Exam 2 study guide
Exam 2 study guide NROSCI 0081
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This 25 page Study Guide was uploaded by Anna Perry on Wednesday October 21, 2015. The Study Guide belongs to NROSCI 0081 at University of Pittsburgh taught by Fanselow,Erika in Fall 2015. Since its upload, it has received 93 views. For similar materials see DRUGS AND BEHAVIOR in Neuroscience at University of Pittsburgh.
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Date Created: 10/21/15
Addiction pt 1 A De nition of Drug Addiction 1 Physical dependence abstinence causes unpleasant withdrawal symptoms that lead someone to start taking a drug again Compulsive drug seeking and drug use driven by a craving for the drug Chronic relapse an addict can have drugfree periods called remissions but then will relapse to using the drug again despite negative consequences quotA behavioral pattern of drug use characterized by overwhelming involvement with the use of a drug the securing of its supply and a high tendency to relapse after withdrawalquot B Current DSM5 terminology 1 DSM5 replaces substance abuse and substance dependence with substance use disorder a The individual has manifested a maladaptive pattern of substance use for at least 12 months that has led to signi cant impairment or distress by clinical standards b At least 2 of 11 additional criteria must be met including failure to stop when trying failure to stop when trying failing to ful ll obligations social impairments etc ll Addiction pt 2 A Personality traits can contribute to the initiation and continuation of drug use 1 2 3 Substance abuse is linked to a cluster of traits impulsivity antisocial tendencies unconventionality aggressiveness and low levels of constraint and harm avoidance Stress reduction Selfmedication for things like stress anxiety and neuroticism Reward sensitivity related to sensation seeking reward seeking extraversion and gregariousness B Sociocultural factors can contribute to drug use 1 2 3 4 When consumed in a group setting drugs may enhance social bonds The user escapes from normal roles and responsibilities Drugs can enhance solidarity within a group Distinct drug subcultures users embrace social rituals surrounding a particular drug and reject conventional social norms and lifestyles C Main Theoretical Routes to Drug Addiction 1 2 The Gateway Theory a Suggests that the use of alcohol and nicotine lead to use of marijuana which leads to the use of harder drugs Cycles a Intoxication including binging b Withdrawal symptoms and bad mood or irritability c Preoccupation with obtaining drug and anticipation of upcoming use d Cycle continues often spiraling downward and becoming addiction D Risk Factors for Drug Addiction 1 2 3 U39Ilgt IG 8 Heritability there can be a genetic contribution of 3080 Growing up in a family with a substanceabusing parent History of physical and emotional abuse especially among women Being with drugusing peers Sociodemographic variables including younger age less education nonwhite ethnicity lack of employment Stress and a person s ability to cope with it Psychiatric disorders often accompany drug abuse a Selfmedication hypothesis b Drugs cause psychiatric disorders c Shared susceptibility Access to drugs E Tolerance A barrier to stopping drug addiction 1 2 3 Tolerance decreased response to a drug after repeated exposure Increasingly larger doses of a given drug must be administered to get the same effect of the drug Characteristics of drug tolerance a The degree of tolerance is dependent on dose and frequency of drug use as well as the environment in which a drug is taken b Tolerance can occur rapidly or after long periods of chronic use or never c Not all effects of a drug show the same degree of tolerance d Multiple biological and behavioral mechanisms explain different forms of tolerance e Reversible once drug use stops F Types of Tolerance 1 Metabolic tolerance occurs when repeated use of a drug reduces the amount of drug that is available in the target tissue brain a The liver inactivates drugs with enzymes so they can be excreted b When the liver encounters frequent doses of a drug that is broken down by a given enzyme it makes more of that enzyme c Thus the drug gets broken down and eliminated from the bloodstream faster d This means some abusers may need higher doses of therapeutic drugs 2 Pharmacodynamic tolerance occurs when changes in neuron function compensates for the continued presence of a drug a The brain tries to maintain homeostasis if activity of neurons within the brain is not maintained it will not function properly b One of the main ways the brain can adapt in order to maintain homeostasis is by changing the number of neurotransmitter receptors available at synapses i More