hallucinogens part 2
hallucinogens part 2 NROSCI 0081
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This 54 page Bundle was uploaded by Arielle Reiner on Thursday October 8, 2015. The Bundle belongs to NROSCI 0081 at University of Pittsburgh taught by Fanselow,Erika in Summer 2015. Since its upload, it has received 24 views. For similar materials see DRUGS AND BEHAVIOR in Neuroscience at University of Pittsburgh.
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Date Created: 10/08/15
Amphetamines 10062015 Amphetamine related drugs 0 All these are stimulants but the subtle differences in the structure of the drug molecules make them have different effects on the brain 0 These are not naturally occurring substances Amphetamine Methamphetamine Adderall 4 versions of amphetamine Diet pills quotbath saltsquot o Ritalin methylphenidate Amphetamine and methamphetamine meth similarities o Amphetamine and meth are both stimulants 0 They mimic activation of the sympathetic nervous system including increased breathing heart rate and blood pressure 0 Like cocaine they both enter the bloodstream quickly if smoked or injected Meth versus cocaine 0 Meth o Stimulant Man made Smoking produces a long lasting high 50 of the drug is removed from the body in 12 hours increases dopamine release and blocks dopamine reuptake 0 limited medical use for ADHD narcolepsy and weight loss cocaine 0 stimulant and local anesthetic 0 plant derived 0 smoking produces a brief high 00000 0000 o 50 of the drug is removed from the body in 1 hour 0 blocks dopamine reuptake 0 limited medical use as a local anesthetic in some surgical procedures amphetamine versus meth the molecules are very similar but the small difference does in uence how they affect the monoamine systems unlike cocaine they can also be taken as pills because they are broken down more slowly by the liver 0 1 metabolite of meth is amphetamine 0 they have different half lives 0 both have much shorter than cocaine so a high lasts longer 0 meth half life 10 hours 0 amphetamine half life 730 hours depending on the pH of the urine review of monoamines the monoamines include o dopamine involved in movement and the brain s reward pathway which is involved in reinforcing pleasurable things including drug use 0 norepinephrine involved in levels of attentionwakefulness cognition and memory formation 0 serotonin affects eating behavior anxiety pain and learning 0 monoaminergic systems send these neuromodulators to many brain regions 0 stimulants affects these systems but different drugs affect them to different degrees and thus have different behavioral effects mechanisms of action for amphetamine and meth 0 both are indirect agonists of the monoamines unlike cocaine which only blocks monoamine reuptake these also release monoamines from nerve terminals amphetamine and meth patterns of use amphetamine and meth users quotspeed freaksquot can go on binges or quotrunsquot for 36 days or more with little sleeping or eating 0 then they crash sometimes barbiturates or other depressant drugs are used to quottake the edge offquot during a run or to help with sleeping afterward speedball combining IV amphetamine or meth with heroin behavioral effects 0 like cocaine these cause heightened alertness increased self con dence exhilaration sense of wellbeing reduced fatigue 0 also improved performance on simple and repetitive motor tasks delay in sleep onset reduction in sleep time amphetamines were distributed to military personnel in WWII o amphetamine can enhance athletic performance so it is one of the primary substances banned in athletic competitions with heavy use both of these can lead to psychotic reactions therapeutic uses amphetamine o prescribed for narcolepsy Adderall o Prescribed for ADHD 0 Combination of 4 slightly different versions of amphetamine o Ritalin methylphenidate o Prescribed for ADHD 0 Not amphetamine o Affects the dopaminergic system more speci cally than the other monoamines so less potential for addiction Desoxyn o Methamphetamine o Prescribed for weight loss and ADHD Meth Street names 0 crank o chalk 000000 0 crystal re glass go fast ice meth speed 0 commercial name 0 desoxyn prescribed for ADHD and weight loss 0 common forms 0 0 white powder or pill crystal meth looks like pieces of glass or shiny blue white rocks of different sizes 0 common ways taken 0 O O O swallowed snorted smoked injected 0 DEA schedule ll Manufacture Meth is often made in small amounts in small capacity production laboratories SCPLs aka 1 pot or shake and bake laboratories Can be made in small batches from relatively common ingredients 0 The method for producing meth is dangerous because it creates a lot of heat and uses ammable materials so there is the danger of explosions o This is a problem in part because SCPLs are often in residential areas 0 Liquid meth a new way to smuggle meth o The meth is dissolved in a liquid and can be smuggled easily with little probability of detection Effects of meth on health Neurotoxic damage 0 Chronic meth use can cause long term neurotoxic damage Dopamine neurons do not die but the nerve endings are quotprunedquot cut back so they are not available to release dopamine These changes are associated with problems with memory and decision making It is not yet clear whether these changes are reversible though there are some indications that they are with long term abstinence Neurotoxic damage as evidenced by brain scans Diet pills Stimulant based diet pills were originally amphetamines The appetite suppressant effects probably result from the release of norepinephrine and serotonin Impossible to separate the appetite suppressant effects from the addictive potential which arises because of the release of dopamine A new medication called Meridia was developed and it acts more selectively on norepinephrine and serotonin o Lacks abuse potential of amphetamines o The effects on norepinephrine causes cardiovascular problems so it was withdrawn from the market Caffeine 10092015 Normal brain 0 Small amounts of dopamine are constantly released and reabsorbed Cocaine Blocks dopamine reuptake Meth Releases a surge of dopamine Bath salts Releases a surge of dopamine and then blocks reuptake What is caffeine 0 The most widely used psychoactive drug in the world 0 About 8090 of adults in the US regularly drink caffeinated beverages and ingest from 200400 mg of caffeine a day which is about 3 cups of coffee 0 A mild psychostimulant Bitter odorless compound 0 Bitterness may be the plant s defense against being eaten Caffeine is produced by plants but there are many dozens Hundreds of other compounds in these plants that are also psychoactive and end up in tea coffee etc History of caffeine use 0 Tea 0 Origins traced back to China in 4th century 0 Plant camellia sinensis 0 Native to China and Southeast Asia O O Cultivated in tropical and subtropical regions Leaves and buds are used to create all types of tea 0 Types of tea differ according to the way they are processed Co ee O 0000 O Discovered by goat herder because of effects observed in goats First cultivated in Yemen in 6th century By 16005 coffee had been introduced to Europe Establishment of coffee houses In 17605 tea was heavily taxed in the English colonies so coffee became the drink of choice Coffee bean many species in caffea genus eg caffea Arabica Coffee fruits not really beans in a biological sense called cherries grown on bushes or trees Cultivated mainly in equatorial