A Case of Treating Cathinone Dependence and Comorbid Depression Using Bupropion

Abstract

Cathinone is a potent CNS stimulant found in khat leaves. Cathinone and synthetic cathinone-derivatives have become popular recreational drugs in recent years, commonly marketed as “legal highs.” In addition to acute physical and psychiatric adverse effects, dependence on these substances is a concern. The following case reports describes a young man with cathinone dependence and depression that was treated using bupropion. Bupropion is a cathinone-derivative with a dual dopamine-norepinephrine reuptake inhibiting mechanism, which is approved for the treatment of depression and smoking cessation. Clinical awareness to the addictive potential of cathinone and cathinone-derivatives is important. Research regarding the potential effectiveness of bupropion in these cases is needed.     

Cigarette smoking as a target for potentiating outcomes for methamphetamine abuse treatment

Introduction and Aims. Cigarette smoking occurs frequently among individuals with methamphetamine (MA) dependence. Preclinical and clinical evidence has suggested that the common co‐abuse of MA and cigarettes represents a pharmacologically meaningful pattern. Methods. The present study is a secondary analysis of a randomised, placebo‐controlled trial of bupropion treatment for MA dependence (bupropion n = 36; placebo n = 37). A hierarchical logistic modelling approach assessed the efficacy of bupropion for reducing MA use separately among smokers and non‐smokers. Among smokers, relations between cigarettes smoked and MA use were assessed. Results. Smoking status did not affect treatment responsiveness in either the bupropion condition or the placebo condition. In the placebo condition, increased cigarette use was associated with an increased probability of MA use during the same time period. This effect was not observed in the bupropion condition. Discussion and Conclusions. Initial smoking status did not impact treatment outcomes. Among smokers, results suggest that bupropion may dissociate cigarette and MA use. The effect was modest and a precise pharmacological mechanism remains elusive. Cholinergic systems may be relevant for MA use outcomes. Future studies should continue to assess the role of smoking in MA treatment outcomes.[Brensilver M, Heinzerling KG, Swanson A‐N, Telesca D, Furst BA, Shoptaw SJ. Cigarette smoking as a target for potentiating outcomes for methamphetamine abuse treatment. Drug Alcohol Rev 2013;32:96–99]     

Stereoselective Metabolism of Bupropion by Cytochrome P4502B6 (CYP2B6) and Human Liver Microsomes

Purpose Hydroxylation of the antidepressant and smoking deterrent drug bupropion is a clinically important bioactivation and elimination pathway. Bupropion hydroxylation is catalyzed selectively by cytochrome P4502B6 (CYP2B6). CYP2B6-catalyzed bupropion hydroxylation has been used as an in vitro and in vivo phenotypic probe for CYP2B6 activity and CYP2B6 drug interactions. Bupropion is chiral, used clinically as a racemate, and disposition is stereoselective. Nevertheless, it is unknown whether CYP2B6-catalyzed bupropion hydroxylation is stereoselective. Methods Hydroxylation of racemic bupropion by recombinant CYP2B6 and human liver microsomes was evaluated using a stereoselective assay. Results At therapeutic concentrations, hydroxylation of (S)-bupropion was threefold and 1.5-greater than (R)-bupropion, respectively, by recombinant CYP2B6 and human liver microsomes. In vitro intrinsic clearances were likewise different for bupropion enantiomers. Conclusions Stereoselective bupropion hydroxylation may have implications for the therapeutic efficacy of bupropion as an antidepressant or smoking cessation therapy, and for the use of bupropion as an in vivo phenotypic probe for CYP2B6 activity.     

Identification of non‐reported bupropion metabolites in human plasma

Bupropion and its three active metabolites exhibit clinical efficacy in the treatment of major depression, seasonal depression and smoking cessation. The pharmacokinetics of bupropion in humans is highly variable. It is not known if there are any non‐reported metabolites formed in humans in addition to the three known active metabolites. This paper reports newly identified and non‐reported metabolites of bupropion in human plasma samples. Human subjects were dosed with a single oral dose of 75 mg of an immediate release bupropion HCl tablet. Plasma samples were collected and analysed by LC–MS/MS at 0, 6 and 24 h. Two non‐reported metabolites (M1 and M3) were identified with mass‐to‐charge (m/z) ratios of 276 (M1, hydration of bupropion) and 258 (M3, hydroxylation of threo/erythrohydrobupropion) from human plasma in addition to the known hydroxybupropion, threo/erythrohydrobupropion and the glucuronidation products of the major metabolites (M2 and M4–M7). These new metabolites may provide new insight and broaden the understanding of bupropion's variability in clinical pharmacokinetics. © 2016 The Authors Biopharmaceutics & Drug Disposition Published by John Wiley & Sons Ltd.     