activated receptors upregulated the more effect of a drug ii Fewer receptors downregulated the less effect of a drug 3 Behavioral tolerance occurs when a person learns to associate the effects of a given drug with the environmental cues that precede the drug s effects a Things associated with taking the drug must elicit physiological responses opposite to the effects of the drug itself 4 Sensitization is enhancement of drug effects after repeated administration of the same dose of a drug 5 Crosstolerance is the repeated use of one drug reducing the effectiveness of another drug lll Addiction pt 3 A The Reward Pathway 1 Causes us to enjoy activities or substances critical for survival 2 Drugs can hijack the brain s quotreward pathwayquot and allowcause the brain to learn really well that drugs pleasure 3 The main job of the reward pathway is to get us to recognize things that quotfeel goodquot and then do them again without necessarily having the initial trigger or instinct eg hunger a b c d InacU a b a b B Anatomical Identifying that the result of a behavior felt good reward Associating quotthat felt goodquot with quothow and where did I do thatquot Initiating the rewarding behavior again Repeating the associations vann If the reward pathway is weakened the rewarding behaviors can still be done but there is little motivation for doing them The synapses between neurons in this pathway become weaker or there is less neurotransmitter Activation If neuronal activity in the reward pathway is enhanced there is a high level of motivation for repeating the rewarding behaviors Stronger synapses or more neurotransmitter available Basis 1 Main Brain Areas Involved a b C d e Ventral tegmental area VTA sends dopamine to Hippocampus memory association for how to do it again Amygdala fear memory for emotional events reward value if you re really excited you remember better Nucleus accumbens reward understanding something felt good Prefrontal cortex planning goals memory plan to get drug and do it again 2 Neurons in the VTA send dopamine via two main pathways involved in reward a b Mesolimbic pathway VTA l HC amyg NAc Mesocortical pathway VTA l prefrontal cortex C Neurochemical Basis 1 Dopamine is critical for the reward pathway If a reward occurs dopamine levels will increase 2 Types a b of drugs Cocaine ecstasy amphetamines inhibit dopamine transporter to reduce reuptake Nicotine excites dopamine neurons c Benzos cannabinoids opioids GHB Decrease activity of inhibitory neurons which release GABA This causes quotdisinhibition a reduction of inhibitionquot 3 The reward pathway can learn that a reward is likely to happen If this rewardinhibition reaction happens repeatedly dopamine levels will rise before the reward actually occurs 4 Repeated activation of the reward pathway can cause biochemical changes in the pathway itself a Dopamine receptors can be downregulated if the reward pathway is stimulated too much andor too frequently b In response to a constant barrage of dopamine the cells receiving it are just trying to shut down c Down regulation weakens the connection between reward and quotthat was pleasurablequot d Since there are fewer dopamine receptors it is difficult to reach the same high i This is reversible 5 If the reward pathway is weak and the drug is no longer available a The reward system has come to expect the drug so when people stop taking it quickly there is much less activation of the reward system which removes the pleasure component IV Addiction pt 4 A Two Types of Drug Dependence 1 Physical dependence de ned by the occurrence of withdrawal syndrome a Withdrawal syndrome set of de ned symptoms associated with a decrease in the blood levels of a particular drug b Symptoms tend to be opposite from the effects of the drug c When the drug is no longer in the body the compensatory mechanisms are still present leading to withdrawal symptoms d Neutral shifts down so the high is lessoned and the low is much lower 2 Psychological dependence desire or compulsion to experience effects of a drug because it produces pleasure or reduces discomfort a Comes about because of the reward pathway b Characterized by cravings B Treatment Strategies 1 Pharmacotherapy a Antagonist therapy Give patients a medication that blocks receptors for the drug someone is addicted to i Prevents drug from producing a high ii No tolerance develops iii Antagonist drugs do not relieve cravings iv Ex Naloxone is used for treating morphine overdose because it binds to opiate receptors and has a higher affinity than morphine and will eventually win so that the morphine can no longer bind to receptors b Agonist therapy give patients a medication that is an agonist at the receptor for the drug someone is addicted to i Reduces drug cravings but