2022-2023
PSYCHOPHARMACOLOGY
Gedoceerd door Sam Willems
,Inhoudsopgave
1. Ancient history ............................................................................................................................................. 5
1.1. Charvet (18th-19th century) .......................................................................................................................... 5
1.2. Moreau de Tours (19th century) .................................................................................................................. 6
1.3. Mantegazza ................................................................................................................................................. 6
2. Influences from Psychology .......................................................................................................................... 7
2.1. Experimental Psychology ............................................................................................................................. 7
2.1.1. Kraeplin ................................................................................................................................................ 8
2.1.2. Rivers ................................................................................................................................................... 8
2.1.3. Hollingworth ........................................................................................................................................ 9
2.1.4. Delaberre and Scripture ...................................................................................................................... 9
- first psychological study on effects of cannabis on consciousness and someone’s motivational will .............. 9
2.2. Biology & comparative psychology = behavioral psychology ...................................................................... 9
2.2.1. Classical Conditioning ........................................................................................................................ 10
2.2.2. Operant Conditioning ........................................................................................................................ 10
2.3. Behavioral pharmacology.......................................................................................................................... 11
2.4. Biological Psychology anc Psychopharmacology ....................................................................................... 12
2.5. Example: Hebbian Learning ....................................................................................................................... 12
2.5.1. Classical condition and hebbian learning explained .......................................................................... 13
2.5.2. Placebo effect explained ................................................................................................................... 14
2.5.3. Application: Placebo-controlled dose reduction (PCDR) .................................................................. 15
3. Influences from Psychiatry ......................................................................................................................... 17
3.1. Early pharmacotherapy (1860-1930: before WOII) ................................................................................... 17
3.1.1. Social background .............................................................................................................................. 17
3.1.2. Therapeutic options for the incurable ............................................................................................... 18
3.2. Experimenting with hallucinogenics (1880 - 1940).................................................................................... 19
3.2.1. Accidental discovery of LSD (1938) .................................................................................................... 20
3.2.2. Applications and the public of LSD (post-WO II)................................................................................ 20
3.2.3. How does LSD work and how is it related to Psychotic Episodes? .................................................... 21
3.2.4. Hallucinogenic experiments .............................................................................................................. 22
3.3. The first antidepressant (1930-1950: during WOII) ................................................................................... 22
3.3.1. Social background .............................................................................................................................. 22
3.3.2. Benzedrine®: The uplifting nasal decongestant ................................................................................ 23
3.3.3. Conquering depression during the heydays of the 20th century ...................................................... 23
3.4. The revolutionary decade (post WW II): ANTIPSYCHOTICS ....................................................................... 24
3.4.1. Social background .............................................................................................................................. 24
3.4.2. Phenothiazines (heel goed kennen) .................................................................................................. 25
3.5. The revolutionary decade (post WW II): ANTIDEPRESSANTS .................................................................... 26
3.6. The revolutionary decade: ANXIOLYTICS .................................................................................................. 27
3.7. The revolutionary decade (post WW II): ANTIMANIC DRUGS ................................................................... 27
3.8. In conclusion .............................................................................................................................................. 28
1. Key concepts of Behavioral Neuroscience .................................................................................................. 29
1.1. Anatomy & Organization of the Nervous System ...................................................................................... 30
1
, 1.1.1. Different nervous systems ................................................................................................................. 31
1.1.2. Central nervous system ..................................................................................................................... 32
1.1.3. The deep brain structures ................................................................................................................. 33
1.1.4. What are cells made of? Including neurons ...................................................................................... 33
1.2. Origin of Signal .......................................................................................................................................... 38
1.3. Neural Communication (zie gedragsneuro) ............................................................................................... 39
1.3.1. Communication within a neuron ........................................................................................................... 40
1.3.1.1. Membrane Potentials ..................................................................................................................... 40
1.3.2. Action potential (zie gedragsneuro) .................................................................................................. 43
1.4. Communication between neurons ............................................................................................................ 45
1.4.1. Synaptic communication ................................................................................................................... 45
1.5. Endocrinergic Communication ................................................................................................................... 51
1.5.1. Subtle differences .............................................................................................................................. 52
1.5.1.1. Endocrinergic neurons .................................................................................................................... 52
1.5.1.2. Endocrinergic glands (specialized structures in our body) ............................................................. 53
2. Principles of psychopharmacology: general framework ............................................................................. 55
3. Key concepts of Psychopharmacology: Pharmacokinetics .......................................................................... 57
3.1. Routes of administration ........................................................................................................................... 57
3.2. Absorption & distribution .......................................................................................................................... 62
3.2.1. Partition coefficient is too high ......................................................................................................... 64
