<b>Can you vaccinate against substance abuse?</b>

Kosten, Thomas R.; Domingo, Coreen

doi:10.1517/14712598.2013.791278

Cited by 27 publications

(28 citation statements)

References 30 publications

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“…Otherwise, the antibodies will rapidly be occupied with inactive or downstream metabolites and the binding capacity readily overcome by taking repeated doses of the abused drug over a short period of time (Kosten and Domingo, 2013). A high antibody specificity also has the advantage of not interfering with endogenous opioids, classic opioid analgesics, or conventional addiction treatment, which again opens for the possibility to combine current opioid substitution therapy with novel immunotherapeutics.…”

Section: Controlmentioning

confidence: 99%

A Monoclonal Antibody Specific for 6-Monoacetylmorphine Reduces Acute Heroin Effects in Mice

Bogen¹,

Boix²,

Nerem³

et al. 2014

J Pharmacol Exp Ther

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Immunotherapy against drugs of abuse is being studied as an alternative treatment option in addiction medicine and is based on antibodies sequestering the drug in the bloodstream and blocking its entry into the brain. Producing an efficient vaccine against heroin has been considered particularly challenging because of the rapid metabolism of heroin to multiple psychoactive molecules. We have previously reported that heroin's first metabolite, 6-monoacetylmorphine (6-MAM), is the predominant mediator for heroin's acute behavioral effects and that heroin is metabolized to 6-MAM primarily prior to brain entry. On this basis, we hypothesized that antibody sequestration of 6-MAM is sufficient to impair heroin-induced effects and therefore examined the effects of a monoclonal antibody (mAb) specific for 6-MAM. In vitro experiments in human and rat blood revealed that the antibody was able to bind 6-MAM and block the metabolism to morphine almost completely, whereas the conversion of heroin to 6-MAM remained unaffected. Mice pretreated with the mAb toward 6-MAM displayed a reduction in heroin-induced locomotor activity that corresponded closely to the reduction in brain 6-MAM levels. Intraperitoneal and intravenous administration of the anti-6-MAM mAb gave equivalent protection against heroin effects, and the mAb was estimated to have a functional half-life of 8 to 9 days in mice. Our study implies that an antibody against 6-MAM is effective in counteracting heroin effects.

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Section: Controlmentioning

confidence: 99%

A Monoclonal Antibody Specific for 6-Monoacetylmorphine Reduces Acute Heroin Effects in Mice

Bogen¹,

Boix²,

Nerem³

et al. 2014

J Pharmacol Exp Ther

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“…Immunopharmacotherapy, specifically through active immunization, has been utilized as a method for the sequestration of drug molecules from the brain and for the reduction of drug effects. By eliciting high-affinity drug-specific antibodies, anti-drug vaccines have been developed as potential therapeutics (see (Kosten and Domingo, 2013; Ohia-Nwoko et al, 2016; Skolnick, 2015; Zalewska-Kaszubska, 2015) for review), for psychomotor stimulants such as MA and cocaine (Kosten et al, 2014) and even recently emerged designer cathinones, such as alpha-pyrrolidinopentiophenone and 3,4-methylenedioxypyrovalerone (Nguyen et al, 2016c). Multiple reports followed a seminal demonstration that an anti-cocaine vaccine produced an attenuation of cocaine-stimulated locomotor increases in male Wistar rats (Carrera et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Effective active vaccination against methamphetamine in female rats

Nguyen

Bremer

Hwang

et al. 2017

Drug and Alcohol Dependence

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Background Immunotherapies directed against methamphetamine (MA) abuse have shown success in rodent models, however only a limited number of studies have investigated active vaccination in female mice and none in female rats. It is critical to determine if potential immunotherapeutic strategies generalize across sex, particularly for drugs that may produce significant sex-differences on behavioral or physiological endpoints. Methods Female Wistar rats were initially vaccinated with keyhole-limpet hemocyanin (KLH) or an anti-methamphetamine-KLH conjugate (MH6-KLH) three times over five weeks and implanted with radiotelemetry devices to assess locomotor activity and body temperature responses to MA. Rats were first exposed to MA via vapor inhalation (100mg/mL in propylene glycol) and then by injection (0.25–1.0 mg/kg, i.p.) and vapor after a final vaccine boost. Results The MH6-KLH vaccine generated an increase in antibody titers across the initial 6-week, 3 immunization protocol and a restoration of titer after a week 14 booster. Locomotor stimulation induced by 0.25 mg/kg MA, i.p, in the KLH group was prevented in the MH6-KLH group. MH6-KLH animals also exhibited an attenuated locomotor stimulation produced by 0.5 mg/kg MA, i.p. No group differences in locomotion induced by vapor inhalation of MA were observed and body temperature was not differentially affected by MA across the groups, most likely because vapor inhalation of MA that produced similar locomotor stimulation resulted in ~10-fold higher plasma MA levels. Conclusions This study confirms the efficacy of the MH6-KLH vaccine in attenuating the effects of MA in female rats.

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“…A promising new approach could be antiaddiction vaccination, which prevents the drug from having an effect 13. Whether vaccination is helpful for abstinent patients, however, is still uncertain.…”

Section: Discussionmentioning

confidence: 99%

Levamisole-contaminated cocaine: a hairy affair

et al. 2015

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SUMMARYLevamisole-contaminated cocaine can induce severe systemic vasculitis. The diagnosis can be challenging, especially when substance abuse is uncertain. We present the case of a 42-year-old woman suffering from vasculitis due to levamisole-contaminated cocaine, who persistently denied substance abuse. Symptoms included ulcerating skin lesions, arthralgia and myalgia, and the occurrence of an ileal intussusception. The definitive diagnosis was made using hair testing for toxins. She recovered through cocaine abstinence, but re-exposure resulted in a severe relapse with glomerulonephritis. Importantly, at time of the relapse, the patient became positive for both myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA) and proteinase 3-ANCA. Cocaine-levamisole-induced vasculitis poses a great clinical challenge. The proper diagnostic strategy and therapy is still controversial. We highlight our diagnostic and therapeutic considerations, including hair testing for definitive proof of exposure. BACKGROUND

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Can you vaccinate against substance abuse?

Cited by 27 publications

References 30 publications

A Monoclonal Antibody Specific for 6-Monoacetylmorphine Reduces Acute Heroin Effects in Mice

A Monoclonal Antibody Specific for 6-Monoacetylmorphine Reduces Acute Heroin Effects in Mice

Effective active vaccination against methamphetamine in female rats

Levamisole-contaminated cocaine: a hairy affair

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