1. Illegal Drug Use in the U.S.
Marijuana
Cocaine
Crack
Amphetamines
Heroin

2. Illicit Drug Use – Drug of Choice
Psychopharmacology2e-Fig R.jpg

3. Illicit Drug Use – Age of Use
Psychopharmacology2e-Fig R.jpg

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

5. History of Drug Use Advances in chemistry Syringe development
Drug laws or lack thereof
Addiction Models
“War on Drugs”
Psychopharmacology2e-Fig jpg

6. History of Drug Use
Psychopharmacology2e-Table jpg

7. Drug Schedule Criteria
Psychopharmacology2e-Table jpg

8. The Most Lethal Drugs
(after Mathias, 1994)

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

10. Addiction Hypotheses
Self-medication hypothesis: Stressful life events could trigger anxiety and mood disorders, such as depression, which in turn could lead to substance use in an attempt at self-medication. Shared etiology hypothesis: certain factors (genetic and/or environmental) contribute to elevated risk of both addiction and other psychiatric disorders. Biopsychosocial model: of addiction includes all the pharmacological, biological, and psychological/ sociocultural factors that influence addiction risk. 10

11. Current DSM V classification
Substance Use Disorder:
A maladaptive pattern of substance use for at least 12 months that has led to significant impairment or distress.
At least 2 of 11 additional criteria must be met:
Craving for the substance
Increasing use of the substance beyond the original intent
Unsuccessful attempts to control or stop using the substance
Development of Tolerance
Development of Withdrawal symptoms
Failure to fulfill major societal obligations
Continued use despite knowledge of social, interpersonal, or health problems caused by the substance
Repeated use of the substance in hazardous situations (e.g., driving a car)
Spending excessive time obtaining the substance
Spending excessive time using the substance
Reduced time spent in other activities because of substance use 11

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

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

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

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

16. 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

17. 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

18. 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

19. 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

20. 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