Impact and Treatment of
Opioid Dependence
Thomas E. Freese, PhD
PI/Director, Pacific Southwest Addiction Technology Transfer Center
Director of Training, UCLA Integrated Substance Abuse Programs
Asst Research Psychologist, UCLA David Geffen School of Medicine
SPLENDID FOR
Wind, Colic, Griping in
the Bowels, Diarrhea
Cholera and Teething
Troubles
Prevalence of Opioid Use and
Abuse in the United States
Rates of Current Heroin Use
• Drug demand data show that, nationally,
current heroin use is stable or decreasing.
Rates of Past-Year Heroin Use – NSDUH, 2009
% of US population
2003
2004
2005
2006
2007
2008
0.1
0.2
0.2
0.2
0.1
0.2
Adolescents (12-17)
0.1
0.2
0.1
0.1
0.1
0.2
Adults (18-25)
0.3
0.4
0.5
0.4
0.4
0.5
Adults (26 & older)
0.1
0.1
0.1
0.2
0.1
0.3
Individuals (12 &
older)
(SAMHSA, 2009)
Who Uses Heroin?
Individuals of all ages use
heroin:
• More than 3.8 million US residents
aged 12 and older have used heroin
at least once in their lifetime.
• Heroin use among high school
students is a particular problem.
Slightly more than 2% percent of US
high school seniors used heroin at
least once during their lifetime.
• Approximately 1.6% of young adults
(CDC,
2009; SAMHSA,
2007) reported lifetime use
(ages
19-28)
Prevalence of Use
 Rates of heroin use are declining among youth • 8th grade use peaked in 1996
• 10th grade use peaked in 1997
• 12th grade use peaked in 2000
 Rates of non-medical use of opioids are increasing
• Rates in all ages peaked in 2007
• Rates highest in 18-25 year olds
(Johnston et al., 2009; SAMHSA, OAS, NSDUH, 2009)
Initiation of Heroin Use
• During the latter half of the 1990s, the annual
number of heroin initiates rose to a level not reached
since the late 1970s.
• In 1974, there were an estimated 246,000 heroin
initiates.
• Between 1988 and 1994, the annual number of new
users ranged from 28,000 to 80,000.
• Between 1995 and 2001, the number of new heroin
users was consistently greater than 100,000.
• Between 2002 and 2008, the number of new heroin
users ranged from 91,000 to 114,000.
(SAMHSA, 2008; 2009)
Other Opioid Use
in a National Survey Population
According to the 2007 National Survey on Drug Use
and Health:
• An estimated 6.9 million persons (2.8% of the U.S.
population aged 12 or older) were currently using certain
prescription drugs nonmedically.
• An estimated 5.2 million were current users of pain
relievers for nonmedical purposes.
• Approximately 4.4 million persons had used OxyContin
nonmedically at least once in their lifetime.
• Non-medical pain reliever incidence increased from
1990 (628,000 initiates) to 2007, when there were 2.1
million new users.
(SAMHSA, 2008; 2009a; 2009b)
Emergency Department Visits Related to
Heroin/Other Opioids
According to the Drug Abuse Warning Network 2004-2008:
• An estimated 200,666 drug misuse/abuse ED visits
were related to heroin.
• One-third (33%) of nonmedical use ED visits were
related to Central Nervous System (CNS) agents.
• Among CNS agents, the most frequent drugs were
opiates/opioid analgesics, specifically:
– Hydrocodone/combinations (22,912 visits)
– Oxycodone/combinations (44,489 visits)
– Methadone (23,498 ED visits)
(SAMHSA, 2009)
New Non-Medical Users of Pain
Relievers
• In 2008 – 2.2 million new non-medical users
(a decline from 2.5 million in 2003, but still a
lot!)
• 6,000 new users per day
• Among youth aged 12-17, females more likely
to use non-medically
• Among young adults aged 18-25, males more
likely to use non-medically (SAMHSA, OAS,
2009)
Treatment Admissions
for Opioid Addiction
