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Drug use, Drug abuse and DRUG TAKING BEHAVIOR IS DRUG ABUSE A PROBLEM? eg…Marijuana? Other drugs? How large is the problem Problem: How to define • Drug addiction? Is once enough? A repetitive behavior pattern associated with increase risk of disease or social problems (Marlatt, 1988)..often characterized by immediate gratification and high relapse rates…but is this the same as “abuse?” • Drug abuse-how to define? Drug Abuse • The self-administration of any drug in a manner that deviates from the approved medical or social patterns within a given culture (Jaffe). • Drug Dependence- a condition in which an individual requires a drug to function normally. A distinction is often made between Physical dependence and Psychological dependence. Physical Dependence • An adaptive state produced by repeated use of a drug which manifests itself by intense physiological disturbances (withdrawal syndrome) when use of the drug is halted (abstinence). • Withdrawal syndrome- a constellation of symptoms that occur when an individual stops using the drug to which dependence has developed. Symptoms typically in reverse direction of the effects caused by the drug. Psychological dependence • A condition characterized by intense drive or cravings for a drug. SO AGAIN…How big is the problem? Problem: How to measure (Reactivity and return rate issues) Illicit drug use reported by state Accuracy of surveys? • • • B.3.1 Screening and Interview Response Rate Patterns In 2004, respondents continued to receive a $30 incentive in an effort to improve response rates over years prior to 2002. Of the 142,612 eligible households sampled for the 2004 NSDUH, 130,130 were successfully screened for a weighted screening response rate of 90.9 percent (Table B.2). In these screened households, a total of 81,973 sample persons were selected, and completed interviews were obtained from 67,760 of these sample persons, for a weighted interview response rate of 77.0 percent (Table B.3). A total of 9,362 (15.2 percent) sample persons were classified as refusals or parental refusals, 2,918 (3.9 percent) were not available or never at home, and 1,933 (3.9 percent) did not participate for various other reasons, such as physical or mental incompetence or language barrier (see Table B.3, which also shows the distribution of the selected sample by interview code and age group). Among demographic subgroups, the weighted interview response rate was highest among 12 to 17 year olds (88.6 percent), females (78.5 percent), blacks (81.9 percent), in nonmetropolitan areas (79.2 percent), and among persons residing in the South (78.7 percent) (Table B.4). The overall weighted response rate, defined as the product of the weighted screening response rate and weighted interview response rate, was 70.0 percent in 2004. Nonresponse bias can be expressed as the product of the nonresponse rate (1-R) and the difference between the characteristic of interest between respondents and nonrespondents in the population (Pr - Pnr). Thus, assuming the quantity (Pr - Pnr) is fixed over time, the improvement in response rates in 2002 through 2004 over prior years will result in estimates with lower nonresponse bias. And How the questions are asked: eg… VS. selected age ranges by month Drug use in the Military? In Different Ethnic groups? • So maybe marijuana use is not so overwhelming? But Alcohol is a drug And Tobacco! And….. For the Sake of Argument • Lets say there is significant drug use and/abuse in our society. • BUT AGAIN…How big is the problem? Depends on how you measure it. Overdoses? DAWN Heroin overdose Not just our problem COSTS of DRUGS in SOCIETY? And money is being lost Incarceration costs- not including lost productivity for families And Psychological “WORRY?” Psychological Impacts? Drugs and Violence So Lets War on Drugs! More money (lost?) it does cost lots of money The “WAR on Drugs” People are being incarcerated And sent up for treatment But is it working? Cocaine production is not down Prices are relatively stable Is the War aimed in the right directions? Costs of the “War on Drugs” Effectiveness of “War?” AND CONCERNS/COSTS in the home and Work place It does create its own economy Should we use drug testing at work? Maybe its necessary What if tests are too sensitive?? Watch out here they come! The wild eyed claim that a third of all people accused of drug use will be innocent is not so ridiculous after all. Figure 4 shows that the proportion of spurious results among people identified as drug users is surprisingly sensitive to test accuracy. An accuracy of 99% is marginal at best. However the biggest surprise is the fact that the proportion of spurious results among people failing drug tests approaches 100% as the proportion of drug users in the general population approaches zero. Drug testing in a drug free population amounts to a witch hunt. SO ? • Whatever your perspective on drug use and abuse, its difficult to argue that drug use is in no way problematic. • Especially when considering the harmful effects of drug addiction/Abuse to the individual and to society. What are the causes of drug Addiction? A difficult question. • • • • MORAL MODEL-character MEDICAL MODEL-disease LEARNING MODEL-reinforcement ENLIGHTENMENT MODE-multifactorial ?? • Genetics • Environment • Concordance rates in identical twins separated at birth…does not completely rule out environmental factors. • Whatever the original causes, • 2 additional factors are necessary before drug addiction will occur….. • Availability – prohibition? • Trying it.