ADAM PRUS: Hello, my name is Doctor Adam Prus,and I'm a professor of psychology at Northern MichiganUniversity.My research interests concern learningabout psychoactive drugs, includinghow they act in the brain and how theyproduce behavioral effects.I conduct psychopharmacology experiments in my laboratoryand I write about psychoactive drugs

ADAM PRUS [continued]: in an introductory segment textbook and psychopharmacologyfor psychology students.In this presentation, I'll be discussingthe way is a drugs of abuse and recreational substances actin the brain to produce their behavioral effects.I will be addressing the following questionsin this tutorial.What is a drug?How do drugs reach the brain?

ADAM PRUS [continued]: What parts of the brain do drugs affect?How do drugs affect neurotransmission?How do drugs produce rewarding effects?What are the effects of stimulant drugs?What are the effects of depressant drugs?What are the effects of cannibals?What are the effects of psychedelic drugs?And how can drugs become addictive?

ADAM PRUS [continued]: It's important to learn about psychoactive drugs,because their use is highly prevalent.The vast majority of humans use the substance caffeine,for example, and many use tobacco and drink alcohol.Consider the following recent statistics in the US.There are over 200 million prescriptionsfor pain-relieving drugs every year.

ADAM PRUS [continued]: Over 114 million drink alcohol on a regular basis.And more than 25 million use marijuana.More than 15 million misuse prescription drugs.And more than 70 million use tobacco products.Caffeine, as I mentioned earlier,is one the most widely used substances.In fact, in the US approximately 90%

ADAM PRUS [continued]: use caffeine from any variety of sources.Now include psychoactive medicationssuch as treatments for ADHD or attention hyperactivitydisorder and one can see the greatthe prevalence of drug use.In fact, students of psychology can hardlylearn about normal human behaviorwithout some knowledge of psychoactive substances.

ADAM PRUS [continued]: [What is a drug?]A drug is a rather imprecise term,and it's difficult to define, but let's try this definition.We'll use the definition "An administered substance thatalters physiological functioning."the term "administered" states that someone takes a substance

ADAM PRUS [continued]: or is given the substance, thus itexcludes something made naturally in the body.This differentiates something like dopamine,the neurotransmitter and hormone,from the dopamine, the same substance thatmight be administered by a physicianto elevate someone's heart rate.The term "physiological functioning"from that definition implies the drug causes or could

ADAM PRUS [continued]: cause some change in the body.This, too, is a challenge.After all, wouldn't food count as a drug?What about a vitamin?We also find that the manner of a drug's use is important.We use the term "instrumental" to referto using a substance toward addressing a specific purpose.For example, using an antidepressant drug

ADAM PRUS [continued]: to treat depression or the drug Vicodin to treat severe pain.We normally consider instrumental useto be the same as being used for therapeutic purposes.The term "misuse" refers to using a substancefor its unintended purpose.For example, someone using a large amount of cough

ADAM PRUS [continued]: syrup to achieve some mind-altering experienceversus using it for treating cough.Recreational drug use consist of using the drugentirely to experience that drug's intoxicating effects.Someone consuming cough syrup mightbe using it instrumentally to treat a coughor misusing it recreationally to experience

ADAM PRUS [continued]: its reality-altering effects.You might think about the instrumentaluse and potential misuse of prescription drugsand other substances in your class discussions.[How do drugs alter brain function?]After entering the brain, drugs produce their effectsby altering neurons, special messagescells in the brain that mediate our behavior.

ADAM PRUS [continued]: After drug is taken, it is absorbed in the bloodstream,and drugs having the correct propertiescan across into the brain throughthe blood-brain barrier.Neurons have three primary parts-- dendrites, a soma,and an axon.Dendrites receive information in the form of chemicalscalled "neurotransmitters," normally from other neurons.

ADAM PRUS [continued]: The soma is the main body of a neuronthat is responsible for a neuron's metabolism.It includes a nucleus of the cell.An axon transmits information from a neuron in the formof neurotransmitters.The terminal of an axon releases neurotransmittersnear the terminal of a dendrite.We refer to this local area as a "synapse."

ADAM PRUS [continued]: The neurotransmitter binds to proteins called "receptors"on the surface of a dendrite.When bound to a neurotransmitter,the receptor causes changes to occur in its neuron, whichcan lead to that neuron releasing neurotransmittersor a variety of other actions.This manner of communication is called "neurotransmission."It is necessary for brain function,

ADAM PRUS [continued]: and this is behind everything we do, think, and feel.Psychoactive drugs alter what we do, think, and feel byinterfering with neurotransmission.A common way that psychoactive drugsdo this is by acting on receptors,either by activating them like a neurotransmitter does-- we callthese drugs "agonists" or by preventing neurotransmitters

ADAM PRUS [continued]: from binding to their receptor-- wecall these drugs "antagonist."For example, the opioid drug heroinserves to act at a particular opioid receptor calledthe "mu opioid receptor."Heroin acts as an agonist for the muopioid receptor because it acts onor activates the receptor like the brain'snatural neurotransmitter does.

