1. http://www.pharmainfo.net/files/u4145/Morphine.jpg http://www.aurorawdc.com/ci/oxycontin.jpg

2. 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.

3. Early History of Opium  Papaver somniferum  Early Egyptian and Greek cultures  India and China  Opiate Dependence  19 th Century Writers and Opium  The Opium Wars  Started by outside incidents  Britain given the island of Hong Kong for winning

4. 19 th Century Discoveries  Morphine isolated and named by Sert ü rner, 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.org http://www.pharmainfo.net/files/u4145/Morphine.jpg

5. 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

6. History of Opioid Use  20 th Century Developments  Changing population of opioid users  1960s  Vietnam and heroin use  1970s-1980s  Current heroin use  Abuse of prescription opioids

7. 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

8. Some Synthetic Opioids  methadone (Dolophine)  meperidine (Demerol)  oxycodone (Percodan)  oxymorphone (Numorphan)  hydrocodone (Vicodin, Lortab)  hydromorphone (Dilaudid)  propoxyphene (Darvon)  pentazocine (Talwin)  fentanyl (Sublimaze)

9. 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.

10. 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

11. Effects on Human Behavior  Subjective Effects (from anecdotal reports)  Opium was commonly used among 19 th 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.

12. 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.

13. 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

14. 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.

15. 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.

16. 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.

17. 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

18. 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.