-”turning on.” • But what then leads to dependence? Commonalities in Drug addiction/abuse • • • • • • • Availability/ Taking the drug Reward Tolerance Dose-stabilization Periods of abstinence Cravings relapse Dose-stabilization Periods of abstinence • Associated with Cravings – (psychological…but obvious physical dependence is not a common denominator. And unfortunately..RELAPSE RELAPSE Principles of drug study: -Multiple effects (side-effects) -No new behaviors -Drug use is neither good nor bad Other factors contributing to drug effect • Type of drug Different drugs can produce different effects…but class systems only take us so far… • • • • • • • • • • • • • • Drugs of Abuse Acid/LSD Alcohol Club Drugs Cocaine Ecstasy/MDMA Heroin Inhalants Marijuana Methamphetamine PCP/Phencyclidine Prescription Medications Smoking/Nicotine Steroids (Anabolic) MJ • euphoria, slowed thinking and reaction time, confusion, impaired balance and coordination/cough, frequent respiratory infections; impaired memory and learning; increased heart rate, anxiety; panic attacks; tolerance, addiction For sedatives, benzodiazepines, Rohypnol • reduced anxiety; feeling of well-being; lowered inhibitions; slowed pulse and breathing; lowered blood pressure; poor concentration/fatigue; confusion; impaired coordination, memory, judgment; addiction; respiratory depression and arrest, death Also, for barbiturates—sedation, drowsiness/depression, unusual excitement, fever, irritability, poor judgment, slurred speech, dizziness, life-threatening withdrawal. for benzodiazepines—sedation, drowsiness/dizziness for flunitrazepam—visual and gastrointestinal disturbances, urinary retention, memory loss for the time under the drug's effects Ketamine, PCP and analogs • increased heart rate and blood pressure, impaired motor function/memory loss; numbness; nausea/vomiting Also, for ketamine—at high doses, delirium, depression, respiratory depression and arrest for PCP and analogs—possible decrease in blood pressure and heart rate, panic, aggression, violence/loss of appetite, depression Hallucinogenics • altered states of perception and feeling; nausea; persisting perception disorder (flashbacks) Also, for LSD and mescaline—increased body temperature, heart rate, blood pressure; loss of appetite, sleeplessness, numbness, weakness, tremors for LSD —persistent mental disorders for psilocybin—nervousness, paranoia Opiate compounds • pain relief, euphoria, drowsiness/nausea, constipation, confusion, sedation, respiratory depression and arrest, tolerance, addiction, unconsciousness, coma, death Also, for codeine—less analgesia, sedation, and respiratory depression than morphine for heroin—staggering gait For stimulants • increased heart rate, blood pressure, metabolism; feelings of exhilaration, energy, increased mental alertness/rapid or irregular heart beat; reduced appetite, weight loss, heart failure, nervousness, insomnia Also, for amphetamine—rapid breathing/ tremor, loss of coordination; irritability, anxiousness, restlessness, delirium, panic, paranoia, impulsive behavior, aggressiveness, tolerance, addiction, psychosis for cocaine—increased temperature/chest pain, respiratory failure, nausea, abdominal pain, strokes, seizures, headaches, malnutrition, panic attacks for MDMA—mild hallucinogenic effects, increased tactile sensitivity, empathic feelings/impaired memory and learning, hyperthermia, cardiac toxicity, renal failure, liver toxicity for methamphetamine—aggression, violence, psychotic behavior/memory loss, cardiac and neurological damage; impaired memory and learning, tolerance, addiction for nicotine—additional effects attributable to tobacco exposure, adverse pregnancy outcomes, chronic lung disease, cardiovascular disease, stroke, cancer, tolerance, addiction Other factors contributing to drug effect Dose and time -All drug effects are dose and time dependent Other contributing factors to drug dependence/abuse • Type of drug… • Route of administration Consider heroin vs. an oral opiate drug Structure of heroin…diacetylmorphine Other contributing factors • Set and setting Effects also determined by brain specific circuits affected…receptor binding Factors influencing drug effects:Systems that the drug affects.. opioid receptors in the brain And receptor subtypes affected Agonism and antagonism Agonism and antagonism • Agonist drugs- promote what ever the natural effect of the NT receptor interaction would normally be • Antagonist drugs- block or inhibit what ever the natural effect of the NT receptor interaction would normally be • Consider agonism and antagonism at the GABA synapse vs the Glut synapse Direct vs Indirect actions How drugs can affect the nervous system Eg…Drugs can affect synthesis …L-DOPA …Reuptake Indirect agonism ACHE inhibitors Direct receptor antagonism Competitive vs non-competitive drug actions Noncompetitive binding Drug addiction and the brain? REWARD SYSTEMS OF THE BRAIN? Animal Models of drug reward and dependence • James Olds and Intra-cranial Selfadministration… • • • • Place preference 2 lever choice Progressive ratio Conflict tests ICSS and brain reward centers? • • • • LH Medial forebrain bundle (MFB) VTA-Accumbens DA agonist