Dynamic Vaccine Blocks Relapse to Compulsive Intake of Heroin.

Dynamic vaccine blocks relapse to compulsive intake of heroin.

Proc Natl Acad Sci U S A. 2013 May 6;
Schlosburg JE, Vendruscolo LF, Bremer PT, Lockner JW, Wade CL, Nunes AA, Stowe GN, Edwards S, Janda KD, Koob GF

Heroin addiction, a chronic relapsing disorder characterized by excessive drug taking and seeking, requires constant psychotherapeutic and pharmacotherapeutic interventions to minimize the potential for further abuse. Vaccine strategies against many drugs of abuse are being developed that generate antibodies that bind drug in the bloodstream, preventing entry into the brain and nullifying psychoactivity. However, this strategy is complicated by heroin’s rapid metabolism to 6-acetylmorphine and morphine. We recently developed a “dynamic” vaccine that creates antibodies against heroin and its psychoactive metabolites by presenting multihaptenic structures to the immune system that match heroin’s metabolism. The current study presents evidence of effective and continuous sequestration of brain-permeable constituents of heroin in the bloodstream following vaccination. The result is efficient blockade of heroin activity in treated rats, preventing various features of drugs of abuse: heroin reward, drug-induced reinstatement of drug seeking, and reescalation of compulsive heroin self-administration following abstinence in dependent rats. The dynamic vaccine shows the capability to significantly devalue the reinforcing and motivating properties of heroin, even in subjects with a history of dependence. In addition, targeting a less brain-permeable downstream metabolite, morphine, is insufficient to prevent heroin-induced activity in these models, suggesting that heroin and 6-acetylmorphine are critical players in heroin’s psychoactivity. Because the heroin vaccine does not target opioid receptors or common opioid pharmacotherapeutics, it can be used in conjunction with available treatment options. Thus, our vaccine represents a promising adjunct therapy for heroin addiction, providing continuous heroin antagonism, requiring minimal medical monitoring and patient compliance. HubMed – addiction

Preventing sin: the ethics of vaccines against smoking.

Hastings Cent Rep. 2013 May-Jun; 43(3): 23-33
Lieber SR, Millum J

The alarming rates of smoking, obesity, and substance abuse pose an enormous challenge for parents and public health officials: how do we prevent children and adolescents from adopting unhealthy behaviors? One new option that may soon be available is the use of nicotine vaccines. Immunological therapies to help smokers stop smoking have shown promise in phase I and II trials; similar therapies could combat smoking addiction before it starts. Nicotine vaccines are distinctive because they confer protection not against infection-the normal target for vaccines-but against enticing pleasures that lead to unhealthy behaviors. As a result, using them preventively in children would be likely to arouse some novel ethical concerns that should be addressed before the vaccines become commonly available and their off-label use as a preventive measure becomes a real option. In this paper, we consider whether it would be ethical for parents to vaccinate their children against smoking if a nicotine vaccine were to be proven effective as a preventive intervention for children or adolescents. We begin by explaining the current state of nicotine vaccine science and suggesting some likely ethical concerns about allowing parents to have their children receive a vaccine. We then present a preliminary argument for making vaccination permissible, at least if nicotine vaccination substantially reduces the probability that someone subsequently becomes a smoker. We consider a series of possible ethical objections, which are useful for identifying the conditions under which it would be ethical for parents to vaccinate their children against smoking. We conclude that it would be permissible for parents to give their child a nicotine vaccine if the following conditions were met: the vaccine is expected to result in a net benefit to each individual vaccinated, the expected harms from the side effects of the vaccine are lower than the nonvoluntary harms caused by smoking, and there are no other, less manipulative methods available that are as effective at preventing smoking initiation. HubMed – addiction

Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics.

Psychopharmacology (Berl). 2013 May 7;
Martínez-Clemente J, López-Arnau R, Carbó M, Pubill D, Camarasa J, Escubedo E

RATIONALE: Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine. OBJECTIVE: The major aims were to investigate the pharmacokinetics and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. METHODS: Mephedrone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized using LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. RESULTS: Mephedrone plasma concentrations after i.v. administration fit a two-compartment model (??=?10.23 h(-1), ??=?1.86 h(-1)). After oral administration, peak mephedrone concentrations were achieved between 0.5 and 1 h and declined to undetectable levels at 9 h. The absolute bioavailability of mephedrone was about 10 % and the percentage of mephedrone protein binding was 21.59?±?3.67 %. We have identified five phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85?±?0.08. Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokinetic-pharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. CONCLUSIONS: We suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude, and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity. HubMed – addiction

A Metaphor Analysis of Recovering Substance Abusers’ Sensemaking of Medication-Assisted Treatment.

Qual Health Res. 2013 May 6;
Malvini Redden S, Tracy SJ, Shafer MS

In this study, we examined metaphors invoked by people recovering from opioid dependence as they described the challenges and successes of using medication-assisted treatment. Metaphors provide linguistic tools for expressing issues that are confusing, complex, hidden, and difficult to state analytically or literally. Using data from eight focus groups with 68 participants representing four ethnic minority groups, we conducted a grounded analysis to show how recovering substance users communicatively constructed addiction and recovery. The primary medication, methadone, was framed as “liquid handcuffs” that allowed those in recovery to quit “hustling,” get “straight,” and find “money in their pockets.” Nonetheless, methadone also served as a “crutch,” leaving them still feeling like “users” with “habits” who “came up dirty” to friends and family. In this analysis, we tease out implications of these metaphors, and how they shed light on sensemaking, agency, and related racial- and class-based structural challenges in substance abuse recovery. HubMed – addiction

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