Psychoactive Drugs

1. Psychoactive Drugs

2. Hip and cool?

3. Faces of Meth • Before After (3 years later)

4. Faces of Meth • Before After (17 months later)

5. Faces of Meth • Before After (3 months later)

6. DSM Abuse/Dependence Categories • 5.1 Alcohol-Related Disorders • 5.2 Amphetamine (Or Amphetamine-Like) Related Disorders • 5.3 Caffeine-Related Disorders • 5.4 Cannabis-Related Disorders • 5.5 Cocaine-Related Disorders • 5.6 Hallucinogen-Related Disorders • 5.7 Inhalant-Related Disorders • 5.8 Nicotine-Related Disorders • 5.9 Opioid-Related Disorders • 5.10 Phencyclidine (Or Phencyclidine-Like)-Related Disorders • 5.11 Sedative-, Hypnotic-, or Anxiolytic-Related Disorders • 5.12 Polysubstance-Related Disorder • 5.13 Other (or Unknown) Substance-Related Disorder

7. Substance-related disorder • Substance-related disorder • Abuse of, or dependence on, a mood- or behavior-altering drug • Substance: Anything that is ingested in order to produce a high, alter one's senses, or otherwise affect functioning • Characterized by • Excessive use of habit forming substances • The use of a substance for a reason other than which it was intended or in a manner or in quantities other than directed • Two general groups: • Substance abuse • Use interferes with social or occupational functioning • Abuse may progress to dependence • Substance dependence • Compulsive abuse behavior • Shows tolerance and withdrawal

8. DSM-IV definition: Substance abuse • A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by one or more of the following in a 12-month period: • failure to fulfill major role obligations at work, school, home • e.g., repeated absences or poor work performance related to substance use; substance-related absences, suspensions, or expulsions from school; neglect of children or household • use in situations in which it is physically hazardous • e.g., driving an automobile or operating a machine • substance-related legalproblems • e.g., arrests for substance-related disorderly conduct • persistent or recurrent social or interpersonalproblems caused or exacerbated by the effects of the substance • e.g., arguments with spouse or children, physical fights

9. DSM-IV definition: Substance dependence (continued) • Tolerance: a need for markedly increased amounts of the substance to achieve intoxication or desired effect • Withdrawal: Physiological and psychological symptoms associated with reduction in heavy substance use> Usually exhibits 2 or more of the following symptoms: • Sweating or rapid pulse Nausea or vomiting • Increased hand tremor Physical agitation • Insomnia Anxiety • Transient visual, tactile, or auditory hallucinations or illusions • Grand mal seizures

10. DSM-IV definition: Substance dependence • The substance is often taken in larger amounts or over a longer period than was intended • There is a persistent desire or unsuccessful efforts to cut down or control substance use • A great deal of time is spent in activities to obtain, use, or recover from effects of the substance • Important social, occupational or recreational activities are given up or reduced • Continued use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance • e.g., illness, marital conflict, job problems

11. How Alcohol Works: Getting in • About 20 percent of alcohol is absorbed in your stomach • The remaining 80 percent is absorbed in your small intestine • How quickly depends on • the percent of the alcohol in the drink • vodka is absorbed faster than beer because vodka has a higher alcohol percentage • how much you've just eaten • a full stomach will slow down alcohol absorption

12. How Alcohol Works: Getting out • Where it goes: Kidneys, Lungs, Liver, Brain • Kidneys and lungs remove about 10% of the alcohol • which is why a breathalyzer test can be used to measure a person's blood alcohol level) • Liver breaks down 90% of the alcohol into acetic acid • Blood alcohol concentration (BAC) • The proportion of alcohol in your blood • Goes up when the body is taking in alcohol faster than it can release it • One ounce of alcohol will increase the average person's BAC roughly 0.03% • BAC and the number of drinks consumed are not always accurate indicators of the level of impairment • There is much variation according to genetics, body weight, gender, and body fat percentage • Tolerance to alcohol varies from one person to another because of the above factors and from adaptation to chronic alcohol use

13. How Alcohol Works: In your brain • Alcohol alters amounts of neurotransmitters • Causes sluggish movements and slurred speech by • Increasing the effects of the inhibitory neurotransmitter GABA • Inhibiting the excitatory neurotransmitter glutamate • Creates a feeling of pleasure by • Increasing the amount of the dopamine in the brain's reward center

