The Skinny on Psychostimulants
Happy 2021 people! Are you as happy as I am that 2020 is finally in the rearview?! Weirdest. Longest. Year. Ever.
That actually makes me think of a new and hilarious commercial I just saw for a big online dating site. It starts out with Satan bored out of his mind in hell, and then he gets a text message from the site saying he’s been matched with a girl, and he’s very intrigued. When they meet, it’s obvious that they’re both instantly smitten. Then the starry-eyed girl introduces herself as 2020. They fall in love. And they live happily (?) ever after… apparently in hell. Unless they stay at her place I guess. Anyway, 2020 is over, even though unfortunately, we’re still schlepping some of its covid baggage, but hopefully not for much longer.
Considering the euphoria surrounding the new year and the stimulation of resolutions, I thought it very fitting that I start with a three part blog series on pharmacological central nervous system stimulants, aka psychostimulants. One of the main compounds in this class of drugs are the amphetamines, and that will be today’s blog topic.
As psychostimulants go, amphetamines are very strong ones; they are a group of very tightly controlled and well monitored schedule II drugs. Add a little carbon atom, bind some hydrogens to it, and you’ve got a methyl group; and that makes it methamphetamine, which everyone’s heard of. When prescription methamphetamine is (very) illegally altered…tah-dah…you’ve got crystal meth, aka speed, ice, crank, etc. Other examples of psychostimulants include caffeine, nicotine, cocaine, and other prescription compounds that I’ll cover next week.
Because of their stimulant activity within the central nervous system, prescription amphetamines are used in the treatment of several disorders, including narcolepsy, obesity, binge eating disorders, and very commonly, ADHD, or attention deficit hyperactivity disorder. They can also be used recreationally in certain populations to get high, to stay awake for long periods of time, and/ or to improve focus and study for exams. In fact, it’s those last two that make amphetamines very popular party favors among college students.
Structurally speaking, amphetamines are drugs that are related to catecholamines, which are chemical messengers that help transmit a message or signal across neural synapses in the central nervous system, from the terminal end of a transmitting nerve cell to the receiving end of a target nerve cell. In an over-simplified explanation, when a signal gets to the end of one neuron, catecholamines help the signal jump to the beginning of the next neuron, hence the name “neurotransmitter.” That message is repeated billions upon billions of times, as there are billions upon billions of neurons in the central nervous system. These neural signals activate emotional responses in the amygdala of the brain, such as fear in a “fight or flight” situation. At the same time, catecholamines also have effects on attention and other cognitive brain functions. Examples of catecholamines include the neurotransmitters dopamine, epinephrine, and norepinephrine. Pharmacologically speaking, amphetamines increase levels of the specific neurotransmitters dopamine and norepinephrine in the neural synapses, which helps the message to make the jump from one neuron to the next. In a way of thinking, amphetamines “speed” the transmission of the message by increasing the levels of these neurotransmitters. Amphetamines increase these dopamine and norepinephrine levels through three different mechanisms of action, at least that we know of: 1) they reverse the direction of the transporter pumps that would normally divert dopamine and norepinephrine away, 2) they disrupt cellular vesicles, thereby preventing the storage of excess dopamine and norepinephrine, which frees them up, and 3) they also promote the release of dopamine and norepinephrine at nerve cell terminals, making them readily available in the synaptic cleft. These three mechanisms combined ensure that there are very high concentrations of dopamine and norepinephrine in the synapses of the central nervous system. The “catecholaminergic” (try that one next time you play scrabble) actions of increasing the levels of dopamine and norepinephrine result in the very strong psychostimulant effects that amphetamines produce.