regions eg Latin America Southeast Asia Africa Chocolate 0 00 Used by early Central Americans in around 1100 BCE primarily as a drink Became popular to eat in 18005 when milk chocolate was invented in the Netherlands Main worldwide source is West Africa Processed from seed of Theobroma cacao tree Most consumed chocolate is in form of cocoa and cocoa butter combined with sugar and fat sweet chocolate or milk chocolate Caffeinated sodas 0 Use rose greatly in the 19905 Energy drinks 0 Use skyrocketed in 2005 Pharmacokinetics of caffeine 0 Typically consumed orally through beverage or pills Absorbed into bloodstream from digestive system stomach and small intestine in 3060 minutes 0 Rate depends on amount of food in stomach and the concentration of caffeine ingested Half life differs by person but is usually about 34 hours Converted to metabolites by the liver 0 Mainly excreted in urine Caffeine metabolism 0 Liver is the primary site where caffeine is broken down smokers metabolize it faster 0 90 of caffeine is excreted as activeinactive metabolites caffeine has psychoactive metabolites known as xanthines pharmacodynamic tolerance some tolerance does develop 0 this is the brain s attempt to maintain homeostasis due to upregulation of adenosine receptors as the brain tries to deal with continued suppression of adenosine activity tolerance to arousal and cardiovascular effects is observed 0 withdrawal symptoms are generally not severe typically headaches fatigue impaired concentration 0 note that while caffeine intake can cause a physical dependence it does not meet the overall criteria necessary to be considered an addictive drug behavioral effects of caffeine 0 generally known for its stimulating and fatigue reducing effects 0 at low to moderate doses 0 alertness energy 0 enhancement of cognitive function increased ability to concentrate at higher doses 0 tension and anxiety 0 can trigger panic attacks in susceptible people 0 at really high doses 0 can get caffeine poisoning which can lead to irregular or rapid heartbeat confusion and seizures How does caffeine affect the brain Caffeine affects the brain and body in a number of ways not all of which are understood Caffeine does not in uence monoamine systems in the same way amphetamine and cocaine do 0 Blocks GABAA receptors these are inhibitory receptors Caffeine also constricts blood vessels in the brain but not in the rest of the body Adenosine receptors Caffeine s main action on the brain is to block receptors for the neuromodulatorneurotransmitter adenosine 0 When adenosine binds to its receptors it causes sedation o Adenosine is released from cells when they become active This acts as a sort of quotbrakequot on what otherwise could be runaway neuronal activity 0 Since caffeine is an antagonist of this process it prevents adenosine from doing its job stimulation via inhibition of an inhibitory effect 0 This results in activation of the brain s circuits Effects of caffeine on other parts of the body Heart 0 Caffeine affects brain centers that regulate the cardiovascular system 0 Directly affects the heart Can increase heart rate and blood pressure and can lead to irregular heartbeat Kidneys 0 Have adenosine receptors 0 Caffeine can promote urine production is a diuretic Respiratory system 0 Increases rate of breathing o Dilates bronchioles of lungs Caffeinism o A conditioned usually associated with doses of over 1000 mg perday o Characterized by restlessness nervousness insomnia increased heart rate Caffeine health risks Possible link with development of heart disease Can increase blood pressure at high doses or in susceptible people May increase cholesterol but this is controversial Digestive system 0 Initially thought caffeine caused stomach irritation but decaf coffee can do the same thing 0 Has been blamed for ulcers but this link did not hold up can exacerbate them however 0 Heartburn 0 May inhibit the absorption of Ca2 Reproductive system 0 Safe during pregnancy May cause low birth weight 0 May reduce changes of getting pregnant 0 Most studies do not support the risk for breast cancer Health advantages of caffeine Can be used to treat migraine headaches o Caffeine constricts blood vessels in the head and neck adenosine relaxes them 0 But too much caffeine can trigger migraines so there is a paradox here that has yet to be explained Lower risk for heart arrhythmias 20 and strokes in women 20 Reduction in Parkinson s disease risk 80 Reduction in rates of some cancers Moderation may be key Health advantages of coffee National Institute of Health study nds that coffee drinkers have a lower risk of death 0 Older adults who drank coffee caffeinated or decaffeinated had a lower risk of death overall than others who did not drink coffee according to a study by researchers from the National Cancer Institute part of the National Institutes of Health and AARP Asked people about their caffeine intake and monitored them for 13 years Men who drank 23 cups of coffee per day were 10 less likely to have died and women were 13 less likely to have died Therapeutic uses for caffeine Mild analgesic effects and can potentiate analgesic properties of aspirin and acetaminophen 0 Treatment of newborns who have periods where breathing stops 0 Studies are underway to determine whether caffeine can help treat asthma type 2 diabetes and neurodegenerative disorders such as Alzheimer s and Parkinson s disease Energy drinks 0 Common brands Red Bull Monster Burn 5 hour energy shots 0 Are they safe 0 O O O 0 They typically contain some caffeine sugar and other ingredients such as taurine ginseng sodium and vitamins The caffeine content varies Red Bull 80 mg similar to a standard cup of coffee Fixx energy shot 400 mg Some people take too much and end up needing medical treatment A few people have died of heart attacks as a result of energy drinks These can be dangerous for kids because they can t manage so much caffeine Caffeine combined with other drugs 0 Red Bull and Vodka O 0 Can caffeine counteract the effects of alcohol In other words can you reverse the effect of a sedative with a stimulant Although caffeine does reduce acoho induced drowsiness effects on manual dexterity balance reasoning and verbal uency remain the phenomenon of quotwide awake drunk A drunk driver may feel more alert after a few cups of coffee but will still have impaired motor skills reaction time and decision making Nicotine 10122015 History 0 Tobacco is indigenous to South America and was rst cultivated there around 5000 BCE 0 Viewed as a gift from the Gods Late 14005 and 15005 0 Columbus introduced tobacco to Europe where its popularity rapidly spread 0 Jean Nicot praised the power of tobacco o Europeans believed that tobacco could cure many diseases 0 16005 0 pipe was most popular form of tobacco use 0 backlash began King James I proposed 4000 tax on tobacco intended to discourage selfabuse First recognition that tobacco is addictive Tobacco dealers were beheaded in China and Turkey 0 18005 0 chewing tobacco is the most powerful form of tobacco o 1826 nicotine was identi ed by chemists scientists concluded that it is a dangerous poison 0 machine rolled cigarettes were invented hand rolled n 2cigarettesminute machine rolled a 1000 cigarettesminute 0 19005 O cigarettes became the most popular form of tobacco Camel gained 43 of the market Cigarette sales skyrocketed after WWII 1964 Surgeon General released a report declaring smoking to be a health hazard 0 19705 rates of