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PRINCIPLES OF DRUG ACTION Outline 1. The Drug Problem 2. Drug Tolerance & Withdrawal 3. Role of Learning in Drug Tolerance and Withdrawal a. Contingent Drug Tolerance b. Conditioned Drug Tolerance c. Conditioned Withdrawal 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 Physical dependence Psychological dependence What does it mean to be addicted? American Psychiatric Association has stopped using the term addiction and addict in their professional writing Due to bad connotation 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 Contingent Drug Tolerance Ethanol-before group received an ethanol injection once every 48 hours Ethanol is an anticonvulsant repeatedly experience this effect Ethanol-after group received ethanol injections on the same bi-daily schedule 1 hour before a convulsive amygdala stimulation 1 hour after each convulsive stimulation Never experience ethanol's anticonvulsant effect Test only the rats in the ethanol-before-stimulation group were tolerant to alcohol's anticonvulsant effect Crowell, Hinson, and Siegel (1981) Two groups of rats Manipulation of context 20 alcohol injections 20 saline injections alternating sequence one every 48 hours. alcohol in context 1 (test room) saline in context 2 (colony room) Tolerance only occurred when the subjects were tested in the same environment in which they had previously received alcohol