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7Ylzjypw[Pvu +Y\N (I\Zl 7YLZJYPW[PVU +Y\N(I\ZL 11 Prescription Drug abuse NN0084 Introduction The National Institute on Drug Abuse (NIDA) supports most of the world’s research on drug abuse and addiction. NIDA-funded research enables scientists to apply the most advanced techniques available to the study of every aspect of drug abuse, including: • genetic and social determinants of vulnerability and response to drugs; • short- and long-term effects of drugs on the brain, including addiction; • other health and social impacts of drug abuse, including infectious diseases and economic costs; • development and testing of medications and behavioral treatments for abuse and addiction; and • development and evaluation of effective messages to deter young people, in particular, from abusing drugs. Included in this document are selections of topic-specific articles reprinted from NIDA’s research newsletter, NIDA NOTES. Six times per year, NIDA NOTES reports on important highlights from NIDA-sponsored research, in a format that specialists and lay readers alike can read and put to use. Selections like the current one are intended to remind regular NIDA NOTES readers and inform other readers of important research discoveries during the periods they cover. We hope the information contained here answers your needs and interests. To subscribe to NIDA NOTES and for further information on NIDA’s drug abuse and addiction research, please visit our Web site at www.drugabuse.gov. ii Table of Contents Basic Science Discoveries Yield Novel Approaches to Understanding the Risks of Prescription Drug Abuse Analgesia (V22-1; September 2008) ...............................1 (V16-3; August 2001) ..................................................33 Morphine-Induced Immunosuppression, From Brain to Research Eases Concerns About Use of Opioids To Spleen (V21-6; June 2008) ............................................6 Relieve Pain (V15-1; March 2000) ..............................35 Alcohol Abuse Makes Prescription Drug Abuse More NIDA Researchers Developing Problem-Free Pain Likely (V21-5; March 2008) ..........................................9 Relievers (V12-6; November/December 1997) ............37 Chromosome 17 Harbors Opioid Dependence Genes UNC Scientist Searches for Effective Analgesics with (V21-5; March 2008) ...................................................11 Low Abuse Potential (V11-3; May/June 1996) ............40 Teen Substance Abuse Continues to Decline NIDA Research Expands Horizon for Analgesia (V21-5; March 2008) ...................................................13 Alternatives (V11-2; March/April 1996) ......................41 Controlling College Students’ ADHD Symptoms Scientists Explore Novel Approaches to Pain Control May Protect Them Against Substance Abuse (V11-2; March/April 1996) .........................................43 (V21-4; October 2007) ................................................15 Meeting Reviews Progress On Prescription Opioid Misuse (V21-3; April 2007) .........................................16 Buprenorphine Plus Behavioral Therapy Is Effective For Adolescents With Opioid Addiction (V21-1; October 2006) ................................................17 First-time Patients Opt for Office-Based Buprenorphine (V21-1; October 2006) ................................................19 High School Seniors Steadily Increase Nonmedical Use of Sedatives Over 15 Years (V21-1; October 2006) ................................................20 NIDA and Scholastic Offer Teens and Teachers New Heads Up (V20-4; March 2006) ..................................21 Studies Identify Factors Surrounding Rise in Abuse of Prescription Drugs by College Students (V20-4; March 2006) ...................................................23 NIDA Responds to Changing Drug Abuse Patterns (V20-2; August 2005) ..................................................25 Confronting the Rise in Abuse of Prescription Drugs (V19-5; January 2005) .................................................27 2003 Survey Reveals Increase in Prescription Drug Abuse, Sharp Drop in Abuse of Hallucinogens (V19-4; December 2004) .............................................29 Facts About Prescription Drug Abuse and Addiction (V16-3; August 2001) ..................................................30 NIDA Scientific Panel Reports on Prescription Drug Misuse and Abuse (V16-3; August 2001) .....................31 iii iv Research Findings Volume 22, Number 1 (September 2008) Basic Science Discoveries Yield Novel Approaches to Analgesia Innovations Research on glial cells and receptors leads to compounds that outperform morphine in preclinical trials. By Lori Whitten, NIDA NOTES Staff Writer For millennia, opioid medications have provided the most The Glial Strategy potent tools for