In this lecture I describe the various amphetamines and how the affect the brain. In particular I focus on methamphetamine – the primary drug of abuse in this class, with focus on metabolism and observed physiological damage and reduced brain volume in methamphetamine users.
Alright let’s get started on lecture number 19 our last lecture we talked about cocaine and generally about psychostimulants this lecture which is quite a bit shorter will focus just on inside amines much of what we talked about in that previous lecture we’ll revisit a little bit here group these are structurally defined a group of drugs use a variety of effects
On the central nervous system and autonomic nervous system as we talked about before with cocaine it’s a sympathomimetic effect because they mimic the effects of the sympathetic nervous system actions i also have indirect actions involving the presynaptic release of both dopamine and norepinephrine and this is one of the significant differences in terms of the
Effects of cocaine versus amphetamines cocaine exerts its primary effect on dopamine whereas amphetamines have a significant effect on norepinephrine in addition to dopamine and so as a result this is pathetic response is much stronger because norepinephrine is the primary neurotransmitter in the sympathetic nervous system so we look at these structures of dopamine
Norepinephrine epinephrine and the unfed amines you can see these structures are relatively similar a phenyl group an ethyl group and an amine group and the structure of amphetamine versus methamphetamine is simply the addition of another methyl group here at the top structure methamphetamine is much more potent than em fed amine which is one of the reasons why it
Has such a high abuse potential so i’m fed of means have long been used to treat a variety of disorders for example the japanese military use methamphetamine for their soldiers back in world war two and i think before that as well so i’m fed amine which is adderall is currently used to treat attention deficit hyperactivity disorder as well as a few other things in
Adults particularly people who have sleep disorders sometimes will take will be prescribed adderall to help with that or as an adjutant treatment adderall is a racemic mix of both dextran level and feta mean so it’s less potent than dextroamphetamine which is dexedrine and so that dextroamphetamine or d amphetamine is the more potent half of the adderall mixture
These have historically been used for weight loss and that’s the primary use for dexedrine as well as to fight fatigue and then amphetamine is used or adderall is used to treat it dexedrine is essentially speed is what most people would refer to that as and in fact it’s been used by truckers in by the military lots of people to induce alertness and wakefulness
Folks so these exert virtually all of their action by causing the release of norepinephrine and dopamine from presynaptic storage vesicles and so they actually cause a release of those neurotransmitters other cocaine blocks the presynaptic ouisa limbic system and nucleus accumbens are associated with the behavior of stimulation and motor activity and so this is
Why in amphetamine users you can get ocd like behaviors and these are stemming from stimulation of the basal ganglia and so you get people who will do obsessive things when they’re fixate and not move away from those activities and in fact with sort of longer-term heavy methamphetamine use there is a a syndrome called frankenstein syndrome and this is when people
Start taking things apart they will take apart their dvd player will take apart whatever they kind of have available in this very ritualized obsessive-compulsive type behavior so the pharmacological effects follow from that release of dopamine from the presynaptic nerve terminals we get an increase flight flight fright response that is dose related metabolites
Mmm fet amines are detectable in urine for 48 hours as mentioned in a previous lecturer 40 percent of the dose of methamphetamine is excreted unchanged this is why roenick heavy methamphetamine users will recycle that urine in a variety of ways harmful effects from these drugs follow from exaggerated doses and responses including insomnia restlessness stereotyped
Behaviors like i was just talking about these purposelessness purpose devack’s or constantly doing the same thing and being unable it’s almost like think it’s stuck and can’t unstick from a behavior can’t get violent paranoid can have delusions also have anorexia this will progressively deteriorate over time biggest problem with them feta mean users in particular
Methamphetamine users is that use goes on for days most cocaine users will have a night then they’ll run out of drugs and money or they’ll just run out of drugs and they’ll go to bed at some point methamphetamine users can go for days with so you can get an fed amine psychosis with paranoid ideation that can be persistent or will resolve when the drug works summary
Of the sort of difference in the way cocaine is used and with its properties so we get the characteristic try out of actions local anesthetic vasoconstriction and psychostimulant short half-life is a few minutes this is more recreational we talk about these sort of weekend warrior user goes out in the weekend parties it up goes back to work on monday whereas with
Methamphetamine which is associated with irreversible brain damage with relatively low use users typically use the drug continuously over 20 times a month often three to four times per day smoking injecting snorting all of these are potential ways in which methamphetamine is used so these have been shown to improve cognitive processing speed attention concentration
And psycho border performance at lower doses and that’s one of the reasons why there is a vibrant trade of adderall on college campuses particularly around finals week is to provide that sort of attention and concentration so that’s what underlies our used to treat adhd in adults and children they can also be used as performance enhancers for athletes although
