Objectives-Alcohol screening and brief interventions in medical settings can significantly reduce alcohol use. Corresponding data for illicit drug use is sparse. A Federally funded Screening, Brief Intervention, Referral to Treatment (SBIRT) service program, the largest of its kind to date, was initiated by the Substance Abuse and Mental Health Services Administration (SAMHSA) in a wide variety of medical settings. We compared illicit drug use at intake and six months after drug screening and interventions were administered.Design-SBIRT services were implemented in a range of medical settings across six states. A diverse patient population (Alaska Natives, American Indians, African-Americans, Caucasians, Hispanics), was screened and offered score-based progressive levels of intervention (brief intervention, brief treatment, referral to specialty treatment). In this secondary analysis of the SBIRT service program, drug use data was compared at intake and at a six month follow-up, in a sample of a randomly selected population (10%) that screened positive at baseline.Results-Of 459,599 patients screened, 22.7% screened positive for a spectrum of use (risky/ problematic, abuse/addiction). The majority were recommended for a brief intervention (15.9%), with a smaller percentage recommended for brief treatment (3.2%) or referral to specialty treatment (3.7%). Among those reporting baseline illicit drug use, rates of drug use at 6 month follow-up (4 of 6 sites), were 67.7% lower (p < 0.001) and heavy alcohol use was 38.6% lower (p < 0.001), with comparable findings across sites, gender, race/ethnic, age subgroups. Among persons recommended for brief treatment or referral to specialty treatment, self-reported improvements in general health (p < 0.001), mental health (p < 0.001), employment (p < 0.001), housing status (p < 0.001), and criminal behavior (p < 0.001) were found. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptDrug Alcohol Depend. Author manuscript; available in PMC 2010 January 1. Conclusions-SBIRT was feasible to implement and the self-reported patient status at six months indicated significant improvements over baseline, for illicit drug use and heavy alcohol use, with functional domains improved, across a range of health care settings and a range of patients.

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Dopamine, serotonin and norepinephrine are essential for neurotransmission in the mammalian system. These three neurotransmitters have been the focus of considerable research since modulation of their production and their interaction at monoamine receptors has profound effects upon a multitude of pharmacological outcomes. Our interest has focused on neurotransmitter reuptake mechanisms in a search for medications for cocaine abuse. Herein we describe the synthesis and biological evaluation of an array of 2-aminopentanophenones. This array has yielded selective inhibitors of the dopamine and norepinephrine transporters with little effect upon serotonin trafficking. A subset of compounds had no significant affinity at 5HT 1A , 5HT 1B , 5HT 1C , D 1 , D 2 , or D 3 receptors. The lead compound, racemic 1-(4-methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one 4a, was resolved into its enantiomers and the S isomer was found to be the most biologically active enantiomer. Among the most potent of these DAT/NET selective compounds are the 1-(3,4-dichlorophenyl)-(4u) and the 1-naphthyl-(4t) 2-pyrrolidin-1-yl-pentan-1-one analogs.

Recently identified trace amine receptors are potential direct targets for drugs of abuse, including amphetamine and 3,4-methylenedioxymethamphetamine (MDMA). We cloned fulllength rhesus monkey trace amine receptor 1 (rhTA 1 ) that was 96% homologous to human TA 1 . The trace amines tyramine and ␤-phenylethylamine (PEA) and the monoamine transporter substrates (Ϯ)-amphetamine and (Ϯ)-MDMA stimulated cAMP accumulation in rhTA 1 -expressing cell lines, as measured by a cAMP response element-luciferase assay. Cocaine did not stimulate cAMP accumulation in rhTA 1 cells, but it blocked [ 3 H]PEA transport mediated by the dopamine transporter. Cotransfection with the human dopamine transporter enhanced PEA-, amphetamine-, and MDMA-mediated rhTA 1 receptor activation, but it diminished tyramine activation of rhTA 1 . Because TA 1 (EGFP-rhTA 1 chimera) was largely intracellular, conceivably the dopamine transporter can facilitate access of specific agonists to intracellular TA 1 . rhTA 1 mRNA expression was detected in rhesus monkey substantia nigra, implying that TA 1 may be colocalized with the dopamine transporter in dopamine neurons. In summary, primate TA 1 receptors are direct targets of trace amines, amphetamine, and MDMA. These receptors could also be indirect targets of amphetamine, MDMA, and cocaine through modification of monoamine transporter function. Conceivably, rhTA 1 receptors may be located on pre-or postsynaptic membranes. Interference with the carrier function of monoamine transporters with a consequent rise of extracellular levels of trace amines could activate these receptors. The cloning of a highly homologous TA 1 from rhesus monkey and demonstration that rhTA 1 receptors are activated by drugs of abuse, indicate that nonhuman primates may serve to model physiological and pharmacological TA 1 -mediated responses in humans.

It is now accepted that (-)-cocaine binds to specific recognition sites associated with monoamine transporters in the mammalian brain. In this study, several analogs of 3 beta-phenyltropane-2 beta-carboxylic acid methyl ester were prepared and their potency for inhibiting the binding of [3H]-3 beta-(4-fluorophenyl)tropane-2 beta-carboxylic acid methyl ester to primate caudate-putamen was evaluated. The synthesis and binding affinity of 3 beta-(3,4- dichlorophenyl)tropane-2 beta-carboxylic acid methyl ester, one of the most potent cocaine congeners yet reported, is presented. The feasibility of synthesizing high-affinity ligands for cocaine recognition sites and their suitability as PET imaging ligands for cocaine receptors in vivo is demonstrated.

How do 'stimulants' reduce hyperactivity in children and adults? How can drugs which raise extracellular dopamine result in psychomotor slowing of hyperactive children when dopamine is known to enhance motor activity, such as in Parkinson's disease? These apparent paradoxes are the focus of this brief review on the mechanism of action of stimulant medications used in the treatment of children, and of an increasing number of adults who meet diagnostic criteria for attention deficit hyperactivity disorder.