doesn t cause high ii Acts at active site but produces different effects iii Ex Nicotine gum or patch c Treatments for opioid dependence i Methadone is an agonist for opioid receptors and can act as a substitution for opiates Prevents withdrawal symptoms Can be used as maintenance treatment or detox treatment ii Buprenorphine is a partial agonist for opioid receptors Overdose is less likely but efficacy is limited Used as detox treatment because it results in fewer withdrawal symptoms iii Naltrexone is an antagonist for opioid receptors and blocks effects of heroin for 24 hours 2 Psychosocial a 12step Program b Cognitive behavioral therapy i Interactive includes building trusting relationship and following protocol to change behavior ii Awareness linkage between events and thoughts iii Challenges maladaptive thinking patterns and tries to replace them with adaptive ones iv Teaches coping skills C The Disease Model 1 Based largely on evidence of the disregulation of brain function in addiction 2 Bene ts a Reduces stigma of addiction b lnvolves the medical profession in treating addiction c Can reduce guilt in addict 3 Criticisms a How does one de ne disease b Addiction can only be diagnosed through clinical signs and symptoms V Stimulants pt 1 Cocaine A Commonly Used Forms 1 Powder puri ed directly from coca leaves 2 Crack prepared by boiling the powdered rom with baking soda a Increases speed with which cocaine is absorbed in the body more addictive B Pharmacokinetics 1 Routes of absorption a Snorting slower way to get cocaine in the bloodstream because cocaine constricts blood vessels in the nose i Blood levels rise slowly peaking after 3060 min b lnhaling from heated crack delivered to bloodstream quickly i Peak blood levels occur within several minutes and are much higher than similar dose of snorted powder ii High only lasts 30 min c Ingestion much less effective because rst pass metabolism 2 What matters is not the blood levels but the amount that actually gets to the brain Since cocaine is somewhat fat soluble it can pass readily through the bloodbrain barrier so it can reach high concentrations in the brain 3 Degradation Cocaine has a short halflife 0515 hours Rapidly broken down by liver and blood enzymes User is usually ready for another dose in 40 min or less The rapid increase in blood levels is followed by a rapid fall in blood levels crash While the halflife is short the metabolites can be present in the urine for days following 00 d e C Behavioral Effects 1 2 3 4 D Short 1 2 3 4 Increases attention causes alertness and eliminates fatigue The rush a A feeling of intense physical pleasure euphoria great selfcon dence and wellbeing b If snorted or taken orally the feeling is less intense Increased movement a Constant motion dopaminergic system b At high doses movement becomes more focused and repetitive Psychoticlike state a Happens at very high doses andor after prolonged use b Resembles schizophrenia term Effects as blood levels rise to toxic levels Energy and alertness become jitteriness paranoia hostility Increased movement becomes repetitive aimless activities Mild increase in heart rate becomes palpitations or chest pains Later effects include headaches nauseavomiting strokes heart attacks seizures E Longterm Effects 1 2 3 4 5 6 F Psyc39h 1 Due to constriction of blood vessels cocaine can cut off blood supply to the area of administration Suppression of appetite can cause malnourishment Damage to heart Neurological changes such as loss of brain tissue and funcUon Panic attacks Paranoid psychosis odynamics Cocaine mimics effects of the sympathetic autonomic PNS a Initiates fightor ight b Increases blood pressure and heart rate c Constricts blood vessels 2 Cocaine binds to reuptake transporters in the axon terminals for monoamine neurotransmitters a End up with more dopamine in synaptic cleft 3 Cocaine can also block voltagegated Na channels so action potentials cannot be transmitted a Can therefore be used as a local anesthetic G ToleranceWithdrawal 1 Tolerance can happen rapidly as in a single quotrunquot a Can also reverse rapidly b Causes cocaine binges c Stages to end of binge Crash exhausted depressed mood Withdrawal inability to experience normal pleasures lack of energy anxiety cravings Extinction withdrawal symptoms subside 2 Withdrawal is rarely lethal H quotCrack babiesquot 1 Use of crack during pregnancy can harm fetus because cocaine constricts blood vessels that supply blood to the fetus 2 Effects premature birth low birth weight strokes brain damage death higher rates of learning disabilities and ADHD l Treating Cocaine Addiction 1 Pharmacological Strategies a Reduce euphoric effects of cocaine andor craving upon cocaine withdrawal Receptor agonists and antagonists that might