What’s New in Pharmacology?Hon. Peggy Fulton Hora , Judge of the Superior Court of California (Ret.)Andrea Grubb Barthwell, M.D., FASAMAmerican Judges Association Sept. 24, 2013 .Kohala Coast, Hawai’i

The Driving Force Behind Crime:Alcohol and Other Drugs

Objectives

To understand the connection between substance abuse and crime

To discuss the benefits of providing substance abuse treatment to individuals in the criminal justice system

To list existing and upcoming medications that allow (or will allow) addicted individuals to achieve and maintain sustained recovery

Disclosures

1. Sativex2. Vivitrol3. Probuphine

The Connection between AOD use and crime

Costs of alcohol

Median of $2.9 billion in 2006, ranging from $420 million in North Dakota to $32 billion in California

Binge drinking = 70% of the cost Includes criminal justice expenses

and motor vehicle crash costs

State Costs of Excessive Alcohol Consumption, CDC (Aug. 13, 2013)

Alcohol and Crime

36.8% Violent 29.1% Property 21.4% Drug 41.2% Public order 41.0% OtherBJS “Alcohol and Crime: 2002-2008”

DWI 1,112,384 arrests Domestic violence (93% in one study) Child maltreatment

Drug Use and Crime

Well-known and well-documented connection between criminal activity and substance abuse

Three types of offenses drug possession or sales related to drug abuse (e.g., stealing to get money

for drugs) related to a lifestyle that predisposes the drug

abuser to engage in illegal activity Many offenses, including violent crime, are

committed by people who have substance abuse disorders

Substance Abuse in the Criminal Justice System

Drug law violations are the most common type of criminal offense (Glaze

and Bonczar 2009) , 1,305,191 arrests (FBI’s Uniform Crime Reporting (UCR) Program 2009)

Only a small percentage of offenders has access to adequate services, especially in jails and community correctional facilities (Taxman et al. 2007; Sabol et al. 2010)

Breaking the Cycle

Offenders who are left untreated for substance abuse disorders often relapse and return to criminal activity

Re-arrest and re-incarceration 66% of the time

Treatment offers the best alternative for interrupting the drug abuse/criminal justice cycle.

Treatment in Criminal Justice System

Cross-agency coordination and collaboration of criminal justice professionals, substance abuse treatment providers, and other social service agencies

Examples: treatment in prison followed by community-

based treatment after release drug courts that blend judicial monitoring and

sanctions with treatment by imposing treatment as a condition of probation

treatment under parole or probation supervision

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MarijuanaCocaineOpiates MethMeth

Heroin use almost doubled

Number of people who were past-year heroin users in 2011 (620,000) vs. 2007 (373,000)

2011 National Survey on Drug Use and Health

More than half of the 36,450 overdose deaths in the United States in 2008 involved a prescription drug

July 16, 2012 The New York Times

Heroin is often cheaper than marijuana, selling for as little as $5 a hit

Overdose deaths

Overdoses have increased almost six-fold in the last 30 years.

Leading cause of accidental death in the United States overting motor vehicle crashes for the first time

The New York Times, Jan. 1, 2012

It is estimated 6.2 million Americans– that is 2.5% of the US population- is abusing prescription drugs

NBCLatino Aug. 12, 2013

More than half of the 36,450 overdose deaths in the United States in 2008 involved a prescription drug.

The New York Times , July 16, 2012

Treatment admissions for abuse of prescription pain relievers have risen 430 percent from 1999-2009

SAMHSA, 2011

10% taking meds not theirs

2.2 million American withopioid dependence

2.2 million people with opioid dependence in the U.S.

Approximately 20 percent of this population is addicted to illicit opioids, such as heroin

The other 80 percent to prescription opioids, such as oxycodone, hydrocodone, methadone, hydromorphone and codeine

Opiate Addiction

Currently, approximately 1 million people in the United States are addicted to heroin1

More than 3 million people over the age of 12 have used heroin at least once2

An estimated 1.4 million people are dependent on or abusing other opiate drugs, including prescription painkillers31. Office of National Drug Control Policy, 2000

2. National Survey on Drug Use and Health (NSDUH), 20043. NSDUH (Ibid).

Estimated Number of Buprenorphine- and Hydromorphone-Related ED Visits More Than Doubles from 2006 to 2010

CESAR FAXU n i v e r s i t y o f M a r y l a n d , C o l l e g e P a r k

A Weekly FAX from the Center for Substance Abuse Research

The estimated number of emergency department (ED) visits related to the nonmedical use of opioid pain killers increased 79% from 201,280 in 2006 to 359,921 in 2010, according to the most recent data from the Drug Abuse Warning Network (DAWN). The greatest increases were seen in buprenorphine- and hydromorphone-related ED visits. In 2006, the nonmedical use of buprenorphine was involved as either a direct cause or a contributing factor in an estimated 4,440 ED visits, compared to 15,778 in 2010—an increase of 255%. The estimated number of visits related to the nonmedical use of hydromorphone increased 161% over the same 5-year period (see figure below). While the number of ED visits for the nonmedical use of buprenorphine and hydromorphone is relatively small compared to other opioid pain relievers, the magnitude of the increase suggests that there may be emerging problems with the nonmedical use of these drugs that warrant the monitoring of their use and related consequences.

