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Drugs and Behavior/PSY 245 - 4/12

by: Kristi Dorsey

Drugs and Behavior/PSY 245 - 4/12 PSY 245

Kristi Dorsey
GPA 3.871

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Lecture notes from 4.12.16!
Drugs and Behavior
Mark Galizio
Class Notes
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Popular in Psychlogy

This 9 page Class Notes was uploaded by Kristi Dorsey on Monday April 18, 2016. The Class Notes belongs to PSY 245 at University of North Carolina - Wilmington taught by Mark Galizio in Spring 2016. Since its upload, it has received 8 views. For similar materials see Drugs and Behavior in Psychlogy at University of North Carolina - Wilmington.


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Date Created: 04/18/16
4.12.16 Phenethylamines  Chemically similar to MDMA but effects can be LSD-like or MDMA-like o Shulgin synthesized and experimented with hundreds of PEAs o 2C-B, 2C-I, 2C-T-2, T7, etc. o The serotonergic-like effects (act like LSD) are said to act like that because they produce vivid visual hallucinations o MDMA drugs do not (big difference between the two) o There are hundreds of these o PEAs are sold in head shops and on internet – some still legal  All of them are potentially illegal because they are analogues of schedule I drugs o Some of them are expressly legal but many of them are not explicitly illegal in the US  Because there’s so many and such very little research on this, most of what we know about some of these drugs is on the internet or what Alexander Shoegin wrote about in his diary-like account  When these drugs are sold on the web or in shops, the doses are also unknown; people are basically guessing about the appropriate dose of these drugs which might be informed by the batch they got last time; which might not be the same drug as what they’re getting this time; as a result there have been a ton of problems with these drugs  Internet preparations of 2C-I and 2C-E led to a substantial number of fatal overdoses last year Wilmington  25 year old Wilmington woman Stephanie Hobson died of 25-I (2C-I NBOMe) overdose July 18, 2012  Went into a coma and her boyfriend who was also there and gave her the drugs and who was also under the influence of the drug did not call 911; really unclear why; for hours she was in trouble and he didn’t call; when he finally did it was too late to save her  Boyfriend Jeremy Leutgens convicted of involuntary manslaughter Sept. 24, 2013 Synthetic Hallucinogens banned by July 2012 Synthetic Drug Abuse Prevention Act (the law that banned several of the bath salts; also banned some of the synthetic cannabinoids spice and K2 but also some of these phenethylamines/PEAs are also covered; particularly so that 2C-E and 2C-I are now illegal)  Dozens more PEAs remain legal  Every year the DEA are looking at these compounds, which ones are being sold legally on the internet, some of them are then banned o When these listed drugs were made illegal, people who sell and synthesize them shifted to other PEAs o The ones that are now available are even less well-known than those o When the DEA sees some that are popular on the web, they ban those, then the chemists and people who sell these drugs shift to different chemical structures o Therefore, some of them are likely to be dangerous Methylated Amphetamines (name captures that these drugs are both chemically similar to the amphetamine drugs that you’ve already studied and the effects in fact are very similar; if you consider MDMA, ecstasy, or the other drugs in this group, if you think of these as being more like amphetamines than LSD, you’ll be on the money  Methylenedixoymethamphetamine/most famous (MDMA OR Ecstasy, XTC, Molly) o Molly tends to be referred to powder form of MDMA  Methylenedioxyamphetamine (MDA)  MDE (Eve)  Number of similar compounds; dozens of PEAs; several of them are ecstasy-like in terms of their actions; famously MDA and then MDE, sometimes known as eve  We think of these drugs as being recent, popping up in the 90s and the 2000s; however, they go back to the turn of the century when the German “Merck” pharmaceutical corporation was first developing the amphetamine compounds; they synthesized MDMA, along with many of the other amphetamines  In some preliminary research, this drug was sort of forgotten/didn’t come back until the 1970s when a few individuals were advocating it as an adjunct to psychotherapy History  Patented by Merck in 1914  Advocated by some as adjunct to psychotherapy (1970s – 80s) o The problems (still under study) with LSD is that the drug is so unpredictable and many patients had bad experiences under the drug o MDMA was thought to have some potential because it doesn’t produce the visual hallucinations that LSD does  Picked up the name “ecstasy” and became significant street drug (1980s) o Particularly in the Southwest and Midwest  Schedule I drug (1986) o Very quickly came under review o Research suggested that there were potential products with this o Basically ended all human research on ecstasy until quite recently where it’s started up again o Didn’t discourage the use of this drug very much o Became one of the most popular drugs in the US and throughout Europe  Prototype “club drug” (1990s) o Most popular drug in Australia o Drug that was used in dance clubs/night clubs o Associated with techno pop music o Classic drug to be used in raves Ecstasy (MDMA): Psychological Effects  Increased alertness, arousal, insomnia –stimulant effects  Euphoria, increased emotional worth (this feeling is unique as told by users)  Entactogen: increased empathy and insight? o DeWit (2014; 