compete with cocaine for access to transporters Moda nil acts on dopamine norepinephrine glutamate GABA Antabuse b Reduce cocaine levels in the bloodstream quotcocaine vaccinesquot that prevent cocaine from binding to dopamine transporters 2 BehavioralPsychosocial Strategies a Counseling individual or group b 12step programs NA c Contingency management program i Based on the idea that drug taking is in part a result of the reinforcing property of a drug ii Develops reinforcers that are not drug related VI Stimulants pt 2 Amphetamine and Related drugs A Amphetamine Related Drugs 1 Amphetamine Methamphetamine Adderall Ritalin Diet pis quotBath saltsquot 2 All are stimulants but have subtle differences in structure which make them have different effects on the brain 3 Not naturallyoccurring 4 Mimic activation of sympathetic autonomic PNS 5 Cathinone primary active ingredient in khat an evergreen shrub 6 Ecstasy also changes levels of monoamines but tends to affect the serotonergic system most B Amphetamine and Methamphetamine Differences 1 Small difference in molecular structure in uences how they affect monoamine system 2 Can both be taken as pis because they are broken down more slowly by the liver a Amphetamine is a metabolite of meth 3 Halflives are different a Longer than cocaine so high lasts longer b Amphetamine 730 hours depending on pH of urine c Meth 10 hours C Mechanisms of Action 1 Both are indirect agonists of monoamines a Enhances the release or action of an endogenous neurotransmitter without agonist activity at the receptors 2 Blocks reuptake of monoamines and release it more easily D Behavioral Effects 1 Both cause heightened alertness increased self con dence exhilaration sense of wellbeing reduced fatigue 2 Improved performance on simple repetitive motor tasks delay in sleep onset reduction in sleep time 3 Amphetamine can enhance athletic performance 4 With heavy use both can lead to psychotic reactions E Therapeutic Uses 1 All stimulants are Schedule II Amphetamine prescribed for narcolepsy Adderall combination of four slightly different versions of amphetamine prescribed for ADHD 4 Ritalin methylphenidate prescribed for ADHD a Affects dopaminergic system differently than the other monoamines so less potential for addiction b Blocks dopamine reuptake but doesn t cause release 5 Desoxyn methamphetamine prescribed for ADHD and weight loss 6 Diet Pills a Appetitesuppressant effects result from release of norepinephrine and serotonin F Behavioral Effects of Meth 1 Behavioral a Anxiety confusion insomnia mood change paranoia b Psychosislike symptoms can last for months to years after some stops using c Psychotic symptoms can be triggered spontaneously by stress d Withdrawal symptoms include depression anxiety fatigue craving 2 Neurotoxic Damage a Dopamine neurons do not die but nerve endings are quotprunedquot so they are not available to release dopamine i Fewer connections b Associated with problems with memory and decision making 3 Physical a Weight loss tooth decay due to dry mouth and poor dental hygiene skin sores premature aging Vll Stimulants pt 3 Caffeine A Naturally occurring in tea coffee chocolate B Pharmacokinetics 1 Typically consumed through beverages or pills 2 Absorbed into bloodstream from digestive system in 3060 min a Rate of absorption depends on amount of food in stomach and concentration of caffeine ingested 3 Blocks GABAA receptors inhibitory JUN 4 Constricts blood vessels in the brain but not in the rest of the body Halflife differs by person typically 34 hours Converted to metabolites by liver a Smokers metabolize caffeine faster liver upgrades enzymes that breakdown nicotine and therefore caffeine is broken down faster as well b 90 of caffeine is excreted as activeinactive metabolites c Has psychoactive metabolites known as xanthines which also have an effect 7 Mainly excreted in urine mm C Pharmacodynamic Tolerance 1 Some tolerance to caffeine does develop in the brain s attempt to maintain homeostasis a Upregulation of adenosine receptors as brain tries to deal with continued suppression of adenosine activity Tolerance to arousal and cardiovascular effects Withdrawal symptoms headaches fatigue impaired concentration 4 While caffeine intake can cause a physical dependence it does not meet overall criteria necessary to be considered an addictive drug D Behavioral Effects of Caffeine 1 At low to moderate doses a Alertness energy b Enhancement of cognitive function increased ability to concentrate 2 At higher doses a Tension and anxiety b Can trigger panic attacks in susceptible people 3 At really high doses a Can get caffeine poisoning b lrregular or rapid heartbeat confusion and seizures E Adenosine Receptors 1 Caffeine s main action on the brain is to block receptors