ADAM PRUS [continued]: The majority of anti-psychotic drugs,which are primarily used to treat schizophrenia,act as antagonists for the dopamine D2 receptor.These drugs are called antagonistbecause they bind to the receptorand prevent the neurotransmitter dopamine from binding to thosereceptors.We think that this mechanism is important for treating

ADAM PRUS [continued]: schizophrenia, which is related to too much dopaminebeing released.Antipsychotics can counteract this extra dopamineby blocking as an antagonist these dopamine D2 receptors.[How do drugs produce rewarding effects?]Drugs that produce rewarding effectstypically act in the brain's reward pathway.

ADAM PRUS [continued]: The brain reward pathway is comprised primarilyof neurons that synthesize and release dopamineas their neurotransmitterA structure called the ventral tegmental areacontains the somas for these particular dopamine neurons.And they extend to a structure called the "nucleus accumbens,"which is commonly referred to as the brain's reward

ADAM PRUS [continued]: center, and other structures in the limbic system.The limbic system consists of structuresinvolved in a variety of functions,including emotional regulation.We'll refer to these dopamine neurons that extend the nucleusaccumbens and other structures the limbic systemas the "mesolimbic dopamine pathway."In the nucleus accumbens, dopaminereleased from these mesolimbic dopamine neurons

ADAM PRUS [continued]: act in a type of receptor called the D2 receptor.This action is associated with rewarding effects.Researchers learn much about the brain's reward pathwayby electrically stimulating neuronsto produce rewarding effects.James Olds, in 1954, was learningto conduct brain electrical stimulation experimentsin laboratory rats when he missed his target structure

ADAM PRUS [continued]: by several millimeters.This is a large distance for a rat brain.However, Olds noticed that the rats seemedto prefer areas of a platform where the implantelectrode have been activated, and careful follow-up studiesconfirmed that a brain reward center existed in the brain,particularly finding that rats would work very hard,and even tolerate stronger bursts of stimulation,

ADAM PRUS [continued]: to receive just a brief moment of reward stimulationon this pathway.We can trace the actions of recreational and abuse drugsto the brain's reward circuitry.[What are the effects of psychostimulant drugs?]Psychostimulant drugs include amphetamine, methamphetamine,

ADAM PRUS [continued]: cocaine, MDMA-- a drug known as "ecstasy,"although this compound has more than a psychostimulant effect,and so-called "bath salts," whichinclude cathinone derivatives.Psychostimulants also include nicotine and caffeineand other related substances.Psychostimulant drugs increase psychomotorand sympathetic nervous system activity,

ADAM PRUS [continued]: the same nervous system responsible for the fightor flight response.We also know that psychostimulant drugsimprove alertness and lead to a positive mood.That's the rewarding aspect of these drugs.Psychostimulant compounds lead to the releaseof excess dopamine from mesolimbic dopamine neurons,including those in the nucleus accumbens.

ADAM PRUS [continued]: We associate a large rapid release of dopamine as a rush.Milder stimulants like nicotine and caffeinehave rewarding effects, but they lack this rush.Every psychostimulant drug is different,but examining the actions of cocaine and amphetamineprovide a glimpse at the ways that a psychostimulantcan produce a large increase in dopamine.

ADAM PRUS [continued]: In this figure, we see the effectsof cocaine acting at a dopamine axon terminal.Cocaine can produce extra dopamine releaseinto that gap called the synaptic cleft in two ways.One, it can interfere with the storage of dopaminein vesicles.If dopamine is not stored, it leaks out and releasesinto the synaptic cleft.

ADAM PRUS [continued]: Dopamine can also prevent the re-uptakea dopamine via the dopamine transporter,also leading to greater concentrationsin the synaptic cleft.In this figure, we see the effects of amphetamine.Amphetamine works in a very similar way.Amphetamine also prevents a storageof dopamine in vesicles, and amphetamine alsointerferes with the re-uptake of dopamine, also leading

ADAM PRUS [continued]: to increase dopamine concentrationsin the synaptic cleft.[What are the effects of depressant and opioid drugs?]Alcohol and other depressant drugs like inhaling gaseshave depressant effects, but they alsoproduce rewarding effects.We can use alcohol as an example of a depressant drugto link the amount consumed with behavioral effects.

ADAM PRUS [continued]: You're probably all familiar with a breathalyzer.If someone's drinking alcohol and theybreathe into a breathalyzer, theymight have a certain reading.For example, blowing a 0.08 blood alcohol concentrationreveals that someone is likely intoxicated, that is,experiencing the pleasurable and/or the depressanteffects of alcohol, included some disinhibition.