2015) subjects on MDMA showed more sociality, empathy, and more o liking for others than those on Meth or placebo o Many psychopharmacologists have advocated that ecstasy’s effects are different enough that they shouldn’t be called hallucinogens o It doesn’t produce vivid hallucinations o There should be a new class of drugs called Entactogen o Effects are hard to discriminate  In drug discrimination procedures, animals respond to ecstasy as if it were amphetamine and vice versa and there aren’t many studies with people but those that have been done are very similar; effects are hard to discriminate o There are a few studies, particularly in more recent years (Harriet Duwet at the Univ of Chicago) has been studying individuals UTI of ecstasy and methamphetamine as well o Generally, she has found that subjects on MDMA (double-blind) show more sociality, more social and they report on questionnaire like studies more of a liking towards others than people on meth or placebo  Both amphetamines and ecstasy, if you take them in a social situation, individuals will talk more than they do under placebo  Dewitt’s studies go like this o Individuals are volunteering to be in a study where they’re going to get a stimulant drug o Told they won’t’ know which drug they’re getting  Hallucinogenic effects are largely absent  They’re interested in studying the effects of the drugs on cognition  Take the drug and wait for about an hour until the drug reaches its full effect then bring you into the test area to go through a computerized test battery o What she’s interested in is what you do in that 60 minute waiting period o How much social behavior is there? o If the individual’s on meth and ecstasy, generally they talk more/have more social interaction compared to placebo conditions o Any stimulant will tend to increase social behavior at low/moderate doses o Is ecstasy different?  You’ll be in a waiting room for about an hour  Some of the people who are in the study are in a group room and you can wait with them if you want  Some individual rooms where you can sit alone and read magazines  Would you rather wait with others or wait alone?  More people chose to wait with others when on ecstasy (seems to be more prosocial behavior with ecstasy compared to meth) Physiological Effects of MDMA  Sympathomimetic effects – also produced by LSD, psilocybin, and peyote, amphetamines, cocaine, nicotine, and caffeine  Stimulant-like effects of these drugs are pretty intense; ecstasy is famous for producing muscle tetany (other stimulants and hallucinogens can produce this too but more prominent in MDMA users o Bruxism (grinding) trismus (clenching jaw) – can be quite uncomfortable/why pacifiers were popular in these all night raves or clubs  Dehydration o Partly an effect of the drug and an effect of dancing all night/intense physical activity while under the influence of the drug o People would drink a lot of water, but losing a lot of salts, so need to drink something with electrolytes (Gatorade)  Hyperthermia (overheating not uncommon; augmented by the effects of the drug)  Tachycardia; like any stimulant, these drugs can produce a dangerous increase in heart rate; especially dangerous in individuals with heart problems  There have been cases of collapse or overdose deaths with ecstasy, but usually due to being overheated and dehydrated  The controversy was over the possibility that ecstasy could produce brain damage Percent High school seniors reporting MDMA use during their senior year  Peaked in about 2001, about this time is when we were getting a lot of data coming out about the hazards of this drug and you can see that the % using ecstasy during their senior year in highschool dropped in the early 2000s and it’s been pretty flat; didn’t go away by any means Ecstasy and the brain (acute levels)  Think of it in terms of effects of amphetamines  MDMA increases release and blocks reuptake of serotonin  MDMA also increases release of (to some degree block reuptake of) dopamine and norepinephrine o Those effects are similar to the effects of amphetamine  What’s different from ecstasy and the serotonergic hallucinogens? o Remember that the serotonergic hallucinogens act only on one/agonists on one highly specific serotonin receptor subtype; whereas, ecstasy is effecting serotonin throughout the brain o That seems to make a big difference although we don’t really understand why LSD vs. Ecstasy  Serotonergic hallucinogens chemical structures vary, but all are agonists of serotonin – 2A receptors (5-HT2A) – that what seems to be critical to produce these pronounced visual hallucinations  Methylated amphetamines (i.e. MDMA ecstasy) stimulates/blocks reuptake of these monoamines o The stimulant drugs that affect all of those collectively just don’t seem to produce those visual hallucinations  The worries are that ecstasy might produce a long-term effect o Long term depletion of serotonin – damage to serotonin neurons in nonhumans o As early as the 1980s, animal research was showing that exposure to relatively high doses of ecstasy would initially increase serotonin levels but eventually deplete serotonin o Some evidence that there was damage to the neurons that contained serotonergic neurons in the brain o That’s what sparked controversy that is still with us today  Big issues: do the findings from the animal literature apply to people? In the controversy, one argument is that in the animal studies, they’re given a huge dose and people don’t ever take doses of that magnitude Are doses used in preclinical research too high?  