for the neuromodulatorneurotransmitter adenosine JUN a When adenosine binds to its receptors it causes sedation 2 Adenosine is released from cells when they become active This acts as a sort of quotbrakequot 3 Since caffeine is an antagonist of this process it prevents adenosine from doing its job a Stimulation via inhibition of an inhibitory effect F Effects of Caffeine on Other Parts of The Body 1 Heart a Caffeine affects brain centers that regulate the cardiovascular system b Can increase heart rate and blood pressure 2 Kidneys have adenosine receptors a Caffeine is a diuretic and can promote urine production 3 Respiratory system a lncreases rate of breathing b Dilates bronchioles of lungs 4 Caffeinism condition usually associated with doses of 1000 mg per day a Characterized by restlessness nervousness insomnia increased heart rate G Health 1 Risks a Possible link with development of heart disease b Can increase blood pressure and cholesterol c Digestive system i Heartburn ii May inhibit absorption of Ca2 d Reproductive system i May cause low birth weight ii May reduce chances of getting pregnant 2 Advantages a Can be used to treat migraine headaches because caffeine constricts blood vessels in head in neck b Lower risk for heart arrhythmias and strokes in women c Reduction in Parkinson s disease risk d Reduction in rates of some cancers 3 Therapeutic uses a Mild analgesic effects and can potentiate analgesic properties of aspirin and acetaminophen b Treatment of newborns who have periods where breathing stops VIII Stimulants pt 4 Nicotine A The tobacco plant is grown in over 100 countries and on 125000 American farms 1 Nicotine is the main psychoactive ingredient in tobacco 2 Psychostimulant but much milder than cocaine and amphetamines 3 Crosses bloodbrain barrier because it crosses through cell membrane rapidly B Routes of Administration 1 Inhalation a Vaporized by the heat at the end of a cigarette and inhaled attached to particles called tar b Tar contains many things some of which are carcinogenic c Inhaled nicotine reaches the brain in 7 seconds which is faster than if it were injected IV 2 Sublingual a Chewing tobacco and snuff b Absorption through lining of mouth or nose 3 Transdermal patch C Metabolism 1 Metabolized in the liver and excreted via the kidneys a Varies from person to person linked to abuse potential 2 The body can metabolize the nicotine from 1 cigarette in about 1 hour 3 Nicotine and tar induce the production of liver enzymes which results in increased metabolism of other drugs D Nicotine Toxicity 1 Tobacco plants may produce nicotine so they will not be eaten by insects or other animals 2 60 mg is a lethal dose standard cig has 158 mg a quotLow levelquot nicotine poisoning nauseavomiting dizziness headache confusion fainting b Acute nicotine poisoning tremors that develop into convulsions death by suffocation caused by paralysis of respiratory muscles E Effects 1 In smokers Increased calmness and reduction of tension 2 In nonsmokers heightened tension lightheadedness dizziness nausea 3 In both improvements in attention cognition motor tasks memory 4 Physiological Effects a b c d Increased activity of sympathetic and parasympathetic braches of the autonomic PNS Increases heart rate and blood pressure Weight loss due to decreased appetite and increased metabolism Constriction of blood vessels in the skin F Sites of Action in the Brain 1 Nicotine is an agonist for nicotinic acetylcholine receptors a b c Ligandgated ion channels that respond to acetylcholine Let Na into the neuron so they are excitatory Multiple subtypes with different effects on postsynaptic cell 2 Sites of action include a b c d Cerebral cortex enhanced cognition vigilance attention Reticular activating system heightened arousal Medulla vomiting center in the medulla directly activated by nicotine Activates sympathetic nervous system ght or ight 3 Nicotine increases activity of dopamine neurons in the VTA speci cally affecting the mesolimbic pathway of the brain s reward pathway a This leads to increased dopamine release in the nucleus accumbens which is critical for the reinforcement of nicotine intake 4 Rewa rd Pathway a b G Tolerance The shorter the interval between administrations of a drug the stronger the reinforcement of the drugtaking behavior Each puff has a reinforcing effect on the pathway 1 Shortterm a Can develop over the course of a day and can wane overnight b A smoker is more sensitive to nicotine in the morning due to temporary inactivation of nicotinic receptors in the brain 2 Longterm a Occurs in people who use tobacco frequently b Due to a compensatory response upregulation making more of nicotinic receptors in the brain 3 Withdrawal a Symptoms include anxiety decrease in ability to enjoy