1. The Science of Drug Action
Pharmacology:
study of the actions of drugs and their effects on living organisms.
Neuropharmacology:
study of drug-induced changes in nervous system cell functioning.
Psychopharmacology:
emphasizes drug-induced changes in mood, thinking, and behavior.
Neuropsychopharmacology:
identifies chemical substances that act on the nervous system to alter behavior.
Bioavailability:
amount of drug in the blood that is free to bind at target sites.
Pharmacokinetic Effect:
component of drug action: the dynamic factors that contribute to bioavailability.
Placebo Effect:
Where belief in a drug may produce real physiological effects despite the lack of chemical activity. 1

2. Pharmacokinetic Factors
Drug Administration
Absorption and Distribution
Binding
Inactivation
Excretion

3. Drugs can acts as Agonists:
Drug Actions
Drugs can acts as Agonists:
Endogenous Exogenous
Drugs can acts as Antagonists:
Competitive Noncompetitive

4. Presynaptic Drug Actions
8. Blockade of NT
degradation
MAO inhibitors
Prozac
Chemical Weapons

5. Postsynaptic Drug Actions

6. Illegal Drug Use in the U.S.

7. Marijuana #1 most widely used illegal drug in US from cannabis sativa
mild hallucinogen
brain has cannabinoid receptors (CB1)
cerebral cortex
hippocampus
basal ganglia
cerebellum
endogenous NTs are:
Anandamide
2-arachidonylglycerol (2-AG)
oleamide
THC is active ingredient
causes
memory loss
impaired tracking ability
lung damage
anxiety or paranoia
Amotivational syndrome
Gateway drug?

8. Drug Schedules US DEA (1989) I: Marijuana II: PCP, Morphine
III: Steroids, Speed
IV: Valium

9. Medicinal Marijuana Multiple Sclerosis Treatment: Cancer Treatment:
Pain
Shaking
Spasms
Spasticity
Fatigue
Sleep Quality
Mobility
Well Being
Cancer Treatment:
MMP-2: enzyme that promotes spread of cancer

10. Trends in ER Drug Mentions
Cocaine
Heroin/Morphine
Marijuana
Meth/Speed

11. Cocaine #2 most popular illegal drug in US
from coca leave in South America
CNS stimulant
is addictive
blocks reuptake of DA, NE, and 5-HT
creates
stereotypic behaviors
nail biting/teeth grinding
pacing
an irregular heartbeat
arterial spasms
seizures
cardiac failure
has a synergistic effect with alcohol

12. Opiates Opium, Heroin, and Morphine CNS depressant is very addictive
human brain has opiate receptors
limbic system
hypothalamus
locus coeruleus
periaqueductal gray
endogenous NT are
endorphins
enkephalins
dynorphins
causes
analgesia/pain suppression
down-regulation of receptors
can lead to death by overdose

13. Opioid Epidemic

14. Hallucinogens LSD, Mushrooms acts as a 5-HT2 agonist causes
vivid images in the absence of input
geometric forms
meaningful images
separation from the body
similar effect as in
oxygen loss
sensory deprivation
can lead to “Bad Trips”
paranoia
depression
confusion

15. Ecstasy (MDMA) MDMA : 3-4 methylenedioxymethamphetamine is related to
Mescaline
MDA
methamphetamine.
it prompts nerve cells to release a flood of serotonin.
bring about the increased awareness of
emotion
intimacy
self-confidence
The ensuing chemical low tide could explain the depression users describe when they are coming down.
damages serotonin cells
damages dopamine cells

16. Ecstasy (MDMA)
Earlier animal studies had shown that repeated ecstasy use damages the serotonin brain cells, which help to regulate mood and behavior.
This image shows that serotonin axons are destroyed in a squirrel monkey after a single dose of MDMA.

