medical settings, the efficacy of such interventions has not been established for drug users presenting in EDs. OBJECTIVES: This article describes the design of a NIDA Clinical Trials Network protocol testing the efficacy of an screening, brief intervention, and referral to treatment model in medical EDs, highlighting considerations that are pertinent to the design of other studies targeting substance use behaviors in medical treatment settings. METHODS: The protocol is described, and critical design decisions are discussed. RESULTS: Design challenges included defining treatment conditions, study population, and site characteristics; developing the screening process; choosing the primary outcome; balancing brevity and comprehensiveness of assessment; and selecting the strategy for statistical analysis. CONCLUSION: Many of the issues arising in the design of this study will be relevant to future studies of interventions for addictions in medical settings. SCIENTIFIC SIGNIFICANCE: Optimal trial design is critical to determining how best to integrate substance abuse interventions into medical care.