1. General Principles of Drug Use
Use is not abuse
Most users do not abuse or form dependence (Who? When? Where? Why?)
Every drug has multiple effects
Although a user might seek only one effect, drugs work at multiple sites in the brain and other organs
Amount matters
Larger doses, more frequent doses, or faster onset of effects can produce different effects compared to small doses
User’s history and expectations affect drug-related effects
Experience and Expectation matters
Drugs are not good or bad
Drugs are chemicals on a shelf that are inactive until they enter the body
Blaming the substance ignores all the factors that may lead to abuse

2. Drug Related Terms Drug
Any substance, natural or artificial, other than food, that by its chemical nature alters structure or function in a living organism
Illicit drug
A drug that is unlawful to possess or use
Deviant drug use
Drug use that is not common within a social group and disapproved
Drug misuse
Drug use in greater amounts than, or for purposes other than, those prescribed
Drug abuse
Substance use in a manner, an amount, or in situations such that it causes social, occupational, psychological, or physical problems
Drug dependence
A state in which an individual uses a drug so frequently or consistently that it would be difficult for the person to stop

3. History of Drug Use Advances in chemistry Syringe development
Drug laws or lack thereof
Addiction Models
“War on Drugs”

4. History of Drug Use

5. Drug Schedule Criteria

6. Correlates of Drug Use Gender Race and ethnicity Level of education
Men use more drugs than women
Race and ethnicity
Caucasians are more likely to drink alcohol than African Americans
Level of education
College graduates are less likely to smoke tobacco than high school graduates
Personality variables
“Impulsive” individuals may use drugs at a higher rate
Genetics
Genetics may play a role in who will develop a substance use disorder
Antecedents
A factor that occurs before an event such as the initiation of drug use
Aggressiveness
Conduct problems
Poor academic performance
Attachment to a drug-using peer group
Parental and community norms that support drug use
Sensation seeking behavior
Motives
Identification with a deviant subculture
Rebelliousness
Fads and cultural trends
Reinforcing properties of drugs
Desire to experience an altered state

7. Drug Related Social Problems
Problems related to taking the drug
Toxicity (poisonous, dangerous, deadly)
Acute/Chronic
Overdose
High BP/Heart Disease/Cancer/Cirrhosis
Physiological/Behavioral
Lifestyle changes
Relationship issues
Driving factors
Secondary Effects
HIV/Hepatitis other infections
Dependence/Addiction
Problems related to drug use as deviant behavior
arrests, fines, jailing
expenses associated with drug prevention and treatment
work related problems
relationship related problems
family related problems

8. Monitoring the Future
Source: Monitoring the Future Study, The University of Michigan.

9. NSDUH
Source: National Survey on Drug Use and Health.

10. NSDUH
Source: National Survey on Drug Use and Health.

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

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

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

14. 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 14

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

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

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

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

19. 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

20. 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

21. Dependence Tolerance Physical dependence Psychological dependence
Three basic processes that may occur with repeated drug use
Tolerance
Tolerance typically precedes physical dependence
Physical dependence
the occurrence of a withdrawal syndrome
If drug use is stopped suddenly, withdrawal symptoms occur, ranging from mild to severe
Physical dependence means the body has adapted to the presence of the drug
Psychological dependence
High frequency of drug use
Craving for the drug
Tendency to relapse after stopping use
Drug-taking is reinforced by consequences (the drug effects)

22. Tolerance and Withdrawal Symptoms
Drug disposition (pharmacokinetic) tolerance
Increased metabolism or excretion reduces the effect of the subsequent dose
May relate to enzyme activity or alteration of urine pH
Behavioral tolerance
Drug may have the same biochemical effect
Reduced behavioral effect as drug user learns to compensate
Pharmacodynamic tolerance
Sensitivity of neurons may change after repeated drug use
May cause withdrawal symptoms

23. 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

24. 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

25. 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