Learning Objectives

1. Learning Objectives Understand what is a “drug” and what makes a drug good vs. bad Understand the major types of street drugs: names, effects, mechanisms Understand what is meant by addiction, tolerance, and withdrawal Understand the biological basis for addiction, tolerance, and withdrawal Treatment options for drug addiction but first… Who can become addicted to drugs and what does a typical person with a drug addiction look like? the faces of drug addiction

2. What is a drug? a substance which, upon entering the body, changes the body or its functioning (antagonists vs. agonists) Is food a drug? Illicit vs. licit drugs Drug Schedules (see handout) What determines where a drug is scheduled? E.g. marijuana So, what makes drugs good or bad?

3. Major categories of Psychoactive Drugs Opiates Depressants Stimulants Psychedelics Marijuana

4. Opiates Major effects: analgesic, hypnotic, euphoria Examples: morphine, heroin, some prescription pain killers, endogenous forms (endorphines) Mechanism: binds to opiate receptors and reduces substance P Abuse Potential: high esp. if injected… though withdrawal symptoms are mild http://heroin crisis - national geographic

5. Depressants mother's little helper Major effects: reduce CNS activity (sedative and anxiolytic effects) used as anti-seizure meds Examples: alcohol, barbiturates, benzodiazepines (Valium, Xanax, Halcion) Mechanism: varies according to the subgroups above, but all work through the GABAa receptor complex Abuse Potential: moderate… though withdrawal can be deadly

6. the GABA receptor

7. body story - alcohol part 1 start at 5:00 min in Alcohol body story - alcohol part 2 At low doses = stimulant At high doses = depressant What explains this paradox? Another paradox: new drinkers get drunk on little, veteran drinkers need a lot… chronic abusers need very little Mechanism of action: inhibits the release of glutamate increases the release of GABA binds to opiate receptors which in turn increase DA binds to serotonin and cannabinoid receptors Why is alcohol use accepted and why do we find intoxication so amusing? Is alcohol use ever good? Are there any health benefits?

8. Barbiturates Effects are similar to alcohol but they do not reduce pain per se (just anxiety) Like alcohol, they decrease glutamate (through a different receptor type) And increase GABA (but bind to barbiturate receptors on GABAa) Benzodiazepines Also affects the GABAa receptor… but suppresses activity in the limbic system Safer than barbiturates

9. Stimulants All increase CNS activity to increase arousal, increase alertness, and elevate mood Cocaine Used legally in some parts of the world, found naturally, in Western world - many forms Cocaine blocks re-uptake of DA and serotonin – more available in the synapse – removes Cortical inhibition of lower structures… can cause minor brain damage High, prolonged use can lead to “cocaine psychosis” Treatment: poor prognosis because of intensity of effects, severe withdrawal symptoms, Tendency to abuse other drugs Selective tolerance: tolerance to the psychological effects but decreased tolerance to Seizure producing effects Does cocaine use during pregnancy affect the fetus?

10. Amphetamines http://www.youtube.com/watch?v=vxLCw0GJHoM&feature=related Synthetic stimulants with medicinal and “recreational” uses Increases DA and norepinephrine release “amphetamine psychosis” METH

11. Psychedelics Create perceptual distortions in the 5 senses, time, and creates sense of ecstasy LSD stimulates serotonin & may impair the brain’s sensory filter Psilocybin & psilocin mushrooms… effects similar to LSD but less intense Ecstasy – MDMA a “rave” drug, stimulates CNS but elevates body temp to dangerously high levels… “easy” to make On the figure, brighter colors reflect greater serotonin transporter binding; dull colors mean less binding capacity. This figure shows a decrease in the MDMA user's ability to remove this important neurotransmitter from the intercellular space. This decrease lasts at least three weeks after the individual has stopped using MDMA. www.chestnut.org/.../Street%20Drugs/ecstacy.html

12. Marijuana Active ingredient = THC binds to cannabinoid receptors Endogenous “marijuana” = anandamide & 2-AG Increase DA levels Cannabinoid receptors found through CNS which explains impairments: cognitive functioning, time and sensory perception distortions memory, movement & co-ordination Is it safe? What effects does it have on the fetus? What about “amotivational Syndrome”? Is it addictive? Withdrawal symptoms are very minor because THC is stored in fat

13. A very Important Take-home Fact …“although drugs may reveal a great deal about brain functioning, the pattern of effects they produce is usually unlike normal functioning; drugs affect wide areas of the brain indiscriminately, whereas normal activation tends to be more discrete and localized.” (Garret, 2009, p.135)

14. Addiction How do we currently define addiction? What is wrong with the hypothesis that addiction stems from attempts to avoid withdrawal symptoms: 1. what motivates drug use before addiction develops? 2. why do addicts willingly withdraw to reset tolerance levels? 3. why do people resume drug use after long periods of abstinence? 4. the addictiveness of a drug is unrelated to severity of withdrawal symptoms Why are withdrawal symptoms typically opposite to the effect of the drug?

15. Neural Basis of Addiction Withdrawal is not necessary for addiction & avoidance of withdrawal is not an explanation of addiction Reward mediated by the release of dopamine from the nAcc may explain addiction Virtually all abused drugs release Dopamine in the nAcc So does food, water, & sex Individuals with reward deficiency syndrome are most vulnerable to addiction Are they self-medicating?

16. Dopamine: Reward & Learning New hypothesis: addiction is a learned behavior, mediated by dopamine Dopamine release is highest when reward is unexpected or different from expected After long term use – the drug itself is not rewarding, but cues associated with it are Consistent with learning theory – “reinforcement” has replaced “reward” Conditioned tolerance - based on learning theory, explains why many addicts die from overdose when taking a drug in the absence of the usual cues Their body is not primed – their body does not take “precautions” and reacts as if taking the drug for the first time

17. Treatment Options Agonist treatments: replacement therapy… ethical concerns? Antagonistic treatments: drugs which block the effects of the abused drug Aversive treatments: drugs produce negative reactions to the abused drug Anti-drug vaccines: antibodies attack the abused drug to degrade it ethical concerns? Examples? Alcoholism: Antabuse … aversive treatment… effectiveness depends on motivation Nicotine patches & gum: agonist replacement therapy Heroin: naltrexone… opiate receptor antagonist

18. Genetics & Addiction Convincing evidence that a vulnerability to addiction is inherited – e.g. alcoholism People with fewer D2 receptors for DA are more likely to become alcoholic They are less sensitive to the negative effects of alcohol so they drink more Serotonin is also lower in alcoholics Alcoholics and their children show reduced EEG response 300 msec after the presentation of a novel stimulus Genetic marker for alcoholism or a simple Correlation?

19. Medical model of addiction Is drug use under voluntary control (and thus a moral issue) or is it a disease? Currently, medical model predominates but some argue… the decision to use the first time is a DECISION DRUG PREVENTION making drug use illegal has never worked reducing the supply/availability isn’t working reduce demand for the drug? education and provide alternatives