Heroin & Other Opioid
Treatment Admissions
• TEDS admissions for
primary opioid abuse
increased from 16% of
all admissions in 1997
to 19% in 2007.
• Admissions for other
opioids have
increased consistently
since the late 1990s –
1% to 5% between
1997 and 2007.
(SAMHSA 2009).
National Treatment Admissions for
Heroin and Other Opiates in 2007
Percentage of Treatment Admissions by Age
25
20
15-17
15
18-19
10
20-24
5
0
Heroin
Other Opiates
(SAMHSA, OAS, 2009)
Percent of Admissions
Primary Heroin Treatment Admissions vs.
Primary Other Opiate Treatment Admissions:
A Side-by-Side Comparison
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
% Male
% White
Heroin Admissions
(SAMHSA, OAS, 2009a; 2009b)
% Injected
% Rec'd
Medication
Other Opiate Admissions
Substance Abuse Challenge:
Prescription Drug Sources: Primarily Friends or Family
Sources of Opioid Pain Relievers Used Non-Medically
Source: SAMHSA, 2005 National Survey on Drug Use and Health, September 2006
Prescription Drug Abuse:
What are we talking about?
Overview
• Three classes of commonly abused Rx drugs
(opioids, sedatives, stimulants)
– What are they?
– How do they act in the brain and body?
– What are their effects?
– Neurobiology
What are opioids?
• Opiate: derivative of opium poppy
– Morphine
– Codeine
• Opioid: any compound that binds to opiate
receptors
– Semisynthetic (including heroin)
– Synthetic
– Oral, transdermal and intravenous formulations
• Narcotic: legal designation
Opioids
Opioids: Acute Effects
– Euphoria
– Pain relief
– Suppresses cough reflex
– Histamine release
– Warm flushing of the skin
– Dry mouth
– Drowsiness and lethargy
– Sense of well-being
– Depression of the central nervous system
(mental functioning clouded)
Long-Term Effects of Opioids
 Fatal overdose
 Collapsed veins
 Infectious diseases
 Higher risk of HIV/AIDS and hepatitis
 Infection of the heart lining and valves
 Pulmonary complications & pneumonia
 Respiratory problems
 Abscesses
 Liver disease
 Low birth weight and developmental delay
 Spontaneous abortion
 Cellulitis
Opioid Receptors
• Receptor types
– mu, delta, kappa
• Receptors located throughout body
– Pain relief: central and peripheral
nervous system
– Reward and reinforcement: deep brain
structures
– Side effects: constipation, sedation, itch,
mental status changes
SOURCE: National Institute on Drug Abuse, www.nida.nih.gov.
Endogenous Opioids
• Produced naturally in body
• Act on opioid receptors
• Examples: endorphins, enkephalins,
dynorphins, endomorphins
• Produce euphoria and pain relief; naturally
increased when one feels pain or
experiences pleasure
Opioid Withdrawal
•
•
•
•
•
•
•
•
•
•
•
Dysphoric mood
Nausea or vomiting
Diarrhea
Tearing or runny nose
Dilated pupils
Muscle aches
Goosebumps
Sweating
Yawning
Fever
Insomnia
Opiates and Reward
Opiates bind to opiate receptors in the nucleus
accumbens: increased dopamine release
Medication-Assisted Treatment Myths
Myth #1: Medications are not a part of treatment.
 The pharmacotherapies that are FDA-approved for
treatment of addiction should be used in conjunction
with psycho-social-educational-spiritual therapy.
Therefore, medications can be used as a part of
treatment, but only one part.
 Medications are used in the treatment of many
diseases, including addiction.
 Making the final decision about whether or not
medications are a part of a client’s treatment is out
of the counselor’s scope of practice.
Medication-Assisted Treatment Myths
Myth #2: Medications are drugs, and you cannot
be clean if you are taking anything.