August 6, 2012Vol. 21, Issue 31

SOURCE: Adapted by CESAR from Substance Abuse and Mental Health Services Administration (SAMHSA), National Estimates of Drug-Related Emergency Department Visits, 2004-2010 - Nonmedical Use of Pharmaceuticals, 2012. Available online at http://www.samhsa.gov/data/DAWN.aspx#DAWN%202010%20ED%20Excel%20Files%20-%20National%20Tables.

Estimated Number of U.S. Emergency Department Visits Related to the Nonmedical Use of Opioid Pain Relievers, 2006 to 2010

NOTES: Nonmedical use includes taking more than the prescribed dose; taking a drug prescribed for another individual; deliberate poisoning by another person; and documented misuse or abuse. Five categories of opioid pain relievers (dihydrocodeine, opium, pentazocine, phenacetin, and all other narcotic analgesics) were not included in the above table because the estimate for either 2006 and/or 2010 did not meet standards of precision (relative standard error greater than 50% or an unweighted count or estimate less than 30).

Drug Name (Common Brand Names)

Number of ED Visits for Nonmedical UsePercent Change

2006 to 20102006 2010

Buprenorphine (Suboxone, Subutex, Temgesic, Buprenex) 4,440 15,778 +255%Hydromorphone (Palladone, Dilaudid) 6,780 17,666 +161%Oxycodone (Oxycontin, Percodan, Percocet) 64,891 146,355 +126%Hydrocodone (Vicodin, Lorcet, Lortab) 57,550 95,972 +67%Methadone (Methadose) 45,130 65,945 +46%Morphine (MS Contin, Morphine IR) 20,416 29,605 +45%Propoxyphene (Darvon) 6,220 8,832 +42%Fentanyl (Actiq, Duragesic) 16,012 21,196 +32%Codeine (Tylenol with Codeine) 6,928 7,928 +14%Meperidine (Demerol) 1,440 1,151 -20%Total Opioid Pain Relievers 201,280 359,921 +79%

85% Ohio drug court clients

Rx drugs and heroin

Drug-exposed infants

“Sharp Rise in Women’s Deaths From Overdose of Painkillers”

The New Your Times, July 2, 2013

Prosecutors file against supplier

What’s New in Pharmacology?

What are Substance Abuse Disorders?

Drug addiction is a complex illness—characterized by intense and, at times, uncontrollable drug craving, along with compulsive drug seeking and use that persist even in the face of devastating consequences.

Addiction produces far-reaching health and social consequences: increases a person’s risk for a variety of other mental

and physical illnesses interferes with a person’s normal functioning in the

family, the workplace, and the broader community Effective treatment programs typically incorporate

many components, including pharmacotherapies.

Pharmacotherapies

Medications can be an important component of effective drug abuse treatment for offenders.

By allowing the brain to function more normally, they enable the addicted person to leave behind a life of crime and drug abuse.

Addiction medications are underused in the treatment of drug abusers within the criminal justice system, despite evidence of their effectiveness.

Opiate Addiction

Heroin, morphine, and some prescription painkillers (e.g., OxyContin, Vicodin, and Fentanyl) are all opiates.

They act on specific (opiate) receptors in the brain

Interact with naturally produced substances known as endorphins or enkephalins– important in regulating pain and emotion

Opiates as a general class of drugs have significant abuse liability.

Narcotic Agonists: Methadone

Methadone maintenance therapy: In the 1960's, methadone gained

recognition as an effective treatment for heroin addiction.

Administered daily, methadone treatment is currently regulated so that only specialized clinics can provide it.

 Patients’ illicit opioid use declines, often dramatically, during methadone maintenance treatment1.1. Condelli WS, Dunteman GH. Exposure to methadone programs and

heroin use. American Journal of Drug and Alcohol Abuse 1993;19:65-78.

