W14 - hallucinogens and club drugs Notes.pdf
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‘dancing with Molly’…..‘something ‘bout Mary she gone off that Molly’….‘a gnashing of teeth’…..‘as we moonshine and molly’…. HALLUCINOGENS, PHANTASTICANTS, AND CLUB DRUGS PSY3142 AGENDA - SAMPLING FORM THIS BROAD CATEGORY Monoamine-like drugs • E.g. LSD, psilocybin, Mescaline Synthetic mescaline...
‘dancing with Molly’…..‘something ‘bout Mary she gone off that Molly’….‘a gnashing of teeth’…..‘as we moonshine and molly’…. HALLUCINOGENS, PHANTASTICANTS, AND CLUB DRUGS PSY3142 AGENDA - SAMPLING FORM THIS BROAD CATEGORY Monoamine-like drugs • E.g. LSD, psilocybin, Mescaline Synthetic mescaline-like drugs • E.g. MDMA/MDA Salvia – unique mechanism among hallucinogens Dissociative anesthetics • E.g. Phencyclidine(PCP) Ketamine, Nitrous oxide 2 Dextromethorphan USE 3 USE 4 5 GLOBAL USE MDMA 6 LSD 7 LSD AND THE MONOAMINE-LIKE DRUGS • Indoleamine (serotonin)-like drugs • • • • • • LSD is similar to serotonin Psilocybin (magic mushrooms) Lysergic acid amide (morning glory seeds) DMT (Ayahuasca - tree bark/vine in South and Central America) Bufotenine (plants and venom from backs of toads) Harmine and harmaline (tropical vine in South America) • Catecholamine (dopamine & norepinephrine)-like drugs • Mescaline is similar to catecholamines dopamine and norepinephrine • Peyote DOSES AND SOURCES • LSD: Hits • 1970s: 100 micrograms • Gel tab, Microdots (candies, sm pills) • Mescaline: dried peyote cactus • Pharmacology • Usually taken orally • Effects begin between 30-90 min. after ingestion • Half-life: 3-5 hours in humans • Metabolized in the liver EFFECTS ON THE BODY • LSD: dilation of the pupils most common (also sometimes nausea, increased heart rate and body temp) • Neurophysiology • Effects on the nervous system are still not clear • effects on 5-HT2A receptors • Locus coeruleus • Cortex • Raphe nuclei SUBJECTIVE EFFECTS • Hallucinogenic Effects • Verbal reports • Largely visual: many consistent elements, similar to those produced in other nondrug hallucinations, similar across cultures Phantasticant and Perpetual Effects • Great emotional significance • Used in religion Entactogenic and Empathogenic Effects • Insight into one’s past and one’s own mind PERCEPTION, BEHAVIOR AND PERFORMANCE • Perception • Keener perceptions • Sight and sound become more acute • Slowing down of time • Behavior and Performance • • • • • Motivation issues Impairs reaction time Performance on a pursuit rotor task may be improved by LSD Functioning on intellectual tasks impaired Impairment of problem-solving and cognitive functions TOLERANCE & WITHDRAWAL • Tolerance develops rapidly • mediated by downregulation of serotonin 5-HT2A receptor • If LSD is take repeatedly, its effects disappear within 2 or 3 days. • No amount of the drug will be effective • Tolerance dissipates quickly, sensitivity returning in a week • Cross tolerance with other hallucinogens • No withdrawal symptoms SELF ADMINISTRATION • Generally not self-administered by nonhumans • Lab animals will work to avoid LSD infusions =Aversive effects • Never continuously consumed in humans HARMFUL EFFECTS • No recorded death from overdose • Acute psychotic reaction • Trailing phenomena • Flashbacks? MDMA 16 ECSTASY AND SYNTHETIC MESCALINE-LIKE DRUGS “Have you seen Molly?” Ecstasy (MDMA) • X, Adam, MDM, M & M, xtc, e, and beanies • White or colored tablets (100 mg) • *often not actually containing MDMA • Originally synthesized by the Merck drug company • Patented in 1914 • No use until the 1960s • Given to patients to enhance intimacy and communication with therapist • Reclassified in 1985; banned due to neurotoxic effects PHARMACOKINETICS • Orally • Peak level in 2 hrs • Metabolized to MDA • Half-life: about 8 hrs • Used more commonly by teens at raves • Associated with increase in sex, wakefulness, endurance, energy, euphoria, sharpened sensory perception, extroversion, sense of closeness to others NEUROPHYSIOLOGY • Increase transmission at synapses that use serotonin, norepinephrine, and dopamine • Causes the release of the neurotransmitter and blocking transmitter reuptake • Affects release of oxytocin BEHAVIOUR AND PERFORMANCE A dose of 75 to 100 mg induces a state similar to that caused by marijuana or low doses of PCP without hallucinations • Enhanced awareness of emotions and sensations • Increased muscular tension = jaw clenching & grinding teeth • Increase in body temperature, headache, nausea, blurred vision, and insomnia, difficulty in concentration, fatigue, and depression SELF-ADMINISTRATION Nonhumans • Readily self-administered by primates • Most reinforcing at moderate doses Human Epidemiology • Increase in the number of users throughout the 