1. States of consciousness Prof. dr. Anton M.L. Coenen NICI – Department of Biological Psychology Radboud University Nijmegen The Netherlands a.coenen@nici.ru.nl

2. States of consciousness Lecture 4. Psychoactive drugs modulating consciousness

3. PSYCHOACTIVE SUBSTANCES AND CONSCIOUSNESS THREE MAIN GROUPS OF DRUGS MODULATE CONSCIOUSNESS CENTRAL STIMULANTS AMPHETAMINES – COCAINE – CAFFEINE - NICOTINE HYPNOTICS – SEDATIVES – ANXIOLYTICS BARBITURATES – BENZODIAZEPINES PSYCHODELICS (MIND-ALTERING DRUGS) ALCOHOL - MESCALINE – LSD – PSYLOCYBINE – OPIATES

4. + + - - - + + BALANCE BETWEEN EXCITATORY AND INHIBITORY SYSTEMS

7. HYPNOTICS AND SEDATIVES BARBITURATES Since 1903 Fischer and von Mering - efficient drugs - high toxicity - modulate chloride channels BENZODIAZEPINES Since1960 Sternbach – safe and efficient – modulate GABA-system

8. HYPNOS

10. EFFECT DEATH COMA ANESTHESIA SLEEP DOSE BENZODIAZEPINES BARBITURATEN

13. Leo Sternbach (1908)

14. The valium structure

18. EEFFECTS OF BENZODIAZEPINES  SEDATIVE / HYPNOTIC  ANXIOLYTIC  MUSCLE RELAXANT  ANTI-CONVULSIVE  AMNESTIC  EEG-CHANGES  TOLERANCE  DEPENDENCY

27. The AIM model may be used to think about the state of the brain in conditions other than sleep. For example, when all three state values fall and the AIM points move to the left lower front corner, the result is coma. Hallucination would be the effect when the internal stimulus strength increases during waking, and AIM moves to the right upper front corner. AIM moves to the left upper rear corner when external stimulus strength is increased, as in electroshock therapy. Whether or not these assumptions are correct can now be tested experimentally.

32. Natives of Amazon prepare a brew of ‘ayahuasca’ (‘vine of the dead, or souls’). With this tea containing powerful hallucinogenic alkoloids, interior sounds are commonly heard, often triggering spontaneous vocalisations.

34. ALCOHOL

35. Alcohol invades all parts of the body (molecules are small and soluble in both fat and water) inhibits the flow of sodium across the membranes expands the surface of membranes facilitates response by the GABA A receptor blocks glutamate receptors increases dopaminergic activity

36. NICOTINE

37. Nicotine binds to a nicotinic receptor, one of the two subtypes of acetylcholine receptors. When nicotine binds to a nicotinic receptor, it opens Na + -channels, allowing sodium to flow into the cell. This depolarises the cell membrane leading to a fast excitation.

38. MARIJUANA

41. COCAINE

42. Cocaine Dopamine Cocaine Central effects

43. When Coca-Cola was first produced, there was a clear reason why it relieved fatigue: It contained cocaine.

49. HEROIN AND MORPHINE

50. Opiates: narcotic analgesics Pain relief Sedation Euphoria Miosis Impaired peristalsis Respiratory depression Inhibition cough reflex a- Opiumanta- Naloxon Morphine Heroine Methadon ……

51. Local Anesthetics

54. Gate Control Theory Melzack and Wall

55. Three classes of psycho-active drugs interfere with consciousness: central stimulants (enhancing), central depressants (diminishing) and psychodelics (‘changing’). Central stimulants activate acetylcholine (nicotine), block GABA (caffeine) or inhibit dopamine re-uptake (amphetamine). Central depressants open chloride channels (barbiturates), or facilitate GABA (benzodiazepines) Psychodelics (‘hallucinogenics’) induce ‘altered states of consciousness (ASC)’, including hallucinations and distorted perception (amphetamine, cocaine, MDMA (ecstacy), LSD). A deep brain depression causes anaesthesia, by opening Cl - channels (barbiturates), by agonistic action on GABA (benzodiazepines) or by antagonistic action on glutamate. Powerful analgetics (pain killers) are morphine and heroine, interfering with opiate receptors and endorphines. The fact that psycho-active drugs modulate neurotransmitter- systems in relation to consciousness pleads for a monistic view of consciousness.