Although neurotoxic doses in non-humans (5-20 mg/kg twice or more/day for several days) are higher than typical human use, people often take several tablets at a time or throughout an night’s binge and a tablet may contain up to 300 mg: 4-5 mg/kg in an average person  If a person takes several MDMA tablets at a dance club, some of these tablets are up to 300 mg  A person in a weekend might take doses of 4-5mg/kg  That’s on the low end of what seems to be neurotoxic in animals, but it’s definitely in the range  Reason to think that people who are heavy users may be giving themselves doses in toxic ranges What’s in the pill?  Use self-reports to study this o Individuals don’t always know what they’re taking  Molly vs. Pills  Piperazines: MCPP, TFMPP o Developed to treat worm infestations o Amphetamine-like stimulants o Now Schedule I o Often sold as “Molly”  o Analyzes drugs that people send in/buy on street o Do an analysis of it and post a picture of the pill, where it was purchased, and what it actually contains o Over the last several weeks and months, some of the pills that people have sent in turn out to be ecstasy o Many of them turn out to be other stuff; sometimes they’re amphetamine, sometimes they’re benzos, sometimes they’re cocaine, some of them contain synthetic opiates  In the late 1990s early 2000s the National Institute on Drug Abuse posted this graphic on its website o Slides of individuals’ brains on the top under control conditions and the bottom were composite/ PET scan data for individuals who are heavy ecstasy users o Basically shows serotonin receptor binding in the brain o The bright whites and orange show high levels of serotonin binding – the darker areas/reds and blacks show low levels or an absence of serotonin binding o What this graph really does show is that heavy users show low levels of serotonin binding o Less serotonin activity in their brains for a period of time o That’s not the way these data were interpreted by highschool instructors, drug counselors, etc.  They began to make the claim that ecstasy makes holes in your brain  This is binding data – looking at areas of reduced serotonin activity  All of the antidepressant drugs elevate serotonin levels in moderate ways and that in depression low levels of serotonin are thought to be characteristic  There have been lots of studies where heavy ecstasy users have been given questionnaires like the Beck Depression Inventory and other stuff and the question is are they different? Do they show anomalies in that?  The other thing serotonin is important for is sleep Ecstasy in Humans  Iversen (2008) review: heavy users more depression, sleep disorders, memory problems than controls  A number of others studies have continued looking at this; doesn’t look like the depression and sleep disorder findings are very consistent  But, the memory problems show up in just about every study that compare users with non-users  What is the proper control group?  Dauman et al. (2004) – Heavy ecstasy users more depression than non-users, but not more than other drug users (if you had a control group of people who used drugs other than ecstasy, they also showed levels of depression that were similar to the ecstasy users o It could be that generally individuals who are reporting high levels of drug use on their surveys are more depressed or are more likely to report depression symptoms o In any case, there doesn’t seem to be any clear evidence that links ecstasy to producing depression  Same problems with memory deficits though  De Sola et al. (2008) – Memory deficits in MDMA users, but also in group matched for THC use that used no MDMA o If you compare ecstasy users with people who don’t use drugs, you see that there are a variety problems with memory tests o But if you have a matched control (matched for how much marijuana they use)  Almost all heavy ecstasy users are heavy pot smokers  3 groups: non-users, ecstasy users, and just as much marijuana but doesn’t use ecstasy  You see that the memory deficits are the same  Not clear that there are functional effects in terms of problems associated with ecstasy Ecstasy in psychotherapy?  Clinical trial for PTSD – Mithoefer (2011; 2013) better improvement with MDMA-aided psychotherapy Medical uses of hallucinogenics?  Anxiety/depression in terminal patients (LSD, psilocybin) – research ongoing o Working with people at John Hopkins who are dying of cancer o They volunteer to take these drugs and they’re seeking the kinds of spiritual experiences that many have reported o Some evidence that the anxiety and depression in these terminal patients can be improved by these drugs  Addiction (psilocybin, ibogaine) – research ongoing o Based on reports by some addicts who have reported that they changed their lives after an experience with one of these drugs o Research is not convincing at this point  PTSD (MDMA) – research ongoing o Seems to be some positive results with this  Depression (ketamine, psilocybin) – research ongoing Anesthetic Hallucinogens  Phencyclidine (PCP, Angel dust, Lovely)  Ketamine (Special K) o Most popular and most widely distributed worldwide  Both of these are scheduled drugs  Methoxetamine (mexxie, roflcopter) o Not banned; legal drug right now o Effects very similar to ketamine o Sold on the internet as mexxie or roflcopter o Effects are very similar to PCP and ketamine so far in his research lab Anesthetic Hallucinogens different than other hallucinogens we have talked about  Glutamate antagonists – they act through a completely different neurotransmitter system (the Glutamate system) o Glutamate is one of the most abundant excitatory neurotransmitters in the brain o These drugs/all of these anesthetic hallucinogens act on that system  Produce a euphoria, numbness, loss