Dynamic vaccine blocks relapse to compulsive intake of heroin

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 a...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 110; no. 22; pp. 9036 - 9041
Main Authors Schlosburg, Joel E., Vendruscolo, Leandro F., Bremer, Paul T., Lockner, Jonathan W., Wade, Carrie L., Nunes, Ashlee A. K., Stowe, G. Neil, Edwards, Scott, Janda, Kim D., Koob, George F.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 28.05.2013
National Acad Sciences
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Abstract 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.
AbstractList 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.
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. [PUBLICATION ABSTRACT]
Author Janda, Kim D.
Stowe, G. Neil
Vendruscolo, Leandro F.
Bremer, Paul T.
Wade, Carrie L.
Edwards, Scott
Koob, George F.
Lockner, Jonathan W.
Nunes, Ashlee A. K.
Schlosburg, Joel E.
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Edited by Richard D. Palmiter, University of Washington, Seattle, WA, and approved February 26, 2013 (received for review November 14, 2012)
Author contributions: J.E.S., L.F.V., C.L.W., G.N.S., S.E., K.D.J., and G.F.K. designed research; J.E.S., L.F.V., P.T.B., J.W.L., C.L.W., A.A.K.N., G.N.S., and S.E. performed research; P.T.B., A.A.K.N., G.N.S., and K.D.J. contributed new reagents/analytic tools; J.E.S., P.T.B., J.W.L., A.A.K.N., G.N.S., K.D.J., and G.F.K. analyzed data; and J.E.S. and G.F.K. wrote the paper.
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Snippet Heroin addiction, a chronic relapsing disorder characterized by excessive drug taking and seeking, requires constant psychotherapeutic and pharmacotherapeutic...
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StartPage 9036
SubjectTerms Animals
Antibodies
Antibodies - immunology
Biological Sciences
Chromatography, Liquid
Drug therapy
Heroin
Heroin - blood
Heroin - immunology
Heroin - metabolism
Heroin dependence
Heroin Dependence - prevention & control
Male
Metabolites
Morphine
Morphine - immunology
Morphine - metabolism
Morphine Derivatives - blood
Morphine Derivatives - immunology
Morphine Derivatives - metabolism
Motivation
Opiates
Opioid analgesics
Pharmacology
Psychotropics
Rats
Rats, Wistar
Relapse
Rodents
Secondary Prevention
Self Administration
Tandem Mass Spectrometry
Vaccination
Vaccines
Vaccines - immunology
Title Dynamic vaccine blocks relapse to compulsive intake of heroin
URI https://www.jstor.org/stable/42657209
http://www.pnas.org/content/110/22/9036.abstract
https://www.ncbi.nlm.nih.gov/pubmed/23650354
https://www.proquest.com/docview/1364610980
https://pubmed.ncbi.nlm.nih.gov/PMC3670323
Volume 110
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