1990s • Increase in number of emergency room admissions between 1994 and 1999 • Use has begun to drop due to perceived risk* WITHDRAWAL AND HARMFUL EFFECTS • Withdrawal not seen • Harmful Effects of Ecstasy: depletion in serotonin • Sleep disorders, depression, persistent anxiety, impulsiveness, hostility, and selective impairment of memory and attention • Effects dissipate after about 6 months once drug is stopped for all but anxiety and hostility which can persist much longer • Most common causes of ecstasy-related deaths: • Heat regulation: increase in body temperature may lead to heatstroke, muscle tissue damage, kidney failure, liver damage, • Electrolyte imbalance: cause the brain to swell resulting in epileptic-like seizures OTHER LETHAL EFFECTS • Causes of death: heart and circulatory problems, liver damage, suicide, and accident • Quality control = impure • Contain drugs such as amphetamine, ephedrine, and PMA (potent with TI = 2.5) • Consumption of alcohol and other drugs increases risk of death SALVIA 24 SALVIA • Salvia • Plant based • visions and dissociative effects • Neurophysiology • kappa ()-opioid receptor agonist & partial D2 DA receptor agonist • Pharmacokinetics • effective only for a short time. from 5 to 30 minutes • Behavioral Effects • intense hallucinations , laughter, loss of motor cordination, perceptional changes, emotional swings, synaesthesia • Tolerance and Withdrawal • No tolerance/possible sensitization, no withdrawal DISSOCIATIVE ANESTHETICS 26 DISSOCIATEIVE ANESTHETICS: PHENCYCLIDINE AND KETAMINE • Phencyclidine (PCP) • Synthetic, dissociative anesthetic • Withdrawn from the marked due to delirium, disorientation, agitation (emergence delirium) • Crystal, angel dust, hob • Ketamine • Veterinary use • Liquid is colorless and tasteless • Swallowed or injected • Converted to powder, snorted • K, Special K, kitkat PHARMACOKINETICS AND DOSE • Weak, lipid soluble bases • Effective orally, inhaled, injected • Ketamine can be snorted, injected, or taken orally. • Oral administration is slowly absorbed. • Typically used intranasally • Effects last from 35 to 40 minutes • Typical oral dose is 175 mg; intranasal dose is 50 mg • PCP peaks in about 10 to 90 minutes • Effects last 4 to 8 hours • Typical does is 5 to 10 mg NEUROPHYSIOLOGY AND EFFECTS Neurophysiology • Block NMDA receptors • Act as reinforcers Behavior and Performance • • • • • Amnesia, schizophrenic behavior, coma Relaxation, warmth, numbness Euphoric feeling, distortions in body image, floating in space Mild depression (24 hrs to a week) Mood changes PROPERTIES, TOLERANCE, WITHDRAWAL • Stimulus Properties • Animals trained to discriminate PCP and ketamine do not generalize this response to any other class of drugs (only those that block NMDA like dextromethorphan) • Tolerance • When used everyday, tolerance develops • Dependence and withdrawal symptoms • Withdrawal • Vocalizations, grinding of the teeth, diarrhea, difficulty staying awake, anxiety, confusion, tremors • No systematic studies of PCP withdrawal in humans have been done SELF-ADMINISTRATION • Self-administered by nonhuman animals • • Has reinforcing effects Self-administration in humans = fairly low rates • Patterns of PCP are similar to LSD. • But, unlike LSD, some occasional users may become chronic users • Popular in metropolitan areas • Not very popular elsewhere • Ketamine seems to be more prevalent among high school students and in club scene HARMFUL EFFECTS • Large doses can cause: disorientation, agitation, hyperactivity and potentially longlasting psychotic behaviour (schizophrenic symptoms) • Not teratogenic • Slows growth of the fetus, precipitates labor, and causes fetal disease • Lethal Effects • A lethal dose of ketamine is 25 X the effective dose for intranasal administration. • Coma, convulsions, respiratory arrest, brain hemorrhage, kidney failure • Possibly lethal if mixed with alcohol or barbiturates due to potentiated lethal effects in combination with such depressants 33 DISSOCIATIVE ANESTHETICS DEXTROMETHORPHAN • Synthetic, opiate-like drug • Robitussin • Dextrophan • Neurophysiology • Bind with low affinity to the NMDA receptor complex • Pharmacological properties similar to the dissociative anesthetics and alcohol EFFECTS Nonhumans • Decrease in locomotor activity, memory impairment (dextromethorphan) • Effects resemble sedatives • Dextrophan caused an increase in motor activity. • Effects resemble PCP Humans • Cough suppressant at low doses with no other effects • High doses, effects are similar to PCP and ketamine • Ataxia, dizziness, euphoria, tactile and visual hallucinations AGENDA • Reviewed various categories & use in general • Individual examples withing many categories: • Pharmacology • Effects 36
