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Definitions

Opiates: drugs naturally found in opium (morphine and codeine)

Opioids: exogenous substances, natural or synthetic, with properties similar to opium

NARCOTICS: another term for opioids This term was originally conceived to refer to

substances that induce “narcosis” or sleep. This term has been used more loosely in the

legal profession to refer to all illicit drugs. Technically, many of these drugs (e.g., cocaine,

marijuana) are not narcotics according to the original definition of this term.

Early History of Opium

Papaver somniferum

Early Egyptian and Greek cultures India and China

Opiate Dependence 19th Century Writers and Opium The Opium Wars

Started by outside incidents Britain given the island of Hong Kong for

winning

19th Century Discoveries Morphine isolated and named by

Sertürner, 1806 Codeine isolated in 1832 Hypodermic syringe developed in 1853 by

Alexander Wood Heroin synthesized in 1874, marketed in

1898 by Bayer Laboratories

Photo from erowid.orghttp://www.pharmainfo.net/files/u4145/Morphine.jpg

History of Opioid Use

Before the Harrison Act Oral opium use common, patent medicines ~ 1850, Chinese introduced opium

smoking to U.S. After 1850s, morphine administered by

injection 1898, heroin introduced

After the Harrison Act Number of oral opium users declined I.V. heroin injection became more common

form of use among recreational users

History of Opioid Use

20th Century Developments Changing population of opioid users 1960s Vietnam and heroin use 1970s-1980s Current heroin use Abuse of prescription opioids

Neuropharmacology of Opioids

Opioid Receptors Mu, Kappa, Delta

Endogenous Opioids (Endorphins) Enkephalins, Dynorphin, Beta-Endorphin The activation of opioid receptors blocks

the transmission of pain signals from the spinal cord and brain stem.

Opioid Antagonists Naloxone Naltrexone

Some Synthetic Opioids

methadone (Dolophine) meperidine (Demerol) oxycodone (Percodan) oxymorphone (Numorphan) hydrocodone (Vicodin, Lortab) hydromorphone (Dilaudid) propoxyphene (Darvon) pentazocine (Talwin) fentanyl (Sublimaze)

Medical Use of Opioids Clinical Uses

Analgesics (pain relief) Antidiarrheals (constipating effects) Antitussives (cough suppressants)

Side Effects Drowsiness Respiratory depression Nausea, vomiting, and constipation Inability to urinate Drop in blood pressure

Tolerance/Dependence Physicians frequently under-prescribe

narcotics, in fear of causing dependence.

Tolerance and Dependence with Opioids

Tolerance begins with initial use, but not clinically

evident until 2 to 3 weeks of frequent use.

occurs most rapidly with high doses given in short intervals.

Physical dependence invariably accompanies severe

tolerance Psychological dependence

common with frequent narcotic use

Effects on Human Behavior Subjective Effects (from anecdotal

reports) Opium was commonly used among 19th

century literary figures and artists. Effects depicted as euphoric, vivid dreamy,

trance-like state. Systematic Studies on Mood

Initial positive mood changes (anxiety reduction, euphoria), but continued use produces more negative mood states, social isolation, and aggression.

Subjective effects differ between experienced and naïve users.

Experience of pain influences subjective effects.

Effects on Human Behavior

Performance In naïve subjects, opioids can slow

performance on psychomotor tasks; cognitive performance is less impaired.

Tolerance develops to these effects in chronic users. People can maintain good health and

productive work for extended periods of opioid use.

Detrimental effects of opioids on performance are diminished when people are experiencing pain.

Behavioral Effects In Nonhuman Laboratory

Studies Unconditioned Behavior

Morphine has biphasic effects on spontaneous motor activity. Low doses increase activity; higher doses

decrease activity. In rats, higher doses also produce stereotypy,

which is distinct from the type of stereotypy produced by amphetamine. e.g., wider range of behaviors, including social

behaviors

Behavioral Effects In Nonhuman Laboratory

Studies Conditioned Behavior Low doses of opioids increase response

rates under schedules that produce low rates of responding (e.g., FI schedules) of positive reinforcement, but higher doses decrease rates.

Low doses increase avoidance responding; high doses slow avoidance responding without disrupting escape behavior (like the depressants).

Unlike depressants, opioids do NOT have antipunishment effects.

Self-Administration

Nonhuman animals readily acquire morphine and heroin self-administration.

Rates and patterns of self-administration are similar between humans and monkeys Daily intake slowly increases over time

and there are no periods of abstinence or voluntary withdrawal.

This is unlike patterns observed with cocaine self-administration, involving alternating cycles of intake and abstinence.

Drug Discrimination with Opioids

Most opioids are readily discriminated by nonhumans (rats and monkeys). Stimulus generalization is observed

between morphine and other mu agonists (e.g., heroin, methadone, codeine).

Partial generalization occurs between mu agonists and mixed agonists (e.g., cyclazocine).

Stimulus generalization generally not found between mu agonists and kappa agonists.

Health Risks

Abuse Potential Subjective and reinforcing effects

contribute to high abuse potential MU agonists (e.g., morphine, heroin,

fentanyl, hydrocodone, Oxycontin) tend to have a high abuse potential.

Mixed or partial agonists (e.g., butorphanol, nalbuphine) generally have low abuse potential.

I.V. Heroin Use and AIDS Risks Over 50% of I.V. heroin users have been

exposed to the AIDS virus

Opioid Dependence & Treatment Withdrawal Symptoms (flu-like symptoms)

runny nose, tears, minor stomach cramps, loss of appetite,

vomiting, diarrhea, abdominal cramps, chills, fever, aching bones, and muscle spasms

Narcotic Substitution Treatments Methadone, levo-alpha acetylmethadol

(LAAM), Buprenorphine Maintaining dependence

Narcotic Antagonist Treatment Naltrexone Prevents user from experiencing high if

opiates used Compliance can be problematic.