The field needs to change terminology to reflect current trends.
“Drugs” are illicit psychoactive substances that are used to achieve a
“high.” “Medications” are available by prescription and are used to
treat an illness, disorder or disease.

Millions of Americans use medications (e.g., Zyban, nicotine patches)
to quit smoking, and this practice is widely encouraged by addiction
professionals.


Physical dependence and addiction are not the same thing.
The goal of addiction treatment is to assist a client in stopping his or
her compulsive use of drugs or alcohol and love a normal, functional
life.
Medication-Assisted Treatment Myths
Myth #2: Medications are drugs, and you cannot
be clean if you are taking anything.
 If appropriately administered, medication-assisted
treatment for addiction will not produce euphoric
effects.
 Pharmacotherapies are effective.
Clinical data
suggest that clients perform better in treatment when
psycho-social-educational-spiritual therapy is
combined with appropriate pharmacotherapies.
Medication-Assisted Treatment Myths
Myth #3: Alcoholics Anonymous (AA) and
Narcotics Anonymous (NA) does not support the
use of medications.
 Neither Alcoholics Anonymous (AA)/Narcotics
Anonymous (NA) literature nor its founding members
spoke or wrote against using medications.
 Even today, AA/NA does not endorse encouraging
AA/NA participants to not use prescribed medications
or to discontinue taking prescribed medications for the
treatment of addiction.
Medication-Assisted Treatment Myths
Myth #3: Alcoholics Anonymous (AA) and
Narcotics Anonymous (NA) does not support the
use of medications.
• The Big Book states, “God has abundantly supplied
this world with fine doctors, psychologists, and
practitioners of various kinds. Do not hesitated to take
your health problems to such persons. Most of them
give freely of themselves, that their fellows may enjoy
sound minds and bodies. Try to remember that though
God has wrought miracles among us, we should never
belittle a good doctor or psychiatrist. Their services
are often indispensable in treating a newcomer and in
following his case afterward.” (Chapter 9, Emphasis added)
Behavioral Interventions
Without question, medication interventions
have been extremely effective and
beneficial to the patient in early, as well
as long-term recovery.
However, it is imperative that
pharmacotherapies are paired with some
form of evidence-based behavioral
therapeutic intervention.
Behavioral Interventions
Psychosocial therapy interventions that have been
thoroughly researched and have shown good efficacy
include:
 Cognitive Behavioral Therapy (CBT)
 Motivational Interviewing (MI)
 Motivational Incentives/Contingency Management
The Addiction Technology Transfer Centers (ATTC) have
developed helpful resources for evidence-based
practices: www.nattc.org/resPubs/bpat/index.html .
Medical Treatments for
Opioid Addiction
Partial vs. Full Opioid Agonist
death
Opiate
Effect
Full Agonist
(e.g., methadone)
Partial Agonist
(e.g. buprenorphine)
Antagonist
(e.g. Naloxone)
Dose of Opiate
A Brief
History of
Medical
Treatment
for Opioids
1882 engraving of the British opium
warehouse in Patna, India
A Brief History of
Opioid Treatment
• Neolithic era (9000 B.C.E. to 3000 B.C.E.)
Opium cultivated for food, anesthesia, and
ritual purposes
• 15th Century: Recreational use of opium
reported, but use was limited by its rarity and
expense
• 1874: Heroin was first synthesized
A Brief History of
Opioid Treatment
• 1964: Methadone is approved.
• 1974: Narcotic Treatment Act limits
methadone treatment to specifically licensed
Opioid Treatment Programs (OTPs).
• 1984: Naltrexone is approved, but has
continued to be rarely used (approved in 1994
for alcohol addiction).
• 1993: LAAM is approved (for non-pregnant
patients only), but is underutilized.
A Brief History of Opioid
Treatment, Continued
• 2000: Drug Addiction Treatment Act of 2000
(DATA 2000) expands the clinical context of
medication-assisted opioid treatment.
• 2002: Tablet formulations of buprenorphine
(Subutex®) and buprenorphine/naloxone
(Suboxone®) were approved by the Food and
Drug Administration (FDA).
• 2004: Sale and distribution of ORLAAM® is
discontinued.
Medications to Treat Addiction
• Addiction is a chronic, relapsing brain
disease characterized by compulsive use
despite harmful consequences
• Medications as part of comprehensive
treatment plan
• Treatment approaches:
– Medications (Bio)
– Therapy, lifestyle changes (Psycho-Social)
• Thorough evaluation and diagnosis essential
Pharmacotherapy in Substance
Use Disorders
• Treatment of withdrawal (“detox”)
• Treatment of psychiatric symptoms or cooccurring disorders
• Reduction of cravings and urges
• Substitution therapy
Naltrexone General Facts

