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
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 legal problems e.g., arrests for substance-related disorderly conduct persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance e.g., arguments with spouse or children, physical fights
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 pulseNausea or vomiting Increased hand tremorPhysical agitation InsomniaAnxiety Transient visual, tactile, or auditory hallucinations or illusions Grand mal seizures
DSM-IV definition: Substance dependence 3. The substance is often taken in larger amounts or over a longer period than was intended 4. There is a persistent desire or unsuccessful efforts to cut down or control substance use 5. A great deal of time is spent in activities to obtain, use, or recover from effects of the substance 6. Important social, occupational or recreational activities are given up or reduced 7. 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
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
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
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
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
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
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)
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.
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 psychological discomfort and intoxication –Nucleus accumbens (Nac) Key structure of the brain responsible for reward, motivation, and addiction –Prefrontal cortex Regulates overall motivational salience and determines the intensity of behavioral responding
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.
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.
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
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
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
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
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
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
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
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)
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)
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
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
Classes of Antidepressants 1. Monoamine Oxidase (MAO) Inhibitors Block the enzyme MAO from degrading neurotransmitters such as dopamine, norepinephrine, and serotonin 2. Tricyclic Antidepressants First-generation antidepressants with a chemical structure characterized by three rings that block serotonin, dopamine, and norepinephrine reuptake transporter proteins 3. 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
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
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 hypericum perforatum (St John's Wort)
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
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
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
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
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
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
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
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
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
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
Long-term Use of Methamphetamine
Longterm Use of Methamphetamine Meth-Mites Users develop obsessive itching and picking of the skin, creating red, irritated, blotchy, and sometimes bloody sores
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
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)
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
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.
Psychedelic Drugs - Tetrahydrocannabinol Active ingredient in marijuana Low to medium use: Relaxation, reduced coordination and blood pressure, disruption in attention, an altered sense of time and space. High use can cause: Depression, hallucinations, delusions, impaired memory, disorientation, cancer. Unclear if it becomes addictive or causes long-term mental abnormalities Lung cancer is high risk of regular use because there is a high level of tar and other chemicals.
Psychedelic Drugs - Serotonin psychedelics Examples: LSD, Dimethyltryptamine (DMT), Psilocybin (mushrooms that belong to the genera Psilocybe, Panaeolus, andConocybe), psilocin, bufotenine Ololiuqui (morning glory seeds) Harmine Alter mood and perception, paranoid ideation, depression, undesirable hallucinations, and/or a confusional state resembling a drug-induced dementia. Persistent flashbacks occur weeks/months after last drug use Psychedelics can precipitate serious depressions, paranoid behavior, or prolonged psychotic episodes.
Drugs, Experience, Context, and Genes Tolerance How do we develop a tolerance to drugs such as alcohol? Metabolic Tolerance Changes in efficiency or capacity to metabolize ethanol resulting in a decrease in the BAC following a given dose of alcohol Number of enzymes needed to break down alcohol may increase Cellular (Functional) Tolerance Activities of brain cells may adjust to minimize the effect of alcohol Characterized by a decrease in pharmacologic or physiologic responsiveness upon alcohol exposure Hypothesized to be mediated by neuroadaptative changes in the CNS Learned Tolerance People can learn to cope with effects of alcohol and therefore may not appear to be drunk
Drugs, Experience, Context, and Genes Why Doesn’t Everyone Abuse Drugs? Genetics? Despite some evidence of a genetic contribution, no gene or set of genes related to alcoholism have been found Any satisfactory explanation of drug abuse will require genetic and learning components Personality Traits? Unusual risk-taking may be trait common to drug abusers Low Frustration and Tolerance - impatient Anxiety Grandiosity - to hide feelings of low self-worth Perfectionism - an idealist Justification Isolation and deep insecurity - loners Exaggerates unpleasant interpersonal relationships Impulsiveness Defiance - a feeling that one does not fit into society Dependence on other persons
Factors that influence drug responsiveness Age: Older individuals are more sensitive to drugs Less effective barriers and less effective at eliminating drugs Body Size: Smaller individuals are more sensitive to drugs Fewer body fluids to dilute drugs Sex Females are more sensitive to drugs Smaller than men on average Homones may also play a role