smoking in women began to rise the tobacco plant 0 grown in over 100 countries 0 grown on about 125000 American farms 0 remains the most pro table crop per acre 0 different curing methods affects taste and nicotine content nicotine the main psychoactive ingredient in tobacco crosses the blood brain barrier nicotine is a psychostimulant albeit a milder one than cocaine and amphetamines routes of administration OOO 0 inhalation o nicotine is vaporized by the heat at the end of a cigarette o it is inhaled attached to tiny particles called tar o tar contains many things some of which contribute to the taste and smell of cigarette smoke and some of which are carcinogenic o inhaled nicotine reaches the brain in 7 seconds which is faster than if it were injected IV sublingual o chewing tobacco and snuff o nicotine absorption is through the lining of the mouth or nose transdermal across the skin 0 nicotine patch nicotine metabolism metabolized in the liver 8090 and excreted via the kidneys the body can metabolize the nicotine from 1 cigarette in about 1 hour 0 metabolism varies from person to person and is linked to abuse potential 0 nicotine and tar induce the production of liver enzymes which results in increased metabolism of other drugs nicotine toxicity tobacco plants may produce nicotine so they will not be eaten by insects or other animals 0 60 mg is a lethal dose 0 low level nicotine poisoning o nausea vomiting 0 dizziness o headache o confusion o fainting acute nicotine poisoning o tremors that develop into convulsions 0 death by suffocation caused by paralysis of respiratory muscles studying the effects of nicotine a typical research study on the effects of nicotine involves asking smokers to abstain from cigarettes for 824 hours and then testing their responses to nicotine with this method it is difficult to tell what is an effect of the nicotine vs the effect of relieving symptoms of nicotine withdrawal effects of nicotine in smokers via non smokers o smokers increased calmness and reduction of tension 0 non smokers heightened tension nausea dizziness lightheadedness studying the psychological and behavioral effects of nicotine what is an effect of the nicotine vs an effect of the smoking ritual itself This can be tested by giving normal cigarettes to some test subjects and ones without nicotine to others and seeing what the differences are In such a research study when subjects were given cigarettes they showed decreases in bad mood better performance on a difficult computer task and less negative responses to pictures showing baddisturbing things o This was true whether they were given cigarettes containing nicotine or cigarettes without nicotine Effects of nicotine itself regardless of whether one is a smoker or not 0 Improvements in 0 Attention o Cognition 0 Memory 0 Motor movement tasks Physiological effects of nicotine at the doses found in cigarettes Increased activity of the sympathetic and parasympathetic branches of the autonomic nervous system Increases heart rate and blood pressure 0 Weight loss due to decreased appetite and increased metabolism Constriction of the blood vessels in the skin ie smokers have cold hands wrinkles etc How does nicotine affect the brain and body 0 Nicotine is an agonist for nicotinic acetylcholine receptors nAChRs o Ligand gated ion channels that respond to the neurotransmitter acetylcholine 0 Let Na into the neuron so they are excitatory 0 There are multiple subtypes of nAChRs that have different effects on the presynaptic ce Nicotine sites of action 0 Sites of action include o Cerebral cortex Enhanced cognition vigilance attention o Reticular activating system Heightened arousal o Medulla Vomiting center in the medulla directly activated by nicotine ie for 1st time smokers o Activates the sympathetic nervous system ght or ight response Nicotine increases activity of dopamine neurons in the VTA speci cally affecting the mesolimbic pathway of the brain s reward pathway 0 This leads to increased dopamine released in the nucleus accumbens NAc which is critical for the reinforcement of nicotine intake ie becoming dependentaddicted How does nicotine affect the reward pathway 0 The shorter the interval between administrations of a drug or another reward the stronger the reinforcement of the drug taking behavior Patterns in smoking behavior 0 Smoking often starts in adolescence 0 Establishing independence and maturity defying parents andor social norms Social acceptance friends smoke Counteracting stress Curiosity Disregarddeny negative aspects of smoking including health consequences 0 3 patterns to follow trying smoking 0 people don t develop smoking habit 0 people develop habit of smoking a few cigarettes a day show few signs of dependence 0 frequent smoking with compulsive use cravings and difficulty stopping nicotine tolerance OOOO 0 short term tolerance O O O O can develop over the course of a day and can wane overnight a smoker is more sensitive to nicotine in the morning after not smoking all night due to temporary inactivation of nicotinic receptors in the brain can happen with even a single cigarette worth of nicotine long term tolerance O 0 occurs in people who use tobacco frequently due 0 a compensatory response up regulation making more of nicotinic receptors in the brain nicotine withdrawal 0 symptoms of nicotine withdrawal 0 O O O O anxiety decrease in ability to enjoy anything cravings irritability depressed mood 0 mild nicotine withdrawal can even happen overnight addictive 0 yes causes physical dependence and addiction 0 1 reason for this is that it is highly reinforcing O nicotine promotes release of dopamine in brain regions that mediate reinforcement o nAChRs in VTA cause the VTA to release more dopamine treatments for tobacco dependence 7075 of smokers in the US would like to quit 4045 try to quit each year success rate for quitting rate is very low treatment strategies 0 prevention health warnings on cigarette packs self help programs these are often not of much bene t individual or group therapy programs pharmacological treatments nicotine replacement nicotine gum patch spray inhaler lozenges a goal is to reduce withdrawal symptoms medication called zyban which may work because it works as a dopamine reuptake inhibitor medication called Chantix which is a partial agonist for nicotine so it reduces cravings possible nicotine vaccine in development 0 00 Negative health consequences of smoking Surgeon general s report 2010 0 Half of smokers who start in adolescence and continue it as a long term habit die prematurely as a result 0 430000 people die each year from tobacco related causes including several types of cancer cardiovascular disease heart attacks respiratory disease 0 other consequences include loss of cognitive function smoking during pregnancy leads to low birth weight and delays infant development possible therapeutic effects of nicotine nicotine can improve memory it might be useful in treating Alzheimer s disease smoking rates are higher in patients with schizophrenia than in the general population might nicotine actually help alleviate some of the cognitive de cits associated with schizophrenia possible treatment for ADHD Electronic cigarettes ecigs Uses a heating element to vaporize liquid nicotine We have very little information on the safety of ecigs 30 of children 12 and under reported trying an ecig no legislation of ecigs but can t be advertised as a cessation therapy Alcohol 10142015 What is