Definitions Drug Use Drug Abuse Drug Dependence Taking a psychoactive substance for non-medical purposes, out of curiosity Drug Abuse Drug use that leads to problems (e.g. loss of effectiveness in society; behavioral psychopathology, criminal acts) Drug Dependence A maladaptive pattern of drug use leading to clinically-significant impairment or distress, associated with difficulty in controlling drug-taking behavior, withdrawal, and tolerance The state of needing a drug to function within ‘normal limits’

Nature of Addiction - a continuum of use? Loss of control  However, addiction is more than mere drug use…

DSM-IV Criteria for Substance Dependence A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12 month period: Tolerance Withdrawal Substance taken in larger amounts or over a longer period than intended Persistent desire or unsuccessful efforts to cut down or control substance use Great deal of time spent in activities necessary to obtain substance, use substance (e.g., chain smoking), or recover from effects Important social, occupational, or recreational activities given up or reduced because of substance use Substance use continued despite knowledge of persistent or recurrent physical or psychological problem likely to have been caused or exacerbated by substance

Physical vs. Psychological Dependence Physical Dependence Withdrawal symptoms in the absence of the drug Tolerance to its effects with repeated use Psychological Dependence “a relatively extreme, pathological state in which obtaining, taking, and recovering from a drug represents a loss of behavioral control over drug taking which occurs at the expense of most other activities and despite adverse consequences” (Altman et al) “a situation where drug procurement and administration appear to govern the organism’s behavior, and where the drug seems to dominate the organism’s motivational hierarchy” (Bozarth)

Classic Models of Addiction Emphasized Causes Example Interventions Moral Personal responsibility; self-control Moral suasion; social/legal sanctions Spiritual Spiritual defect Prayer; 12-step faith-based treatment (e.g. AA) Temperance Drugs Control of supply; calls for abstinence Educational Ignorance Education Conditioning Classical/operant conditioning Counterconditioning; extinction

Classic Models of Addiction continued Emphasized Causes Example Interventions Biological Heredity; brain physiology; self-medication Risk identification; calls for abstinence; medical treatment Psycho-dynamic Personality; defense mechanisms Psychoanalysis Family Dynamics Family dysfunction Family therapy Social Learning Modeling; expectancies Positive role models; rational restructuring of expectancies Sociocultural Environmental; cultural; economic Social policy; social services

Physical Dependence or Withdrawal Model (Negative Reinforcement) Some drugs produce physical dependence and withdrawal symptoms upon cessation of drug-taking. Withdrawal symptoms are produced by the body in order to compensate for the unusual effects of the drug. Withdrawal symptoms are generally the opposite of the effect produced by the drug. Addicts continue to use drugs in order to avoid withdrawal. Over time, drugs no longer have the same rewarding effects - they merely allow the person to feel “normal.”

Inadequacies of Withdrawal Model Not all abused drugs generate withdrawal symptoms (cocaine, amphetamine). Different drugs produce different withdrawal symptoms with different neural bases. Once dependent you should continue taking drug, but people spontaneously stop. Once drug-abstinent, users should not relapse since motivation has disappeared, but they do. No explanation as to why people take drugs in the first place.

Positive Incentive (Hedonic) Models (Positive Reinforcement) Drugs produce pleasure - a “high.” Some drugs provide indirect positive incentive - they disinhibit behavior that is normally suppressed (e.g., alcohol and social skills). Most drugs of abuse stimulate the brain’s reward circuits. All known drugs of abuse stimulate release of DA/opioids in the nucleus accumbens Animals will work to micro-inject drugs of abuse and electrically stimulate the same parts of the brain Normal rewards (food, drink, sex) also stimulate DA release

Animal Models of Reinforcement (cont.) Self-administration Animals work for reinforcing drugs (IV, oral, inhalant) Schedules of reinforcement (fixed, progressive ratio)

DA release following VTA stimulation

Drugs that are and are not self administered by animals Alcohol Amphetamine Barbiturates Caffeine Cocaine Nicotine Opiates Procaine (n.a. by humans) PCP THC Imipramine Mescaline (abused by humans) Phenothiazines Scopolamine

Drug Dependence Among Ever-Users Tobacco Heroin Cocaine Alcohol Stimulants Marihuana 10 20 30 40 % Dependent

Opponent Process Model (Solomon, 1977) Drug-use initially motivated by positive reinforcement Over time, tolerance to rewarding effects, but abstinence leads to withdrawal Drug use ultimately maintained by negative reinforcement

Current Traditional View (based on opponent process model) Initiation of drug taking is primarily driven by anticipated pleasure (facilitated by peer pressure, social facilitation, curiosity). For most drugs, pleasure becomes primary motivator and drug craving becomes cued by drug related stimuli. For some drugs (e.g., alcohol, cocaine, heroin) pleasure is enhanced by reversing unpleasant aspects of normal life. For some drugs (e.g., nicotine, caffeine, heroin, alcohol), drug-taking leads to dependence and withdrawal which adds additional motivation to continue drug-taking habit and makes “giving up” difficult. This withdrawal state can also be associated with environmental cues, and increases the tendency for relapse.