ADAM PRUS [continued]: 0.08 is a common legal limit for driving a motor vehiclein most states.An alcohol concentration of 0.32, on the other hand,is associated with a stupor, an inabilityto form memories from the present, that is, a blackout.Higher blood alcohol concentrationscan lead to unconsciousness and death, somethingwe call "alcohol poisoning."

ADAM PRUS [continued]: We trace the effects of depressantsto acting on receptors for a type of neurotransmittercalled GABA, which stands for "gamma aminobutyric acid."These effects can occur both in the ventral tegmental areaand the nucleus accumbens to produce rewarding effects.Acting on this receptor in other parts of the braincan account for the depression effects on brain function.

ADAM PRUS [continued]: Depressant drugs connect in a variety of other sectorsas well, but they tend to share effects on the GABA receptors.Opioids, or also called "opiates,"include morphine, codeine, heroin, fentanyl,and many others.They act upon opioid receptors in the brain.The brain produces its own opioid compounds,such as beta endorphin, to serve as neurotransmitters

ADAM PRUS [continued]: for those receptors.These receptors have downstream effects on mesolimbic dopamineneurons and have direct effects on the nucleus accumbensto produce rewarding effects.Opioids act in other parts of the brain to reduce pain[What are the effects of cannabis?]Cannabis, the plant that marijuana comes from,

ADAM PRUS [continued]: enhances mood and produces a relaxing effectthrough acting on special receptorsin the brain called "cannabinoid receptors."The primary psychoactive compoundresponsible for cannabis' effectsis delta-9-tetrahydrocannabinol, or delta-9-THC for short.Marijuana and synthetic marijuana,sometimes referred to as "herbal marijuana alternatives,"

ADAM PRUS [continued]: produce a positive mood through which THC or similar compoundsact on cannabinoid receptors in the nucleus accumbensand in then the ventral tegmental area.The broad effects of these cannabis compoundsare traced to other structures in the brain.So this image shows the various placesin the brain and the body where cannabis

ADAM PRUS [continued]: can act on cannabinoid receptors to produce its effects.As we mentioned earlier, cannabiscan produce rewarding effects by actingin the ventral tegmental area and the basal ganglia.Cannabis can affect cognitive functioningby acting in the cerebral cortex and hippocampus.Cannabis can help reduce pain back in the thalamus,

ADAM PRUS [continued]: can enhance appetite by acting in the hypothalamus,can produce inhibition of motor functionby acting in the basal ganglia and the cerebellum.And can produce various effects on physiological functioningand the immune system by acting on receptors in the body.The brain produces cannabis-like neurotransmitters referred to

ADAM PRUS [continued]: as "endocannabinoids" to act upon these receptors the brain.One of the endocannabinoids is a compound called "anandamide."[What are the effects of psychedelic drugs?]Psychedelic drugs produce reality-altering experiencesthat can include hallucinations, feelings of disembodiment,

ADAM PRUS [continued]: and delusions and other effects, dependingon the particular drug used.The three general types of psychedelic drugsthat will be discussed include hallucinogens,such as LSD and mescaline.Mixed stimulant-psychedelics such as MDMA or ecstasy.And Dissociative anesthetics such as PCP.

ADAM PRUS [continued]: Hallucinogens have hallucinationsas their primary effect.Common hallucinogens consist of LSD, Psilocybin sidethen a mescaline.The hallucinations tend to be an altered perceptionof real things, such as distorted awaitingor kaleidoscopic forms of real images in a visual field.

ADAM PRUS [continued]: LSD closely resembles part of the neurotransmitter serotonin,suggesting that the serotonin system isimportant for hallucinogenic effects.Mixed stimulant-psychedelics includethe features how hallucinogens but also have psychostimulantaffects.The drug MDMA, or ecstasy, is an example of a mixed

ADAM PRUS [continued]: stimulant-psychedelic.MDMA is chemically related to the psychostimulantamphetamine, thus leading to effects on dopaminelike amphetamine does.Yet the properties of MDMA may alsoalter the serotonin system.MDMA is referred to as an empathogen, a compound thatenhances empathy.Some recent clinical studies have found promising data

ADAM PRUS [continued]: showing that MDMA facilitates therapy for PosttraumaticStress Disorder, perhaps by easing a patient's abilityto discuss and cope with the past traumatic event.Dissociative aesthetics are sedative and pain-relievingdrugs that produce feelings of disconnectedness from the body.These compounds also produce depressant and stimulant

ADAM PRUS [continued]: effects.Dissociative anesthetics include ketamine, known a Special K,and phencyclidine known as PCP or Angel Dust.Drugs in this category inhibit neurotransmissionby the neurotransmitter glutamate.[How can drugs become addictive?]

