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

Illicit Drug Use – Drug of Choice Psychopharmacology2e-Fig-09-01-1R.jpg

Illicit Drug Use – Age of Use Psychopharmacology2e-Fig-09-01-2R.jpg

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

History of Drug Use Advances in chemistry Syringe development Drug laws or lack thereof Addiction Models “War on Drugs” Psychopharmacology2e-Fig-09-03-0.jpg

History of Drug Use Psychopharmacology2e-Table-09-01-0.jpg

Drug Schedule Criteria Psychopharmacology2e-Table-09-02-0.jpg

The Most Lethal Drugs (after Mathias, 1994)

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

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

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

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

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

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

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

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

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

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

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

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