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 19 th Century Writers and Opium The Opium Wars Started by outside incidents Britain given the island of Hong Kong for winning
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
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 20 th 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 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.
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.