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Drug abuse can seem counterintuitive, but from a biological standpoint, it makes sense. The brain's neural pathways control behaviors, with the mesolimbic pathway reinforcing behaviors, including drug use. Dopamine plays a crucial role in drug reinforcement, leading to a cycle of down-regulation and increased drug tolerance. Combining drugs or increasing doses can have risky consequences. Alcohol, a potent drug, affects GABA activity, leading to relaxation but can result in addiction and withdrawal. Stimulants like cocaine and amphetamines directly enhance dopamine activity, leading to intense cravings and potential depression. By exploring the biological concepts behind drug abuse, we gain insight into why people engage in harmful behaviors.
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A contemporary perspective on drug abuse Terry Bazzett Department of Psychology SUNY Geneseo
Why do people abuse drugs? • Drug abuse seems counterintuitive. • Health problems • Social problems • Relationship problems • Financial problems • From a biological perspective it is intuitive. • Our brains reinforce useful behaviors • The brain does not distinguish between useful behaviors and drug use.
Neural pathways control behaviors • The nigrostriatal pathway controls movement
Neural pathways control behaviors • The mesolimbic pathway reinforces behavior
Neural pathways reinforce behaviors • The mesolimbic pathway is “designed” to • Reinforce useful behaviors • Reinforce naturally occurring behaviors • This is a perfectly good design • Useful behaviors can be bypassed • Using electrical stimulation • Using drugs • This is abuse of a perfectly good design
Dopamine… a common denominator • The mesolimbic pathway uses dopamine (DA) • Drugs of abuse typically stimulate DA pathways • In general, reinforcement is correlated with DA activity • Drugs that inhibit DA are not pleasurable
Secondary effects • While DA reinforcement is the primary driving force for drug use, other effects contribute. • Depressants for those who are anxious • Stimulants for those who want greater arousal • Hallucinogens for those who want altered experiences • Opiates for those who want sedation • Etc.
Why not enjoy drugs? • If drugs stimulate a natural system, what’s the harm in enjoying them? • For occasional recreational use, probably nothing. • When use becomes heavy or persistent, problems may arise. • Drugs are generally more potent than natural reinforcers • Drugs are “easier” than natural reinforcers • The reinforcement pathway may down-regulate.
What is down-regulation • Biological systems strive for homeostasis • When systems are highly active, the body responds by decreasing activity. • Down-regulation is part of the biological basis for drug tolerance (habituation)
What is down-regulation • Decrease in transmitter release (rapid) • Decrease in receptor sensitivity (slower) • Decrease in receptor sites (slower)
The down side of down-regulation • Once down regulation occurs, a vicious cycle begins. • More drug is required to feel intoxication • More drug use results in greater down-regulation • A down-regulated reinforcement circuit means • Increases in drug are needed • Pleasure in natural reinforcers is decreased
Compensating for down-regulation • When a system becomes less responsive: • You can increase your drug dose • Combine drugs to potentiate effects • Combine drug with arousing behavior (e.g. sex) • Each of these has its own risks
Increasing drug dose • Primary risk of overdose • Secondary economical problems • Secondary side-effect problems
Combining drugs • Sometimes used to potentiate DA while also compensating for secondary effects • Speedball as example of a deadly combination • Many other combinations may be used
Combining drugs and sex • Combining a DA releasing behavior with a DA stimulating drug potentiates effects • Many drugs impair cognitive function, leading to risky sex behavior
Alcohol • The misnomer of “drugs and alcohol”. • Alcohol is a drug • Highly addictive • Extremely potent • Deadly… overdose, accidents, combined with other drugs • Deadly… withdrawal
Alcohol – Biology • Indirectly enhances DA systems • Alcohol enhances GABA activity • Increased GABA activity = relaxation • Most anti-anxiety drugs also increase GABA • Many people self-medicate with alcohol • GABA down-regulation • Results in anxiety in the absence of alcohol • In extreme cases withdraw = seizures/death