14. How Alcohol Works: In your brain • Alcohol affects multiple areas of the brain • In the Cortex it affects our thought processes • depresses behavioral inhibitions, causing less inhibition • slows down the processing of information from the senses • interferes with thought processes, making it difficult to think clearly • In the Cerebellum it affects our kinesthetic senses • interferes with the integration of information from movement and balance sensory organs, resulting in staggering • In the Hypothalamus and pituitary it influences our emotional state • Depresses nerve centers that control sexual arousal and performance • Sexual urges may increase, but sexual performance will decreases • In the Medulla it affects our vital life functions • Induces sleepiness, slows breathing, and lowers body temperature

15. Stages of Alcohol Intoxication • Euphoria (BAC = 0.03 to 0.12 percent) • Become more self-confident, attention span shortens, flushed, judgment reduced, trouble with fine movements • Excitement (BAC = 0.09 to 0.25 percent) • Become sleepy, have trouble understanding or remembering things, uncoordinated balance and body movements • Confusion (BAC = 0.18 to 0.30 percent) • Become confused and emotional, dizzy and may stagger, slurred speech • Stupor (BAC = 0.25 to 0.4 percent) • Can barely move, stand or walk, may vomit, may lapse in and out of consciousness • Coma (BAC = 0.35 to 0.50 percent) • They are unconscious, lower-than-normal body temperature, breathing is slower and more shallow, heart rate may slow • Death (BAC more than 0.50 percent) • The person usually stops breathing and dies

16. Substance-related disorders • People with substance-related disorders also commonly suffer from other psychological disorders, a condition known as comorbidity • Substance abusers also likely to have: • disruptive disorders (conduct or oppositional defiant disorder, impulse-control disorders) • mood disorders (e.g., depression, dysthymia) • anxiety disorders (e.g., PTSD; social phobia)

17. Prevention • Substance abuse and dependence tend to develop rapidly following first use • suggesting that a slim window of opportunity exists to prevent substance disorders once drug use has begun • Conclusions of a study by • Reebye, P, Moretti, MM, and Lessard, JC (1995) Conduct disorder and substance use disorder: comorbidity in a clinical sample of preadolescents and adolescents. Canadian Journal of Psychiatry, 40(6): 313-9.

18. Neural Basis of Drug Cravings • Mesolimbic Dopamine Pathway • = System of neurons connecting • Ventral Tegmental Area (VTA) • Activated by activities that produce pleasure • Also involved in security motivation, avoidance, and fear-conditioning, Seeking food and companionship and avoiding physical and psychologicaldiscomfort and intoxication • Nucleus accumbens (Nac) • Key structure of the brain responsible for reward, motivation, and addiction • Prefrontal cortex • Regulates overallmotivational salience and determines the intensity of behavioralresponding

19. Mesolimbic Pathway and Addictive Behavior • Almost every drug abused by humans has been shown to increase dopamine levels in the Mesolimbic Pathway • Mesolimbic Pathway and Psychotic Behavior • Abnormally high dopamine levels in the mesolimbic pathway are strongly linked to psychosis and schizophrenia • Responsible for psychotic affects of addictive drugs • Mesolimbic Pathway and Creative Drive • Moderate levels of dopamine in the mesolimbic pathway increases general arousal and goal directed behaviors and decreases latent inhibition; all three effects increase the creative drive of idea generation • Flaherty, A.W, (2005). "Frontotemporal and dopaminergic control of idea generation and creative drive". Journal of Comparative Neurology 493 (1): 147-153.

20. Neural Basis of Drug Cravings • Sustained dopamine release • promotes drug-seeking behavior • causes pathophysiological synapse changes along the Mesolimbic Pathway, the prefrontal cortex, and nucleus accumbens (brain damage) • Hyperresponsive to stimuli predicting drug availability • Reduced capacity to regulate neurotransmission • Sources: • Phillips, et al. (2003). Nature, 422, 614-818. • The Neural Basis of Addiction: A Pathology of Motivation and Choice. Peter W. Kalivas, Ph.D. and Nora D. Volkow, M.D. Am J Psychiatry 162:1403-1413, August 2005.