Generic Name:
naltrexone hydrochloride

Marketed As:
ReVia and Depade

Purpose:
To discourage opioid use by reducing or eliminating the
euphoric effects experienced by consuming exogenous
administered opioids.

Indication:
In the treatment of alcohol dependence and for the
blockade of the effects of exogenous administered
opioids.
 Year of FDA-Approval: 1984
Naltrexone Administration
Amount: one 50mg tablet
Method: mouth
Frequency: once a day
Can be crushed, diluted or mixed with food.
Abstinence requirements: must be taken at least 710 days after last consumption of opioids;
abstinence from alcohol is not required;
Appropriate Populations
Age Range:
 18 to 65 years old
Adolescents:
 Has not been tested or FDA-approved.
Elderly:
 Has not been tested or FDA-approved.
Pregnancy:
 Has not been adequately tested on pregnant or nursing
women; Pregnancy Category C designation, used only if
the potential benefit justifies the potential risk to the fetus.
Polysubstance Abusers:
 Has not been adequately tested with this population.
How Does Naltrexone Work?
1. Opioids enter the system and activate the areas of
the brain known as the ventral tegmental area and
the nucleus accumbens (the pleasure centers).
2. In response to this increased endogenous opioid
activity, dopamine is released.
3. Since dopamine is a main reward neurotransmitter,
increases in the nucleus accumbens makes the user
feel good.
4. The brain remembers those good feelings
caused by the dopamine and opioids.
5. The brain desires to repeat the behavior again to get
the same good feelings.
How Does Naltrexone Work?
• Naltrexone is an opioid
receptor antagonist
and blocks opioid
N
receptors.
By blocking opioid
receptors, the
“reward” and acute
reinforcing effects
from dopamine are
diminished, and
alcohol consumption
is reduced.
N
= naltrexone
N
N
Post-Synaptic Neuron
N
Opioid
Receptor
N
N
Opioid Replacement Goals
•
•
•
•
•
Reduce symptoms & signs of withdrawal
Reduce or eliminate craving
Block effects of illicit opioids
Restore normal physiology
Promote psychosocial rehabilitation and nondrug lifestyle
Methadone General Facts
(information from medication package insert)
 Generic Name:
methadone hydrochloride
 Marketed As:
Methadose and Dolophine
(among others)
 Purpose:
To discourage illicit opioid use due to cravings or the desire to
alleviate opioid withdrawal symptoms.
 Indication:
For the treatment of moderate to severe pain not responsive to
non-narcotic analgesics; for detoxification treatment of opioid
addiction; for maintenance treatment of opioid addiction, in
conjunction with appropriate social and medical services.
 Year of FDA-Approval: 1964
Methadone General Facts
(information from medication package insert)
•
•
•
Amount: maintenance dose of 80 to 120mg
Method: mouth
Frequency: once a day
•
The effect of consuming food with methadone has not been
evaluated and therefore, is not recommended.
•
Abstinence requirements: must be abstinent from opioids long
enough to experience mild to moderate opioid withdrawal
symptoms.
•
Initial dose will vary depending upon the client’s usage pattern,
but should not exceed 40mg.
Risk of Overdose: Just like with any opioid, overdose is
possible. In the event of an overdose, appropriate medical
treatment should be sought.
Methadone General Facts
(information from medication package insert)

