The Science of Addiction



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Drugs, Brain and Behavior The Science of Addiction Mark Stanford, Ph.D. Santa Clara County Dept of Alcohol & Drug Services Addiction Medicine Division Association for Medical Education & Research In Substance Abuse (AMERSA) Associate Professor Psychopharmacology - Dept. of Biological Sciences and Mathematics, UC Berkeley Extension and Cal State Hayward

Presentation Objectives Understand what the scientific research says about drug addiction Dispel several myths and misunderstandings about drug addiction See what the research says about the effectiveness of drug addiction treatment

In just the last 10 years, advances in science have revolutionized our views about drug abuse and addiction, showing us that: abuse is a preventable behavior addiction is a treatable disease

Science can influence perceptions about the nature of illness and subsequently, change the way it is viewed and treated. For instance, during the Renaissance Period, the root of psychosis and schizophrenia were considered to be witchcraft and demonic possession. Therefore, treatment included trepanation - the boring of holes in the skull to release the evil spirits. This illustration shows a colonial surgeon attempting a trepanation procedure, which required up to 60 minutes of constant drilling.

In the 19 th century, some treatments were designed to induce fear. Spinning the patient until loss of consciousness occurred was thought to help rearrange the contents of the brain. In the 1940 s newer techniques included insulin shock and frontal lobotomies.

Actually, the evidence is that schizophrenia is a biologically-based disease of the brain. This evidence is supported by brain imaging showing precisely the wave of tissue destruction that takes place in the brain that is suffering from schizophrenia.

How we used to perceive and treat drug and alcohol addiction In the past, society viewed drug addiction as a moral flaw. Popular "treatments" involved imprisonment, sentencing to asylums, and churchguided prayer.

Actually, the evidence is that drug addiction is a biologically-based disease of the brain

Addiction is a Brain Disease Prolonged Use Changes the Brain Healthy Brain Cocaine Addict Brain in Fundamental and Lasting Ways

used to be

Your Brain on Drugs Today Front of Brain Back of Brain 1-2 Min 3-4 5-6 YELLOW shows places in brain where cocaine goes (striatum) 6-7 7-8 8-9 9-10 10-20 20-30 Fowler et al., Synapse, 1989.

Science has added an important piece to the understanding of addiction Traditional Neurobiological Psychosocial Physiological

Even though there is the science, several common myths about addiction still persist, including: Addiction is a moral weakness You have to hit rock bottom to recover You have to want treatment for it to be successful Alcohol is not really a drug Drug abuse is more common among minorities

What is Drug Addiction? Drug Addiction: A compulsive need for continued use despite adverse consequences and an inordinate amount of time spent looking for, being under the influence of and/or recovering from the effects of drugs

What is Drug Addiction? A chronic and relapsing condition characterized by: compulsive drug seeking and use and, continued use despite harmful consequences A brain disease because drugs change the brain they change its structure and how it works. The changes can be long lasting. ASAM. 2004. NIDA. 2007

Addiction is a Chronic Illness Because: It has both a genetic and environmental basis influencing its development and manifestation Recovery from it is often a long-term process requiring repeated treatments Relapses can occur during or after successful treatment episodes Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recovery

Why Do People Take Drugs in The First Place? To feel good To have novel: feelings sensations experiences AND to share them To feel better To lessen: anxiety worries fears depression hopelessness

After Using Drugs For A While A Person May Not Be Able To Just Stop Because...

Vulnerability Why do some people become addicted while others do not?

We Know There s a Big Genetic Contribution to Drug Abuse and Addiction.Overlapping with Environmental Influences that Help Make Addiction a Complex Disease.

Biology/genes Biology/ Environment Interactions Environment IFH + high tolerance = 60% IFH + low tolerance = 15% Marc Schuckit. UCSD. 2002.

Do Drugs Cause Addiction?

Many drugs, but few with abuse potential There are about 15,000,000 substances in the world. However, of these only about 55,000 are available for human consumption.