Alcohol – the great social stimulant • The cortex actively inhibits impulsive behavior • GABA activation inhibits this inhibition • Alcohol reduces ability to control impulsive behavior • Impulsive behaviors • Driving while drunk • Unprotected sex • Consuming additional drugs (including alcohol)
Alcohol – treating addiction • Down regulated GABA treated with benzodiazapines (anti-anxiety meds). • Down regulated DA system may require antidepressant drugs • Cold turkey is ill-advised
Stimulants • Includes cocaine, amphetamine, Ritalin, etc • Highly addictive • Highly reinforcing • Intense cravings • Relatively mild physical withdrawal
Stimulants – Biology • Directly enhance DA activity • Also increase norepinephrine (NE) = excitation • Increased NE = awake and alert • Some people self-medicate with stimulants • Most people use stimulants to enhance the party • DA and NE down-regulation • Results in depression/lethargy when drug not used • These symptoms increase craving/desire for drug
Stimulants – treating addiction • Down regulated DA system may require antidepressant drugs • Lethargy has to be waited out • Cold turkey is difficult because of cravings, but not typically dangerous
Opiates • Includes morphine, codeine, heroin, oxycodone, suboxone (buprenorphine), etc. etc. etc. • Highly addictive • Highly reinforcing • High cravings • Moderate physical withdrawal
Opiates: Not just a “street drug” "If (Surgeon General Jocelyn Elders) wants to legalize drugs, send the people who want to do drugs to London and Zurich, and let's be rid of them. -- Rush Limbaugh show, Dec 9, 1993 “I am addicted to prescription pain medication.” -- Rush Limbaugh show, Oct 10, 2003
Opiates – Biology • Indirectly enhances DA systems • Directly enhance endogenous opiate systems • Sedation • Extreme analgesia • Some claim reduction of “emotional pain” • DA and opiate down-regulation • Results in depression/pain when drug not used • These symptoms increase craving/desire for drug
Opiates– treating addiction • Down regulated DA system may require antidepressant drugs • Opiate withdrawal can be tempered with methadone • Methadone is another opiate system stimulant • Methadone treatment creates it’s own problems • Cold turkey is difficult because of cravings, but not typically dangerous
Marijuana • Smoked or ingested orally • Not particularly addictive • Not particularly reinforcing • Relatively mild cravings • Mild physical withdrawal
Marijuana – Biology • Indirectly enhances DA activity • Directly stimulates cannabinoid receptors • Anandamide is our “endogenous marijuana” • Functions are unknown… guesses? • DA and Cannabinoid down-regulation • Mild depression/anxiety when drug not used • These symptoms increase desire for drug
Marijuana – treating addiction • Down regulated DA system may require antidepressant drugs • Anti-anxiety drugs may be prescribed • Cold turkey is typical for this drug
When good mice go bad. • Visit the mouse party for fun information
MDMA – Ecstasy • 3,4-methylenedioxy-N-methylamphetamine • Increases serotonin, DA, and NE release • Considered a stimulant • But… many variations exist • Lack of control in manufacturing • amphetamine, methamphetamine, ephedrine, caffeine, are all cheaper substitutes
MDMA – Biology • Comparatively little known about dependence • Withdrawal often accompanied by dysphoria • Studies indicate neurotoxic effects • Serotonin and DA neurons degenerate in animals • Too soon to know about long-term human effects • Some concern about early life sub-threshold loss
MEPH/MDPV – Bath Salts • Key ingredients • MEPH (Mephedrone) • MDPV (methylenedioxypyrovalerone) • But… as with MDMA • Cheaper variations may exist • All components likely to have stimulant effects
MEPH/MDPV – Biology • MEPH • Enhances release of DA • May enhance release of other transmitters • MDPV • Blocks re-uptake (deactivation) of transmitter after it has been released • This is an effect similar to cocaine • Agitation, anxiety, overdose can cause death
Salvia Divinorum • Currently not illegal • Little research exists on effects • Addictive potential seems low • Little or no effect on brain DA (?) • Concerns over use still exist Salvia smoking video
Salvia Divinorum - Biology • Binds to opioid receptor sites • Response similar to serotonin hallucinogens
Spice/K2 – synthetic cannabis • Currently not illegal • Herbs mixed with synthetic cannabinoids • Synthetic cannabinoids have unknown effects • Concerns over use • Can trigger psychosis in predisposed individuals • Predisposed individuals are most inclined to use • Myocardial Infarction has been reported in several young healthy users
Spice/K2 - Biology • Binds to cannabinoid receptor sites • Very little is known beyond this…