Addiction Center Report

(1)

A Message from the Director

D

uring the past year and a half I had the opportunity to direct the activities of the National Institute on Drug Abuse (NIDA) at the National Institutes of Health. The annual budget of this Institute approached $1 billion to support research into the cause and consequences of drug abuse. The willingness of the American people to spend this money to better understand the process of drug abuse, acknowledges the public concern that drug abuse is one of the leading health problems of this nation. We all agree, something must be done to

diminish its devastating impact on our society, our communities, and our

families. Because of NIDA’s research support, scientists have learned a great deal about the neurobiology of addiction, the long and short-term changes in the brain caused by the frequent use of drugs of abuse, the mechanisms of drug relapse, and the naturally occurring brain systems activated by these substances. We have also determined that chemicals of abuse activate brain pathways likely associated with compulsive behaviors such as those leading to obesity and its medical sequelae. Because of this research, we know that the prefrontal cortex of the brain is particularly vulnerable to the effects of these drugs hampering this associative structure from establishing appropriate priorities and making correct decisions regarding individual welfare and unnecessary risk taking. It has also been suggested that congenital damage to this brain structure, likely associated with ADHD or head trauma as often occurs in automobile accidents, may be the

underlying cause that leads to increased vulnerability of these individuals to substance abuse problems. While the results from exciting research such as this have been

provocative and intellectually fascinating, the real contribution of these scientific efforts and investment of public dollars is the potential for these discoveries to lead to the development of more effective strategies to prevent and treat drug abuse disorders. Thus, as the acting director of NIDA I faced the dilemma of trying to find ways to translate the exciting scientific discoveries to help reduce the impact of drug abuse on our nation. Several relevant principles became evident as I wrestled with this enormous challenge:

• There is great frustration because of the enormous cost of drug abuse in terms of dollars, and personal and public health; consequently, the public and politicians have become impatient and want something done immediately.

• There are no simple solutions to these problems that will receive universal acceptance.

• Biomedical research has helped us to understand why drug abuse and addiction occurs and what are the consequences, but how can that information be

The

Utah

Addiction

_Report

Center

Volume 1

Issue 1

December 2003

Dedicated to research, clinical training, and education in chemical addiction

education clinical

training research

Institutional Advisory Board

»

See Message page 6

A. Lorris Betz, M.D., Ph.D. Louis H. Callister, J.D. Edward B. Clark, M.D. Jay Graves Ph.D. Patrick Fleming, LSAC, MPA Raymond Gesteland, Ph.D. Bernard I. Grosser, M.D. Glen W. Hanson Ph.D, D.D.S, Barbara N. Hardy, Ph.D. John R. Hoidal, M.D. Maureen Keefe, RN, Ph.D John W. Mauger, Ph.D. Ross VanVranken, ACSW

Kim Wirthlin, MPA

Glen W. Hanson, Ph.D, D.D.S

Utah Addiction Center University of Utah

Health Sciences Center 546 Chipeta Way, Suite 466 Salt Lake City, Utah 84108

C

ontaCt

U

s University of Utah Health Sciences Center 546 Chipeta Way, Suite 466 Salt Lake City, Utah 84108 Phone: (801) 581-8216 Fax: (801) 587-7858

E-mail: [email protected] Internet: http://uuhsc.utah.edu/uac/

(2)

automatically fates a person to a life of substance abuse. “This is simply not true. Students – and their teachers – need to understand that environmental and behavioral factors, including the choices made during high school, can effectively counteract any genetic predisposition to addiction.”

“If we expect young people to make informed decisions about how to use drugs appropriately, it is critical that they be accurately informed,” Hanson says. “By providing training to life science teachers, this program takes advantage of the background and teaching skills of these highly trained educators and makes it possible for them to integrate reliable and science-based perspectives of substance abuse into their curricula.”

For the teachers, the week proved to be an enlightening, albeit exhausting, professional development experience. They will return next summer to

investigate the genetics of nicotine addiction in closer detail. This program dovetails with the University’s NIDA funded Genetics of Addiction research program, which aims to identify genes involved in nicotine addiction.

When completed, the materials will be published free of charge for a worldwide audience on the Learning Center website (http://gslc.genetics.utah.edu), which receives over 40,000 visits per week during the academic year.