alcohol 0 Alcohol ethanol is the most widely used psychoactive drug in the world o It is so ingrained in our society that many people mistakenly separate drugs and alcohol as 2 distinct things Ethanol is created by the reaction between sugar and yeast in a process called fermentation 0 Different origins of sugars change the nal alcohol product grapeswine grainbeer o Ethanol can be further re ned by boiling and collecting the ethanolwater solution in a process called distillation o This produces a much higher percentage alcohol mixture commonly known as a hard liquor Ethanol is classi ed as a CNS depressant and a sedative hypnotic History of alcohol 0 From wine 0 Alcohol has been used for almost the entirety of human civilization Since about 10000 BC 0 Egyptians became one of the rst civilized people to mass produce beer and wine Used in religious ceremonies Wine and mead production proli c in ancient Greece 0 Development of distillation in the medieval period allowed for the creation of much higher alcohol percentage beverages Most of these spirits were used for medicinal purposes 0 To 4 Loko 0 beer came to America on the May ower which carried more beer than water brewing process sanitizes O colonial life revolved around alcohol 0 early 19th century temperance movement 0 led to 18th amendment prohibition in 1919 violent gangs and speakeasys o prohibition repealed in 1933 and we ve been drinking ever snnce 0 alcohol administration the most common route of alcohol administration is orally uptake occurs rapidly through the GI tract stomach small intestine alcohol passes through the liver and into the brain alcohol readily crosses many membranes which upsets many uid balances binge drinking gt5 drinks in about 2 hours for males 0 can be dangerous due to slow excretion of alcohol from the body blood alcohol content alcohol in the body is most commonly measured by the ethanol content of the blood 1gdL 1 BAC can be detected either through blood sample or exhalation testing 0 Small of alcohol excretion occurs through the lungs Quantity of food in the stomach has an effect on the absorption of alcohol 0 Drinking on an empty stomach is a good way to put yourself in danger The standard drink Talking about dosages of alcohol can be difficult 0 Different alcohol values of different alcoholic drinks The standard drink is a measurement based on the volume of the drink and the alcohol 0 Easier to measure the amount of alcohol entering the body Alcohol metabolism Alcohol is metabolized in the liver by the enzyme alcohol dehydrogenase o This produces acetaldehyde which is a toxic molecule Acetaldehyde breaks down via acetaldehyde dehydrogenase and an oxidation reaction 0 Enzyme activity levels can be in uenced by experience drug action and genetics etc Gender differences in alcohol effects One important and interesting thing to note about alcohol metabolism is that there are inherent differences in males and females After a given dose of alcohol females may achieve a BAC as much as 2530 higher than males 0 Due to enzyme activity and body composition Females are also more likely to develop long term side effects of drinking 0 Rates of organ damage some cancers and socialpsychological issues more likely to arise in females following long term alcohol consumption Alcohol elimination Alcohol is mainly excreted through the urine after being processed by the body 0 Some alcohol does leave the body unprocessed through the lungs and sweat glands as well as urine Alcohol has a very slow rate of excretion from the body 0 Top of chart is nicotine with a half life of 30 minutes 0 Alcohol shows a much slower rate of excretion that is constant no matter the concentration 0 This leads to a very dangerous situation where alcohol enters much faster than it can be excreted Behavioral effects of alcohol BAC o O O O 0203 minimal effects slight relaxation mild mood elevation 0506 decreased alertness relaxed inhibitions mildly impaired judgment 08 1 loss of motor coordination slower reaction times less caution 1416 major impairment of mental and physical control slurred speech exaggerated emotions blurred vision serious loss ofjudgment large increases in reaction time 225 staggering inability to walk or dress without help tears or rage with little provocation mental confusion double vision 3 conscious but in a stupor unaware of surroundings 45 coma lethal for 50 of the population neurochemical effects of alcohol glutamate O O 0 alcohol is an antagonist at NMDA receptors NMDARs NMDARs are involved with learning and memory Alcohol reduces the effect of glutamate release lowering excitation in the brain 0 Reduced glutamate activity in the hippocampus is thought to be responsible for the memory problems that occur from drinking GABA 0 Alcohol works at both sides of the synapse to stimulate GABA release and increase the function of GABA receptors 0 Activation of these receptors increases inhibition in the post synaptic cell 0 Downstream Excitatory cells gt inhibition Inhibitory cells gt reduced inhibition 0 Dopamine 0 Alcohol increases dopamine activity in reward pathways Opioids 0 Alcohol increases the release of natural opioids ie endorphins that modulate pain mood feeding and stress Effects of memory 0 People who drink an excessive amount of alcohol will often experience a lack of memory the previous night 0 This is called a blackout 0 They are becoming more common 0 ln 1 study 40 of college students reported experiencing blackouts o Caused by inhibition in regions in the brain that record new memories eg the hippocampus o Often associated with risky behavior including ghts and drunk driving 0 Blackouts should be taken seriously Effects on the developing brain 0 Fetal alcohol syndrome 0 As alcohol can pass readily through the placenta it can directly affect a developing fetus 0 Alcohol abuse during pregnancy leads to many defects including physical changes brain abnormalities and behavioral symptoms 0 Teens and young adults 0 Alcohol has a variety of effects on the developing brain of young adults Increased risk of alcohol abuse Decreased hippocampal volume impaired learning Alcohol overdose Alcohol has a very low therapeutic index about 6 Luckily the body has a number of defenses against alcohol overdose o Vomiting typically occurs at a BAC of 15 0 People typically pass out at 35 0 However because of low levels of excretion BAC can continue to increase after vomiting or passing out o The primary dangers of alcohol poisoning include choking and respiratory depression 0 Signs Unconsciousness Vomiting Slowirregular breathing Coldclammybluish skin 0 In cases of suspected alcohol poisoning don t be stupid and call an ambulance 0 Pennsylvania medical amnesty law 2011 creates immunity from prosecution if seeking help for another individual in cases of a drug overdose Cross reaction with other drugs 0 Alcohol has many cross reactions with other drugs 0 Possible drug effects 0 Any sedatives will escalate depressive effects increasing risk of coma and death 0 OTC drugs can have adverse side effects Avoid Tylenol acetaminophen when dealing with a hangover 0 Numerous other drugs including antidepressants antipsychotics narcotics and heart medications can all have serious side effects when combined with alcohol The hangover o A hangover is a period of acute withdrawal following alcohol consumption 0 Symptoms Headache Nauseavomiting General negative outlook on life Exact cause of the hangover is unknown many theories try