Some fine motor coordination is lost so you’re probably not gonna want to use em fetta means to go golf um or you know anything else that requires fine but it can act as a performance enhancer high doses of course is associated with anxiety serious toxicity over focusing so we go from focused concentration to obsessive compulsive behavior and those ritualized
Behaviors we talked about these drugs are prone to compulsive abuse physical dependence is easily induced in humans and in animals alike tolerance can develop quickly drawl can be associated with increased appetite extensive sleeping and depression had a friend of my mom’s her son was home trying to get off of meth and i said you know feed him and let him sleep he’s
Gonna sleep a lot he’s gonna need to sleep for a long period of time to kind of recover and then have to deal with that depression sunset amine users also often have reduced working memory capacity and there is evidence of the dark modafinil which has low abuse potential can be used to help treat those executive function difficulties let’s spend just a few minutes
Talking about methamphetamine because this is the primary amphetamine of abuse in the united states and really the world it’s also known as ice speed cranked crystal tina it’s readily manufactured from available chemicals which includes pseudoephedrine which is why c2f a drain is now more difficult to get you have to get it from a pharmacist and you will only buy
It is a potent form of amphetamine crystal methamphetamine is really the smokeable form it’s actually heated and vaporized orb rapidly when smoked which continues for four hours the half-life of methamphetamine is 11 hours and so one dose of n fet amine is going to take 55 hours up to 66 hours to be up that’s almost three full days so keep that in mind it’s a long
Long term use drug that it isn’t stays in your system for a very long time and again 40% of that is excreted unchanged so important you know methamphetamine is very neurotoxic you use there are a variety of toxicities including strokes in psychosis can get behavioral mental changes that can persist leading to some speculation about long-term brain injury rodent
Studies we see loss of both dopaminergic and 5ht serotonergic neurons and the rhesus monkey this has been shown to persist for four years after use in humans we see about a six to eight percent reduction in frontal and cortical and basal ganglia and neural neuronal density or normal content and methamphetamine abusers that are abstinent for 12 months and so there
Is certainly clear in vivo evidence for a neuronal injury in eps and abstinent methamphetamine users so what you can see from these graphs is reduced hippocampal volume increased ventricular volume so that’s an increase in the fluidic space in the brain certificate reductions in the cingulate gyrus and medial prefrontal cortex and overall volume physical toll of
Long term use of methamphetamine smoking meth certainly destroys the teeth enamel that vasoconstriction constriction and long-term starvation results in dramatic damage to the body and looks along with that sort of picking at skin we talked about with cocaine users that sleep deprivation can result in some serious psychosis and so they have this belief or feeling
That there is something crawling under their skin and so they will pick at kut at their skin to try to get at those things so this is the same individuals after 10 years of meth use pretty bad drug another good example that you can see this guy on the right he’s one of those people that’s been picking at his skin and scarred his skin pretty dramatic so that’s a
Summary of methamphetamine use it has a large reputation particularly in the gay community about its actual properties in fact if you’re interested in learning more about that there’s a great documentary called ken sex from the bbc and that’s actually what it’s called people will actually get together use methamphetamine engage in large group activities lots of
Unprotected sex again that sexual risk-taking is pretty extreme with this type of drug so other non-m fetta means stimulants included f adran not very used today and its primary effects were on adrenalin methylphenidate which is ritalin has a short half-life it blocks the dopamine transporter with presynaptic terminals and is used to treat adhd pseudoephedrine
Is primarily used as a decongestant so drugs like sudafed and mucinex if you buy it from the pharmacist will include the pseudoephedrine and then finally i’m a dolphin l and this is a very different type of drug its primary uses to treat narcolepsy it’s actually a drug called provigil and so it can actually help increase alertness and a weakness in sleep to five
People and also appears to fight fatigue and depression patients and as i said a moment ago in recovering methamphetamine users in the dauphin all has been shown to improve working memory and executive functions so how do we treat stimulant dependency well there are no pharmacological treatments a lot of people work with contracting negative reinforcement and
Positive reinforcement pharmacological ideas are based on the mechanism of action again that often all has been shown to improve working memory but not much really has been shown to be that effective potentially antidepressant treatment might also be appropriate one idea is to intercept the drug before it reaches the brain so increasing metabolism metabolizing
Enzymes they are working on a vaccine for cocaine use which is coupled combin in cholera toxin greater or lesser extent basically there’s a it’s designed to generate drug specific antibodies that will bind to other cocaine or amphetamines and prevent it from travel that’s quite a ways off right now have to rely on abstinence and simply getting people to want to
Be sober and not want to all right well that’s our discussion of methamphetamines we’ll be talking about psychedelic drugs in our next lectures
Transcribed from video
Lecture 19 Amphetamines By Paul Merritt