Jennifer Logan, Ph.D., is the co-director of the University of Utah Genetic Science Learning Center and Principal Investigator for the Genetics of Addiction Program grant.

»

Genetics

continued from page 3

Matthew Dugan of Dorchester, MA sketches his ideas for a teaching activity.

Did You Know?

interesting news from Join Together Online

Teen Smoking, Pot Use Linked

Teenage tobacco users are 14 times more likely to use marijuana than their nonsmoking peers, according to a new report from the American Legacy Foundation and the National Center on Addiction and Substance Abuse.

Source: WCBV-TV

Veterans and Substance Abuse

In 1999, veterans accounted for more than 65,000 admissions for substance abuse treatment. In 1999, the criminal justice system was the most common source of referral for all veterans.

Source: Substance Abuse and Mental Health Services Administration. (2001) The DASIS Report: Veterans in Substance Abuse Treatment. Office of Applied Studies, Rockville, MD.

Active Girls Less Likely to Use Drugs

New research shows that high-school girls who are on a sports team and are physically active are less likely to engage in risky behavior such as using drugs. No similar pattern was found among high-school boys.

Source: New York Times

Canadians Differ From Americans in College Student Drinking Habits

More Canadian students drink alcohol but American students drink more according to the first comparison of national alcohol studies among college/ university students.

Source: The Journal Addiction

D

rug and alcohol addiction lie at the root of one in four

deaths in the United States. Yet less than one third of primary care physicians carefully screen their patients for substance abuse or dependence, according to the National Center on Addiction and Substance Abuse at Columbia

University.1

The reason? Primary care physicians report discomfort in

discussing substance abuse issues with patients, resistance on the part of patients and a general skepticism about the effectiveness of treatment programs. All of which point to a shortfall in effective training to recognize and treat the symptoms of substance abuse.

The Utah Addiction Center is responding to this need by teaming with local healthcare professionals and the University of Utah School of Medicine to create and present a new addiction education curriculum for medical residents in primary care specialties.

The Addiction Education for Primary Care Residents program, funded by a grant from the Edward G. Callister Foundation, will provide a series of seminars and training sessions for first-year residents in internal medicine, pediatrics, obstetrics/gynecology and family and preventive medicine. UAC Associate Director Barbara Hardy, Ph.D., and curriculum developer Jennifer Logan, Ph.D., are leading the effort, in collaboration with a development team that includes psychiatrist Michael Measom, M.D., clinical psychologist Kelly Lundberg, Ph.D., internal medicine specialist Scott Stevens, M.D., and obstetrics/ gynecology specialist Robert Andres, M.D.

“This first-of-its-kind program will provide primary care physicians with critical perspectives and skills to help them be more effective as they confront the potentially devastating consequences of chemical abuse,” states UAC director Glen Hanson, Ph.D., D.D.S., “It will help them become more aware of the nature of drug abuse and addiction and their implications as a disease process.”

Through interactive sessions, residents will develop patient interviewing and screening skills. In addition, they will evaluate and address the many issues that accompany substance abuse, including family issues, co-occurring illnesses, and chronic pain. Along with its didactic component, the program will provide Internet-based resources that include local referral options and quick-reference materials.

Curriculum planning and development will take place during the 2003-4 academic year, and the program will be piloted with first-year residents during 2004-5. Following the pilot program, the UAC aims to develop the curriculum into a national model that can be used to train healthcare professionals in a variety of disciplines.

“Chemical addiction and substance use disorders account for more deaths, illnesses, and disabilities than does any other preventable health condition. This curriculum will prepare physicians to recognize and respond to this serious health issue,” says Hardy.

1_{Missed Opportunity: National Survey of Primary Care Physicians and Patients on Substance Abuse}_{. Reported by the National Center}

on Addiction and Substance Abuse, Columbia University, April 2000. Find the full report online at http://www.casacolumbia.org/usr_ doc/29109.pdf.

Addiction Education for Primary

Care Residents Program

clinical

training

Jennifer Logan, Ph.D.

Co-director, Genetic Science Learning Center University of Utah

(3)

K

ids are smart. They ask good questions. Some of which, their teachers find, are tough to address in the classroom:

“Why isn’t marijuana legal?”

“If a drug probably won’t hurt me, why shouldn’t I try it?” “My parents drink beer. How bad can it be?”

