Age-Related Differences in the Disposition of Nicotine and Metabolites in Rat Brain and Plasma.

Age-Related Differences in the Disposition of Nicotine and Metabolites in Rat Brain and Plasma.

Nicotine Tob Res. 2013 Jun 4;
Vieira-Brock PL, Andrenyak DM, Nielsen SM, Fleckenstein AE, Wilkins DG

INTRODUCTION: Studies have evaluated the behavioral and neurochemical impact of nicotine administration in rodents. However, the distribution of nicotine and metabolites in rat brain and plasma as a function of age has not been investigated. This is a significant issue because human adolescents have a greater risk for developing nicotine addiction than adults, and reasons underlying this observation have not been fully determined. Thus, in this present study, we evaluated the impact of the transition from adolescence (postnatal day [PND 40]) to adulthood (PND 90) on nicotine distribution in rats. METHODS: PND 40, 60, and 90 rats received a single injection of (-) nicotine (0.8mg/kg, subcutaneously). Liquid chromatography tandem-mass spectrometry was used to measure concentration of nicotine and metabolites in selected biological matrices. RESULTS: Nicotine, cotinine, and nornicotine were detected in rat striata and frontal cortex 30min, 1hr, 2hr, and 4hr after a single administration. These and several additional metabolites (nicotine-1′-oxide, cotinine-N-oxide, norcotinine, and trans-3′-hydroxycotinine) were also detected in plasma at these same timepoints. The mean concentration of nicotine in brain and plasma was lower in PND 40 versus PND 90 rats. In contrast, the mean concentration of nornicotine was higher in the plasma and brain of PND 40 versus PND 90 rats. CONCLUSIONS: Nicotine and metabolite distribution differs between adolescent and adult rats. These data suggest that adolescent rats metabolize nicotine to some metabolites faster than adult rats. Further studies are needed to investigate the potential correlation between age, drug distribution, and nicotine addiction. HubMed – addiction


Characteristics of perinatal women seeking treatment for marijuana abuse in a community-based clinic.

Arch Womens Ment Health. 2013 Jun 5;
Tzilos G, Hess L, Kao JC, Zlotnick C

In the US, marijuana continues to be the most frequently used illicit drug among women of childbearing age, including pregnant and postpartum women. Given the critical window for treatment during the perinatal period, more information is needed about the characteristics of women who abuse marijuana and about their unique needs with the goal of improving clinical services and outcomes for both women and their infants. Objectives: To (1) identify a profile of perinatal women seeking treatment for primarily marijuana abuse and (2) report birth outcomes in a subset of pregnant women with marijuana abuse. Methods: This retrospective clinical chart review study examined 67 adult perinatal women patients (54 % ethnic minority) who attended an inner-city, hospital-affiliated outpatient program specializing in substance abuse treatment for women. Of all pregnant women, 26 % reported positive urine screens during the first trimester, 41 % during the second trimester, and 27 % during the third trimester. While the subset of pregnant women was small, exploratory results suggest that infants whose mothers continued to use marijuana during their pregnancies were born at a lower gestational age than mothers who abstained; t(29)?=?2.04, p <0.05. Conclusion: Identifying potential barriers to treatment could help improve retention in community-based treatment programs during pregnancy and the postpartum period. HubMed – addiction


Addiction: White House seeks “third way”: policy emphasizes prevention, treatment, recovery.

JAMA. 2013 Jun 5; 309(21): 2201-2
Kuehn BM

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Addiction Potential of Phentermine prescribed during Long-term treatment of Obesity (APPLO Trial).

Int J Obes (Lond). 2013 May 17;
Hendricks EJ, Srisurapanont M, Schmidt SL, Haggard M, Souter S, Mitchell CL, De Marco DG, Hendricks MJ, Istratiy Y, Greenway FL

Objective:To investigate if phentermine treatment induces phentermine abuse, psychological dependence (addiction), or phentermine drug cravings in overweight, obese and weight loss maintenance patients. To investigate whether amphetamine-like withdrawal occurs after abrupt cessation of long-term phentermine treatment.Design:Clinical intervention trial with interruption of phentermine treatment in long-term patients.Subjects:269 obese, overweight or formerly obese subjects (age: 20-88y, BMI: 21-74) treated with phentermine long-term (LTP, N=117), 1.1 – 21.1 years, or short-term (ATP, N=152), 4-22 days, with phentermine doses of 18.75-112.5 (LTP) and 15-93.75 (ATP) milligrams/day.Measurements:Module K of the Mini International Neuropsychiatric Interview modified for phentermine (MINI-SUD), Severity of Dependence Scale (SDS), 45-item Cocaine Craving Questionnaire-NOW (CCQ-NOW) modified for phentermine (PCQ-NOW), and Amphetamine Withdrawal Questionnaire (AWQ) modified for phentermine (PWQ).Results:MINI-SUD interviews were negative for phentermine abuse or psychological dependence in all LTP patients. SDS examination scores were low for all LTP and ATP patients indicating they were not psychologically dependent upon phentermine. PCQ-NOW scores were low for all LTP and ATP patients indicating neither short-term nor long-term phentermine treatment had induced phentermine cravings. Other than an increase in hunger or eating, amphetamine-like withdrawal symptoms did not occur upon abrupt phentermine cessation as measured by sequential PWQ scores.Conclusions:Phentermine abuse or psychological dependence (addiction) does not occur in patients treated with phentermine for obesity. Phentermine treatment does not induce phentermine drug cravings, a hallmark sign of addiction. Amphetamine-like withdrawal does not occur upon abrupt treatment cessation even at doses much higher than commonly recommended and after treatment durations of up to 21 years.International Journal of Obesity accepted article preview online, 17 May 2013; doi:10.1038/ijo.2013.74. HubMed – addiction


A systematic review of reported cases involving psychotic symptoms worsened by aripiprazole in schizophrenia or schizoaffective disorder.

Psychopharmacology (Berl). 2013 Jun 5;
Takeuchi H, Remington G

RATIONALE: Numerous case reports have suggested that aripiprazole can worsen psychotic symptoms in schizophrenia. OBJECTIVES: We reviewed reported cases which have suggested that aripiprazole can worsen psychotic symptoms in schizophrenia and evaluated each regarding quality of the causal relationship. METHODS: A systematic literature search was conducted on August 18, 2012, using the PubMed and the EMBASE. Twenty-two cases met the following inclusion criteria: (1) diagnosis of schizophrenia or schizoaffective disorder, (2) worsening of psychotic symptoms associated with aripiprazole, and (3) aripiprazole dose ?30 mg/day. Information about the causal relationship between aripiprazole and increased psychotic symptoms was extracted. The quality of the causal relationship was evaluated according to the modified guidelines for evaluation of drug-associated events and classified as “questionable,” “moderately suggestive,” or “highly suggestive.” RESULTS: Patients were chronic in at least 15 cases, and prior antipsychotic dose exceeded recommended guidelines in 19 cases. Psychotic symptoms worsened after simply adding aripiprazole to the current regimen in eight cases. Besides psychotic symptoms, increasing agitation (nine cases), aggression (11 cases), and/or activation (seven cases) were reported. Clinical resolution occurred after aripiprazole discontinuation in eight cases. Regarding causal relationship, 11 cases were classified as “highly suggestive,” three as “moderately suggestive,” and eight as “questionable”. CONCLUSIONS: Clinicians should be vigilant when adding aripiprazole to patients with chronic schizophrenia also receiving relatively high doses of other antipsychotics, and discontinuation of aripiprazole should be considered if psychotic symptoms and/or agitation/aggression/activation increase. HubMed – addiction