to explain the symptoms 0 Dehydration Frequent urination alcohol is a diuretic o Headaches Blood vessel dilation in the brain 0 Nausea lrritation of the GI tract 0 The best cure for a hangover is to refrain from heavy drinking 0 Otherwise uids rest and a pain reliever except Tylenol will help relieve symptoms Tolerance Long term metabolic tolerance 0 Like many drugs people can develop a tolerance 0 Mostly due to the increase of enzyme activity in the liver 0 However there are neurochemical changes that occur as a result of a frequent alcohol usage and cause a tolerance to the effects of alcohol 0 Acute tolerance o Tolerance can even develop during a single drinking session 0 This generally results in a reduction in the high of the drinking experience and leads to dangerous behavior Addiction 0 Alcohol use disorder AUD is the most prominent addiction disorder with an estimated 18 million diagnosed cases 0 AUD is de ned in the DSM5 as meeting 2 of 11 criteria relating to abuse of alcohol in the last 12 months 0 Criteria Compulsive use Loss of control Drinking in spite of consequences Risk factors for addiction 0 There are numerous risk factors that in uence propensity for AUD 0 Important considerations include Genetic differences in alcohol metabolism Number of drinks per day Self medication Relative with an AUD o The only proven risk factor is a negative risk factor 0 Acetaldehyde dehydrogenase activity is reduced in those with Asian ancestry Produces a negative reaction to alcohol that discourages further drinking Withdrawal symptoms Withdrawal from alcohol abuse typically lasts 24 days 0 Major symptoms quotdelirium tremensquot n headaches n irritability a confusion I hallucinations n disorientation 0 minor symptoms tremor anxiety vomiting high blood pressure 0 withdrawal generally follows a pattern of over excitation in the brain due to the inhibition produced by alcohol long term effects 0 alcohol abuse affects a variety of organs including the heart brain and liver damage is caused by alcohol its metabolites and liver in ammation damage includes 0 liver cirrhosis scarring due to hepatitis which leads to liver failure 0 heart at small levels alcohol use can actually help the cardiovascular system at higher levels increased risk of heart disease 0 reproductive system testicular atrophy decreased fertility miscarriage cognitive de cits alcohol has a variety of effects on mental function damage includes shrinkage of many brain regions due to cell loss 0 frontal lobe personality decision making 0 temporal lobe dementia memory formation 0 cerebellum coordination these effects are permanent as the neurons do not replenish pharmacological treatments disul ram antabuse inhibits the activity of ADH 0 produces a negative reaction as metabolite buildup provokes negative response 0 however also produces the same negative effects that provoke long term liver damage naltrexone antagonist therapy affects opioid receptors and reduces endorphin release following alcohol ingestion 0 initial studies proved effective 0 larger studies are needed behavioralpsychosocial treatments alcoholics anonymous AA 0 organization that is made of alcoholics o 12 step program promotes a constant ght against alcoholism 0 ts the disease model of alcohol abuse 0 cognitive behavioral therapy 0 replacing cues that trigger drinking habits with other less destructive cues psychedelic therapy positive 0 although there are many negatives associated with alcohol usage there are a few positives as well 0 line between positive and negative effects is very thin bene ts of moderate usage include o cardiovascular lowered risk of heart disease possible protection against cancer bene ts similar to exercise 0 diminished risk of death lt2 drinksday gt 20 decrease in risk gt2 drinksday gt 30 increase in risk epigenetics o the explanation for alcohol heredity 0 not all of the heredity of alcohol can be explained by simple gene cs 0 enter epigenetics the study of the chemical modi cations that occur to DNA but do not alter the sequence code a functionally epigenetic changes to DNA strands often turn on or off gene expression a additionally these changes can be passed down through germ cells sperm and egg cells exposure to alcohol alters to expression of genes involved in alcohol metabolism and the reward pathway transference of fear conditioning from father to son Cannabis 10162015 Cannabis is a plant that is used mainly for 2 things 0 Hemp 0 Strong ber in the stem that can be used for rope cloth and paper Psychoactive and medical effects 0 THC is the main psychoactive ingredient 0 Leaves and owers can be dried and used for their psychoactive components Marijuana o A name for the cannabis plant and drug preparations made from it Cannabinoid Related to cannabis What is THC Abbreviation for delta9tetrahydrocannabinol 0 Found in the resin of the plant which is mostly in the owers THC content quotdrug qualityquot can vary widely depending on the strain the growing conditions the time of harvest eg depends on when the owers are picked at the peak of owering quotclear highquot after peak owering quotstonedquot Low grade marijuana is made from the leaves which have a low THC content about 1 quotheadache potquot Higher grade is made from the owers buds and THC content can be 78 on average quothospital potquot but not for medicinal use History 0 Early history BCE is difficult to determine though THC and caffeine and nicotine were found in the internal organs of an Egyptian mummy from about 950 BCE By about 1000 AD use of cannabis as an intoxicant has spread to the eastern Mediterranean and European explorers brought back stories of its psychoactive effects 0 In Europe by the 18405 recreational use of cannabis was popular among the artists and intellectuals as a way to enhance creativity 0 European explorers brought cannabis seeds to the New World to produce hemp for rope and cloth but it was not until the early 20th century that marijuana began to have a social impact in the US Forms of marijuana Rolled into a cigarette joint Hashish o Resin of the plant only 0 THC content can vary substantially about 8 20 Hash oil 0 Made from boiling cannabis leaves 0 Very high THC content about 2070 0 Can be used to lace tobacco or marijuana cigarettes Use peaks in the late teens Routes of administration and pharmacokinetics Marijuana is usually smoked o THC is rapidly absorbed through the lungs 0 Most of the THC is gone in a few hours but it can accumulate in organs in the body 0 Half life for THC is about 2030 hours 0 Some metabolites can least several days and some of these do have psychoactive effects 0 With a large dose of THC there can be remnants of it in the body for up to 3 weeks 0 THC is very lipid soluble Can also be eaten 0 Less THC gets to the brain rst pass metabolism because of enzymes in the liver o Takes longer for the THC to get to the brain 0 The effects of the THC take longer to start and generally last longer 0 The high can be more intense than with smoking because it is easy to take more THC than with smoking Pharmacodynamics There are cannabinoid receptors in the brain They are activated by chemicals made in the body which are known as quotendocannabinoidsquot quotendo means inner or containing Cannabinoid receptors are found in multiple locations in the body including the brain the immune system and the GI tract Endocannabinoids may play a role in learning control of anxiety and reducing the perception of pain In the brain