Biologic Approaches to Treat Substance-Use Disorders

Abstract

In contrast to traditional pharmacodynamic approaches to treat substance-use disorders (SUDs), the use of biologics (vaccines, monoclonal antibodies, and genetically modified enzymes) is based on a pharmacokinetic principle: reduce the amount of (and, ideally, eliminate) abused drug entering the central nervous system (CNS). Preclinical studies indicate that biologics are effective in both facilitating abstinence and preventing relapse to abused substances ranging from nicotine to heroin. While data are still emerging, the results from multiple clinical trials can best be described as mixed. Nonetheless, these clinical studies have already provided important insights using 'first-generation' tools that may inform the development of effective and commercially viable biologics to treat tobacco-, cocaine-, and methamphetamine-use disorders.

Keywords: cocaine; methamphetamine; monoclonal antibodies; nicotine; substance use disorders; vaccines.

Figure 1

Effects of NicVAX^® on smoking behavior: Panel A: Seven day point prevalence abstinence rates in smokers with high (top 30% based on AUC) and low (bottom 70%) antibody titers compared with placebo injections over 52 weeks. Panel B: Percentage of patients exhibiting end of study abstinence (8 weeks of continuous abstinence, weeks 45-52), grouped by antibody levels. Panel C: Time required to achieve 8 weeks of sustained abstinence before week 46 and continuous abstinence through to week 52 stratified by antibody titer (see Panel A). Ab, antibody, AUC, area under the curve. From reference [6], with permission.

Figure 2

RBP-8000 accelerates the hydrolysis of cocaine: Non –treatment seeking subjects with a DSM-IV diagnosis of cocaine abuse were administered an IV infusion of cocaine (50 mg) over 10 minutes. RBP-8000 (100 or 200 mg) or matched placebo was infused 1 minute after completion of cocaine infusion. Blood samples were collected between 2-720 minutes post RBP-8000 (or placebo) infusion. Symbols: Green squares, cocaine + matched placebo; magenta circles, cocaine + matched placebo; blue squares: cocaine + RBP-8000 (100 mg); red circles: cocaine + RBP (200 mg). The data used to generate this figure is taken from [26].