How does a teacher deal with such questions? One way is to ask students to craft their own answers, providing them with reliable information sources and effective guidance. This past July, 20 middle- and high-school life science teachers from around the nation gathered at the University of Utah to develop educational materials that will help teachers and students alike address challenging questions about substance abuse and addiction.

Their work is part of the University of Utah Genetic Science Learning Center’s

Genetics and Addiction Program, a three-year effort funded by a Science Education Partnership Award from the National Institute on Drug Abuse. Through this program, the Learning Center and its teacher partners will create an

extensive Internet-based resource for exploring the many factors that contribute to substance abuse, including heredity, neurobiology, and behavioral and

environmental risk factors.

“The Genetics and Addiction Program is an exciting approach to introduce

concepts of drug abuse and addiction into secondary education,” states UAC director Glen Hanson, Ph.D., D.D.S “This is a very effective mechanism to get the word out concerning what is considered to be the number one public health problem in our country.”

Teachers in the program were recruited from diverse life science classrooms from Seattle to Boston. During the week-long July course, they met with researchers and addiction experts to learn about the topic and begin developing educational materials. Guest presenters for the course included Hanson, who discussed the biology

of addiction, and clinical psychologist Kelly Lundberg, Ph.D., who reviewed risk and protective factors related to addiction. Jeffrey Botkin, M.D., MPH, University of Utah Vice President for Research Integrity, talked with the group about ethical issues surrounding genetic testing for predisposition to diseases such as addiction.

While Genetics and Addiction Program materials will be designed to meet

national education standards for the life science classroom, their scope extends well beyond talk of the scientific method, brain cells and signaling pathways. “It’s important for us to place the science of addiction in context with the many social and ethical aspects of this disease,” states Learning Center co-director Louisa Stark, Ph.D. “Not all students can immediately relate to the genetics and science

of addiction, but the broader impact of the disease directly affects each one of them.” Encouraging discussion of real-life scenarios, Stark says, can provide the hook that engages students in learning about the science behind addiction. Furthermore, a common misconception among students, Stark notes, is that a genetic predisposition to addiction

Genetics and Addiction Program

Marcia Butler of Philadelphia, PA shares her perspective with the group.

Jeffrey Botkin, M.D., MPH, discusses bioethical issues in addiction with the group.

From left: Mario Godoy-Gonzalez of Royal City, WA, Marilyn Pendley of Newton, NC, Crystal King of Salt Lake City, UT and RevaBeth Russell of Springville, UT work together to develop curriculum on the risks of addiction.

»

See Genetics page 7

Education

converted into clinical practice?

• We have identified new targets and strategies we believe will help us to improve our prevention and therapeutic efforts, but bias against drug abuse makes it difficult to develop new medications and implement novel treatments.

• Integration with other medical fields is key to making progress with prevention and treatment of substance abuse.

• It is better to educate than to use scare tactics--people desensitize to fear, but not to truth and reality. • If we don’t comprehend the big picture, we will not be able to get past the inconsequential details. • There is much to do: to be successful, support from leaders in the community and government is

essential.

With the conclusion of my commitment to NIDA, I recently returned to the University of Utah and the State of Utah to resume my activities as a scientist and the new director of the Utah Addiction Center. I find myself facing the very same dilemmas I wrestled with at the national level, i.e., how can we in Utah take advantage of the ever escalating research discoveries to more effectively reduce the terrible public and personal burdens of drug abuse? Through the UAC, I am anxious to devote the time and energy necessary to work with those who desire to diminish the devastation of chemical addiction. Together we can have a meaningful positive impact, separately, progress with be slow and fragmented.

B

ecause drugs affect the brain’s circuitry, Yale University School of Medicine researchers say

adolescent drug addiction should be considered a developmental disorder, the New York

Times reported June 24.

As adolescents develop, the researchers said, the changing motivational circuitry of their brain makes them vulnerable to the effects of alcohol and other addictive drugs.

For the research, lead author Dr. R. Andrew Chambers analyzed three factors of teen behavior and their relationship to brain functioning. They included attraction to novelty, less-than-adult levels of judgment, and an overriding interest in sex.

According to Chambers, the brain’s complex motivational circuitry consists of chemical reactions that make certain experiences more enjoyable than others. At the center of this circuitry is the chemical dopamine, which has been linked to the addictive effects of drugs.

In a teenager’s brain, Chambers said, the circuitry that releases chemicals associated with new experiences and the motivation to repeat them develops much faster than the brain mechanism that restrains urges and impulses.