21. Can Drugs Cause Brain Damage? • Drugs that have been associated with brain damage or cognitive impairments: • Amphetamines • MDMA (“ecstasy”): Serotonin neurons • Methamphetamine: Dopamine neurons • Cocaine: • Blocks cerebral blood flow • Phencyclidine (PCP or “angel dust”): • Blocks NMDA receptors • Drugs that have NOT been associated with long-lasting brain damage • LSD • Marijuana • Opiates

22. Psychoactive Drug • A chemical substance that acts primarily upon the CNS where it alters brain function, resulting in temporary changes in perception, mood, consciousness, and behavior • Most psychoactive drugs exert their effects by influencing chemical reactions at synapses • Agonist • Substance that ENHANCES the function of a synapse • Cause excessive release of a neurotransmitter • Block re-uptake off a neurotransmitter • Antagonist • Substance that BLOCKS the function of a synapse

23. An Acetylcholine Synapse: Example of Drug Action Whole eggs, liver, beef steak, and soy are among foods naturally rich in choline Black widow and cobra venom & ACh: Paralysis Botulinum toxin & ACh: denervation and local paralysis Nicotine & ACh: An increase in conductance of the ion(s) for which that channel is selective Nerve agents Pesticides muscle relaxant, poison

24. Psychoactive drug classification • One can classify a drug by it’s most pronounced behavioral or psychoactive effect • Sedative Hypnotics and Anti-anxiety Agents • Antipsychotic Agents • Antidepressants • Mood Stabilizers • Narcotic Analgesics • Psychomotor Stimulants • Psychedelics and Hallucinogens

25. Psychoactive drugs: Anti-anxiety Agents and Sedative Hypnotics • Central nervous system depressants • They bind to GABA (inhibitory neurotransmitter) receptors and increase its effect • The GABAA Receptor Has Two Sites: • Sedative-Hypnotic Site: Alcohol and barbituates • Antianxiety Site: Benzodiazepines

26. Psychoactive drugs: Anti-anxiety Agents and Sedative Hypnotics (continued) • Barbituates • Produce sedation and sleep (e.g., Phenobarbital, alcohol) • Can also produce general anesthesia, coma, and death • Used as an anesthetic • Other uses: Replaced by benzodiazepines, which have less potential for abuse and danger of lethal overdose • Benzodiazepines • Minor tranquilizers • Antianxiety agents • Drugs that reduce anxiety (e.g., Valium, Xanax) • Used to treat anxiety, insomnia, agitation, seizures, muscle spasms, and alcohol withdrawal

27. Psychoactive drugs: Anti-anxiety Agents and Sedative Hypnotics (continued) • Allopregnanolone • Natural hormone (a neurosteroid) produced by pineal gland • Reduces anxiety and creates calm at times of stress (conflicting evidence) • Higher levels in women than in men • Thought to make women more sensitive to alcohol than men • Associated with premenstrual symptoms

28. Psychoactive drugs: Antipsychotic Agents • Major Tranquilizers (Neuroleptic) • Drugs used to treat psychosis - a loss of contact with reality (hallucinations, delusions, disorganized thinking) • Examples: schizophrenia, mania, and delusional disorder • Blocks the D2 dopamine receptor • The normal effect of dopamine release is reduced • Mechanism of therapeutic action is still not understood • Immediate effect of reducing motor activity • After short period of use, there is a reduction in the symptoms of schizophrenia • Negative side effect: Dyskinesia (impaired control of movement)

29. Psychoactive drugs: Examples of Antipsychotic Agents • Zyprexa- acute manic episodes and maintenance of bipolar disorder • Solian- positive (high dose) and negative (low dose) symptoms of schizophrenia • Seroquel- bipolar disorder, schizophrenia, and chronic insomnia (low dose)

30. Dopamine Hypothesis of Schizophrenia • Proposal that schizophrenia symptoms are due to excess activity of the neurotransmitter dopamine • Evidence • Antipsychotic drugs block D2 receptors • Amphetamine promotes release of dopamine and can also produce symptoms similar to schizophrenia • But there is still no conclusive evidence of dopamine-related differences in the brains of schizophrenic patients

31. Psychoactive drugs: Antidepressants • Although antidepressants affect synapses very quickly, their antidepressive actions take weeks to develop • About 30% and 50% of patients with depression fail to respond to antidepressants, suggesting that other neurotransmitters are likely involved • Antidepressant drugs tend to lose efficacy over the course of treatment • Therapeutic effects of antidepressants typically do not continue once the course of medication ends • Most antidepressants are known to produce tolerance • They are not addictive, but can produce psychological withdrawl • Virtually all major antidepressant drugs suppress REM sleep • a common side effect of most antidepressants is an increase in vivid dreams

