Proc Natl
Acad Sci U S A. 2013 May 6. [Epub ahead of print]
Dynamic vaccine blocks relapse to compulsive intake of heroin.
Schlosburg JE, Vendruscolo LF, Bremer PT, Lockner JW, Wade CL, Nunes AA, Stowe GN, Edwards S, Janda KD, Koob GF.
Committee on the Neurobiology of Addictive Disorders and Departments of
Chemistry, Immunology, and Microbial Science, The Scripps Research Institute, La
Jolla, CA 92037.
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.
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