“You have a situation where the motivational brain areas are particularly active,” Chambers said, “and the part of the brain that is supposed to inhibit impulses is not working well, because it is sort of under construction.”

As a result, Chambers said, teenagers are more likely to try drugs than other groups. Furthermore, experimenting with drugs during adolescence has more of an impact on the brain.

The research is published in the June 2003 issue of the American Journal of Psychiatry.

Chambers, R., Taylor, J., & Potenza, M. (2003) Developmental Neurocircuitry of Motivation in Adolescence: A Critical Period of Addiction Vulnerability. American Journal of Psychiatry, 160(6): 1041-1052.

Yale Study Terms Addiction a

Developmental Disorder

Research

Article courtesy of:Join TogetherOnline

Researcher: Andrew Chambers, M.D.

Assistant Professor of Psychiatry, Yale School of Medicine

»

Message

(4)

HOW BUPRENORPHINE CAME TO BE:

The Drug Abuse Treatment Act of 2000 (DATA) lays a new foundation by making medications for treatment of addiction more accessible than they traditionally were. Utah’s Senator Orrin Hatch was an important sponsor

of this legislation. Prior to the passage of DATA, approved medications available to treat addictions have been limited to disulfiram (Antabuse®), naltrexone (ReVia®),

nicotine replacement products, bupropion (Zyban®) and the controlled substances methadone and LAAM.

Methadone or LAAM (Levo-Alpha Acetyl Methadol) maintenance is the most effective treatment available for opioid addiction, but the medications are controlled substances and the availability is strictly limited since they can only be used in and prescribed by specially licensed clinics and doctors. The majority of licensed clinics are in large urban areas and some states have no licensed clinics at all. Many such clinics rely on public funding and must limit the number of patients treated. The “drug trade” and its addict victims have spread into all states and all areas of our country (urban, rural, farming, industrial, conservative, liberal, young, old). DATA makes treatment more accessible. It eliminates most of the rules and barriers that limit the accessibility of methadone or LAAM. Because of DATA, in 2003 any physician who takes an 8 hour training course can prescribe certain medications to treat addiction in the privacy, comfort, and convenience of their offices and have it dispensed from local pharmacies.

Buprenorphine, in sublingual tablets (Suboxone® and Subutex®), is the first medication made available to physicians and addicts as a result of DATA. Buprenorphine is effective for the treatment of opioid dependence, including heroin, oxycodone, morphine, hydrocodone and other opioids. In controlled clinical studies, buprenorphine has been compared to various doses of methadone maintenance and to LAAM maintenance. Outcome measures have included duration of abstinence (from abused opioids) measured by urine drug tests, patient self report, and duration of retention in treatment. Buprenorphine (28mg 3 times/week average dose) has been found to be superior to methadone 20mg/d and equal to methadone 90mg/d or LAAM 100mg three times/week..

WHAT EXACTLY IS BUPRENORPHINE:

Buprenorphine is classified as a “partial” agonist at mu opioid receptors. Heroin and methadone are “complete” agonists. Naloxone (Narcan®) and naltrexone (Revia®) are receptor antagonists or “blockers”. Heroin, methadone, and other “complete” agonists show a linear dose/effect response. The higher the dose of a “complete” agonist which is given, the greater the clinical effects will be. In an overdose, the effects of a “complete” agonist are maximal and with opioids, this means a shut down of the respiratory and cardiovascular control centers in the brain. This may result in respiratory and/or cardiac arrest and possibly death. A receptor antagonist, such as naloxone or naltrexone can reverse this overdose effect.

A “partial” agonist, like buprenorphine, shows a plateaued dose/effect response. The effect tops out at a defined level and if the dose is increased, no additional effect is observed. With “partial” agonists, overdose is less likely and less common than with “complete” agonists. Giving an antagonist to someone chronically using heroin or methadone will rapidly produce a withdrawal reaction. An unusual aspect of “partial” agonists is that they can act as antagonists when a high dose of a “complete” agonist is already working at the mu opioid receptor. That is, if a patient is actively using high doses of heroin or already on methadone maintenance at over 30-50mg/d, taking buprenorphine could cause withdrawal reactions. Therefore, prior to beginning buprenorphine treatment, the patient must be off of heroin to the point of showing some withdrawal symptoms or be tapered to a low dose of methadone before switching to buprenorphine.