the cannabinoid receptors are found on the presynaptic neuron Endocannabinoids are released from the postsynaptic neuron and go up to their receptors presynaptic neuron When the cannabinoid receptors are activated they inhibit release of a number of neurotransmitters including glutamate and GABA Effects of marijuana on the body Appetite stimulation AKA the munchies Heart 0 Increased heart rate this could be a risk for people with heart problems Lungs 0 Reduced air ow there may be a link between smoking marijuana and lung cancer but this is still being studied Reproductive system 0 Marijuana does not make males or females sterileinfertile o It can reduce the likelihood of pregnancy because it suppresses hormones that regulate the reproductive systems Males reduced sperm count Females irregular menstrual cycles 0 Because marijuana does not affect the breathing center in the brainstem it is less dangerous than drugs that do such as alcohol and barbiturates because it will not lead to respiratory depression 0 There is no published report of anyone dying from cannabis overdose large margin of safety but there is still a risk with high doses but not due to a direct neurochemical effect of the drug Tolerance Tolerance to THC can develop but not as de nitively as with other drugs such as cocaine and amphetamines Frequent users can feel less high with time but can get a placebo high sometimes smaller than a normal high 0 There is evidence for pharmacodynamics tolerance including down regulation of cannabinoid receptors Dependence About 10 of people who ever try marijuana will become dependent o It is rare for users to have a signi cant craving for marijuana It is rare users will have difficulty controlling use of the drug as much as with cocaine or amphetamines Addiction o It was originally thought there was no risk of addiction to marijuana because it didn t affect the dopamine reward pathway 0 Recent studies in animals suggest it can increase dopamine release from the VTA which can affect the reward pathway so the jury is still out scienti cally o It is critical to realize that activation of the dopaminergic reward pathway is not all or nothing 0 Anything pleasurable can activate the reward pathway 0 Maybe things like food sex and marijuana only increase dopamine somewhat whereas a drug like cocaine increases dopamine much more and is thus more addicting Withdrawal 0 Typically mild even from high doses andor regular use involving irritability restlessness insomnia sweating mild nausea depressed mood o Akin to withdrawal from nicotine Effects on the brain o The high 0 Marijuana doesn t t neatly into other drug categories eg stimulants depressants opiates 0 Many people don t get high the rst few times 0 Subjective experience of the high varies widely but can include Increased sensory perception Visual images may seem more intense or more meaningful Feelings often seem more intense 0 Generally the user interprets these changes in cognition and feelings as positive but the interpretation also depends on the situation in which they occur 0 Can get hallucinations paranoia andor agitation at very high doses 0 Many users nd it hard to describe the high 0 Perception of time changes usu slows down quotpot timequot 0 Perhaps these phenomena occur because the hippocampus is one of the main regions of the brain affected by cannabinoids The hippocampus is involved in the formation of new memories Inhibition of memory formation not recall by marijuana is its most wellestablished negative effect on mental func on One of the 2 main endocannabinoids can affect memory 0 Memory and mental function 0 Marijuana reduces creation of new memories but not old ones 0 Can reduce problem solving abilities mental exibility 0 Effects on memory and other cognitive functions can last up to 48 hours 0 Driving while high on marijuana is not safe Marijuana dose impact driving because it decreases attention concentration and the ability to make corrections Re exes might be ne unlike with alcohol but driving is still not safe Does marijuana kill brain cells It is still not clear which changes in brain function are permanent and which are not This is very dif cult to study in part because you can t control the marijuana intake well and certainly it is impossible to blind the study if you are not controlling marijuana intake from the start Currently most of the scienti c evidence suggests that for most doses and rates of use most people do not experience loss of neurons from using marijuana There might be subtle types of damage caused by recreational marijuana use that haven t been identi ed Does marijuana use do permanent harm if it is used during adolescence It is affecting a stilldeveloping brain Would this change the way neurons connect o If so this is less exible than some of the other brain changes we ve talked about eg changes in numbers of neurotransmitter receptors Cognitive impairments 0 These may be long lasting and this may be particularly true of people who start in their teens 0 Studies of occasional recreational use are dif cult to do Psychological disorders 0 Marijuana use can cause psychotic symptoms hallucinations delusions similar to those experienced in schizophrenia o The vast majority of users never show these symptoms but what if someone is predisposed to psychosis ie for genetic reasons Does marijuana have legitimate medicinal uses In 1937 the Marijuana Tax Act essentially stopped all legal medical use Marijuana was declared a DEA schedule drug as of 1970 In 1988 after 2 years of hearings the administrative law judge for the DEA Francis L Young wrote that marijuana was one of the safest therapeutically active substances known to man and that marijuana ful lled the legal requirement of currently acceptable medical use 0 His order that marijuana be moved to schedule II was overruled by the DEA An argument against medicinal use of smoked marijuana is that there is a danger of damage to the lungs and there are carcinogens in the smoke Proponents of medical marijuana point out that there are non smoking ways to deliver marijuana and it is otherwise very safe Potential medical uses 0 Control of nausea related to chemotherapy A drug called Marinol is actually used for this and classi ed as a DEA schedule ll drug but some say the medicine is not as effective as marijuana itself 0 Glaucoma o Seizures Still being researches There may be strains of marijuana that would minimize the high for those who don t want it Hallucinogens 1 10212015 A description of the rst LSD trip 0 Albert Hofmann was the rst person to ingest LSD and he did so quite by accident 0 quotLast Friday April 16 1943quot LSD mein sorgenkind development of LSD LSD was developed as a potential new circulatory and respiratory stimulant an analeptic 0 Compound 25 in this project LSD25 didn t work as an analeptic so it was not used for anything 0 5 years later Albert Hofmann reexamined LSD25 because he thought it might still have some promise as a medication 0 1 day while making LSD25 in his lab he accidentally ingested some and had to go home which is when he experienced the effects quoted LSD was then produced under the name Delysid quotfor the purpose of helping neurotic patients uncover repressed thoughts and feelingsquot De nition of a hallucination Hallucinogens 0 Drugs that can change one s thought processes mood and perceptions without producing a state of delirium At high doses can cause people to perceive that an experience is