anything cravings irritability depressed mood b Can happen even overnight H Health 1 Half of smokers who start in adolescence and continue as a longterm habit die prematurely as a result 2 430000 people die each year from tobaccorelated causes a Several types of cancer b Cardiovascular disease heart attacks c Respiratory disease 3 Other consequences a Loss of cognitive function b Smoking during pregnancy leads to low birth weight and delays in infant development 4 Possible therapeutic effects of nicotine a Can improve memory b Smoking rates are higher in patients with schizophrenia than in the general population IX Alcohol A Classi ed as a CNS depressant and a sedative hypnotic B Ethanol is created by the reaction between sugar and yeast in a process called fermentation C Administration 1 Administration is orally and uptake occurs rapidly through the GI tract 2 Passes through liver and into brain 3 Readily crosses many membranes upsetting uid balances 4 Blood Alcohol Content a Measured by ethanol content of the blood 1gdL 1 b Can be detected through blood sample or exhalation testing c Small of alcohol excretion occurs through the lungs 5 Quantity of food in the stomach has an effect on the absorption of alcohol D Metabolism 1 First enzyme makes something toxic and enzyme 2 comes in to remove it 2 Gender Difference a After a given dose of alcohol females may achieve a BAC 2530 higher than males b Females have less metabolic enzymes c Also due to body composition 3 Elimination a Mainly excreted through the urine though some does leave the body unprocessed through lungs and sweat glands b Alcohol has a very slow rate of excretion that is constant no matter the concentration E Neurochemical Effects of Alcohol 1 Glutamate a Alcohol is an antagonist at NMDA receptors which are involved in learning and memory b Reduces effect of glutamate release lowering excitation in the brain c Reduces glutamate activity in the hippocampus is thought to be responsible for the memory problems that occur from drinking 2 GABA a Alcohol works at both sides of the synapse to stimulate GABA release and increase the function of GABA receptors b Activation of these receptors increases inhibition in the post synaptic cell 3 Dopamine a Alcohol increases dopamine activity in reward pathways 4 Opioids a Alcohol increases the release of natural opioids endorphins that modulate pain mood feeding and stress F Effects 1 On the Developing Brain a As alcohol can pass readily through the placenta it can directly affect a developing fetus and leads to many defects including physical changes brain abnormalities and behavioral symptoms b In teens increased risk of alcohol abuse decreased hippocampal volume impaired learning 2 Bene ts a Lowered risk of heart disease possible protection against cancer bene ts similar to exercise 3 Overdose a Alcohol has a therapeutic index of 6 b The body has a number of defenses against alcohol overdose vomiting passing out c Primary dangers of alcohol poisoning include choking and respiratory depression 4 Alcohol has many cross reactions with other drugs 5 Long Term Effects a Alcohol abuse effects a variety of organs including heart brain and liver b Damage is caused by alcohol its metabolites and liver in ammation c Damage includes i Liver Cirrhosis or liver failure ii Heart at higher levels alcohol increases risk of heart disease iii Reproductive system testicular atrophy decreased fertility miscarriage d Cognitive De cits damage includes shrinkage of many brain regions due to cell loss i Frontal lobe personality decisionmaking ii Temporal lobe memory formation dementia iii Cerebellum Coordination 6 The Hangover a A hangover is a period of acute withdrawal following alcohol consumption b Symptoms include headache nausea vomiting c Dehydration alcohol is a diuretic d Headaches blood vessel dilation in the brain e Nausea lrritation of GI tract G Tolerance 1 Long term metabolic tolerance a Develops due to increase in enzyme activity in the liver X 2 3 b There are neurochemical changes that occur as a result of frequent alcohol usage and cause a tolerance to the effects of alcohol Acute tolerance a Tolerance can develop during a single drinking session b Generally results in reduction in the high of drinking Withdrawal a Typically lasts 24 days b Major symptoms delirium tremens headaches irritability confusion hallucinations disorientation c Minor symptoms tremor anxiety high blood pressure vomiting d Generally follows a pattern of overexcitation in the brain due to inhibition produced by alcohol H Treatments 1 3 4 5 CannabE Disul ram antabuse inhibits activity of Alcohol dehydrogenase a Produces negative reaction as metabolite buildup provokes negative response Naltrexone antagonist therapy affects opioid receptors and