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ARRA Investments in Substance Abuse Treatment Research


Public Health Burden
Both illicit and licit drugs impose an extraordinary public health burden, with an estimated 22.2 million persons (nearly 9 percent of the population) classified with substance dependence or abuse in the past year. This translates into societal costs of over $600 billion dollars annually in increased health care costs, crime, and lost productivity. New research will capitalize on recent discoveries that have uncovered an expanded range of possible brain targets, which will help bring about more effective medications and enhance behavioral therapies to treat addiction and counter its effects on the brain.

Immunotherapy for Treating Drug Abuse and Addiction
Several ARRA-funded grants are investigating immunotherapy approaches, including vaccines, which work by stimulating the body’s immune system to produce antibodies. These antibodies target drug molecules while they are still in the bloodstream, preventing them from entering the brain and exerting their psychoactive/toxic effects. This area of study is an ARRA Signature Project. Vaccines are being developed for a variety of drugs of abuse, as the following examples illustrate.
  • Cocaine: Currently, no medications exist for treating stimulant addiction. Thus, NIH is funding two ARRA preclinical grants striving to enhance cocaine vaccine potency by increasing the effectiveness of neutralizing antibodies for eventual use in human trials.1
  • Nicotine: Eradicating Tobacco Abuse and Addiction is another “Signature Project”. Several grants are funded to improve the efficacy of a nicotine vaccine and to expedite its continued development towards FDA approval. Among these: (a) animal models are being improved to more closely simulate the human route of nicotine intake, while (b) human studies are using brain imaging to clarify mechanisms underlying vaccine efficacy to further improve immunotherapy for smoking addiction, and (c) effectiveness trials are comparing placebo vs. vaccine treatment in smokers who want to quit.2
  • Methamphetamine: Chronic methamphetamine abuse changes brain structure and function, producing cognitive impairment, which can persist for some time. Two ARRA grants are addressing immunotherapies for methamphetamine abuse, including: (a) an animal study that seeks to trigger healing responses in the brain and improve methamphetamine-induced cognitive impairment and (b) research to make and effectively use vaccines in humans to stimulate strong antibody responses, and thereby garner the best chance of success in preventing relapse.3
  • Drug overdose: Because vaccines take time to generate an antibody response, a different approach is needed to treat acute drug toxicity. An ARRA-funded study will produce a monoclonal antibody programmed to react against methamphetamine, amphetamine and MDMA (ecstasy) in the blood, preventing them from entering the brain, and rendering them inactive. The antibody will be tested for safety and efficacy in animal models, in preparation for human trials. If effective, this medication could be used in emergency rooms to mitigate the effects of overdose, as well as to prevent relapse.4
Other Promising Medications for Addiction
Several ARRA grants are testing promising medications for substance use disorders, examples of which follow:
  • Buprenorphine is an effective medication for the treatment of opioid addiction, including heroin and prescription pain medications. It is hoped that an alternative formulation [subcutaneous (under the skin) implant] of buprenorphine will prove more effective than the standard daily sublingual tablet form by preventing poor treatment adherence and medication diversion.5
  • Exposure to drug cues frequently triggers relapse in patients addicted to drugs of abuse. Another grant will build on advances in treating conditioned fear and anxiety and other cognitive disorders to uncover the neurobiological underpinnings of extinction learning (i.e., reducing reactivity to drug cues). This knowledge will inform development of new medications for addiction.6
  • Marijuana is the most commonly reported abused drug among adolescents in substance abuse treatment. Several ARRA grants are developing medications to diminish withdrawal symptoms (which often prompt relapse) and to promote abstinence, some being tested in combination with established behavioral therapies.7
Innovative Interventions to Reduce Drug Use and Other Risky Behaviors
Many interventions for treating drug abuse and related risky behaviors are emerging into practice. Among these, web-based technologies stand to broaden the reach of and improve the delivery of evidence based treatments. Other interventions build on recent behavioral and epidemiological research findings to affect beneficial health outcomes in high-risk populations.
  • Ninety percent of smokers start in adolescence. An ARRA grant will develop and test the efficacy of an incentive-based smoking cessation program aimed at motivating a tobacco-free lifestyle in adolescents, research with implications for shaping teen attitudes and perceptions.8
  • In partnership with the Whitman Walker Clinic, an ARRA grantee will conduct a randomized controlled trial of a web-based medication adherence program for HIV-positive individuals, presented within the framework of a stress and mood management program—which could conceivably expand the reach of adherence programs and improve the mental health of those infected with HIV.9



  1. 1RC2DA028906-01, -- Development of a Flagellin-Cocaine Conjugate Vaccine--Mizel, Steven B. (NC); 1RC2DA028847-01 -- Adenovirus-based Anti-Cocaine Vaccine -- Crystal, Ronald G. (NY)
  2. 3R01DA010714-13S2, -- Immunization to Block the Effects of Nicotine -- Pentel, Paul R. (MN); 3R01DA010714-13S1 -- Immunization to Block the Effects of Nicotine -- Pentel, Paul R (MN) .; (b) 1R01DA025598-01 -- Innovative Interventions for Smoking Cessation -- Hatsukami, Dorothy K. (MN); (c) 1RC2DA028837-01 -- Phase III Study of a Nicotine Vaccine for Smoking Cessation -- Kessler, Paul D. (MD)
  3. 1RC1DA028537-01, -- Preclinical Testing of a Novel Immunotherapy [recombinant T cell receptor ligand] -- Huckans, Marily; Loftis, Jennifer M. (OR); (b) 1 U01 DA023898-01 -- Developing Immunotherapies for Methamphetamine Abuse -- Kosten, Thomas R. (TX)
  4. 1RC2DA028915-01 -- Chimeric anti-Methamphetamne Monoclonal Antibody for Treating Stimulant Toxicity -- Gentry, W Brooks; Holtz, R Barry. (AR)
  5. 1RC2DA028910-01 -- A Six-Month RCT of Probuphine Safety and Efficacy in Opioid Addiction -- Beebe, Kathrine L. (CA)
  6. 3R01DA024315-02S1 -- Strategies for Enhancing Extinction of Drug-Seeking Behavior -- Kantak, Kathleen M. (MA)
  7. 1RC2DA028984-01 -- Transdermal Cannabinoid Prodrug Treatment for Cannabis Withdrawal and Dependence -- Stinchcomb, Audra L (KY); 1R01DA026777-01 — A Controlled Trial of N-Acetylcysteine (NAC) in Cannabis Dependent Adolscents — Gray, Kevin M (SC); 1R01DA026778-01 — Biobehavioral effects of topiramate on cannabis-related outcomes in adolescents — Miranda, Robert (RI)
  8. 1R01DA026450-01 -- Incentive-Based Intervention for Smoking Cessation and Prevention in High Schools -- Krishnan-Sarin, Suchitra. (CT)
  9. 1RC1DA028505-01 -- Test of a Web-based Program to Improve Adherence to HIV/AIDS Medications -- Cook, Royer F. (VA)


 
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