HOW IS BUPRENORPHINE DIFFERENT:

Characteristics of heroin or other abused opioids (oxycodone, demerol, percocet, lortab) includes: used by injection, oral, smoked, or snorted routes, short half life and duration of action (6 hr), withdrawal symptoms begin within 4-6 hr, sporadic dosing based on need and availability, high cost ($50-$400/day), avoidance of contact with health care

Buprenorphine: A New Window

of Opportunity for Addictions

Treatment

clinical

training

Chris Stock, Pharm D.Mental Health Center, VA Salt Lake City Health Care System

100 % Activity (endogenous ligand)

Increasing Effect

Overdose/ death

Full agonist - Heroin

Partial agonist - Buprenorphine

Antagonist - Narcan

Increasing Dose

Understanding Receptor Function

professionals, illegal substance(s) often obtained through criminal behaviors, and users are involved with a subculture peer group providing little or no opportunity to address psychosocial problems.

Characteristics of methadone and LAAM include: administered by oral route (slower onset, less “high” or euphoria), long half life (more than 24-36 hr), withdrawal symptoms only begin after 24 - 72 hours, consistent daily dosing, low cost ($3-10/day), daily contact with health care professionals, drugs are legal and federally regulated, medication is “packaged with” the availability of counseling, education and social rehabilitation programs, but only available from licensed clinics and

physicians.

Characteristics of buprenorphine include: sublingual dosage form with naloxone incorporated to prevent diversion and possible abuse (Suboxone®), long half life (24-36 hr), usually only mild withdrawal due to “partial” agonist properties begin after 24-72 hours, consistent dosing daily or 3 times a week, cost approximately $20/day, frequent contact with health care

professionals, legal and federally regulated option,availability from any physician with interest in treating addiction.

CAUTIONS ABOUT USING BUPRENORPHINE:

Some precautions to consider with buprenorphine include the possibility of drug interactions. Concurrent use of benzodiazepines (Valium®, Ativan®, Xanax® and others) with buprenorphine has resulted in death in several patients. Other drug interactions to be aware of involve drugs which inhibit certain liver enzymes (CYP 3A4) which may enhance buprenorphine effects and worsen sedation from it. Some examples of medications which can do this are antifungal agents (e.g. ketoconazole), macrolide antibiotics (e.g., erythromycin), HIV protease inhibitors (e.g. ritonavir, indinavir and saquinavir). In theory, the opposite can occur with medications which are inducers of liver enzymes which would result in less buprenorphine effect or withdrawal reactions. This has not been thoroughly investigated, but patients on phenobarbital, carbamazepine, phenytoin, or rifampicin should be closely monitored.

HOW DO YOU TAKE BUPRENORPHINE:

Buprenorphine sublingual tablets (Subutex® and Suboxone®) must be put under the tongue and allowed to melt or dissolve. Unlike some other sublingual medications that rapidly dissolve, buprenorphine may take 2 to 10 minutes for each tablet to dissolve. Do not place more than two tablets under the tongue at the same time. Tablets cannot be chewed or swallowed because the medicine will not work if swallowed and withdrawal symptoms may occur because no medication is available.

INFORMATION ON THE INTERNET:

SAMHSA (Substance Abuse and Mental Health Services Administration) has established a website to provide information about this important new medication for patients, counselors, physicians and pharmacists. The website address is: www .buprenorphine.samhsa.gov/. The website has a link to a “physician locator” map of physicians trained and interested in treating opioid addiction with buprenorphine.

GETTING BUPRENORPHINE IN UTAH:

Currently the Utah connection on the locator map lists 5 Utah physicians who are have completed the training and asked to be listed on the “locator”. Only 2 of these physicians are located away from the Wasatch Front. Each qualified physician can treat up to 30 patients at a time with buprenorphine. In addition, 3 licensed treatment programs in Utah provide methadone/LAAM maintenance. In 1999, there were 1438 Utahns treated for heroin addiction. It is obvious that the current treatment demand exceeds the availability of opioid substitution treatment (maintenance treatment with methadone, LAAM or buprenorphine).