reduces endorphin release following alcohol ingestion Alcoholics Anonymous 12 step program CBT Psychedelic therapy A THC is the main psychoactive ingredient in cannabis 1 2 3 Marijuana name for cannabis plant and drug preparations made from it a Hashish resin of the plant b Joint rolled into a cigarette c Hash oil made from boiling leaves Cannabinoid related to cannabis THC is found in the resin of the plant mostly in the owers a THC content can vary widely depending on strain growing conditions time of harvest B Pharmacokinetics 1 Usually smoked because THC is rapidly absorbed through the lungs 2 Halflife is 2030 hours 3 THC is very lipidsoluble and can go through membranes rapidly 4 Marijuana can also be eaten a Less THC gets to brain rst pass metabolism b Takes longer for THC to get to brain but effects generally last longer c High can be more intense C Pharmacodynamics 1 There are cannabinoid receptors in the brain a They are activated by chemicals made in the body which are known as endocannabinoids i May play a role in learning control of anxiety and reducing perception of pain b These receptors are found in multiple locations in the body including the brain immune system and GI tract 2 Cannabinoid receptors are found on the presynaptic neuron 3 Endocannabinoids are released from the postsynaptic neuron and go up to their receptors presynaptic neuron a D Effects When cannabinoid receptors are activated they inhibit release of glutamate and GABA 1 On the body goom Appetite stimulation Increased heart rate Reduced air ow Can reduce likelihood of pregnancy because it suppresses hormones that regulate the reproductive systems Marijuana does not affect the breathing center in the brainstem and does not lead to respiratory depression 2 On the brain a Subjective experience of the high varies widely but can include i Increased sensory perception ii Visual images may seem more intense iii Feelings often seem more intense iv Can get hallucinations paranoia and agitation at very high doses b The hippocampus is one of the main region of C the brain affected by cannabinoids Inhibition of memory formation by marijuana is its most wellestablished negative effect on mental function d Reduces creation of new memories but not old ones e Can reduce problem solving abilities 3 Tolerance and Dependence a Tolerance to THC can develop there is evidence for pharmacodynamic tolerance including downregulation of cannabinoid receptors b 10 of people who try marijuana become dependent c Marijuana can increase dopamine release from the VTA which can affect the reward pathway so jury is still out on addictiveness d Withdrawal is typically mild irritability restlessness insomnia sweating mild nausea depressed mood E Medical Effects 1 Control of nausea related to chemotherapy 2 Glaucoma 3 Seizures Xl Hallucinogens pt 1 A Drugs that change one s thought processes mood and perceptions without producing a state of delirium B Current Use 1 LSD is the most commonly used hallucinogen but only by a small percentage of population C Hallucinogen Group 1 LSDor serotoninlike 1 LSD lysergic acid diethyl amide a Made in a lab in to 40 s but similar molecules have be found in seeds of morning glory plants and fungus on rye b Most commonly dissolved in liquid and put on tabs Typical doses are 50150 ug c Tolerance develops rapidly which is one reason use is infrequent 2 Psilocybin Mushrooms a Contain psilocybin which is converted to the compound psilocin which can enter the brain b Often consumed as dried mushrooms c Effects milder and shorter than LSD 3 Peyote Cactus mescaline a Likely been used as a hallucinogen by native people in mexico for thousands of years b Hallucinogenic ingredient is mescaline which is more similar to amphetamine actually very similar to norepinephrine in structure c Users get physical effects of amphetamine but psychoactive effects are more like LSD 4 Others a DMT somewhat similar effects as LSD but whole trip is over within an hour b Bufotenine found in skins of some toads also a brief trip can cause temporary paralysis c 2CB Synthetic hallucinogen with LSDlike effects d Ayahuasca an herbal tea containing DMT and harmala alkaloids e Salvia divinorum plant that causes an intense brief and often unpleasant hallucinatory experience when smoked D Hallucinogen Group 2 Belladonna alkaloids 1 Have been used medically for thousands of years 2 Usually obtained from prescription medications that contain them or from Jimsonweed 3 Active ingredients a Atropine has effects outside the brain and can be lethal b Scopolamine enters brain easily and causes psychoactive effects 4 Mimic shutdown of the parasympathetic nervous system dry mouth pupils dilate heart rate increases airway passages in lungs dilate Can also cause a dangerous