Interestingly, of these 55,000 substances.... only about 25 drugs have abuse potential

Drugs With Abuse Potential Uppers: CNS Stimulants. Amphetamine, methamphetamine, cocaine Downers: CNS Depressants. Alcohol, benzodiazepines (like valium, etc), barbiturates (like seconal, etc.), Inhalants, etc. All-arounders: Hallucinogens. LSD, mescaline, MDMA (XTC), psilocybin (magic mushrooms), PCP, etc. Pain Killers: Opioids. Heroin, codeine, morphine, vicodin, fentanyl, Oxycontin, etc.

Why do some drugs have abuse potential and others do not?

100 years ago not much was known about drugs and abuse potential

Prior to the 1950 s, not much was known about the brain/behavior link, let alone the addictive nature of drugs.

In the late 1800s, Coca Cola actually did not contain small amounts of cocaine but a lot of caffeine. It was like the Starbucks of the time.

Even 50 years ago, not much was known about drugs and abuse potential

Research in the 1970 s began to investigate the nature of addiction. From the 1990 s, dramatic advances were made about the biobehavioral basis of addictions and improved treatment methods based on scientific research.

Behaviors that result in the experience of release from a biological tension (i.e. eating) make us feel good. This feel good response is registered in a certain part of the brain.

Behaviors experienced as pleasurable are processed in certain areas of the brain called the brain reward pathway. The fancy name for this brain area is called the mesocorticolimbic pathway.

Natural Rewards The brain's reward pathway is necessary for survival since it motivates important activities such as food seeking and eating, mating, and parenting. Food Water Sex Nurturing

Natural Rewards Elevate Pleasure % of Basal DA Output 200 150 100 50 0 Empty FOOD Box Feeding NAc shell 0 60 120 180 Time (min) DA Concentration (% Baseline) 200 150 100 Sample Number SEX Female Present 1 2 3 4 5 6 7 8 15 10 5 0 Copulation Frequency Mounts Intromissions Ejaculations Di Chiara et al., Neuroscience, 1999. Fiorino and Phillips, J. Neuroscience, 1997.

Drugs and alcohol effect the same areas in the brain s reward pathway...... But in a way that is dangerous and potentially fatal!

Effects of Drugs on Brain Reward Pathways % of Basal Release 1100 1000 900 800 700 600 500 400 300 200 100 0 Accumbens AMPHETAMINE DA DOPAC HVA 0 1 2 3 4 5 hr Time After Amphetamine % of Basal Release 400 300 200 100 0 Accumbens COCAINE DA DOPAC HVA 0 1 2 3 4 5 hr Time After Cocaine % of Basal Release 250 200 150 100 NICOTINE Accumbens Caudate % of Basal Release 250 200 150 100 Accumbens MORPHINE Dose (mg/kg) 0.5 1.0 2.5 10 0 0 1 2 3 hr Time After Nicotine 0 0 1 2 3 4 5hr Time After Morphine Di Chiara and Imperato, PNAS, 1988

If taking drugs make people feel good or better, what s the problem?

Repeated use of drugs and alcohol saturate the brain s reward pathway to the point that: the person becomes conditioned to the intense level of drug-induced pleasure, the normal level of natural rewards are no longer experienced as very pleasurable, and after chronic use, the brain s reward pathway becomes drained so that nothing is pleasurable not even the drugs!

Drugs impair the brain s chemical balance and therefore affect mood, thought & behavior = The brain s own feel good chemicals (dopamine) = Drugs of abuse increase dopamine action

Repeated drug use impacts the brain by reducing available dopamine and other brain chemicals With repeated exposure to drugs, brain dopamine becomes reduced and behavior becomes unstable

Withdrawal occurs when drugs have depleted critical brain chemicals needed for emotional health & balance When the drug is gone, there s not enough brain dopamine. Why is this important? What is the function of dopamine?

NEWS FLASH!!! All Brains Are Actually Not Alike! Brains actually differ from person to person!