Limitations of Opponent Process Models Drug withdrawal is much less powerful at motivating drug-taking behavior stress seems to be more powerful Withdrawal symptoms are maximal within a few days after cessation of drug use, but susceptibility to relapse continues to grow for weeks to months. Cues typically fail to elicit conditioned-withdrawal. Craving is different from withdrawal.

Aberrant Learning (beyond pleasure and pain) Cues that predict the availability of rewards can powerfully activate DA circuitry in both animals and humans (Schultz, 1998), sometimes even better than the reward itself. Therefore, the transition to addiction results from the ability of drugs to promote this type of aberrant learning.

Monkey VTA Study (Schultz et al, 1990s) Monkeys classically-conditioned to associate light with food After learning, VTA neurons increase firing to light instead of food Decreased firing if light-cued food doesn’t appear Baseline DA = expected reward Increased firing = better than expected Reduced firing = worse than expected

Problems with Aberrant Learning Models Most have focused at the level of neuronal systems Few have provided a psychological step-by-step account of how aberrant learning could actually produce addiction. Are the associations S-S or S-R learning? are they explicit or implicit?

Implicit Learning (Tiffany, 1990) Drug-taking habits are caused by aberrant learning, because drugs subvert neuronal mechanisms involved in implicit learning (unconscious S-R or S-S processes). Urges and cravings are of secondary importance to force of habit (automaticity). “…with sufficient practice, performance on any task can become automatic…” and “drug-use behavior in the addict represent one such activity, controlled largely by automatic processes” Over-learned habits become so automatic that they essentially become compulsive

Problems with Automaticity Models They mistake automatic performance for motivational compulsion. Habits (brushing teeth, driving) are not intrinsically compulsive, no matter how automatic they are Would you sacrifice your home, your job, your friends to engage in teeth brushing behavior? Many aspects of addictive drug pursuit are flexible and not habitual

Incentive –Sensitization Model (Robinson and Berridge, 1993) Addictive drugs produce long-lasting changes in brain organization The brain systems that are changed include those normally involved in the process of incentive motivation and reward. Addiction renders these systems hypersensitive (“sensitized”) to drugs and drug-associated stimuli These sensitized systems mediate a component of reward termed incentive salience or “wanting” (not pleasure or “liking”).

Incentive Sensitization Drug-induced sensitization of brain systems (DA) that mediate incentive-salience causes drugs and drug-associated stimuli to become compulsively “wanted” The activation of the sensitized system can occur both implicitly or explicitly These systems can be dissociated from neural systems that mediate the hedonic effects of drugs (opioids), i.e., how much they are “liked” (wanting is not liking).

Psychomotor Sensitization Many drugs produce psychomotor-activating effects amphetamines, cocaine, opiates, alcohol, nicotine, MDMA These effects last from months to years after drug use is discontinued Some individuals sensitize readily, whereas others are more resistant (may explain susceptibility to addiction) genes, hormones, stress hormones, past trauma…? stress causes sensitization and may bias addiction addiction may make an individual hypersensitive to stress

Incentive-Sensitization Model Addiction may be triggered by drug cues as a “learned” motivational response but it is not a disorder of aberrant learning per se It is a disorder of aberrant incentive motivation due to drug induced sensitization of neural systems that attribute salience to particular stimuli.

Cocaine Cues Study (Grant et al, 1996) PET = Positron Emission Tomography Radioactive marker injected Scanner detects light waves from decay

Cocaine Study continued Cocaine addicts and controls shown cocaine cues and neutral cues Cocaine cues in addicts elicited craving, brain activation Activation correlated with craving in Dorsolateral Prefrontal Cortex, Amygdala, Cerebellum

Smoking Stroop Study (Gross et al, 1993) RED BLUE GREEN Congruent RED BLUE GREEN Incongruent Normal Stroop effect: takes longer to name ink color when incongruent with word MATCH SMOKE PACK Smoking BOARD PAINT BRUSH Neutral Smoking Stroop: 12-hour abstinent smokers take longer to name ink color for smoking words than neutral words

Impairments in Frontocortical Function May be responsible for “irrational” behavior of addicts Poor decision-making May exacerbate incentive-sensitization