Chapter 8 Opener

1. Chapter 8 Opener

2. 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%)

3. 200 years ago there were few regulations on drugs. None at the federal level • There were also fewer drugs • Tobacco • Alcohol • Opium

4. 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

5. 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 1858. • Allowed purified drugs to be injected directly into blood stream • Civil war soldiers often developed opiate addictions • Soldier’s Disease

6. 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)

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

8. 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)

9. 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

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

11. 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

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

14. 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

15. 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

18. 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

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

20. Box 8.1 The “Gateway” Theory of Drug Use

21. 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.

22. 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?

23. 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

24. 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

25. 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

27. 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

29. 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

30. 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)

32. 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

33. 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

34. 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

35. 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.

36. 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

37. 4.23 Rat in an operant chamber

38. 4.24 The drug self-administration method

39. 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

40. 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.

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

42. 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?

43. 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.

44. 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

45. 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

46. 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

47. 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

48. 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?

49. 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

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