Pregnancy:
Methadone is the preferred method of treatment for
medication-assisted treatment for opioid dependence in
pregnant women. An expert review of published data on
experiences with methadone use during pregnancy
concludes that it is unlikely to pose a substantial risk. But,
there is insufficient data to state that there is no risk.
Methadone has not been adequately tested on pregnant
women. Therefore, methadone has a Pregnancy Category C
designation, meaning that it should be used during
pregnancy only if the potential benefit justifies the potential
risk to the fetus. Caution should be exercised when using
methadone with this population.
Methadone General Facts
(information from medication package insert)
 Pregnancy:
 Detoxification is relatively contraindicated unless done in
hospital with monitoring.
 Babies born to mothers who have been taking opioids
regularly prior to delivery may be physically dependent and
may experience opioid withdrawal symptoms. It is known
that methadone is excreted through breast milk, and a
decision should be made whether to discontinue nursing or
to discontinue the medication, taking into account the
importance of the medication to the mother and continued
illicit opioid use.
Methadone General Facts
(information from medication package insert)

Addictive Properties:
Chronic administration produces physical dependence.
Since methadone is an opioid, it does have a high abuse
liability and does produce withdrawal symptoms when the
medication is ceased too abruptly or tapered down too
quickly.

Third-Party Payer Acceptance:
Covered by most major insurance carriers, Medicare,
Medicaid and the VA.
Understanding
DATA 2000
Drug Addiction Treatment Act
of 2000 (DATA 2000)
• Expands treatment options to include both
the general health care system and opioid
treatment programs.
– Expands number of available treatment slots
– Allows opioid treatment in office settings
– Sets physician qualifications for prescribing
the medication
DATA 2000:
Physician Qualifications
Physicians must:
• Be licensed to practice by his/her state
• Have the capacity to refer patients for
psychosocial treatment
• Originally limited to 30 patients later
expanded to allow for 100 patients after
the first year of experience
• Be qualified to provide buprenorphine and
receive a license waiver
DATA 2000:
Physician Qualifications
A physician must meet one or more of the following
qualifications:
–
–
–
–
Board certified in Addiction Psychiatry
Certified in Addiction Medicine by ASAM or AOA
Served as Investigator in buprenorphine clinical trials
Completed 8 hours of training by ASAM, AAAP, AMA,
AOA, APA (or other organizations that may be
designated by Health and Human Services)
– Training or experience as determined by state medical
licensing board
– Other criteria established through regulation by Health
and Human Services
Development of
Tablet Formulations of Buprnorphine
• Buprenorphine is marketed for opioid treatment
under the trade names of Subutex®
(buprenorphine) and Suboxone®
(buprenorphine/naloxone)
• Over 25 years of research
• Over 5,000 patients exposed during clinical trials
• Proven safe and effective for the treatment of
opioid addiction
Buprenorphine:
A Science-Based Treatment
Clinical trials have established the effectiveness of
buprenorphine for the treatment of heroin
addiction. Effectiveness of buprenorphine has
been compared to:
• Placebo (Johnson et al. 1995; Ling et al. 1998;
Kakko et al. 2003)
• Methadone (Johnson et al. 1992; Strain et al.
1994a, 1994b; Ling et al. 1996; Schottenfield et
al. 1997; Fischer et al. 1999)
• Methadone and LAAM (Johnson et al. 2000)
Why was Buprenorphine/Naloxone
Combination Developed?
• Developed in response to increased reports
of buprenorphine abuse outside of the U.S.
• The combination tablet is specifically
designed to decrease buprenorphine abuse
by injection, especially by out of treatment
opioid users.
Why Combining Buprenorphine and
Naloxone Sublingually Works
• Buprenorphine and naloxone have different
sublingual (SL) to injection potency profiles
that are optimal for use in a combination
product.
SL Bioavailability
Injection to Sublingual
Potency
Buprenorphine 40-60%
Buprenorphine ≈
Naloxone 10% or less
