Substance Abuse vs. Substance Dependence (DSM IV)

• Dependence– Three or more of the following in the same 12 month

period• Tolerance• Withdrawal• Often using more of the substance than intended• Desire or unsuccessful efforts to cut down on use• Great deal of time spent in activities related to obtaining the

substance• Important social, occupation, or recreational activities given

up because of the substance• Substance use continued despite knowledge of a persistent

problem caused by the substance

• Abuse– One or more of the following in a 12 month

period• Failure to fulfill major role obligations at work,

school, or home• Recurrent use in hazardous situations• Recurrent legal problems• Continued use despite social or interpersonal

problems caused or exacerbated by the substance

• Note that tolerance or withdrawal are not present

• Why is this distinction (abuse vs. dependence) useful?

Prevalence of Substance Use Disorders in the United States

• 9% of the adult population (appx. 20 million people) experienced some type of disorder in the past year (Grant et al., 2004a; b; c)

• 8.5% experienced alcohol abuse or dependence in the past year

• 2% experienced drug abuse or dependence– Why don’t the percentages add up?

• Approximately 12% of adolescents report a lifetime history of substance abuse or dependence (Costello et al., 2003)

• Those with SUDs are more likely than others to experience mood, anxiety, and personality disorders (Grant et al., 2004 b; c), and an association exists between substance use and some disordered eating behaviors (Dansky et al., 2000)

• SUDs cost at least 300 billion annually (e.g., sick leave, lost productivity, treatment costs) (Harwood, 1998; Rice, 1999).

Alcohol

• Metabolism of alcohol– Alcohol absorbed from stomach and

metabolized in liver by alcohol dehydrogenase (ADH)

– Women may have less ADH, which could partially explain less efficient alcohol metabolism

– Slower gastric emptying allows more ADH metabolism

• Why is this important?

– Aspirin inhibits ADH– This ADH pathway metabolizes approximately

one drink per hour – http://depts.washington.edu/mcsurvey/bal/

index.php

• Most important effect of alcohol is on the gamma-aminobutyric acid (GABA) system– GABA neurotransmitters are primarily

inhibitory and anxiolytic (anxiety-reducing)– Alcohol binds to GABA receptors in the brain,

results in sedative and anxiolytic effects– However, chronic alcohol use causes the

GABA system to not function on its own-meaning alcohol is required for it to function

• What are the clinical implications of this?

• Alcohol also inhibits the NMDA receptor (related to a number of excitatory physiological processes)

• Low doses of alcohol activate norepinephrine system and dopamine pathways-brain’s reward center (e.g., feelings of pleasure)

• Clinical features of alcohol– Intoxication

• Measured by the percentage of alcohol in the bloodstream (i.e., blood alcohol content)

– In this country it’s usually grams of alcohol/1000grams of blood (e.g., BAC of .20% = 2 grams/1000 grams)

– .08 is legal intoxication– .25 is “blackout” territory– .40 or higher may result in death

– Withdrawal• Recall that long-term use of alcohol down-

regulates inhibitory GABA receptors (alcohol takes its place) and inhibits NMDA (excitatory) receptors When alcohol is removed, decrease in inhibiting GABA and increase in NMDA

– Results in tremor, sweats, anxiety, agitation, etc. – Seizures and delirium are also possibl

» Clinical implications?

• May also induce other psychiatric disorders– Note difference between induced and co-occurring

• A host of medical problems are associated with alcohol abuse and dependence

• Most common involve the liver– Why? – Hepatic Steatosis (fatty liver) is most common, and

reversible– Alcohol hepatitis– Cirrhosis (about 10-20% of heavy drinkers)

» Liver tissue replaced by scar tissue

Opioids

• Because of their strong physiologically addicting properties, they have a well-defined syndrome of administration, tolerance, and withdrawal– Unlike some other substances, linear progression in

use is most common

• Opioids bind to specific receptors in the brain (mu, kappa, and delta)– This has clinical implications for opioid antagonists

(e.g., naltrexone) that bind to the same sites

• Most opioids have short half-lives– Clinical implications?

• Principle legitimate use of opioids is pain relief

• Opioids cause respiratory system to be less sensitive to carbon dioxide, which stimulates breathing– Impact of this?