3.2.2. Partition coefficient is moderate drug .............................................................................................. 64
3.2.3. Partition coefficient is too low........................................................................................................... 65
3.3. Depot binding (niet heel erg in detail kennen) .......................................................................................... 68
3.4. Inactivation & biotransformation .............................................................................................................. 69
3.5. Excretion .................................................................................................................................................... 72
3.6. Pharmacokinetics: summarize ................................................................................................................... 73
4. Key concepts of Psychopharmacology: Pharmacodynamics ....................................................................... 74
4.1. CNS-Behavioral Categorization of Drugs ................................................................................................... 74
4.2. From synaptic activity… ............................................................................................................................. 75
4.2.1. Drugs as ligands ................................................................................................................................. 76
4.2.3. Dynamic reactions: downregulation and upregulation ..................................................................... 81
4.3. … To behavioral effects .............................................................................................................................. 83
4.3.1. From a drug action to a drug effect ................................................................................................... 83
4.3.2. Dose Response Curves (DRCs) ........................................................................................................... 83
4.3.4. Tolerance ⬄ sensitization ................................................................................................................. 84
4.3.5. Kinetics and dynamics interact with each other ................................................................................ 85
1. Preclinical research .................................................................................................................................... 87
1.1. Animal research and ethics....................................................................................................................... 88
1.1.1. The challenge of testing with animals: .............................................................................................. 89
1.1.2. Focus on construct validity ................................................................................................................ 89
1.1.3. Other quality checks: ......................................................................................................................... 89
1.2. How do we study psychiatric disorders in rodents? ................................................................................... 90
1.3. Example of an animal model ..................................................................................................................... 90
1.4. The 3 R’ and moral principles: research with animals requires moral guidelines ...................................... 92
2
, 2. Clinical research ......................................................................................................................................... 93
2.1. Methodological issues ............................................................................................................................... 94
2.2. Post-marketing research, phase IV ............................................................................................................ 98
2.2.1. FDA/FAGG assessment ...................................................................................................................... 98
2.2.2. Increased regulations = increased costs: discussion ......................................................................... 99
2.3. INCB – International Narcotics Control Board ........................................................................................... 99
After a drug has been approved by the FDA: Phase IV ................................................................................... 102
1. Therapy (non)adherence .......................................................................................................................... 104
1.1. Defining therapy (non)adherence ............................................................................................................ 104
1.2. Factors related to therapy (non)adherence ............................................................................................. 105
1.3. societal problems related to therapy (non)adherence ............................................................................ 109
1.3.1. Social biases ..................................................................................................................................... 109
2. The case of Scott Martin: introduction + instructions ............................................................................... 111
4.1. Getting to know Scott .............................................................................................................................. 111
4.2. Treatment adherence: a new hope ......................................................................................................... 111
4.3. The short-term effects of Lithium ............................................................................................................ 111
4.4. The 6-week follow-up .............................................................................................................................. 112
4.5. Putting strain on Scott’s treatment adherence ....................................................................................... 112
4.6. Remarkable effects come in small packages ........................................................................................... 112
3. How to improve Therapy Adherence ........................................................................................................ 112
1. .................................................................................................................................................................. 114
1.1. Defining substance use disorder .............................................................................................................. 114
1.1.1 Different degrees of substance use disorder.................................................................................... 114
2. What’s in a name ..................................................................................................................................... 115
2.1. Dependency ............................................................................................................................................. 115
2.2. Addiction ................................................................................................................................................. 116
2.3. Abuse ....................................................................................................................................................... 116
2.4. Substance induced disorders or SIDs ....................................................................................................... 116
2.5. "Behavioural addictions" ......................................................................................................................... 117
3. Biopsychosocial mechanisms of SUD ........................................................................................................ 118
3.1. The mesolimbic pathway - The reward system ....................................................................................... 118
3.2. The neurobiology of tolerance and withdrawal ...................................................................................... 119
3.3. Hebbian learning ..................................................................................................................................... 120
3.4. Homeostatis and opponent Proces Theory .............................................................................................. 121
3.5. Evaluation in cravings.............................................................................................................................. 122
3.6. The social network hypothesis ................................................................................................................. 123
4. Treatment strategies of SUDs ................................................................................................................... 123
3
PSYCHOPHARMACOLOGY