CONCLUSIONS:

DATA 2000 opens an additional window of opportunity for addicts by providing easier access to effective treatment. It currently provides one additional tool for physicians to use in helping to fight addiction and further improves the quality of life for their addicted patients. Buprenorphine is the first tool within this new toolbox for offering hope to opioid addicts. Opioid addicts wanting treatment should ask a health care provider about buprenorphine treatment. More Utah physicians are needed to take this path to treat addictions and further remove existing barriers and limitations to available treatment. Researchers must continue exploring new medications to treat addictions to the variety of psychoactive substances being abused.

In 1999, there

were 1438 Utahns

treated for heroin

addiction.

(5)

HOW BUPRENORPHINE CAME TO BE:

The Drug Abuse Treatment Act of 2000 (DATA) lays a new foundation by making medications for treatment of addiction more accessible than they traditionally were. Utah’s Senator Orrin Hatch was an important sponsor

of this legislation. Prior to the passage of DATA, approved medications available to treat addictions have been limited to disulfiram (Antabuse®), naltrexone (ReVia®),

nicotine replacement products, bupropion (Zyban®) and the controlled substances methadone and LAAM.

Methadone or LAAM (Levo-Alpha Acetyl Methadol) maintenance is the most effective treatment available for opioid addiction, but the medications are controlled substances and the availability is strictly limited since they can only be used in and prescribed by specially licensed clinics and doctors. The majority of licensed clinics are in large urban areas and some states have no licensed clinics at all. Many such clinics rely on public funding and must limit the number of patients treated. The “drug trade” and its addict victims have spread into all states and all areas of our country (urban, rural, farming, industrial, conservative, liberal, young, old). DATA makes treatment more accessible. It eliminates most of the rules and barriers that limit the accessibility of methadone or LAAM. Because of DATA, in 2003 any physician who takes an 8 hour training course can prescribe certain medications to treat addiction in the privacy, comfort, and convenience of their offices and have it dispensed from local pharmacies.

Buprenorphine, in sublingual tablets (Suboxone® and Subutex®), is the first medication made available to physicians and addicts as a result of DATA. Buprenorphine is effective for the treatment of opioid dependence, including heroin, oxycodone, morphine, hydrocodone and other opioids. In controlled clinical studies, buprenorphine has been compared to various doses of methadone maintenance and to LAAM maintenance. Outcome measures have included duration of abstinence (from abused opioids) measured by urine drug tests, patient self report, and duration of retention in treatment. Buprenorphine (28mg 3 times/week average dose) has been found to be superior to methadone 20mg/d and equal to methadone 90mg/d or LAAM 100mg three times/week..

WHAT EXACTLY IS BUPRENORPHINE:

Buprenorphine is classified as a “partial” agonist at mu opioid receptors. Heroin and methadone are “complete” agonists. Naloxone (Narcan®) and naltrexone (Revia®) are receptor antagonists or “blockers”. Heroin, methadone, and other “complete” agonists show a linear dose/effect response. The higher the dose of a “complete” agonist which is given, the greater the clinical effects will be. In an overdose, the effects of a “complete” agonist are maximal and with opioids, this means a shut down of the respiratory and cardiovascular control centers in the brain. This may result in respiratory and/or cardiac arrest and possibly death. A receptor antagonist, such as naloxone or naltrexone can reverse this overdose effect.

A “partial” agonist, like buprenorphine, shows a plateaued dose/effect response. The effect tops out at a defined level and if the dose is increased, no additional effect is observed. With “partial” agonists, overdose is less likely and less common than with “complete” agonists. Giving an antagonist to someone chronically using heroin or methadone will rapidly produce a withdrawal reaction. An unusual aspect of “partial” agonists is that they can act as antagonists when a high dose of a “complete” agonist is already working at the mu opioid receptor. That is, if a patient is actively using high doses of heroin or already on methadone maintenance at over 30-50mg/d, taking buprenorphine could cause withdrawal reactions. Therefore, prior to beginning buprenorphine treatment, the patient must be off of heroin to the point of showing some withdrawal symptoms or be tapered to a low dose of methadone before switching to buprenorphine.