actually happening when in fact it is not by de nition a hallucination As lower doses can cause milder disturbances of perception thought and emotion but not complete fabrication of unreal events 0 Sometimes these drugs are said to mimic mental illness but they don t really do so 0 Can cause a psychotic experience a susceptible person but not quite like a psychotic episode in schizophrenia Related word 0 Psychedelic 0 Late 19505 0 quotmind expandingquot categories of hallucinogens 0 group 1 LSD or serotonin like 0 LSD o Psilocybin o Mescaline peyote 0 Others DMT Bufotenine 2CB Ayahausca Salvia Divinorum Group 2 Belladonna alkaloids o Jimsonweed which contains atropine and scopolamine Group 3 dissociative anesthetics o PCP o Ketamine special K o Dextromethorphan in cough syrup History of hallucinations Hallucinogens have a rich history and a great diversity of uses 0 Known to the early Greeks 0 Use of peyote cactus by Native Americans in what is now the southwest US and northern Mexico o Siberian hunters discovered y agaric mushroom because the reindeer grazing on them had abnormal behavior Current use of hallucinogens LSD is the most commonly used hallucinogen but is a small percentage of the population Powerful experience that is not typically quotfunquot Law enforcement has made hallucinogens difficult to get Native Americans and others use hallucinogens for religious purposes What is a typical hallucinogen trip like The experience varies widely depending on a user s previous drug experience expectations and the setting in which the drug is taken Common effects include o Trips starting with nausea jitteriness an increase in blood pressure heart rate and breathing o For low doses slight distortion of sensory perception often visual distortions o For higher doses usions pseudohallucinations or actual hallucinations Can include feeling as though one is watching one s actions from outside one s body Synesthesia confusion of the senses eg seeing sounds or hearing colors Time is distorted Often at the peak of the trip users describe a sense of profound understanding enlightenment or being quotone with the worldquot As the trip wanes can experience anxiety fatigue quototherworldly sensequot How to make a bad trip stop There is no good way to do this 0 Typically just need to wait for the liver and kidneys to do their jobs o If a trip is a bad one the most that can usually be done is to receive support from other people hopefully sober friends Hallucinogen group 1 LSD or serotonin like LSD lysergic acid diethyl amide 0 Made in a laboratory in the 19405 but similar molecules have been used for thousands of years and are found in Fungus on rye Seeds of certain morning glory plants 0 Administration Most commonly is dissolved in liquid and drops of this are put onto absorbent paper which is put on the tongue LSD is the most potent of commonly used hallucinogens a Typical doses are 50150 ug 1 millionth of a gram Tolerance develops rapidly which is 1 reason use is typically infrequent eg once a week to once a month 0 Typical trip 030 mins a mild ght or ight response heart rate and blood pressure increase pupils dilate 3060 mins a visual patterns feelings of unreality lack of coordination 14 hours a bizarre visual effects euphoria slow passage of time 47 hours a waning of above effects 712 hours a returning to normal late effects a headache fatigue contemplative state can also experience synesthesia which is confusion of the senses eg seeing sounds or hearing colors psilocybin mushrooms magic mushrooms shrooms O O O 0 contain psilocybin which is converted to the related compound called psilocin only psilocin can enter the brain so it is the main psychoactive ingredient often consumed as dried mushrooms are similar to LSD in the effects they produce though the effects are often milder and shorter peyote cactus mescaline O O O o DMT 0 has likely been used as a hallucinogen by native peoples in Mexico for thousands of years hallucinogenic ingredient is mescaline the chemical structure of mescaline is not similar to other hallucinogens more similar to amphetamine actually quite similar to the neuromodulator norepinephrine in structure users get the physical effects of amphetamine eg increased heart rate and blood pressure but the psychoactive effects are more like LSD usually consumed as dried plant peyote button Somewhat similar effects as LSD but the whole trip is over within an hour 0 Bufotenine 0 Found in the skins of some toads 0 Also a brief trip 0 Can cause temporary paralysis 2CB o a synthetic hallucinogen with LSDlike effects Ayahuasca 0 An herbal tea containing DMT and harmala alkaloids Salvia divinorum 0 Plant that causes an intense brief and often unpleasant hallucinatory experienced when smoked Group 2 belladonna alkaloids Have been used medically for thousands of years and ritually for evenlonger Are usually obtained from prescription medications that contain them or from jimsonweed Active ingredients 0 Atropine Has effects outside the brain and can be lethal o Scopolamine Enters brain easily and causes the psychoactive effects Belladonna alkaloids mimic shutdown of the parasympathetic nervous system 0 Dry mouth Pupils dilate Heart rate increases Airway passages in the lungs dilate OOO 0 Can also cause a dangerous rise in body temperature 0 Block one type of acetylcholine receptor that is important for memory so users don t often remember the experience 0 The trip 0 Delirium that users only remember as strange dreams often with the sensation of ying Group 3 dissociative anesthetics PCP angel dust O O 0 Was originally tested as a potential anesthetic agent but it caused symptoms in patients that were not compatible with surgical use Then it became a street drug Forms include Pills Powder for snorting Rocks that can be smoked or injected Can also coat tobacco marijuana or parsley leaves Can produce a state similar to getting drunk taking amphetamine and taking a hallucinogen simultaneously Users often get in trouble with the law Poor driving skills Bad judgment Not attending to their environment lnsensitive to pain Can be out of touch agitated belligerent At high doses Muscle rigidity General anesthesia Coma Seizures Respiratory depression High body temperature High blood pressure 0 Ketamine special k 0 O O 0 Like PCP this was originally tested as an anesthetic but it caused adverse reactions Usually is a solution for injection or a powder to be snorted At low doses similar to being drunk At high doses feelings of being cut off from reality including out of body and near death experiences khole o DXM dextromethorpha n O 0 Main ingredient in cough syrup To get a psychoactive effect need to drink from a quarter of a typical bottle of cough syrup to 2 whole bottles this can cause nausea and vomiting At high doses causes hallucinations a dissociative state and delirium Hallucinogens 2 Categories of hallucinogens Group 1 LSD or serotonin like 0000000 0 LSD Psilocybin Mescaline peyote DMT Bufotenine Ayahuasca Salvia divinorum 2CB group 2 bellanodda alkaloids o jimsonweed which contains atropine and scopolamine group 3 dissociative anesthetics O O o Dextromethorphan in cough syrup Pharmacokinetics of hallucinogens PCP Ketamine special k 10212015 0 Usually ingested and can be absorbed easily through the lining of the stomach and intestines o PCP is an exception and is usually smoked or injected 0 Time to feeling the effects of a drug and the duration of the effects differ depending on