and antagonist effects From ICSS to DSA Drugs that are self-administered by laboratory animals alcohol amphetamine barbiturates caffeine cocaine nicotine opiates e.g. morphine procaine phencyclidine (PCP) THC (active component in marijuana) Drugs that are not self-administered by laboratory animals imipramine mescaline phenothiazines scopolamine Brain ccts of drug reward: Intra-cranial drug infusion Microdialysis techniques ICCS increases DA release in Nucleus Accumbens Drugs increase DA release in accumbens What about ICSS in Humans What about reward Circuits in the Human? Human ICSS • Heath 1962 • The pleasure seekers • Hedonism makes our world go round, but it goes a lot deeper than our obsession with sex, drugs, rock 'n' roll and chocolate. Neuroscientists are completely rethinking how our brains give us pleasure, and as a result are starting to believe that the quest for pleasure may underpin every decision we make. It may even have laid the foundations of consciousness, as Helen Phillips explains. • IT WAS an outlandish, ethically questionable experiment, but this was the 1960s after all. Psychiatrist Robert Heath of Tulane University in New Orleans hoped to cure his patients' depression, intractable pain, schizophrenia, suicidal feelings, addiction, and even homosexuality - which in those days was considered a psychiatric disorder - by drowning them out with pleasure, induced by an electrode implanted deep in their brains. • In our own experience, pleasurable sensations were observed in three patients with psychomotor epilepsy. The first case was V.P., a 36-year-old female with a long history of epileptic attacks which could not be controlled by medication. Electrodes were implanted in her right temporal lobe and upon stimulation of a contact located in the superior part about thirty millimeters below the surface, the patient reported a pleasant tingling sensation in the left side of her body "from my face down to the bottom of my legs." She started giggling and making funny comments, stating that she enjoyed the sensation "very much." Repetition of these stimulations made the patient more communicative and flirtatious, and she ended by openly expressing her desire to marry the therapist. Stimulation of other cerebral points failed to modify her mood and indicated the specificity of the evoked effect. During control interviews before and after ESB, her behavior was quite proper, without familiarity or excessive friendliness. • The second patient was J.M., an attractive, cooperative, and intelligent 30-year-old female who had suffered for eleven years from psychomotor and grand mal attacks which resisted medical therapy. Electrodes were implanted in her right temporal lobe, and stimulation of one of the points in the amygdala induced a pleasant sensation of relaxation and considerably increased her verbal output, which took on a more intimate character. This patient openly expressed her fondness for the therapist (who was new to her), kissed his hands, and talked about her immense gratitude for what was being done for her. A similar increase in verbal and emotional expression was repeated when the same point was stimulated on a different day, but it did not appear when other areas of the brain were explored. During the control situations the patient was rather reserved and poised. • In another controversial experiment in 1972, Dr. Heath wired up a homosexual man's pleasure centers in order to help him "cure" his homosexuality. During the initial three-hour session, subject "B-19" stimulated himself some 1,500 times. Dr. Heath wrote of the experiment, "During these sessions, B-19 stimulated himself to a point that he was experiencing an almost overwhelming euphoria and elation, and had to be disconnected, despite his vigorous protests." Since unnatural methods can bring about unnatural results, energizing the man's electrodes as he looked at erotic pictures of women temporarily "cured" him of his homosexuality, but once the electrodes were removed, he went back to normal. • It is interesting to note that while the animal literature suggests that brain stimulation has positive, reinforcing effects, the human literature indicates that relief of anxiety, depression and other unpleasant affective conditions may be the most common "reward" of electrical brain stimulation in humans. Patients with electrodes in the septum, thalamus, and periventricular gray of the midbrain often express euphoria because the stimulation seems to reduce existing negative affective reactions (even intractable pain appears to loose its affective impact). However, many psychiatrists caution that this may not reflect an activation of a basic reward mechanism (Delgado, 1976; Heath et al., 1968). Relief from chronic anxiety has been reported during and even long after stimulation of frontal cortex. Again, the experiential response appears to be relief rather than reward per se (Crow&Cooper, 1972). • Compulsive thalamic self-stimulation: a case with metabolic, electrophysiologic and behavioral correlates by Portenoy RK, Jarden JO, Sidtis JJ, Lipton RB, Foley KM, Rottenberg DA. Pain. 1986 Dec;27(3):277-90 ABSTRACT • A 48-year-old woman with a stimulating electrode implanted in the right thalamic nucleus ventralis posterolateralis developed compulsive selfstimulation associated with erotic sensations and changes in autonomic and neurologic function.