Exploring Psychopharmacology: Understanding Effects of Psychoactive Drugs

1. PSYCHOPHARMACOLOGY • The scientific study of psychoactive drugs and their effects.

2. General Principles of Psychopharmacology • 1. Drug use in of itself is neither good nor bad…it just is. • Let’s study the phenomena objectively, without preconceived moral judgment. • 2. All drugs have multiple effects • Therapeutic and side-effects may be context dependent..i.e. SSRIs may be used as a sleep aid, or drowsiness may be seen as a side effect.

3. General Principles of Psychopharmacology 3. Drugs do not produce effects that are outside the organisms behavioral repertoire. • Instead they may magnify or diminish “normal behaviors, or alter the probability or context of responses, etc.. 4. Drug effects are influenced by “non-specific” factors • In many cases the environmental context may alter a drugs’ effects. The physiological state and Psychological “set” of the individual may also have major influences.

4. Non-specific Factors • “Set” The physiological and psychological state of the user. Setting The environment and social context in which the drug is taken

5. Cigarettes to “get going” or to “chill out”

6. Non-specific drug effects cont’ The “Placebo Effect” Effects NOT based on specific biological actions of the drug, but instead are produced in some way by the Expectations of the user.

7. Placebo Effect- • Placebo- Latin for "I shall please.” • A placebo is an inert substance,..sugar pill..sham medication • Typically about 35% + of subjects are responsive. • Has been effective in treating Pain, anxiety, depression, etc. • Some people may even experience placebo side effects/withdrawal

8. General Principles of Psychopharmacology Drug Effects are influenced by “Pharmacokinetics

9. Pharmacokinetics • the influences of route of drug administration, drug absorption, drug distribution, drug transformation, and drug elimination. • These factors influence how fast and how much of a drug gets to its’ sites of action, as well as the duration of a drugs’ effects.

10. General Principles of Psychopharmacology cont’ • Psychokinetic studies clearly indicate that drug effects are: • 5. Dose-dependent • Consider the effects of mild coffee vs espresso!

12. General Principles of Psychopharmacology • 6. Drug Effects are Time-Dependent • Consider early intoxication vs late

13. Early Later Way Late

14. Drug Effects are influenced by “Pharmacodynamics” • Drug effects on the target tissue • psychoactive drugs produce effects in the central nervous system (CNS) • Many psychoactive drugs bind to “Neurotransmitter receptors” • And alter the activity of brain cells ( neurons) and their functional relationships with other neurons • More on this later

15. General Principles of Psychopharmacology cont’ • Pharmacodynamic studies clearly indicate that drug effects are: • 7. dependent on the type of drug and its’ site of action

16. DRUG SITES OF ACTION (more when we cover the nervous system) • Different Psychoactive Drugs affect different Neurotransmitter Systems in the Brain that in turn have different consequences for behavior, thought and mood.

17. Classical Neurotransmitters • Acetylcholine • In the brain, it appears to be involved in learning/memory, attention as well as sleeping and dreaming.

18. Classical Neurotransmitters cont’ Dopamine • implicated in movement control • Parkinson’s Disease • Dopamine excess may be involved in Schizophrenia. • involved in the “reward system of the brain.”

19. Classical Neurotransmitters cont’ • Norepinephrine • primarily involved in control of alertness/vigilance. • Possible involvement in mood state

20. Classical Neurotransmitters cont’ • Serotonin • plays a role in the regulation of mood • It also has a role in the control of eating, sleep and arousal.