pain relief. Yet, although they are the best Dr. Watkins’ research team, in collaboration with we have, opioids fall short of being ideal analgesics: They Dr. Kirk W. Johnson and colleagues at Avigen Inc. of have unpleasant side effects, their efficacy diminishes with Alameda, California, recently relieved neuropathic pain ongoing use, they cause physical dependence, and they in rats by giving them AV411 (also called ibudilast; see pose significant risks for abuse and addiction. Moreover, “AV411 for Pain Relief Without Opioid Side Effects” opioids do not quell all types of pain. For example, they on next page), a compound that inhibits glial cell activ- provide only partial, often temporary relief to people with ity. In other animal studies by Dr. Watkins and other neuropathic pain, which commonly develops when disease researchers, various compounds that inhibit glial cells have or trauma injures nerves and typically produces burning, reduced or abolished pain that simulated many types of stinging, or tingling that doesn’t cease. human chronic neuropathic pain. They also have boosted NIDA-supported research teams are advancing along eight-fold the acute pain relief afforded by morphine. separate paths to develop new compounds that match or Dr. Watkins and colleagues discovered the analgesic exceed the pain relief provided by opioids while avoiding potential of glial cell inhibition through pioneering their shortcomings. Dr. Linda R. Watkins and colleagues research that implicates glial cells in the amplification at the University of Colorado at Boulder are pursuing the and long-term maintenance of pain. Their investigations implications of their discovery that glia—nonneuronal showed that tissue or nerve inflammation or damage that nervous system cells—play a previously unrecognized is associated with neuropathic pain heightens activity of key role in the generation of neuropathic pain and in two types of glial cells—microglia and astrocytes—in the spinal cord. The activated glia release biochemicals—including proinflamma- tory cytokines and chemokines, nitrous oxide, and prostaglandins—that excite spinal cord neurons to transmit strong and persistent pain signals to the brain. The finding that glial cells modulate pain in the spinal cord prompted the researchers to explore glial cell inhibi- tion as a broad strategy for controlling many types of pain. Adapted from: Experimental Neurology 80(1):1-13, 2003. Dr. Watkins’ findings extend the roster After spinal cord damage, glial cells called astrocytes proliferate and expand. of important functions attributed to glial cells. It was previously known, for example, that glia maintain hospitable opioid tolerance and withdrawal. Dr. Philip S. Portoghese microenvironments for neurons and provide them with and collaborators at the University of Minnesota and molecular support for carrying out their cellular functions. Louisiana State University are tinkering with opioid mole- Another glial cell activity, clearing cellular debris away cules to capitalize on recent findings showing that opioids from neurons, can last for years—a fact, the researchers produce pain relief by mechanisms separate from those suggest, that may have important implications for the long that produce their less desirable effects. During the past duration of chronic pain. year, both groups have reported highly promising results. 1 Enhancing Opioids And Making Them Safer AV411’s ability to enhance opioid efficacy could be espe- Working with researchers at the University of Adelaide cially valuable for chronic pain patients with histories of in Australia, Avigen has completed an exploratory clini- drug abuse. At a NIDA-sponsored panel at the annual cal trial to test AV411 in patients with neuropathic pain. Society for Neuroscience meeting on November 2, 2007, Patients in the study, who were predominantly diagnosed Dr. Watkins reported preliminary results suggesting that with painful diabetic neuropathy, received fixed regimens the medication counters the opioid-induced reward sensa- of AV411 as well as concomitant analgesics, including tions that can raise such patients’ risk for relapse. Using opioids. Preliminary results indicated that patients receiv- an established experimental model to assess reward, the ing AV411 reduced their opioid use, suggesting that researchers repeatedly infused rats with morphine in a test AV411 relieved pain or reduced opioid tolerance. chamber, then let the animals decide whether to spend time in that chamber or another. The idea that glial modulatory compounds might counter- act opioid tolerance emerged from studies to understand Rats that had been pretreated with AV411 spent roughly the biochemical basis for that phenomenon. In experi- equal amounts of time in both chambers; their
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