ADAM PRUS [continued]: Drug addiction has been a significant research areafor decades, in order to understand addictionand to find ways to treat addiction.We know that addiction for drugs tendsto begin simply with enjoying a drug's rewarding effects.We can link the pleasurable drug effectsto actions in the brain reward pathway.As drug use starts to become common practice,

ADAM PRUS [continued]: the body adjusts to the drug acting in the system.If a drug is enjoyable, the drug will become less enjoyable.If a drug reduces pain, then eventually the drugwill become less effective at reducing pain.In an effort to achieve the same effects as before,a user will take larger amounts of the drug, a process

ADAM PRUS [continued]: that we call "tolerance."We can consider tolerance using the Opponent-ProcessTheory, which is shown here in this image.Before addiction, someone is enjoying,on the left-hand side, the drug's effect,and there's no opposing process that the bodywould be adapting to with the drug being commonly used.But during drug addiction, we find

ADAM PRUS [continued]: that the body responds in an equivalent wayto the drug's effects, which we call an opposing process.If someone takes the usual amount of drugand the body produces that opposing process,someone may feel very little or no effects from that drug.If they take, in the next row down,a larger amount of drug, that affect

ADAM PRUS [continued]: will overcome the body's opposing effects.But now, when we get to that last row,if someone does not take the drug,the body produces its opposing processes anywaysand those lead to physiological withdrawal effects.While the Opponent-Process Theoryhelps us understand the role that avoiding withdrawal

ADAM PRUS [continued]: effects plays in maintaining drug use,it seems insufficient to help us understand a person'spreoccupation with drug seeking, the abilityof people or parts of our environment permight provide reminders that can trigger drug seeking againin a current or even a former user.Such reminders might contribute to relapse.

ADAM PRUS [continued]: It's also difficult to understandwhy someone is willing to sacrifice all she or he hasan order to use a drug.We think that the answers to these questionslie in the incorporation of other brain areas in drug use.In this figure, we have the brain-reward pathway, but alsosome other areas where drugs during addictioncan affect the brain.

ADAM PRUS [continued]: So for example, we have the ventral tegmental areaand the nucleus accumbens node on the figure,and this can be involved in producingthe pleasurable effects of a drug,but as drug use continues, we incorporate other areas.For example, the amygdala and the orbital frontal cortexare involved in pairing the environmentswith those enjoyable drug affects.

ADAM PRUS [continued]: We also find the hippocampus becomes involvedin incorporating the larger context, the largerenvironment of drug useThe dorsal lateral prefrontal cortexbecomes involved as drug use continues.The dorsal lateral prefrontal cortexis involved in our executive functionsfor planning our goals and making important decisions.

ADAM PRUS [continued]: As drug addiction begins to involvethe dorsal lateral prefrontal cortex,users begin planning around drug use and drug seekingand reminders in the environment that we mentionedearlier involved with the orbital frontal cortexand amygdala.Because of that biological link, people

ADAM PRUS [continued]: begin drug seeking when they incorporate remindersabout former drug use.So putting this all together, we thinkthat drug addiction occurs through progressingin three stages.The first stage is intoxication.That's enjoying the drug's acute effects.And this involves the reward circuitrythat we mentioned earlier.

ADAM PRUS [continued]: As drug use continues, drug userscan experience withdrawal symptoms.This involves, of course, repeated useand the body developing opposing actions to the drug suchthat withdrawal affects are produced when the drug's noton board.And this includes structures like the amygdala,the hypothalamus, and the autonomic nervous system.

ADAM PRUS [continued]: As drug use continues, individualscan develop a preoccupation and anticipation for drug use.And this involves drug behavior orientingfrom natural reinforcers to drug reinforcers.And this can include the prefrontal cortex,the amygdala, the thalamus, and also the hippocampus.

ADAM PRUS [continued]: [Conclusion]To conclude, let's review what we've learned in this video.Drugs are administered substances thatcause physiological changes.Drugs that produce rewarding effectsdo so by acting in direct and direct wayson the brain's reward pathway.We considered different classes of abuse

ADAM PRUS [continued]: and recreational substances, including psychostimulants,which increased physiological and behavioral activity.Depressants, which dampen physiological and behavioralactivity but also produce rewarding effects.Cannabis, which has rewarding and relaxing effects,along with some medicinal effects.And psychostimulant drugs, which cause

ADAM PRUS [continued]: reality-altering experiences.Abused and recreational substancescan lead to drug addiction, whichconsist of compulsive, harmful usethat users lose an ability to control.Addiction involves learning and memory systems in the brain.I write in some length about these and otherpsychopharmacology topics in An Introduction

ADAM PRUS [continued]: to Drugs and the Neuroscience of Behavior,an introductory textbook psychopharmacology writtenfor undergraduate psychology studentsand for other students in the social sciences.