HOW IS BUPRENORPHINE DIFFERENT:

Characteristics of heroin or other abused opioids (oxycodone, demerol, percocet, lortab) includes: used by injection, oral, smoked, or snorted routes, short half life and duration of action (6 hr), withdrawal symptoms begin within 4-6 hr, sporadic dosing based on need and availability, high cost ($50-$400/day), avoidance of contact with health care

Buprenorphine: A New Window

of Opportunity for Addictions

Treatment

clinical

training

Chris Stock, Pharm D.Mental Health Center, VA Salt Lake City Health Care System

100 % Activity (endogenous ligand)

Increasing Effect

Overdose/ death

Full agonist - Heroin

Partial agonist - Buprenorphine

Antagonist - Narcan

Increasing Dose

Understanding Receptor Function

professionals, illegal substance(s) often obtained through criminal behaviors, and users are involved with a subculture peer group providing little or no opportunity to address psychosocial problems.

Characteristics of methadone and LAAM include: administered by oral route (slower onset, less “high” or euphoria), long half life (more than 24-36 hr), withdrawal symptoms only begin after 24 - 72 hours, consistent daily dosing, low cost ($3-10/day), daily contact with health care professionals, drugs are legal and federally regulated, medication is “packaged with” the availability of counseling, education and social rehabilitation programs, but only available from licensed clinics and

physicians.

Characteristics of buprenorphine include: sublingual dosage form with naloxone incorporated to prevent diversion and possible abuse (Suboxone®), long half life (24-36 hr), usually only mild withdrawal due to “partial” agonist properties begin after 24-72 hours, consistent dosing daily or 3 times a week, cost approximately $20/day, frequent contact with health care

professionals, legal and federally regulated option,availability from any physician with interest in treating addiction.

CAUTIONS ABOUT USING BUPRENORPHINE:

Some precautions to consider with buprenorphine include the possibility of drug interactions. Concurrent use of benzodiazepines (Valium®, Ativan®, Xanax® and others) with buprenorphine has resulted in death in several patients. Other drug interactions to be aware of involve drugs which inhibit certain liver enzymes (CYP 3A4) which may enhance buprenorphine effects and worsen sedation from it. Some examples of medications which can do this are antifungal agents (e.g. ketoconazole), macrolide antibiotics (e.g., erythromycin), HIV protease inhibitors (e.g. ritonavir, indinavir and saquinavir). In theory, the opposite can occur with medications which are inducers of liver enzymes which would result in less buprenorphine effect or withdrawal reactions. This has not been thoroughly investigated, but patients on phenobarbital, carbamazepine, phenytoin, or rifampicin should be closely monitored.

HOW DO YOU TAKE BUPRENORPHINE:

Buprenorphine sublingual tablets (Subutex® and Suboxone®) must be put under the tongue and allowed to melt or dissolve. Unlike some other sublingual medications that rapidly dissolve, buprenorphine may take 2 to 10 minutes for each tablet to dissolve. Do not place more than two tablets under the tongue at the same time. Tablets cannot be chewed or swallowed because the medicine will not work if swallowed and withdrawal symptoms may occur because no medication is available.

INFORMATION ON THE INTERNET:

SAMHSA (Substance Abuse and Mental Health Services Administration) has established a website to provide information about this important new medication for patients, counselors, physicians and pharmacists. The website address is: www .buprenorphine.samhsa.gov/. The website has a link to a “physician locator” map of physicians trained and interested in treating opioid addiction with buprenorphine.

GETTING BUPRENORPHINE IN UTAH:

Currently the Utah connection on the locator map lists 5 Utah physicians who are have completed the training and asked to be listed on the “locator”. Only 2 of these physicians are located away from the Wasatch Front. Each qualified physician can treat up to 30 patients at a time with buprenorphine. In addition, 3 licensed treatment programs in Utah provide methadone/LAAM maintenance. In 1999, there were 1438 Utahns treated for heroin addiction. It is obvious that the current treatment demand exceeds the availability of opioid substitution treatment (maintenance treatment with methadone, LAAM or buprenorphine).

CONCLUSIONS:

DATA 2000 opens an additional window of opportunity for addicts by providing easier access to effective treatment. It currently provides one additional tool for physicians to use in helping to fight addiction and further improves the quality of life for their addicted patients. Buprenorphine is the first tool within this new toolbox for offering hope to opioid addicts. Opioid addicts wanting treatment should ask a health care provider about buprenorphine treatment. More Utah physicians are needed to take this path to treat addictions and further remove existing barriers and limitations to available treatment. Researchers must continue exploring new medications to treat addictions to the variety of psychoactive substances being abused.

In 1999, there

were 1438 Utahns

treated for heroin

addiction.

(6)