of motor coordination, blurred vision  Rapid eye movement (nystagmus – show up more dramatically than with other drugs)  Distortions of body image not visual hallucinations – in the K-hole o Might tell you they can’t move and their legs are enormous o Feel as if their mind is away from/outside their body and they can see themselves  That’s what we mean by dissociation  High rate of psychotic episodes some long-term – model for schizophrenia? PCP is linked with a lot of problems (not so much the other two) o These drugs have been problematic o High rate of psychotic episodes that have occurred, particularly with PCP o Ketamine seems more mild o Nobody knows about methoxetamine o Hot topic is whether these drugs might be modeling the symptoms of schizophrenia (looking into whether or not glutamate might be playing a role in schizophrenia  Ketamine as a rapid treatment for depression? o Ketamine is sometimes used in humans as an anesthetic o PCP and ketamine sometimes called an animal tranquilizer o Used to produce anesthesia in humans o Can perform surgery on someone under the influence of PCP and ketamine; they can talk, but they’re conscious, respiration is good; in terms of anesthetic, it’s safe o Problem with PCP is people would sometimes have bad trips under the influence or when coming down on it  PCP never used in human surgery (people coming down with a bad trip and jumping off a table after surgery) but sometimes used in veterinary medicine o Ketamine still used as anesthesia in humans  In one case an individual was undergoing a medical procedure  Person very severely depressed  When they came out of the surgery, they reported that their depression was listed  Ketamine given to people as a treatment for depression – has produced a rapid lifting of depression  Clinical trials going on all over the country looking at the possibility that ketamine can produce rapid treatment for depression  How long do these effects endure?  Two things that are key is the relief from depression was very rapid/instant o Antidepressants take daily use for 10 days to 2-3 weeks before they start working; slow and there’s a period of 1-3 weeks where person is taking the medication but not experiencing any benefits from it  Seems to be weeks and months later o After ketamine, start person on antidepressant medication o If the depression stays gone, is it because of the antidepressants and ketamine? Naturally-Occurring Opiates  Opium (original opiate) – from the poppy plant  Native to the Middle-East and Asia o More than 90% of the world’s opium is grown in Afghanistan  The poppy has always been a symbol of the two-sided coin that is drug use o We’ve always had poppies on the front of the book as red o Poppy on this current addition is white o The art director said that opium poppies are usually white o Nice pretty poppy to illustrate the benefits of opiate drugs in particular, most important pain relievers in the world o Have relieved more human suffering than any medical procedure in history  When you think of what’s bad about drug, the prototype drug of addiction is heroin o That’s the other side/less positive side of opiate drugs  The opium poppy – discovery of its psychoactive effects go back to Ancient Egyptians  Greeks used opiate to treat pain and for euphoric effects  Widespread drug throughout Asia  Only when petals fall off and it forms a seed pod is when it’s ready for harvest o Take seed pod and cut it with razor blade/knife o Gummy sap oozes out of seed pop o Gathered, dried, and becomes a dark/gummy substance called opium o Can be taken orally or smoked to produce these psychoactive effects Naturally-Occurring Opiates  Opium – from the poppy  Morphine – from opium  Codeine – from opium  Opium is not a name for the drug itself; it’s a name for the dried resin produced from the poppy; it contains two different biologically active chemicals (both opiate drugs – morphine and codeine)  In the 19 century, a German pharmacologist isolated this morphine from the opium product and took it and found that it produced an intensely pleasurable, blissful, and dreamlike state, so he actually named this product after the Greek God of Dreams (Morpheus)  Morphine, because of its pain-relieving and dream-like properties, is the major active ingredient in opium but it also contains codeine  Both of which are capable of delivering the psychoactive effects of opium th  Morphine was widely used/hailed when it was discovered in the 19 century, as a God send, because it was so much more powerful at relieving pain than was opium itself  Physicians in Europe basically hailed morphine as a savior  It was prescribed so liberally and so often to people that were in pain that it became known as the “Soldier’s Disease” in Civil War America o Became addicted to it  Around the turn of the century, another German pharmacist discovered that with a slight twist of the morphine molecule, he could make a drug that was 10-20x more powerful at relieving pain than morphine o The pain relieving effects were seen as heroic and the drug was called heroin o The Bayer pharmaceutical firm began to market heroin as an ingredient in aspirin o Those historic events set the stage for what was to come o Widespread use of heroin and morphine in Europe and the US became a major addiction problem o In 1914, the Harrison Act was passed (first major drug laws targeted primarily at heroin and morphine – became the first illegal drugs in the US  Naturally occurring opiates are opium directly from the poppy; codeine and morphine from opium; and then a slightly synthesized from morphine, heroin


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