Gedoceerd door Sam Willems
,Inhoudsopgave
1. Ancient history ............................................................................................................................................. 5
1.1. Charvet (18th-19th century) .......................................................................................................................... 5
1.2. Moreau de Tours (19th century) .................................................................................................................. 6
1.3. Mantegazza ................................................................................................................................................. 6
2. Influences from Psychology .......................................................................................................................... 7
2.1. Experimental Psychology ............................................................................................................................. 7
2.1.1. Kraeplin ................................................................................................................................................ 8
2.1.2. Rivers ................................................................................................................................................... 8
2.1.3. Hollingworth ........................................................................................................................................ 9
2.1.4. Delaberre and Scripture ...................................................................................................................... 9
- first psychological study on effects of cannabis on consciousness and someone’s motivational will .............. 9
2.2. Biology & comparative psychology = behavioral psychology ...................................................................... 9
2.2.1. Classical Conditioning ........................................................................................................................ 10
2.2.2. Operant Conditioning ........................................................................................................................ 10
2.3. Behavioral pharmacology.......................................................................................................................... 11
2.4. Biological Psychology anc Psychopharmacology ....................................................................................... 12
2.5. Example: Hebbian Learning ....................................................................................................................... 12
2.5.1. Classical condition and hebbian learning explained .......................................................................... 13
2.5.2. Placebo effect explained ................................................................................................................... 14
2.5.3. Application: Placebo-controlled dose reduction (PCDR) .................................................................. 15
3. Influences from Psychiatry ......................................................................................................................... 17
3.1. Early pharmacotherapy (1860-1930: before WOII) ................................................................................... 17
3.1.1. Social background .............................................................................................................................. 17
3.1.2. Therapeutic options for the incurable ............................................................................................... 18
3.2. Experimenting with hallucinogenics (1880 - 1940).................................................................................... 19
3.2.1. Accidental discovery of LSD (1938) .................................................................................................... 20
3.2.2. Applications and the public of LSD (post-WO II)................................................................................ 20
3.2.3. How does LSD work and how is it related to Psychotic Episodes? .................................................... 21
3.2.4. Hallucinogenic experiments .............................................................................................................. 22
3.3. The first antidepressant (1930-1950: during WOII) ................................................................................... 22
3.3.1. Social background .............................................................................................................................. 22
3.3.2. Benzedrine®: The uplifting nasal decongestant ................................................................................ 23
3.3.3. Conquering depression during the heydays of the 20th century ...................................................... 23
3.4. The revolutionary decade (post WW II): ANTIPSYCHOTICS ....................................................................... 24
3.4.1. Social background .............................................................................................................................. 24
3.4.2. Phenothiazines (heel goed kennen) .................................................................................................. 25
3.5. The revolutionary decade (post WW II): ANTIDEPRESSANTS .................................................................... 26
3.6. The revolutionary decade: ANXIOLYTICS .................................................................................................. 27
3.7. The revolutionary decade (post WW II): ANTIMANIC DRUGS ................................................................... 27
3.8. In conclusion .............................................................................................................................................. 28
1. Key concepts of Behavioral Neuroscience .................................................................................................. 29
1.1. Anatomy & Organization of the Nervous System ...................................................................................... 30
1
, 1.1.1. Different nervous systems ................................................................................................................. 31
1.1.2. Central nervous system ..................................................................................................................... 32
1.1.3. The deep brain structures ................................................................................................................. 33
1.1.4. What are cells made of? Including neurons ...................................................................................... 33
1.2. Origin of Signal .......................................................................................................................................... 38
1.3. Neural Communication (zie gedragsneuro) ............................................................................................... 39
1.3.1. Communication within a neuron ........................................................................................................... 40
1.3.1.1. Membrane Potentials ..................................................................................................................... 40
1.3.2. Action potential (zie gedragsneuro) .................................................................................................. 43
1.4. Communication between neurons ............................................................................................................ 45
1.4.1. Synaptic communication ................................................................................................................... 45
1.5. Endocrinergic Communication ................................................................................................................... 51
1.5.1. Subtle differences .............................................................................................................................. 52
1.5.1.1. Endocrinergic neurons .................................................................................................................... 52
1.5.1.2. Endocrinergic glands (specialized structures in our body) ............................................................. 53
2. Principles of psychopharmacology: general framework ............................................................................. 55
3. Key concepts of Psychopharmacology: Pharmacokinetics .......................................................................... 57
3.1. Routes of administration ........................................................................................................................... 57
3.2. Absorption & distribution .......................................................................................................................... 62
3.2.1. Partition coefficient is too high ......................................................................................................... 64