rise in body temp 5 Block one type of acetylcholine receptor that is important for memory so users often don t remember the experience 6 The trip delirium that users remember as strange dreams E Hallucinogen Group 3 Dissociative anesthetics 1 Anesthetics that have many effects on brain activity and produce effects different from typical anesthetics a They cause a dissociative state that is the closest of all the hallucinogens to resemble psychosis 2 PCP a Forms include pills powder or rocks b Can produce a state similar to getting drunk taking amphetamine and taking a hallucinogen simultaneously c Users often get in trouble with the law due to poor driving skills bad judgment not attending to their environment insensitive to pain d Can be out of touch belligerent and agitated e At high doses muscle rigidity general anesthesia coma seizures respiratory depression high body temperature high blood pressure 3 Ketamine a At low doses similar to being drunk b At high doses feelings of being cut off from reality including outof body and neardeath expedences 4 DXM Dextromethorphan a Main ingredient in cough syrups b Drank from bottle c At high doses causes hallucinations a dissociative state and delirium XII Hallucinogens pt 2 A Pharmacokinetics of Hallucinogens 1 Usually ingested but can be absorbed easily through the lining of the stomach and intestines a PCP is an exception usually smokedinjected 2 Time to feeling effects and duration of said effects differ depending on drug a If drug is fatsoluble the effects will be felt faster because it can easily get into the bloodstream and cross the bloodbrain barrier b Duration depends on how fast a drug is degraded 3 B Effects 1 Overdosebad effects of hallucinogens can be divided into two categories a Those that cause mainly psychological problems LSD b Those that are more physically dangerous PCP 2 Hallucinogens rarely have physical withdrawal but produce a rapid tolerance potentially by down regulation of serotonin receptors 3 Low abuse potential besides dissociative anesthetics 4 Flashbacks the reexperiencing following cessation of use of a hallucinogen of one or more of the perceptual symptoms that were experienced while intoxicated with the hallucinogen a Can be triggered by marijuana and maybe SSRls b Occur because LSD may permanently alter the brain C How do serotoninlike hallucinogens work 1 LSD and psiocin are chemically similar to serotonin a Effects of serotonin include regulating sleep and maintaining normal body temperature b Drugs that enhance the effects of serotonin can treat depression and overeating c There are many types of serotonin receptors i Many are in the cerebral cortex ii One speci c type can trigger hallucinations when stimulated 2 Serotonergic neurons in midbrain and hindbrain send their axons throughout the brain a Also affects convergence of outside stimuli and internal thoughts and feelings D Ecstasy 1 Similar to both amphetamine and mescaline in structure a Has both stimulant and hallucinogenic effects 2 Administration a Usually taken as pis b Well absorbed from GI tract peak blood levels in an hour c Effects last 36 hours 3 Ecstasy binds to the serotonin transporter a Blocks reuptake b Also promotes release of serotonin 4 Effects a Behavioral i Enhanced perception of sensory stimuli distorted time perception ii Euphoria and increased con dence iii Desire to interact with others iv lncreased empathy and connection with people b Physical i lncreased activity stimulation of sympathetic nervous system c Longterm 5 i Residual anxiety impaired memory ii Longterm loss of serotonin axons iii Decreased function of serotonin neurons d ToleranceWithdrawal a After multiple exposures the positive effects are not as pronounced b A hangover effect may occur after using including insomnia depression and difficulty concentrating 6 Can be lethal under certain circumstances 7 a Heart attack or brain hemorrhage b Overheating Danger a Main problem is overactivation of sympathetic nervous system b Dangerous effects due to dehydration body temp physical activity c Can cause seizures at extremely high doses d Few overdoses and deaths E How do Belladonna alkaloid hallucinogens work 1 2 Prevent action of muscarinic acetylcholine receptors a Receptors are found in the brain and other parts of body b Increase heart rate and are involved in formation of memories Can increase heart rate and body temp to dangerous levels F How do dissociative anesthetics work 1 2 They are antagonists for NMDA glutamate receptors PCP and ketamine also indirectly cause a release of dopamine and this contributes to the fact that users can become dependent on them PCP can cause death from overdose at 25 times a single recreational dose
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