21. Classical Neurotransmitters cont’ • Endorphin/ Enkephalin • Modulates the experience of pain • Controls breathing and heart rate, cough reflex, nausea and vomiting • Modulates feelings of euphoria and reward

22. Classical Neurotransmitters cont’ GABA • Most prevalent inhibitory neurotransmitter in the brain • GABA secreted by “local” interneurons all over the brain. • Implicated in relaxation/anti-anxiety

23. More on….Pharmacokinetics • Administration • Absorption • Distribution • Biotransformation • Excretion

24. DRUG ADMINISTERED DRUG ABSORBED DRUG DISTRIBUTED DRUG METABOLIZED DRUG ELIMINATED

25. Routes of Administration • Oral • Intramuscular (IM) • Intraperitoneal (IP) • Intravenous (IV) • Inhalation • Intracranial (IC) • Intracerebroventricular • Topical

26. Inhalation- a fast route From lungs a direct shot to brain through carotid artery

27. Absorption • Moving from the site of administration to the bloodstream • Drugs first travel in the bloodstream to get to sites of action • How fast do drugs leave the site of administration? • Route • Acidity/Alkalinity • Absorption relates to bioavailability • The amount of the drug that reaches the bloodstream and/or site of action

28. Distribution • Refers to factors influencing a drug’s ability to get to its site of action after absorption • First Pass effect • Depends on route of administration • Protein Complexing

29. Role of the Liver in the “First Pass Effect.”

30. BRAIN LUNGS INHALATION RIGHT SIDE OF HEART LEFT SIDE OF HEART INTRAVENOUS INJECTION ORAL LIVER INTESTINE INTRAMUSCULAR INJECTION

31. Protein complexing Proteins in the bloodstream may bind to the drug and slow or prevent its distribution

32. Distribution-Depot binding Bone, Fat, Muscle, non-specific binding of drug ..affects distribution

33. Distribution-Blood-brain barrier limits drug access to brain

34. Biotransformation/Metabolism Drug Metabolization – Enzymes break down the drug molecules to prepare them for ELIMINATION • Biotranformation occurs mainly in LIVER, but can occur in the nervous system, or in the blood stream as well • Enzymes break down drugs into metabolites • Metabolites can be active or inactive • Some drugs are not transformed at all..

35. Metabolism usually occurs at a characteristic rate for a given drug Drug Half-Lifes The amount of time necessary for one half of the active compound to be metabolized ** Note most drugs obey the law of first order Kinetics

36. Drug Elimination • Drugs are excreted in a variety of ways • Urine • Breath • Feces • Sweat • Can be excreted changed or unchanged (alcohol vs. psylocibin)

37. Trace Amounts may be detectable for long periods of time

38. Hence: Drug testing

39. Methods used by Psychopharmacologist Dose-Response Curve • Plots the relation between the dose of the drug and the size of the effect

40. EFFECT DOSE (DRUG AMOUNT PER UNIT OF BODY WEIGHT)

41. REACTION TIME Seconds DOSE ALCOHOL (g/kg)

42. DRC Characteristics • Slope • gradual versus steep % of Maximal Effect Drug Dose -Slope reflects sensitivity of effect to drug dose

43. POTENCY • THE DOSE OF A DRUG REQUIRED TO PRODUCE A GIVEN EFFECT (LOWER VALUE = MORE POTENT) • Maximum efficacy • upper dose where response levels out

44. Drug A is more Potent than Drug B

45. REMEMBER THAT ALL DRUGS HAVE MULTIPLE EFFECTS…… • SO DRCs can be developed for each effect..

46. NUMBER OF WORDS REMEMBERED DOSE ALCOHOL (g/kg)

47. Aggressive Behavior DOSE ALCOHOL (g/kg)

48. LOSS OF CONSCIOUSNESS COMA DEATH REACTION TIME % OF INDIVIDUALS SHOWING EFFECT DOSE ALCOHOL (g/kg)

49. ED50 • NOT-THE DOSE OF A DRUG REQUIRED TO PRODUCE A 1/2 MAXIMAL EFFECT • ED50 IS- THE DOSE OF A DRUG REQUIRED TO PRODUCE A GIVEN EFFECT IN 50% OF THE INDIVIDUALS TESTED

50. LD50 • THE DOSE OF A DRUG THAT WILL PRODUCE LETHALITY IN 50% OF THE INDIVIDUALS TESTED