3.2.2. Partition coefficient is moderate drug .............................................................................................. 64
3.2.3. Partition coefficient is too low........................................................................................................... 65
3.3. Depot binding (niet heel erg in detail kennen) .......................................................................................... 68
3.4. Inactivation & biotransformation .............................................................................................................. 69
3.5. Excretion .................................................................................................................................................... 72
3.6. Pharmacokinetics: summarize ................................................................................................................... 73
4. Key concepts of Psychopharmacology: Pharmacodynamics ....................................................................... 74
4.1. CNS-Behavioral Categorization of Drugs ................................................................................................... 74
4.2. From synaptic activity… ............................................................................................................................. 75
4.2.1. Drugs as ligands ................................................................................................................................. 76
4.2.3. Dynamic reactions: downregulation and upregulation ..................................................................... 81
4.3. … To behavioral effects .............................................................................................................................. 83
4.3.1. From a drug action to a drug effect ................................................................................................... 83
4.3.2. Dose Response Curves (DRCs) ........................................................................................................... 83
4.3.4. Tolerance ⬄ sensitization ................................................................................................................. 84
4.3.5. Kinetics and dynamics interact with each other ................................................................................ 85
1. Preclinical research .................................................................................................................................... 87
1.1. Animal research and ethics....................................................................................................................... 88
1.1.1. The challenge of testing with animals: .............................................................................................. 89
1.1.2. Focus on construct validity ................................................................................................................ 89
1.1.3. Other quality checks: ......................................................................................................................... 89
1.2. How do we study psychiatric disorders in rodents? ................................................................................... 90
1.3. Example of an animal model ..................................................................................................................... 90
1.4. The 3 R’ and moral principles: research with animals requires moral guidelines ...................................... 92
2
, 2. Clinical research ......................................................................................................................................... 93
2.1. Methodological issues ............................................................................................................................... 94
2.2. Post-marketing research, phase IV ............................................................................................................ 98
2.2.1. FDA/FAGG assessment ...................................................................................................................... 98
2.2.2. Increased regulations = increased costs: discussion ......................................................................... 99
2.3. INCB – International Narcotics Control Board ........................................................................................... 99
After a drug has been approved by the FDA: Phase IV ................................................................................... 102
1. Therapy (non)adherence .......................................................................................................................... 104
1.1. Defining therapy (non)adherence ............................................................................................................ 104
1.2. Factors related to therapy (non)adherence ............................................................................................. 105
1.3. societal problems related to therapy (non)adherence ............................................................................ 109
1.3.1. Social biases ..................................................................................................................................... 109
2. The case of Scott Martin: introduction + instructions ............................................................................... 111
4.1. Getting to know Scott .............................................................................................................................. 111
4.2. Treatment adherence: a new hope ......................................................................................................... 111
4.3. The short-term effects of Lithium ............................................................................................................ 111
4.4. The 6-week follow-up .............................................................................................................................. 112
4.5. Putting strain on Scott’s treatment adherence ....................................................................................... 112
4.6. Remarkable effects come in small packages ........................................................................................... 112
3. How to improve Therapy Adherence ........................................................................................................ 112
1. .................................................................................................................................................................. 114
1.1. Defining substance use disorder .............................................................................................................. 114
1.1.1 Different degrees of substance use disorder.................................................................................... 114
2. What’s in a name ..................................................................................................................................... 115
2.1. Dependency ............................................................................................................................................. 115
2.2. Addiction ................................................................................................................................................. 116
2.3. Abuse ....................................................................................................................................................... 116
2.4. Substance induced disorders or SIDs ....................................................................................................... 116
2.5. "Behavioural addictions" ......................................................................................................................... 117
3. Biopsychosocial mechanisms of SUD ........................................................................................................ 118
3.1. The mesolimbic pathway - The reward system ....................................................................................... 118
3.2. The neurobiology of tolerance and withdrawal ...................................................................................... 119
3.3. Hebbian learning ..................................................................................................................................... 120
3.4. Homeostatis and opponent Proces Theory .............................................................................................. 121
3.5. Evaluation in cravings.............................................................................................................................. 122
3.6. The social network hypothesis ................................................................................................................. 123
4. Treatment strategies of SUDs ................................................................................................................... 123
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