32. Classes of Antidepressants • Monoamine Oxidase (MAO) Inhibitors • Block the enzyme MAO from degrading neurotransmitters such as dopamine, norepinephrine, and serotonin • Tricyclic Antidepressants • First-generation antidepressants with a chemical structure characterized by three rings that block serotonin, dopamine, and norepinephrine reuptake transporter proteins • Second-Generation Antidepressants • Action is similar to first-generation antidepressants, but is more selective in its action on the serotonin reuptake transporter proteins; also called atypical antidepressants • Selective Serotonin Reuptake Inhibitors (SSRIs) • Block the reuptake of serotonin into the presynaptic terminal

33. Psychoactive drugs: Second-Generation Antidepressants • Action is similar to older (tricyclic) antidepressants, but with fewer side effects • Paroxetine (e.g. Paxil, Seroxat, Aropax) is a selective serotonin reuptake inhibitor (SSRI) • Used to treat the symptoms of depression, obsessive-compulsive disorder, post-traumatic stress disorder, panic disorder, generalized anxiety disorder, social phobia/social anxiety disorder, and premenstrual dysphoric disorder • Bupropion (e.g. Wellbutrin, Zyban) is a norepinephrine and dopamine reuptake inhibitor (NRDI) • Also used for smoking cessation, seasonal affective disorder, and Attention Deficit Disorder • Side effects: Nausea, diarrhea, headaches, sexual (loss of libido, failure to attain an erection or reach orgasm, Bupropions may increase libido slightly

34. The most commonly prescribed antidepressants • In the US in 2005: • Sertraline (e.g. Zoloft, Lustral, Apo-Sertral, Asentra, Gladem, Serlift, Stimuloton) • Escitalopram (e.g. Lexapro, Cipralex) • Fluoxetine (e.g. Prozac, Sarafem, Fluctin, Fontex, Prodep, Fludep, Lovan) • Venlafaxine (e.g. Effexor XR, Efexor) • Citalopram (e.g. Celexa, Cipramil, Talohexane) • Paroxetine (e.g. Paxil, Seroxat, Aropax) • Trazodone (e.g. Desyrel, Trazolan) • Amitriptyline (e.g. Elavil) • Bupropion (e.g. Wellbutrin, Zyban) • The most commonly prescribed antidepressant in Germany is reported to be concentrated extracts of hypericumperforatum (St John's Wort)

35. Psychoactive Drugs: Narcotic Analgesics • Drugs with sleep-inducing (narcotic) and pain-relieving (analgesic) properties • General effects of narcotic analgesics • sedation, slowed reflexes, raspy speech, sluggish "rubber-like" movements, slowed breathing, cold skin, and possible vomiting

36. Psychoactive Drugs: Narcotic Analgesics - Opiates • Many of these drugs are derived from opium, an extract of the seeds of the opium poppy plant • Opiates are potentially addictive • Continued use of narcotic analgesics will build a tolerance • Pure opioids (from the plant) • Codeine: ingredient of cough medicines and pain relievers • Morphine: powerful pain reliever • Synthetic opioid • Methadone

37. Psychoactive Drugs: Morphine • Acts directly on the synapses of the nucleus accumbens to relieve pain • Morphine binds very strongly to the mu-opioid receptors • Causes higher incidence of euphoria and dependence (addiction) as compared to most other opioids • Morphine has recently been found to be endogenously produced by humans • made by cells in the heart, pancreas and brain

38. Psychoactive Drugs: Narcotic Analgesics • Nalorphine and Naxolone • Blocks the effects of morphine • useful in reversing the effects of narcotic overdoses • Heroin • An opiate drug synthesized from morphine • More fat soluble and penetrates the BBB faster than morphine, therefore it produces very rapid pain relief • Once in the brain, heroin is rapidly metabolizes back into morphine • the morphine molecule binds with opioid receptors and produces the subjective effects of the heroin high

39. Psychoactive Drugs: Endorphins • Peptide hormone that acts as a neurotransmitter and may be associated with feelings of pain or pleasure • produced by the pituitary gland and hypothalamus • resemble opiates in their abilities to produce analgesia and a sense of well-being • Endorphins are released during stress, such as during long, continuous workouts, when the level of intensity is between moderate and high, and breathing is difficult • Do endorphins cause the runner's high? …. not likely • changes in mood state occur when people exercise on opioid antagonists (e.g., Nalorphine) • high appears to come from completing a challenge rather than as a result of exertion