You’ll notice that I keep saying amphetamines, plural. Why? Because like the neurotransmitters dopamine and norepinephrine it effects, amphetamines are chiral molecules; this is a fancy way of saying that in their three dimensional world, they can exist in different forms called enantomers (more scrabble points!) that are mirror images of each other. I know this sounds complicated, but it’s really not. Think of it as “handedness.” Your left and right hands are mirror images of one another: they look similar, except the placement of the fingers and thumbs are mirror images, and they can do pretty much the same things, like hold a fork or a pencil, but the way they do so differs slightly. The same is true of amphetamines. The two enantiomers of amphetamines are usually referred to as dextroamphetamine (also denoted as d-amphetamine) and levoamphetamine (also denoted as l-amphetamine). All prescription amphetamines boil down to four variations of the amphetamine molecule, which have markedly similar, but potentially slightly variable effects: dextroamphetamine, aka dexadrine; lisdexamphetamine, which is a precursor or pro-drug of dextroamphetamine; methamphetamine, aka methamphetamine HCL, which has that methyl group I mentioned before; and mixed amphetamine, which is essentially a mixture of dextroamphetamine and levoamphetamine at a specific ratio.
Of those four active forms of amphetamines, there are several brand name drugs on the market, some of which have generic forms available. They are all oral formulations that may be immediate-release, which are typically taken twice a day, or extended-release, which are obviously released more slowly and taken once a day.
Adderall XR (generic available)
Dexedrine (generic available)
ProCentra (generic available)
The desired effects of amphetamines include: stimulation (thank you Captain Obvious), increased alertness, cognitive enhancement, euphoria, and mood lift. Amphetamines have been around for a long time and when taken as prescribed, they’re fairly safe, but there are potential negative side effects. These can include insomnia, hyperfocus, GI irritation, headache, anxiety, slight increase in heart rate and blood pressure, and anorexia. There is addiction potential associated with amphetamines, and there is a short and fairly mild associated withdrawal period where one might feel some fatigue, sleep a lot, and experience strange dreams.
When taken as directed, and by mouth, usually 20mg – 40mg per day, amphetamines are fairly safe. However, when smoked, injected, or snorted, they are decidedly UNsafe; especially in large doses. I’ve seen people take up to 1000mg per day… though not for long. Why? Because they usually end up dead of overdose. What happens if you choose to use amphetamines in large quantities and/ or via routes other than oral? Hallucinations, delusions, psychosis, seizures, cardiovascular collapse/ arrest, stroke… the bottom line is it ain’t pretty, people, so don’t do it.
Because amphetamines have multiple mechanisms of action and thereby are very strong psychostimulants, I generally restrict their use to adults only, and choose to use another type of psychostimulant in children called methylphenidate. And that will be the topic next week in psychostimulants part 2 of 3.
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Thank you and be well people!
How Cocaine Kills
Cocaine is a potent, illegal stimulant that affects the body’s central nervous system. It is extracted from the green leaves of the coca plant, and people in South and Central America have chewed these leaves and used them in teas medicinally and as a mild stimulant for thousands of years. But somewhere along the line, these people learned that this humble leaf could be processed in a way that extracted and concentrated its active components to create a substance called cocaine, a white powder stimulant that is anything but mild.
Cocaine goes by a lot of different slang terms and street names, mostly based on its appearance, effects, or drug culture: C, blow, coke, base, flake, nose candy, and snow are some examples. At the peak of its use here in the 1970’s and 1980’s, cocaine began to influence many aspects of American culture. Glamorized in songs, movies, and throughout the disco music culture, cocaine became a very popular recreational drug. It seemed everyone was using it, from celebrities to college students to suburban moms looking to turn up at the disco on Saturday night. It was so popular in the disco scene that people openly snorted it on the dance floor at Studio 54. But powder cocaine would soon take a back seat to its trashy cousin from the wrong side of the tracks: crack cocaine, or crack. Crack is an off-white crystalline rock made by cooking down powder cocaine with God knows what else for bulk, and the crack rock is then smoked in a pipe. This form of cocaine created a scourge of epidemic proportions and ruled the streets throughout the 1980’s and early 1990’s. Crack is whack and crack was king then, and it’s still around today. It’s actually named for the cracking sound the crack rock makes when it’s smoked. While it’s the same drug as powder cocaine and has the same effects, smoking crack gives a more immediate high than snorting powder cocaine. But it doesn’t last long, so to stay high, crack users have to “hit” the pipe over and over, constantly, 24/7, for hours and ultimately days on end. Crack also has street names: rock, gravel, sleet, and nuggets to name a few. And combined drugs also have street terms, like speedballs, which are a mixture of cocaine with heroin or other opiate. Every illegal drug and drug combination you can imagine has a list of street names…Cocoa Puffs, Bolivian Marching Powder, Devil’s Dandruff…Every time I think I’ve heard them all, a patient uses one that’s new to me.