Narcotic Agonists: Buprenorphine

Buprenorphine Long-acting partial agonist that acts on the same

receptors as heroin and morphine Relieves drug cravings without producing the same

intense “high” or dangerous side effects. Abuse-deterrent formulation with naloxone▪ Naloxone has no effect when Suboxone is taken as prescribed,

but if an addicted individual attempts to inject Suboxone, the naloxone will produce severe withdrawal symptoms

Currently available in two formulations that are taken sublingually:▪ a pure form of the drug▪ a more commonly prescribed formulation called Suboxone (a

combination with naloxone)

Narcotic Agonists: Buprenorphine

NIDA-supported basic and clinical research showed that, alone or in combination with naloxone, buprenorphine significantly reduced opiate drug abuse and cravings and was a safe and acceptable addiction treatment. 

Trading one drug for another?

Simply substituting one addictive drug for another?

Taking these medications as prescribed allows patients to hold jobs, avoid street crime and violence, and reduce their exposure to HIV by stopping or

decreasing injection drug use and drug-related high-risk sexual behavior.

Patients stabilized on these medications can also engage more readily in counseling and other behavioral interventions essential to recovery.

U.N. Report Criticizes Harsh, Unhelpful Addiction Treatment

Condemns denying patients long-term maintenance treatment with methadone or buprenorphine

“A particular form of ill-treatment and possibly torture of drug users is the denial of opiate substitution treatment”

Considered a human rights violation when it occurs in jails and prisons

UN General Assembly Feb. 1, 2013

Narcotic Antagonists: Naltrexone

Naltrexone an opioid receptor blocker, or antagonist—it

blocks opioids from binding to their receptors and thereby prevents their euphoric and other effects.

Highly effective in reversing the effects of opiate overdose

No potential for abuse, and it is not addictive Noncompliance is a common problem Best suited for highly motivated, recently

detoxified patients who desire total abstinence because of external circumstances

Narcotic Antagonists: Naltrexone

Revia Daily pill Problem is medication compliance Subject to diversion

Naltrexone, cont.

Vivitrol long-acting injectable version of

naltrexone, called Vivitrol, was approved to treat opioid addiction.

Because it only needs to be delivered once a month, this version of the drug can facilitate compliance

Naltrexone, cont.

Offers an alternative for those who do not wish to be placed on agonist/partial agonist medications

Side effects such as injection site reactions

Alcohol

Intoxication can impair brain function and motor skills.

Heavy use can increase risk of certain cancers, stroke, and liver disease.

Alcoholism or alcohol dependence is a diagnosable disease characterized by a strong craving for alcohol, and/or continued use despite harm or personal injury.

Alcohol abuse, which can lead to alcoholism, is a pattern of drinking that results in harm to one's health, interpersonal relationships, or ability to work.

Alcohol (cont.)

Acamprosate (Campral®) acts on the gamma-aminobutyric acid (GABA)

and glutamate neurotransmitter systems Reduces symptoms of protracted withdrawal,

such as insomnia, anxiety, restlessness, and dysphoria.

Has been shown to help dependent drinkers maintain abstinence for several weeks to months,

May be more effective in patients with severe dependence.

Alcohol (cont.)

Disulfiram (Antabuse®) Interferes with degradation of alcohol, Causes accumulation of acetaldehyde, which, in turn,

produces a very unpleasant reaction that includes flushing, nausea, and palpitations if a person drinks alcohol.

Utility and effectiveness are limited because compliance is generally poor.

Can be effective among patients who are highly motivated

Some patients use it episodically for high-risk situations It can also be administered in a monitored fashion,

such as in a clinic or by a spouse, improving its efficacy.

Alcohol (cont.)

Naltrexone blocks opioid receptors that are involved

in the rewarding effects of drinking and the craving for alcohol.

It has been shown to reduce relapse to problem drinking in some patients.

Vivitrol also FDA-approved for treating alcoholism, and may offer benefits regarding compliance.

Alcohol (cont.)

Topiramate Is thought to work by increasing inhibitory

(GABA) neurotransmission and reducing stimulatory (glutamate) neurotransmission

Precise mechanism of action is not known. Although it has not yet received FDA approval

for treating alcohol addiction, it is sometimes used off-label for this purpose.

Topiramate has been shown in studies to significantly improve multiple drinking outcomes, compared with a placebo.

What’s new?Roadside devices, CBT, brain imaging

The State of the Science: New Medications Possibilities for Drug Abuse Genomics and

epigenetics High resolution

mapping of targeted brain areas

Anti-addiction vaccines

Medication combinations

Medicines Under Development: Vaccines

Anti-drug vaccines seek to induce antibodies that bind their target drugs and drug metabolites

Results in drug-antibody complexes that are too large to cross the blood-brain barrier

In effect, keep drug from reaching brain

The vaccine makes oxycodone visible to the immune system by linking it to the highly immunogenic protein keyhole limpet hemocyanin (KLH). Antibodies formed in response to the vaccine “see” and bind to oxycodone as if it were part of the KLH molecule.