What if a person has genetically determined low dopamine activity? How might drugs be experienced? = Brain dopamine level = Drugs of abuse

Dopamine D2 Receptors are Lower in Addiction DA D2 Receptor Availability Cocaine DA DA DA DA DA DA DA DA DA DA DA DA Meth Reward Circuits Non-Drug Abuser Alcohol DA DA DA DA DA DA Heroin Control Addicted Reward Circuits Drug Abuser

DA Receptors and the Response to Methylphenidate (MP) High DA receptor Low DA receptor high low Dopamine receptor level As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999.

Neuroscience Research and Brain Imaging Technology

Science shows that prolonged drug use changes the brain in fundamental and long-lasting ways

Methamphetamine

A critical part of addictions treatment is the prevention of relapse behaviors. Drug craving behaviors are triggered by a conditioned response of the nervous system when re-exposed to an environmental cue it has associated with drug use. And... this conditioned response can last a lifetime.

Conditioned Response Pavlov s Dogs Meat Meat + Bell Bell Stanford s Cats Food Sound of can opener + food Sound of can opener Addiction Drug Drug + Trigger Trigger Mouth Waters Mouth Waters Mouth Waters pacing for food pacing for food pacing for food Craving Craving Craving

A Conditioned Response Brain activity changes in response to cocaine-related cues from normal to craving behaviors (elapsed time) Composite slide N=23, cocaine addicted men with min. 6 years clean and sober. Childress. 2003.

Memories Appear to Be A Critical Part of Addiction Its about people, places and things

Is continued drug abuse a voluntary behavior?

The initial decision to use drugs is mostly voluntary. However, when drug abuse takes over, self control becomes seriously impaired. Brain imaging studies show physical changes in areas of the brain critical to judgment, decision making and self control. These changes alter the way the brain works. ASAM. 2005

What s Being Done About All of This?

What does the Science say about the best ways to TREAT drug addiction?

Facts of Addiction Treatment Substance abuse is a preventable behavior Addiction is a brain disease that is treatable A chronic disorder requiring multiple strategies and multiple episodes of intervention Treatment works in the long run Treatment is cost-effective NIDA. 2001.

Scientific research has identified some of the fundamental principles that are important in drug addiction treatment

Matching Treatment to Individual s Needs No single treatment is appropriate for all individuals Effective treatment attends to multiple needs of the individual, not just his/her drug use Treatment must address medical, psychological, social, vocational, and legal problems

Addiction Medicine Medications can be an important element of treatment for many patients, especially when combined with counseling and other behavioral therapies. Alcohol: Naltrexone, Disulfiram, Acamprosate, Odansetron Opiates: Methadone, Buprenorphine, Naltrexone, Nicotine: Nicotine replacement (gum, patches, spray), Zyban, Chantix Stimulants: None to date (3 in development)

Duration of Treatment Depends on patient problem/needs Less than 90 days is of limited/no effectiveness for residential/outpatient setting A minimum of 12 months is required for methadone maintenance Longer treatment is often indicated

Motivation to Enter/Sustain Treatment Effective treatment need not be voluntary Sanctions/enticements (family, employer, criminal justice system) can increase treatment entry and retention Treatment outcomes are similar for those who enter treatment under legal pressure vs voluntary

HIV/AIDS, Hepatitis and Other Infectious Diseases Drug treatment is disease prevention Drug treatment reduces likelihood of HIV infection by 6 fold in injecting drug users Drug treatment presents opportunities for screening, counseling and referral

Self-Help and Drug Addiction Treatment Compliments and extends treatment efforts, but are not treatment Most commonly used models include 12-Step (AA, NA) and Smart recovery Most treatment programs encourage self-help participation during/after treatment

Treatment works!

www.drugabuse.gov NIDA NATIONAL INSTITUTE ON DRUG ABUSE

And in Santa Clara County, visit us at www.sccdads.org

Thank You!