Memory-related effects of cholinergic receptor ligands in mice as measured by the elevated plus maze test

The purpose of our experiments was to examine the influence of cholinergic receptor ligands on memory-related behavior in mice using the elevated plus maze (EPM) test. The EPM test allows the exploration of different memory processes (acquisition and consolidation), depending on the time of drug treatment. The time necessary for mice to move from the opened arm to the enclosed arm (i.e., transfer latency, TL) was used as an index of memory. Our findings reveal that for both the processes of acquisition and consolidation, treatment with nicotine (0.035 or 0.175 mg/kg, free base, sc) shortened TL on the second day of the experiments (TL2), thus improving memory processes. Treatment with scopolamine (0.3 or 1.0 mg/kg, ip) significantly increased TL2 values, thus impairing cognitive processes. Moreover, we found that treatment with nicotine, at the non-effective doses used during testing, prevented scopolamine-induced memory impairment by inducing a decrease in TL2 values. Next, we evaluated the influence of bupropion (10 or 20 mg/kg, ip), a drug currently used for smoking cessation in humans, on memory-related behavior induced by treatment with nicotine and scopolamine. An acute injection of bupropion (10 or 20 mg/kg) prior to injection with either nicotine (0.035 mg/kg) or scopolamine (1.0 mg/kg) significantly prevented nicotine-induced memory improvement or scopolamine-induced memory impairment. Bupropion treatment can diminish the rewarding (dependence-producing) effects of nicotine and also the cognitive effects that are related to addiction. Our studies further indicate the great involvement of the cholinergic system in memory processes and the potential for the development of more effective pharmacotherapies for memory impairment-like human disorders in which the cholinergic pathways have been implicated.     

Bupropion for adults with attention-deficit hyperactivity disorder: meta-analysis of randomized, placebo-controlled trials

Aim: The aim of this study was to systematically review the efficacy, acceptability and tolerability of bupropion in comparison to placebo. Only randomized‐controlled trials were included in the meta‐analysis. Methods: MEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in October 2010. Study populations comprised adults with any subtype of attention‐deficit hyperactivity disorder, attention‐deficit disorder, hyperkinetic disorder, minimal brain dysfunction, minimal cerebral dysfunction or minor cerebral dysfunction. Efficacy outcomes were pooled mean changed scores of the ADHD rating scale (ADHD‐RS) and the overall response rates. The overall discontinuation rate was considered as the measure of acceptability. Results: A total of 349 participants (n for bupropion treatment = 175) in five published randomized, controlled trials were included. Bupropion sustained‐ or extended‐release was the experimental treatment in all studies. The pooled mean changed score of the ADHD‐RS of the bupropion‐treated group was greater than that of the placebo‐treated group with a weighted mean difference (95%CI) of 5.08 (3.13–7.03). The overall response rate of the bupropion‐treated group was significantly greater than that of placebo‐treated groups with a relative risk (95%CI) of 1.67 (1.23–2.26). However, the pooled overall discontinuation rate and the pooled discontinuation rate due to adverse events were not significantly different between groups with a relative risk (95%CI) of 1.11 (0.71–1.72) and 0.87 (0.08–9.79), respectively. Conclusion: The evidence suggests that bupropion is superior to placebo and effective for the treatment of ADHD in adults. However, its acceptability and tolerability were not significantly higher than those of placebo.     

Safety and efficacy of naltrexone for weight loss in adult patients – a systematic review

IntroductionThis is a report of a systematic review of the safety and efficacy of naltrexone or naltrexone/bupropion on weight loss.Material and methodsThe databases Medline, PubMed, and Embase as well as the Cochrane Controlled Trials Register for randomized controlled trials were searched for studies published from January 1966 to January 2018. A meta-analysis, randomised controlled trials, controlled trials, uncontrolled trials, cohort studies and open-label studies were analysed.ResultsOf 191 articles, 14 fulfilled the inclusion criteria: 1 meta-analysis, 10 randomized controlled trials, and 3 studies without randomization were found. In these studies, the efficacy and safety of naltrexone/bupropion in obesity were analysed. In the majority of these studies, patients with at least 5% or 10% weight loss, as a primary outcome, were investigated. Generally, naltrexone/bupropion treatment can be a promising therapy for obese patients, including when combined with mental health treatment.ConclusionsBased on these studies, it can be said that naltrexone/bupropion treatment is effective in the weight loss of overweight subjects. The naltrexone/bupropion treatment was well tolerated by the patients, and side effects were rarely reported.