So, what’s the attraction? What does cocaine do for you? Captain Obvious says… it gets you high. Cocaine creates a strong sense of exhilaration. You feel invincible, carefree, alert, and euphoric, and have seemingly endless energy. It makes you more sensitive to light, sound, and touch. It makes you feel confident, competent, and increases performance and output. For intense Type A individuals, cocaine is a requirement, on par with oxygen. These individuals want maximum performance, maximum fun, maximum sales…maximum everything. Period. And cocaine delivers. It works by increasing the feel good neurotransmitters dopamine, serotonin, and norepinephrine by blocking their reuptake. No reuptake equals more feel good neurotransmitters equals more feeling good. To be candid, when just starting to use, and in small amounts, people can actually do fairly well using cocaine. They feel great and are more productive, and that’s how smart people get involved with it. At first, it seems there’s no down side, it’s up up up….on top of the world. But as they say, what goes up must come down. Whether you snort, smoke, shoot, or suck on it, using cocaine is a very sharp double-edged sword. I’ve seen people go six, eight months, using every day, and for a short time, for all appearances it works for them; they feel great, they’re focused, performing well. But then without warning, they’re not. They crash, their performance sinks into the abyss. They go into an impaired state, a mental fog, and their neurotransmitters betray them. They become paranoid, confused, disorganized, hopeless, and lost.
Using cocaine even once can lead to addiction. As with many drugs, the more you use it, the more your body gets used to it, and that creates the need for a larger dose and/or using the drug more often in order to get the same effect. Cocaine is a potent chemical, and both the short-term and long-term effects of using are dangerous to physical and mental health. Riddle me this: how many old crack addicts are out there? I can tell you, not too many. Why? Because they’re all dead of heart attack, stroke, arrhythmia, respiratory failure, seizures, and sudden death. Whether you use cocaine once, use on occasion, or you’re a habitual user, the risk of seizure, stroke, cardiac arrest, respiratory failure, and even sudden death, is equal. Equal. No matter how little you use or how rarely you use. And the first time you use can also be your last chance.
So exactly how can you kill yourself with cocaine? Let us count the ways….cocaine’s potency and molecular makeup causes serious physiological consequences. No matter what form you use it in, it increases your blood pressure, increases your heart rate (aka your pulse), and it constricts the arteries that supply blood to your heart, all at the same time. So now, you’re asking the heart to pump faster and harder (because it has to pump against your increased blood pressure), and without as much blood flow (and therefore not as much oxygen and energy) as it was getting before the cocaine was in your system, and tah-dah! What can you get? Arrhythmias. Simply put, that’s when your heart can’t keep good time, it beats erratically and sporadically. Without conversion, you have a heart attack. Your heart basically stops beating and you die. And just remember, as you get older, your body is not as resilient. You may or may not have a lethal heart attack at 20, but you sure will at 50. How else can you kill yourself with cocaine? Using can cause you to go into a state where you’re unable to control your temperature, so it gets very high, you get restless, have tremors, dilated pupils, nausea, vomiting, complete disorientation, and mental confusion. If the fever gets too high, you can have seizures, which can lead to death. It happens every day. You also have to take into account potential accidents resulting just from being high, without your normal faculties, and being unable to take care of yourself. Freak accidents while high can be deadly. Remember too that cocaine is cut with crazy stuff- ground glass can cause internal bleeding, and diuretics and laxatives can cause electrolyte imbalance, both of which can kill you. And these days, cocaine is often cut with fentanyl- an opiate 50 times more powerful than pure heroin- which causes hundreds of overdose deaths each day. If you freebase cocaine or smoke crack, the chemicals used to cut it can cause sudden acute respiratory failure where you stop breathing and die, or they can damage the lungs over time and cause respiratory failure and the same result- death. If you use IV (intravenous needle injection) and share needles, you expose yourself to all sorts of potentially lethal infections, including Hepatitis, HIV and AIDS. If you choose to suck on crack, the chemicals used to cut it may be caustic and potentially damage the throat and/ or stomach and cause bleeding, or they may cause intestinal death and decay; these can potentially lead to death.