17. Ecstasy (MDMA) Control Users
BRAIN CHANGES appear prominently in positron emission tomography (PET) scans of Ecstasy users as well as people who abstain. Drug users (right), though, have far less serotonin activity, as is indicated by the dark areas, compared to the controls (left). New studies show that this difference may contribute to permanent brain damage.
Serotonin Activity

18. (yellow is more; green is less)
Ecstasy (MDMA)
In the new work, Johns Hopkins University researchers working with squirrel monkeys and baboons found that two or three sequential doses of the drug—the amount typically taken by young adults at all-night "raves"—killed dopamine neurons, which are involved in controlling movement, emotional and cognitive responses and the ability to feel pleasure. Indeed, some 60 to 80 percent of the dopaminergic nerve endings in a region of the brain known as the striatum were destroyed after just one multi-dose regimen.
Control
MDMA
Dopamine Neurons
(yellow is more; green is less)

19. MDMA Induced Cortical Brain Damage
Induced Cortical Thinning
(Kish et al 2010):
Parietal Cortex
Occipital Cortex
Temporal Cortex
Frontal Cortex
Cingulate Cortex
MDMA Induced Cortical Brain Damage
Induced Grey Matter Reduction (Daumann et al 2011):
Cingulate Cortex
Serotonin Transporter Deficiency
(Kish et al 2010):
Visual Cortex

20. Alcohol CNS Depressant is a great inhibitor causes
slowing of brain activity that controls reason
slowing of reaction time
depression of respiration
increase in aggressiveness
increase in risk of digestive tract cancers
increase in heart disease
decrease in sex drive
memory loss
depression
cirrhosis of the liver
fetal alcohol syndrome
brain cell death

21. Models of Addiction Moral Model Disease Model
Physical Dependence Model
Reward Model

22. Intra-Cranial Self-Stimulation
ICSS:
Electrodes are
placed in the
Medial Forebrain
Bundle (MFB)

23. Microdialysis Data Dopamine levels in Nucleus Accumbens
following self-administration of cocaine
in rats

24. Reward Pathway Ventral Tegmental Area (VTA) to
Nucleus Accumbens via the
Medial Forebrain Bundle and then to
the Prefrontal Cortex

25. Drug Rush PET scans of Human Cocaine Addicts:
Brain area activation during the Drug Rush:
Nucleus
Accumbens
Amygdala
Sublenticular
Extended
Amygdala
VTA

26. Drug Craving PET scans of Human Cocaine Addicts: Nucleus Accumbens
and the
Amygdala
Brain area activation during Drug Craving:
Craving becomes stronger as the drug wears off

27. Drug Addiction
Initially the CREB protein dominates leading to Tolerance and the feeling of discomfort with the absence of the drug
But the CREB protein falls after a few days if drug use discontinues
But Delta fosB stays elevated for weeks after the discontinued use of the drug leading to Drug Sensitivity

28. Drug Tolerance
During drug use VTA cells are stimulated and release Dopamine triggering the reward circuit
Dopamine binds the receptors of the Nucleus Accumbens and increases cAMP and Ca2+
ion concentrations
cAMP and Ca2+ activate the CREB protein
CREB activates the Dynorphin gene to make the Dynorphin protein
The Dynorphin protein is released back on the VTA where it inhibits Dopamine release depressing the reward circuit and causing the user to need more drug for the same high

29. Neurobiology of Drug Addiction
Drug Sensitivity
Neurobiology of Drug Addiction
During drug use VTA cells are stimulated and release Dopamine triggering the reward circuit
Dopamine stimulates the formation of Delta fosB
Delta fosB inactivates the Dynorphin gene and activates the CDK5 gene
The CDK5 protein stimulates dendritic spine growth in the Nucleus Accumbens
Nucleus
Accumbens
neuron
Increasing Drug Sensitivity/Addiction

30. Drug Sensitivity/Addiction
Nucleus Accumbens neurons in non-human animals:
Non-Addictive Drugs
Cocaine
Greater density of Dendritic Spines
Contributes to Drug Sensitivity (increased risk of drug relapse)
Delta fosB may be the contributing factor of increased spine growth