40. Psychoactive Drugs: Behavioral Stimulants • Stimulates the sympathetic nervous system to increase motor behavior and elevate a person’s mood and level of alertness by increasing synaptic activity of the monoamine neurotransmitters: • dopamine (primarily), norepinephrine and serotonin • Physical effects: Overall agitation, prevents sleep, reduces appetite, speeds up breathing and heart rate and widens the pupils

41. Psychoactive Drugs: Behavioral Stimulants • Low to moderate doses • Induce wakefulness, increase activity, decrease appetite • Produce feelings of euphoria, well-being and self-confidence • Stereotypic behaviors - brief, repetitive actions (e.g., arranging of objects, grooming, and persistent repetition of words) • High doses • Produce a psychosis (vivid hallucinations and paranoid ideation) • Often indistinguishable from paranoid schizophrenia • Can cause periods to become irregular or even stop in women • Emotional effects: • At first - feel more energetic, cheerful and confident • Come down - feel sad, helpless, hopeless, nervous, angry, violent • Regular users – psychotic symptoms (e.g., delusions, hallucinations, & paranoia) that can develop into paranoid psychosis

42. Psychoactive Drugs: Behavioral Stimulants • Cocaine • Obtained from the leaves of the coca plant • Addictive • Derivates such as Novocaine are used as local anesthetics • Dopamine agonist: blocks the reuptake of dopamine • Amphetamine • Initially an asthma treatment • Study aid • Improvement of alertness and productivity • Weight-loss aid

43. Psychoactive Drugs: Behavioral Stimulants • Caffeine • Inhibits the enzyme the normally breaks down the second messenger cyclic AMP • Increase in cAMP leads to an increase in glucose production within cells, which makes more energy available and allows for higher rates of cellular activity • Results in increased activity of dopamine (causes stimulating effects) and serotonin (to a lesser extent - causing positive changes in mood) • Nicotine • A cholinergic agonist -- it acts by stimulating nicotinic acetylcholine receptors • Low dose stimulation of the central nervous system is followed by depression at high doses • Chronic use of nicotine leads tolerance and dependence

44. Psychoactive Drugs: Speed - Methamphetamine - Amphetamines • Toxic effects on the brain • A single high dose of meth has been shown to damage nerve terminals in the dopamine-containing regions of the brain • As much as 50% of the dopamine-producing cells in the brain can be damaged after prolonged exposure to relatively low levels of speed • Serotonin-containing nerve cells may be damaged even more extensively • Messes with every aspect of mood, emotion, sleep and appetite

45. Long-term Use of Methamphetamine

46. Longterm Use of MethamphetamineMeth-Mites • Users develop obsessive itching and picking of the skin, creating red, irritated, blotchy, and sometimes bloody sores

47. Psychoactive Drugs: Psychedelic Drugs • Alter sensory perception and cognitive processes • Range from seemingly non-toxic to extremely toxic • Do NOT cause hallucinations • Hallucinations are perceptions that have no basis in reality, but that appear entirely realistic • ”Hallucinations" induced by psychedelic drugs are more accurately described as a modification of regular perception • the subject is usually quite aware of the illusory and personal nature of their perceptions

48. Psychedelic Drugs: Four main types • Acetylcholine psychedelics • Norepinephrine psychedelics (e.g., mescaline) • Tetrahydrocannabinol (THC): active ingredient in marijuana • Serotonin psychedelics (e.g., lysergic acid diethylamide)

49. Psychedelic Drugs - Acetylcholine psychedelics • Examples: PCP, angel dust, crystal, dust, embalming fluid, DOA, surfer; street K, special K • Distort perception of sight and sound and produces feelings of detachment (dissociation) • Some effects include • agitation, euphoria, disinhibition, rigidity, unable to speak, unresponsive to pain, including unpredictable violent reactions to environmental stimuli, Schizophrenia-like psychotic states; Flashbacks • Effects are directly caused by the toxicity to one's body

50. Psychedelic Drugs - Norepinephrine psychedelics • Examples: mescaline, DOM (also as STP), TMA, MDA, MDMA (ecstasy),MMDA, DMA, and drugs from nutmeg (myristin and elemicin) • Mental Effects • Sensation and perception impairment, loss of a sense of time, disorganization of thought and psychotic reactions. • Physical Effects • Speed up the heartbeat and increase the blood pressure, dilates pupils, increases blood sugar level, raise body temperature, cause heavy perspiration and nausea. • Large doses, mescaline lowers the blood glucose.