Chapter 8 Opener

Frequency of drug use 2002 survey of illicit drug use 19.5 million Americans 12 years old or older –8.3% of the population 71 million – tobacco –About 30% 120 million – alcohol –About 50% –16 million – heavily (7%)

200 years ago there were few regulations on drugs. None at the federal level There were also fewer drugs –Tobacco –Alcohol –Opium

Factors contributing to modern views on drugs. 1) Alcohol temperance movement –Benjamin Rush founded (late 1700s, early 1800s) Advocated abstaining from hard liquor Okay to have moderate beer or wine consumption –Rush pointed out physiological consequences of alcohol use –Also pointed out impairment of moral faculty Many still think of alcohol use negatively –Also probably influenced peoples view of drug use Drug use = criminal behavior

2) Advances in chemistry as well as a major advancement in drug delivery influenced the potency of drugs –Opium was purified to morphine –Coca was purified to cocaine Hypodermic syringe was invented in –Allowed purified drugs to be injected directly into blood stream Civil war soldiers often developed opiate addictions –Soldier’s Disease

3) increasing availability of purified drugs, combined with lack of drug control laws led to growing use in many forms. Cocaine was a major ingredient in a variety of tonics –Vin Mariani – Wine with coca (1863) –Coca cola (1886)

Heroin synthesized by Bayer laboratories –Nonaddictive cough remedy –Meant to substitute for codeine.

4) Medicalization of drug addiction (second half of twentieth century) –Addiction viewed as a disease –Addicts should be treated by medical association Modern view continues –Alcoholics anonymous (AA) –Narcotics anonymous (NA) –National Institute on Drug Abuse (NIDA)

Drugs and the law The federal government is strongly against legalization or decriminalization of currently illegal drugs. Began with passage of the Pure Food and Drug Act (1906) –Mandated accurate labeling

Harrison Act (1914) Regulated the dispensing and use of opiates and cocaine 1.Use only for medical purposes 2.Pharmacists and physicians must be registered with treasury dept. and keep records of their inventory 3.Those selling the drug must pay a tax 4.Patented medicines with small amounts of opiates or cocaine remained legal.

Consequences of Harrison Act Addiction not considered a disease at this point, so patients that had been getting drugs from physicians to maintain their addiction were cut off. –Turned to the street –drug prices sky rocketed

What is addiction? Early views focused on physical dependence –Physical withdrawal symptoms Alcohol (Delirium Tremens) Opiates (kicking the habit; cold turkey) –Prescription meds?

More recent view of addiction Compulsive drug seeking behavior –Drug craving Chronic relapsing disorder –Individuals are considered still addicted even when in remission (drug-free period) –There are often relapses Drug use persists despite harmful consequences to the addict –Physical –Social

American Psychiatric Association has stopped using the term addiction and addict in their professional writing –Due to bad connotation Dirty heroin addicts Crack heads They use the term substance related disorders –Two general disorders Substance Dependence (more severe) Substance Abuse

Note that merely using a drug, even if it is illegal, does not necessarily indicate a substance related disorder The use must be maladaptive There are also substance induced disorders –Cocaine psychosis –Amphetamines

Progression of drug use Gateway theory –Alcohol and cigarettes are gateways for marijuana –Marijuana is gateway for other illicit drugs

Box 8.1 The “Gateway” Theory of Drug Use

Problems with Gateway Theory 1) Population studied is usually highschool students –Given surveys Probably not hard-core users Hardcore users drop out. When heavy users of illegal drugs are studied it has been shown that marijuana is often used prior to other “hard” drugs –But marijuana is often used before alcohol and tobacco.

2) These studies are correlational –Correlation does not imply causation –Does the fact that marijuana use reliably precedes the use of “hard” drugs mean that marijuana use causes abuse of harder drugs? What else could be playing a role?

Continuum of drug use drug use also occurs along a continuum –Some people that experiment with drugs do not continue to substance abuse or dependence Drugs are not instantly addictive –Some people do –Why some do and some don’t is an important research question. Also people can move in both directions along the continuum. –They don’t necessarily have to fall farther and farther into abuse. –They can move in a direction of less problematic use or abstinence

8.5 Patterns of opioid drug use over a 20-year period in ten heroin addicts This slide supports the view that addiction is a chronic relapsing disorder It also shows how many drug users move along the continuum of drug use

Which drugs are most addictive? Two sets of standards –Legal standards Set by the Controlled Substances Act of 1970 Five different schedules of drugs –Note that alcohol and nicotine are not on the drug schedule –Can be bought without prescription –Scientific standards Reflected by expert views of addictive potential