Naloxone
SOURCE: Amass et al., 2004.
2:1
≈ 15:1
Buprenorphine/Naloxone:
What You Need to know
• Basic pharmacology, pharmacokinetics, and
efficacy is the same as buprenorphine
alone.
• Partial opioid agonist; ceiling effect at higher
doses
• Blocks effects of other agonists
• Binds strongly to opioid receptor, long acting
The Use of Buprenorphine in the
Treatment of Opioid Addiction
Induction
Maintenance
Tapering Off/Medically-Assisted
Withdrawal
Induction
Induction Phase
Working to establish the appropriate
dose of medication for patient to
discontinue use of opiates with minimal
withdrawal symptoms, side-effects, and
craving
Direct Buprenorphine Induction
from Short-Acting Opioids
• Ask patient to abstain from short-acting opioid
(e.g., heroin) for at least 6 hrs. and be in mild
withdrawal before administering
buprenorphine/naloxone.
• When transferring from a short-acting opioid, be
sure the patient provides a methadone-negative
urine screen before 1st buprenorphine dose.
SOURCE: Amass, et al., 2004, Johnson, et al. 2003.
Direct Buprenorphine Induction
from Long-Acting Opioids
• Controlled trials are needed to determine
optimal procedures for inducting these
patients.
• Data is also needed to determine whether
the buprenorphine only or the
buprenorphine/naloxone tablet is optimal
when inducting these patients.
SOURCE: Amass, et al., 2004; Johnson, et al. 2003.
Direct Buprenorphine Induction
from Long-Acting Opioids
• Clinical experience has suggest that induction
procedures with patients receiving long-acting
opioids (e.g. methadone-maintenance patients) are
basically the same as those used with patients
taking short-acting opioids, except:
– The time interval between the last dose of medication and
the first dose of buprenorphine must be increased.
– At least 24 hrs should elapse before starting
buprenorphine and longer time periods may be needed
(up to 48 hrs).
– Urine drug screening should indicate no other illicit opiate
use at the time of induction.
Stabilization and
Maintenance
Stabilization Phase
Patient experiences no withdrawal
symptoms, side-effects, or craving
Maintenance Phase
Goals of Maintenance Phase:
Help the person stop and stay away from
illicit drug use and problematic use of
alcohol
1. Continue to monitor cravings to prevent
relapse
2. Address psychosocial and family issues
Maintenance Phase
Psychosocial and family issues to be addressed:
a) Psychiatric comorbidity
b) Family and support issues
c) Time management
d) Employment/financial issues
e) Pro-social activities
f) Legal issues
g) Secondary drug/alcohol use
Medically-Assisted
Withdrawal
(a.k.a. Dose Tapering)
Buprenorphine Withdrawal
• Working to provide a smooth transition from a
physically-dependent to non-dependent state, with
medical supervision
• Medically supervised withdrawal (detoxification) is
accompanied with and followed by psychosocial
treatment, and sometimes medication treatment
(i.e., naltrexone) to minimize risk of relapse.
Medically-Assisted Withdrawal
(Detoxification)
• Outpatient and inpatient withdrawal are both
possible
• How is it done?
– Switch to longer-acting opioid (e.g.,
buprenorphine)
• Taper off over a period of time (a few days to weeks
depending upon the program)
• Use other medications to treat withdrawal symptoms
– Use clonidine and other non-narcotic medications
to manage symptoms during withdrawal
Fitting
Pharmacotherapies
into Treatment
Four Legs of Addiction
Think of this concept as a chair, with each leg
representing a component of a patient’s treatment plan.
Psychological
Biological
Spiritual
Social
All four legs are required to “support” the patient, and if
one leg is missing, the chair will be unstable and unable
to accomplish its goal.
Holistic Treatment
The treatment plan must also address the
multiple needs of the individual:
 sexual orientation

disabilities
 gender differences

employment issues
 homelessness

developmental needs
 family dynamics

co-occurring disorders
 children/prenatal care
 cultural, racial, religious norms
 legal issues
For more information, contact:
Thomas E. Freese, PhD
tfreese@mednet.ucla.edu
Download the presentation from:
www.psattc.org
Additional information on
addiction research:
www.uclaisap.org