We report a short synthetic route for synthesizing 2,3-substituted piperazine acetic acid esters. Optically pure amino acids were efficiently converted into 1,2-diamines that could be utilized to deliver the title 2,3-substituted piperazines in five steps with a high enantiomeric purity. The novel route facilitated, for the first time, the synthesis of 3-phenyl substituted-2-piperazine acetic acid esters that were difficult to achieve using other methods; however, in this case, the products underwent racemization.
Methamphetamine (MA) is a highly addictive stimulant with recent upward trends in prevalence and associated public health problems. Drug demand, as assessed by hypothetical purchasing tasks, has been useful in addictions research and may help our understanding of the factors influencing MA use. However, no studies have assessed MA demand using current models of demand. The purpose of the current study was to assess demand for MA using a hypothetical drug purchasing task. Given high rates of cigarette smoking among MA users, it was of interest also to assess and compare demand for MA relative to cigarettes. Participants consisted of non-treatment-seeking volunteers with MA use disorder (N ϭ 18), of whom 17 reported daily smoking. Results showed the exponentiated demand model provided a good fit to consumption data. Results from Bayesian generalized linear modeling demonstrated multiple positive relationships (posterior probability Ն75%) between self-reported drug use (days MA used in the past 30 days, cigarettes smoked per day) and indices of demand for each drug (Q o , O max , P max , and break point). Comparing MA to cigarettes, results from Bayesian generalized linear mixed modeling revealed greater abuse liability for MA compared to cigarettes (posterior probability Ն99%) based on ␣ and essential value. Overall, the findings of the current study support the feasibility and validity of the exponentiated demand model for assessing demand for drugs among individuals with MA use disorder. Public Health SignificanceMethamphetamine is a significant public health concern with increasing negative impact. Behavioral economic measures, such as drug demand, may provide key insight into the decision making processes involved in methamphetamine use.
Background Brain ventricles have been reported to be enlarged in several neuropsychiatric disorders and in aging. Whether human cerebral ventricular volume can decrease over time with psychiatric treatment is not well-studied. The aim of this study was to examine whether inpatients taking serotonin reuptake inhibitors (SRI) exhibited reductions in cerebral ventricular volume. Methods Psychiatric inpatients, diagnosed mainly with depression, substance use, anxiety, and personality disorders, underwent two imaging sessions (Time 1 and Time 2, approximately 4 weeks apart). FreeSurfer was used to quantify volumetric features of the brain, and ANOVA was used to analyze ventricular volume differences between Time 1 and Time 2. Inpatients’ brain ventricle volumes were normalized by dividing by estimated total intracranial volume (eTIV). Clinical features such as depression and anxiety levels were collected at Time 1, Time 1.5 (approximately 2 weeks apart), and Time 2. Results Inpatients consistently taking SRIs (SRI + , n = 44) showed statistically significant reductions of brain ventricular volumes particularly for their left and right lateral ventricular volumes. Reductions in their third ventricular volume were close to significance ( p = .068). The inpatients that did not take SRIs (SRI-, n = 25) showed no statistically significant changes in brain ventricular volumes. The SRI + group also exhibited similar brain structural features to the healthy control group based on the 90% confidence interval comparsions on brain ventricular volume parameters, whereas the SRI- group still exhibited relatively enlarged brain ventricular volumes after treatment. Conclusions SRI treatment was associated with decreased brain ventricle volume over treatment.
Background and ObjectivesThis study examined how a promoter variant of TH (rs10770141) affects subjective effects of cocaine in 65 nontreatment‐seeking individuals with cocaine dependence.MethodsParticipants received cocaine/saline intravenously, and TH genotypes were evaluated.ResultsHomozygous individuals for the minor T allele reported greater “good” and “bad” subjective effects to cocaine than those with the major C allele.Discussion and ConclusionsTH rs10770141 modulates subjective effects of cocaine in participants with cocaine dependence.Scientific SignificanceThese results are among the first to indicate that homozygosity of the T allele of rs10770141 modulates greater sensitivity to cocaine.
Background Natural disasters can affect mental health and result in symptoms of depression, anxiety, and post-traumatic stress disorder (PTSD). Playback Theatre (PT) is a form of improvisation where actors play-back personal stories told by audience members. Whether PT can be therapeutic in post-disaster settings is not known. Method We used a series of PT performances and studied levels of depression, anxiety, and PTSD symptoms in a sample of 13 people affected by Hurricane Harvey that happened in Houston, TX, August 2017. Brain imaging, specifically resting state functional connectivity of the amygdala was also studied before and after the PT performances. Results Both anxiety ( p = .001, Cohen’s d = –1.25) and PTSD ( p = .002, Cohen’s d = –1.0) symptoms significantly decreased after a series of 4 PT performances from January 2019 – February 2019. Depression reduction was not significant. We performed resting state functional connectivity (RSFC) MRI before and after the series of performances. We used the right and left amygdala as seeds for RSFC analysis and found that the connectivity between the left amygdala and the bilateral supramarginal gyri was increased after PT. The bilateral supramarginal connectivity with the default mode and the saliency networks increased too, which correlated with reduction in anxiety scores. Conclusions PT may offer a form of intervention for anxiety caused by disasters. An increase in left amygdala/supramarginal gyri connectivity may be the underlying mechanism.
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