the drug o If a drug is very fat soluble lipid soluble the effects will be felt faster because it can easily get into the bloodstream and cross the blood brain barrier o The duration of a trip depends on how fast a drug is degraded eg by enzymes in the liver Overdose Overdosebad effects of hallucinogens can be divided into 2 general categories 0 1 Those that cause mainly psychological problems LSD like drugs 0 2 Those that are more physically dangerous belladonna and PCP like drugs withdrawal 0 hallucinogens rarely have withdrawal symptoms 0 most hallucinogens produce rapid tolerance potentially by down regulation of speci c types of serotonin receptors abuse hallucinogens generally have a low abuse potential relative to most other recreational drugs exceptions to this are the dissociative anesthetics ketamine and PCP because they affect the dopaminergic reward pathway and can be highly addictive and difficult to quit hallucinogen ashbacks ashbacks are de ned as the reexperiencing following cessation of use of a hallucinogen of 1 or more of the perceptual symptoms that were experienced while intoxicated with the hallucinogen about 45 of recreational users and 3060 heavy users get ashbacks can be triggered by marijuana and maybe SSRls selective serotonin reuptake inhibitors a class of antidepressants why would ashbacks occur 0 LSD may permanently alter the brain 0 Suggestion by context How do hallucinogens work 0 Less is known than most other psychoactive drugs 0 There are multiple neurochemical routes to hallucinatory states though each of these routes has a somewhat distinct hallucinatory effect 0 These drugs may interfere with normal gating letting in or restricting of sensory information causing overloading of the cortex How do serotonin like hallucinogens work LSD and psilocin are chemically similar to the neurotransmitter serotonin 0 Effects of serotonin are complicated but include regulating sleep and maintaining normal body temperature 0 Drugs that enhance the effects of serotonin can treat depression and overeating Why would these drugs differ in their effects Eg why would this class of antidepressants not cause hallucinations 0 Answer there are many types of serotonin receptors Many of these are in the cerebral cortex 1 speci c type can trigger hallucinations when stimulated serotonergic neurons serotonergic neurons in midbrain and hindbrain send their axons throughout the brain serotonin affects eating behavior anxiety pain and learning 0 also affects convergence of outside stimuli and internal thoughts and feelings MDMA ecstasy E XTC Molly Adam 0 Drug molecule 5 similar to both amphetamine and mescaline in structure 0 Thus it has both stimulant and hallucinogenic effects 0 Synthetic drug that became popular in the 19805 for recreational use often at raves Quickly became a schedule drug 1985 0 There is a pervasive problem with ecstasy being sold on the street and not really being pure MDMA Administration 0 Usually taken as pills note that there is a signi cant danger from contaminants 0 Well absorbed from GI tract peak blood levels in an hour 0 Effects last 36 hours Pharmacokinetics o Ecstasy binds to the serotonin transporter 0 Blocks reuptake 0 Also promotes release of serotonin o Affects monoamines to a lesser degree 0 Effects 0 Causes a combination of amphetamine and hallucinogen like effects 0 Behavioral effects Enhanced perception of sensory stimuli distorted time perception Euphoria and increased con dence Desire to interact with others Increased empathy and connection with people 0 Physical effects Increased activity Stimulation of the sympathetic nervous system a Increased heart rate and blood pressure a Increased body temperature and sweating Tolerance and withdrawal 0 Most users report that after multiple exposures the positive effects of the drug are not as pronounced o A hangover effect may occur after using ecstasy that includes insomnia depression and difficulty concentrating 0 Usually doesn t follow the compulsive pattern seen with cocaine heroin etc 0 Can be lethal under certain circumstances Heart attack or brain hemorrhage Overheating n The combination of taking ecstasy with prolonged and vigorous dancing raises body temperature to dangerous levels and some users have died of heatstroke How dangerous 0 Main problem is overactivation of sympathetic nervous system Dangerous effects due to dehydration and body temperature increase and physical activity Increased body temperature may contribute to muscle breakdown and kidney failure Can cause seizures at extremely high doses Relatively few overdoses deaths 0 Long term effects Some studies show residual anxiety impaired memory Long term loss of serotonin axons in monkey cerebral cortex after high doses Decreased function of serotonin neurons in chronic human ecstasy users but it is not clear whether this happens with occasional use How do the belladonna alkaloid hallucinogens work 0 These drugs prevent the action of muscarinic acetylcholine receptors an anticholinergic effect 0 These receptors are found in the brain and in other parts of the body 0 They increased heart rate and are involved in the formation of memories Myths about hallucinogens There is no credible research on hallucinogens LSD will make you crazy LSD will break chromosomes disrupt DNA and can cause birth defects Dangers with use of hallucinogens Users cannot be sure what they are really taking if they buy on the street 0 For example Street LSD is only actual LSD 50 of the time Any drug synthesized in an underground laboratory can have contaminants in it from the manufacturing process Hallucinogenic mushrooms can be misidenti ed While LSD psilocybin and mescaline do not usually cause dangerous physical effects they can lead to bad trips involving intense anxiety and fear 0 quotOne person s enlightenment can be another person s hellquot Flashbacks o Reemergence of parts of a hallucinogenic experience in the absence of the drug are relatively uncommon but can last for years after abstinence Psychotic episodes 0 Some people experience psychotic episodes as a result of taking hallucinogens but this seems to mostly occur only in people who were previously diagnosed with a psychotic disorder such as schizophrenia Ketamine may kill neurons at high doses Belladonna alkaloids 0 Can increase heart rate and body temperature to dangerous levels that can be lethal o The doses taken to get hallucinogenic effects are toxic The behavioral effects themselves such as delirium are signs of overdose 0 Note that overdoses of these drugs can be treated only if medical personnel know what the intoxicating drug is PCP can cause death from overdose at 25 times a single recreational dose 0 Can cause body temperature to rise to 108 degrees F 0 Blood pressure can get high enough to cause a stroke 0 Breathing can stop 0 Seizures can occur 0 Can have long periods that resemble paranoid schizophrenia Drug interactions The most dangerous interactions are PCP and sedatives such as alcohol because these all cause respiratory depression and the effects can add up and be fatal Another problem is taking something without knowing it eg PCP and marijuana Dangerous drug combinations 0 PCP like drug and sedatives including alcohol 0 Atropine like drug and anything that stimulates the cardiovascular system or raises body temperature eg ecstasy o Hallucinogens with amphetamine like actions eg mescaline and stimulants
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