Two experts rated abuse potential of various drugs –Jack Henningfield, formerly Chief of Clinical Pharmacology at the Addiction Research Center at NIDA –Neil Benowitz, addiction researcher at University of California at San Francisco 1) presence and severity of withdrawal 2) how reinforcing the drug is (from human and animal studies) 3) the degree of tolerance produced by the drugs 4) degree of dependence –Difficulty quitting –Relapse 5) degree of intoxication

Overall rankings –Heroin (1.9) –Alcohol (2.5) –Cocaine (2.65) –Nicotine (3.35) –Caffeine (5.0) –Marijuana (5.4) Two of the top 4 substances are legal Marijuana is lowest on this list, but a schedule 1 drug. Keep in mind long term consequences were not included. Note that low numbers indicate the most serious abuse potential Also note how closely the two experts rated the drugs on the various measures

Models of Drug Abuse and Dependence The physical dependence model Once physically dependent, attempts at abstinence lead to unpleasant withdrawal symptoms Thus, the person is motivated to take the drug again. –Negative RF Take drug (behavior) Remove withdrawal (consequence)

Wikler (1980) posited that withdrawal could be classically conditioned Certain contexts where drug seeking behavior occurs can become associated with withdrawal. –They are there to find drugs, so they are likely in an abstinence state Thus, an addict could be free from acute drug withdrawal, but experience withdrawal exposed to the right environmental stimuli (CS) –Note that drug craving is part of the CR

Cocaine dependent individuals show increased desire to get high, and craving for cocaine after seeing a video of a person obtaining and then smoking crack cocaine. Blue lines are controls (never taken cocaine). Notice that the y-axis represents a change score. The cravings went up when confronted with drug stimuli

Critique of physical dependence model 1) Some drugs do not cause physical dependence but remain highly addictive –Cocaine 2) The model does a good job of explaining drug taking behavior after a person has become dependent –but doesn’t do a good job of explaining the drug use that led to dependence in the first place

3) Has difficulty explaining high levels of relapse following drug detoxification. –Wikler attempts to explain using his conditioned withdrawal model Evidence that withdrawal symptoms associated with environmental stimuli causing renewed drug use is limited. Drug cravings are often considered more psychological, rather than a physical withdrawal symptom.

Positive Reinforcement model Unlike the physical dependence model that focused on negative reinforcement this model focuses on positive reinforcement. A lot of animal work has shown the reinforcing properties of drugs One very important procedure is self- administration

4.23 Rat in an operant chamber

4.24 The drug self-administration method

Progressive-ratio schedule Allows researchers to measure how reinforcing different drugs (or different doses of drugs) are relative to one another 1) CRF schedule (continuous reinforcement) –Every bar press = drug injection 2) once well trained you can test with a progressive ratio –Keep increasing the FR (fixed ratio) required to get the injection –Determine break point

Most drugs that humans abuse will be self- administered by animals. If animals are given unlimited access to cocaine they can take so much drug as to cause seizures –Don’t eat –Stop grooming –Can die Most studies limit drug taking sessions to a few hours per day.

Why are abused drugs rewarding? –Hijack the reward pathway? –Neural mechanisms of reward –Discovered with intracranial self stimulation (ICSS) Olds and Milner (1954)

Interaction between drugs of abuse and ICSS –Researchers determine how much current is required to be rewarding (cause lever pressing) The lower the threshold = more sensitive reward circuit –Drugs of abuse lower the threshold for ICSS Indicates that the drug is working on the same neural pathway as the ICSS –Withdrawal increases threshold Analogous to negative mood states in human withdrawal?

Drugs that acutely reduce the threshold for ICSS also increase synaptic DA levels in the nucleus accumbens –Enhancing firing of VTA neurons Opiates Nicotine ethanol THC –Inhibiting reuptake or increasing release at terminals Cocaine amphetamine.