So in the beginning of your cocaine career, you’ll feel great- super powerful, confident and competent. High. But shortly into your cocaine career, you’ll find that the magic is gone. The genie is out of the bottle. The high just isn’t the same, no matter how much you use or how you use it. So you chase that high…and you’ll chase it for the rest of your life, but to no avail. The high is replaced with the craving for the high. I’ve never seen a drug with cravings as powerful as cocaine. They’re just unbearable cravings, and they can last indefinitely. I’ve seen many, many cases where they last for years. I see patients now who have had these horrendous cravings for years, and I expect they’ll have them for the rest of their lives. They were lured in by the shiny bauble that is cocaine, and cocaine showed them a great time. Then cocaine turned on them, closed the door and threw the bolt, leaving them to want/need/crave what they had, likely forever. It’s just not worth it. I treat addictions of all kinds: heroin, alcohol, marijuana, benzodiazepines, you name it. For the most part, people with these addictions comply with treatment and come to their follow-up appointments. But cocaine addicts are a different story. They’ll come to my office once, all committed to stopping the cocaine, but you never see them again. They vanish…poof! They don’t do well in treatment, because the cravings are so strong that they can’t resist, so they take off and use again. The cocaine cravings are bar none the strongest I’ve ever seen. Now, the withdrawal from cocaine isn’t bad at all. It’s not like an alcohol withdrawal or withdrawing from Xanax or heroin. Those are gnarly, even potentially dangerous. With cocaine withdrawal, you can get depressed, you sleep a lot, you get vivid dreams, you want to eat a lot, you can’t think super clearly for let’s say three to seven days, but there is no real treatment needed for it, just comfort measures- keep the person cool, keep them hydrated, keep them fed, and allow them to rest- and they’ll bounce back. Now, one thing that sure does come up is that, because the cravings for cocaine are so intense, as soon as they’ve slept and ate and they’re back on their feet, it’s sayonara sucka! They bolt. They’re out again, they’re using, they’re smoking, they’re shooting, they’re shoving it up their nose, they’re putting it in their mouth, wherever and however they can use it. If they had a decent time period of not using, they may get that first super awesome high; but then they’ll inevitably spend the rest of the binge chasing that high, but they won’t find it.
Now, you might ask how intelligent, successful, type A people get involved with cocaine when they know it will lead to their eventual mental and physical collapse and possible death? Because these people know that in the short term it will increase their work performance, their ability to think, their social acumen, and their confidence. I always ask my patients what price they’re willing to pay for this temporary condition. Most don’t have an answer. I think that’s because they think nothing bad will come of their using, but I know different because I’ve seen different.
A true story from when I worked in the emergency department at Roosevelt Hospital: there was some sort of summer festival in Central Park, and evidently a guy locked himself in a portajohn so he could smoke crack. It’s summer, there’s no ventilation in the portajohn, and crack causes an increase in body temperature, so this guy had to be hot. But he was also high, so he was confused as to where he was and how to get out. People reported hearing him freaking out in the portajohn, kicking the walls and pounding on the door, but they couldn’t get past the locked door and he couldn’t follow their instructions to unlock the door and open it. So he was all worked up on top of being overheated, so his muscles heated his body up even more. Eventually, NYFD came and got him out of the portajohn, and he was brought to the ER, where I saw him. He was very hot and very dehydrated and very high. I started cool IV fluids and ordered an alcohol bath, but the damage was done. In short order, he developed something called rhabdomyolysis, where the muscles begin wasting away and all the muscle fibers enter the blood stream and shut the kidneys down. Despite our best efforts, he died. The family was very upset. They knew he was smoking crack, but couldn’t stop them. Every attempt to put him in treatment ended with him running away to use. And he was no slouch, no crack bum; he was a regional manager for Ace Hardware, in charge of like 20 stores. And he wound up basically killing himself in a portajohn. What a waste.