Medicines Under Development: Heroin Vaccine

Developed at the Scripps Research Institute 

Creates antibodies against heroin and its psychoactive metabolites

Causes effective and continuous sequestration of brain-permeable constituents of heroin in the bloodstream following vaccination.

Efficient obstruction of heroin activity in treated rats

Still in preclinical trialsJoel E. Schlosburg, Leandro F. Vendruscolo, Paul T. Bremer, Jonathan W. Lockner, Carrie L. Wade, Ashlee A. K. Nunes, G. Neil Stowe, Scott Edwards, Kim D. Janda, and George F. Koob . Dynamic vaccine blocks relapse to compulsive intake of heroinPNAS 2013 : 1219159110v1-201219159. From: http://www.pnas.org/content/early/2013/05/02/1219159110.abstract

Medicines Under Development: Cocaine Vaccine

Developed by researchers at Weill Cornell Medical College

Researchers tested the anti-cocaine vaccine in primates

Vaccine prevented cocaine from reaching the brain and producing “high”

Vaccine is designed to induce anti-cocaine antibodies that isolate cocaine, preventing access to the central nervous system

Still in preclinical trials

Medicines Under Development: Oxycodone Vaccine

Developed by researchers at the University of Minnesota

Vaccine as a potential aid in the treatment of oxycodone and hydrocodone abuse and dependence

Vaccine aims to lower motivation to take prescription opioids by blocking rewarding and reinforcing effects

Vaccinating rats before injecting them with oxycodone or hydrocodone reduced the amount of drug reaching the brain by an average of 86 percent after a 0.1 mg/kg dose, and 54 percent after a 0.5 mg/kg dose.

New meth med?

Ibudilast reduces craving and improves cognitive functioning

Small study at UCLA

FDA approval in future

Huffington Post, April 3, 2013

Medicines Under Development: Methamphetamine

AV411 (also called ibudilast) reduced methamphetamine seeking in animal models of stress- and drug-induced relapse

AV411 affects the brain's glial cells rather than neurons, may avoid side effects caused by other anti-addiction medications

Medicines Under Development: Orexin Receptor-blockers

Possible use in treating cocaine abuse and unhealthy eating

Fosters transition from casual use to dependence: orexin neurotransmission mediates dopamine release after cocaine use

Rats that had been treated with orexin antagonist SB334867 did not work as hard to get cocaine as rats that had not been injected

Medicines Under Development: Gabapentin

Marijuana-dependent outpatients who were treated with gabapentin in a pilot clinical trial reported fewer symptoms of drug withdrawal than patients who received a placebo.

Gabapentin might reduce withdrawal symptoms that discourage quitting and drive relapse.

Gabapentin Facilitates Abstinence. Patients who received gabapentin used less marijuana during treatment than did a comparison group that received placebo, according to both self-report and urinalysis.

Medications Under Development:Sativex

Patch Developed for THC Transmucosal patch increases drug's

absorption Delivery method for medical

purposes Sativex – sublingual delivery

University of Mississippi, Dec. 15, 2012

Pueraria lobata (Kudzu)

“Heavy” drinkers (>26 drinks/week)

Kudzu extract for 7 days Significant reduction in number of

beers consumed

Lukas, SE, et al., “An extract of the Chinese herbal root kudzu reduces alcohol drinking by heavy drinkers in a naturalistic setting,” Alcoholism: Clinical & Experimental Research 29:756-762, 2005

Dihydromyricetin (DHM)

Counteract the effects of alcohol

Chinese raisin tree used as hangover cure for centuries

Interacts with GABA receptors where alcohol binds

Journal of Neuroscience, 2012

Other new tricks

Marijuana breathazyzer

Roadside breath test for drugs First to detect

alprazolam (the active ingredient in Xanax and other anti-anxiety drugs) and

benzoylecgonine (a cocaine byproduct) in exhaled breath

Journal of Breath Research (April 25, 2013)

Extinction Learning

“Molecular Roots of Cocaine Addiction in Brain Uncovered: Promising New Anti-Addiction Drug Revealed”

“Scientists Identify Compound That May Block Cocaine Craving in Animal Study”

Johns Hopkins, May 22, 2013

4/20 Tours

Legal?- “Highs”

In Conclusion

Treatment is an effective intervention for drug abusers, including those who are involved with the criminal justice system.

One of the goals of treatment planning is to match evidence-based interventions to individual needs at each stage of drug treatment.

Pharmacotherapy, one viable treatment option, can help normalize brain function and facilitate abstinence.