• Opioids cross placental barrier• Opioids result in changes at the receptor

site by opioid occupation (i.e., the site does not function as it should)– Removal of the opioid causes the withdrawal

syndromes (recall the half-life issue)

• Opioid intoxication– Euphoria, anxiety relief, slow respiration,

impaired judgment

• Opioid withdrawal– Craving, sweating, tremors, irritability,

insomnia, nausea, etc.

• Opioid overdose– Decreased respiration, cardiovascular

collapse– Treated usually with opioid antagonist

• Clinically, perhaps the most challenging issues associated with opioid addiction involves dealing withdrawal– Extremely uncomfortable for the individual– Withdrawal symptoms can be alleviated by

introducing a substance that is a same-receptor agonist as the opioid, but presumably less addicting

• Clonidine suppresses many withdrawal symptoms• Methadone maintenance

– Longer half-life than most opioids, administered once a day

– Idea is to reduce drug-seeking behavior

– Usually used with long-term users

– Heavily regulated

• Long-acting antagonist like naltrexone may also be used

Marijuana

• Most common “illicit” drug in the US• Most potent active ingredient is delta-9-

tetrahydrocannabinol (THC)– Main psychoactive substance

• Peak effect occurs about 20 minutes after ingestion, although some effects immediately– Euphoria, sensory alteration, time perceptions– Activates pleasure/reward system in brain

• Effects of marijuana use– Poor reaction time– Decreased coordination– High doses can result in panic attacks, hypervigilance– Some evidence that heavy use is associated with

psychotic disorders (effect size is small, though)– Issue of “amotivational syndrome” is unclear

• What causes what-common issue in behavioral research• Probably does not cause permanent cognitive damage• Inhibits learning in the moment-could be a problem for

habitual users

• Withdrawal symptoms can occur, but not as intense as other drugs

Club Drugs

• MDMA (ecstasy)– Dramatic psychological effect of feeling close

and related to others• Explains popularity at “raves”

– Most likely neurotoxic in humans (destroys serotonin neurons)

– “Rush” occurs about 20-40 minutes after ingestion

– Can result in increased desire for sex (although performance is inhibited)

– MDMA affects many systems, but primarily works as an indirect serotonin agonist (blocks serotonin reuptake while also releasing serotonin stores)

– Subsequent doses produce diminished high and greater side effects-drug tends to be used much more sporadically

• Doesn’t have the withdrawal symptoms of other drugs-no negative reinforcement motivation

• Clinical implications?

– Ketamine• Main result is a dissociative episode

– GHB• Results in relaxation, tranquility, numbing,

disinhibition• Dose response curve is steep-OD can easily occur

Other Hallucinogens

• Effect of hallucinogen is not predictable

• Can result in accidents and suicides

• Flashbacks are a unique feature

• LSD is most common – Period of effect is usually 8-12 hours– Does not cause physical dependence

Cocaine

• Cocaine occurs in the leaves of the coca plant (Peru, Columbia)– Chewing the leaves seems to have a mild

effect

• “Powder” cocaine is cocaine hydrochloride– 30-120 minutes for peak effects

• Intravenous or smoking cocaine (crack) causes an almost instant effect

• Cocaine is a stimulant, impacts many reward areas of the brain (GABA, dopamine, serotonin)– Blocks the reuptake of dopamine, serotonin, and

norepinephrine– Results in increased energy, alertness, self-

confidence, etc.

• Chronic use results in depletion of these neurotransmitters, though (paradox of drug use)

• Cocaine has a short rush and 15-20 minutes of euphoria, but then withdrawal and craving– Withdrawal is not physiological-results primarily in

psychological cravings– Clinical implications?

• Primary medical complication involves increased workload on the heart, which leads to a number of cardiovascular problems

• Cocaine also passes the placental barrier

Methamphetamine

• Produces similar effects as cocaine, but 10 to 12 hour half life as opposed to 20-120 minutes of cocaine

• Produces typical amphetamine symptoms (euphoria, enhanced self-esteem, but leading to paranoia, anxiety, etc.)

• Effects multiple organ systems

Sedatives/Benzodiazepines

• The issue of using benzodiazepines often comes up in treatment settings– Useful for anxiety and insomnia

• Barbiturates were first generation of sedatives-easy to OD on

• Benzos have slower onset, less abuse potential, harder to OD on