When I think about the stereotypical Type A individual doing cocaine to excel in the workplace, I think of a Wall Street broker. I had a patient, a broker who worked on the Exchange floor. This guy was 40 when he first came to me, said he was on the fast track, that he wasn’t going to make $700,000K a year for much longer. He said he had to be sharp, had to be quick at all times and at all hours, no complacency, so he’d been using cocaine. I warned him about the potential dangers of piling cocaine on top of such a high stress job, but no matter what I said, he wouldn’t give it up. His motto was “Damn the torpedoes- full speed ahead!” He was getting away with using. Six months, seven, gaining on eight, he worked constantly, but he was the man, top trader, taking home fat 6-figure bonuses. After just over eight months on the cocaine, the piper insisted on his payment. He had a heart attack at 41, and when the ER doctor took his history, he readily admitted to using cocaine for eight months. With further questioning, he also reported having periods of confusion over the previous six months. His solution was to use more cocaine in an attempt to regain the sharpness it had once brought him in the beginning, but it didn’t work. What the cocaine did do was really keep him up at night. His solution for this was to drink four martinis every night in order to come down and get some sleep. He was doing this every day of the week for about seven months: cocaine throughout the day and martinis in the night. The cardiologist ordered a whole bunch of tests and it soon became clear that the heart attack that sent him to the ER was not his first. And unfortunately it wouldn’t be his last. His heart muscle was quite damaged from the ups and downs of the cocaine and alcohol fueled roller coaster he had boarded months before. I suspect that he never totally got off that ride, despite having another three heart attacks. Each one was progressively worse and made more obvious his mental and physical decline. At the age of 43, a massive fourth heart attack punctuated his life with a period. The man that burned the candle at both ends had burned himself out.
No tales of caution would be complete without mentioning the models and the housewives. They like cocaine because it helps them lose weight and stay thin. And because the cocaine stimulates them, they like to take Xanax and drink alcohol at night to come down. I can spot the cocaine/alcohol/Xanax Barbies at 50 yards, because they actually turn gray. I’m serious- their skin turns gray and they get too thin. The whole program makes them look like victims of concentration camps. And they wind up forgetting normal daily activities- forgetting to pick the kids up, forgetting when dinnertime is, forgetting how to do the homework with the kids, forgetting how to accomplish simple banking transactions- everything gets screwed up. In my career, I have lost count how many husbands have sincerely asked me if I think that their cocaine/alcohol/Xanax Barbie wives are: A. Going crazy, B. Exhibiting symptoms of early onset Alzheimer’s disease or dementia, or C. Showing signs of having a brain tumor.
I’ll tell you this one last quick story about a patient I saw a few days ago. Her name is Julia, and she is a 33-year-old out, loud and proud lesbian. She’s very intelligent, a paralegal, and lives with her girlfriend of several years, Paola. She was introduced to cocaine after coming out and getting involved in the lesbian scene at age 21. She used cocaine daily- and in increasing amounts- for ten years, because she said it stimulated her libido and helped her reach orgasm. She stopped using cocaine when she had a heart attack at age 31. Unfortunately, the heart muscle was significantly damaged, and now she is unable to tolerate even mild exertion, such as that which happens during sex. So…the cocaine she used for ten years to increase her libido and help her reach orgasm has caused her current inability to have passionate sex with her girlfriend. How’s that for cruel irony?
Cocaine is relentless and seductive…initially it can feel amazing, a ladder that lets you climb to the top of the world. Then cocaine is vicious, it sinks its hooks into you, which very few people manage to completely free themselves from. The perceived benefits aren’t worth the cost, which, as with some of my former patients, can be your life. It’s simply not worth it. I hope you get the take home message of all the many ways that cocaine can kill you, and that you understand how smart people find themselves tangled up in using cocaine, but also how even smarter people manage to stop using cocaine.
For more details and stories about addictive drugs like cocaine, check out my book, Tales from the Couch, available in my office and on Amazon.com.Learn More
Dr. Mark Agresti discusses the recent news with Charlie Sheen; his actions, his outbursts and his personality.
Dr. Mark Agresti, West Palm Beach Drug & Alcohol Detox Specialist, Psychiatrist
Call (561) 842-9550 or email: firstname.lastname@example.org Dr. Agresti today to get psychiatric help today.Learn More