Keep in mind that DA release in the nucleus accumbens is not necessarily the only factor in the rewarding properties of drugs –Lesion mesolimbic pathway (VTA-NA) 6-OHDA in NA Abolishes self administration of cocaine and amphetamine Animals will still self administer alcohol and heroin. –For some drugs there is more to reward than just the mesolimbic pathway

Incentive-sensitization model of drug addiction Distinguishes between drug liking (high) and drug wanting (craving) With repeated drug use drug wanting increases, even though drug liking does not increase (and may even decrease). According to the model, different brain regions control liking and wanting. Repeated drug use sensitizes wanting –No sensitization and perhaps tolerance to liking. Perhaps mesolimbic pathway is more important for drug wanting than drug liking? The brain changes associated with drug wanting are long lasting. Leading to high relapse rates

Opponent Process model This was originally posited as a general approach to understanding motivation Strong emotions one way will cause swings of strong emotions the other way when the stimulus is removed –Jump out of airplane = strong sense of fear –Followed by intense pleasurable sense of relief when you land safely. Drugs = intense pleasurable high followed by unpleasant withdrawal –Euphoria followed by depression

a process = manifest affective episode b process = underlying opponent process a process last for the duration of the episode –Time falling from plane b process starts a little later and lasts longer a-b = top part of the following graph. –Indicates the swing in affect just after the stimulus is removed Land on the ground

After many times jumping from the plane –a process is reduced –b process is enhanced Thus, the pleasure of jumping from a plane is greater and the fear much reduced How would this work with drugs as an example? Similar to incentive sensitization model?

Critique of incentive-sensitization and opponent-process models They are the more modern view Both preferable to physical dependence and positive reinforcement models. –Incentive sensitization probably does a better job of explaining drug craving –Opponent-process seems to do a better job of explaining the dysphoria associated with abstinence

The disease model of addiction Widely accepted –World health organization –American medical association Two kinds of disease models –Susceptibility models –Exposure models

Susceptibility models –Inherited suceptibility to uncontrolled drug use. –Loss of control - start drinking = can’t stop until intoxicated Exposure models –Emphasize the brain alterations that occur with prolonged drug use.

Critique of disease model There is no laboratory test that can identify the underlying cause of the disease. –It is defined only by its symptoms This is an old argument in the psychiatric and psychological literature –Do we treat underlying causes Can’t simply treat symptoms, have to find the underlying reasons –Freud –Do we treat symptoms If you cure the symptoms is there still a disease? –Behaviorists Many psychological disorders are defined simply by their symptoms. –DSM IV – TR –We do not know what causes the disorder

Critique of disease model cont. Use of drugs occurs on a continuum. There is no clear distinction between nonaddictive behavior and addictive behavior –Obesity –Blood pressure The cut off points are somewhat arbitrary

Toward a comprehensive model of drug abuse and dependence Pulling everything together It is important to understand what leads to initial experimentation with drugs –These factors may be very different from what maintains drug use later in life It can take years to decades for dependence to develop Implies initial use factors different from abuse factors

Three factors involved in experimental drug use According to Petraitis et al. (1995). –Three types of factors Social/interpersonal Cultural/attidudinal Intrapersonal –Three levels of influence Proximal –most direct influence Distal –Not as predictive of immediate drug use as proximal, but more so than ultimate. Ultimate –not immediate influence but may determine long term risk

Factors involved in the development and maintenance of drug use Drug related factors –Reinforcing effects of the drug Examples –Euphoria –Mood elevation –Relief from withdrawal –Relief from anxiety –Functional enhancement »Ritalin and Adderall (study drugs)

Drug related factors cont. Discriminative subjective effects of drugs –Produce internal states that can serve as cues to control animal behavior Used to study how similar drugs are for an animal. –Train to nose poke with amphetamine, but not saline –Test with cocaine? –Considered analogous to the subjective effects that people experience when they take a drug.

Drug related factors cont. Certain environments may become associated with drug states –The person or animal expects to feel drug effects in that environment Could contribute to drug seeking behavior Soldiers addicted to heroin in Vietnam often stopped taking the drug when they returned home. –Apparently with less difficulty –Perhaps because removed from the environmental cues associated with the drug

Drug related factors cont. Aversive affects of drugs –We all know that drugs can have aversive effects Alcohol – hangover Cocaine – anxiety –These effects apparently do not override the positive effects Heroin – good sick

Risk Factors Stress and the ability of the person to cope with stress –People under stress often relapse –Animals will increase self administration under stress Comorbidity –Often psychological disorders are associated with increased substance use.

Risk Factors cont. Familial and sociocultural influences –Adult children of alcoholics = increased risk –Social facilitation – alcohol with friends –Escape from social responsibilities –Group solidarity – some cultures identify with heavy alcohol use Irish? Russians? –Drug subculture? Reject “straight” lifestyle and social norms. Genes –Inherited characteristics may influence abuse potential

Protective factors How to help abusers remain abstinent –Avoid drug related cues –New social groups –Life structure

8.17 Factors involved in the development and maintenance of compulsive drug use