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Methamphetamine is the second most abused drug in the U.S. We bring you up to speed on the basics in this episode.

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Published On: 02/21/2022

Duration: 20 minutes, 52 seconds

Related Article: “A Novel Treatment for Methamphetamine Use Disorder,” The Carlat Psychiatry Report, February 2022

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Chris Aiken, MD, and Kellie Newsome, PMHNP, have disclosed no relevant financial or other interests in any commercial companies pertaining to this educational activity.

Transcript:

Methamphetamine is the second most abused drug in the U.S. Today, we’ll bring you up to speed on the basics.

Welcome to the Carlat Podcast, keeping psychiatry honest since 2003. I’m Chris Aiken, the editor in chief of the Carlat Report. And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue.

KELLIE NEWSOME: In this month’s Carlat Report we covered a ground-breaking clinical trial from the New England Journal of Medicine. The study looked at the combination of Bupropion and Naltrexone in methamphetamine abuse, and today we’ll take a deeper dive into this disorder, but first a preview of the CME questions for this episode.

CHRIS AIKEN: Which form of methamphetamine is commonly inhaled?

A. Crank

B. Speed

C. Ice

D. Rock

KELLIE NEWSOME: Sit in a room with 20 random strangers, and chances are that one of them has tried methamphetamine in their lifetime. After marijuana, meth is the most commonly used drug in America. 

But how is meth any different from a drug that we often prescribe: Amphetamine, which goes by the more innocuous brand names of Adderall, Evekeo, Dexedrine, Mydayis and Vyvanse? Well, both drugs act in the same way. They cause nerve cells to release more dopamine and norepinephrine, and – to a lesser extent – block the reuptake of those monoamines. The difference is that methamphetamine is much more potent. Compared to amphetamine, methamphetamine pumps out about twice as much dopamine. But all this is dose dependent, and high doses of either drug are dangerous. 

And here is what methamphetamine abuse causes: anxiety, paranoia, hallucinations, delirium, mania, depression. People who use meth can develop stereotyped compulsive behaviors. They may spend tedious hours taking apart a device like a clock and putting it back together, or fidgeting with buttons on their clothes or pulling hairs or biting nails to the point of bleeding. By the way, you can see all those problems with Adderall and other amphetamine prescriptions if the dose goes too high.

Those are just the mental problems. On the medical side, methamphetamine abuse can cause seizures, heart attacks, stroke, acute aortic dissection and aneurysms, and pulmonary hypertension. Less serious are muscle cramps and constipation. For reasons that are unclear, teeth can decay rapidly in meth users, giving them a distinctive look called “meth mouth.” The nose can perforate from sniffing it, and skin infections and lesions can pop up from IV use – a phenomena called “speed bumps.”

CHRIS AIKEN: Psychosis is one of the big problems with methamphetamine. Meth psychosis looks very much like acute schizophrenia – delusions, hallucinations of all types. They may think cameras are watching them in their office or that the police are following them. Texts and social media are easy for anyone to misinterpret, and those misinterpretations get more extreme with meth abuse. Just ask the patient to show you the Facebook posts they are riled up about, and it’s often much more benign than what their mind has made it out to be. The internet is also ripe with conspiracy theories that are easily downloaded into the meth-infused mind.

KELLIE NEWSOME: Speaking of which, it seems like the rise in conspiracy theories has paralleled the rise in amphetamine and methamphetamine abuse. Perhaps just a coincidence – we can’t find any research that connects the two. If you have any leads, write to us at asktheeditor@thecarlatreport.com.

CHRIS AIKEN: Here are the actual rates of psychosis on meth and stimulants. About 1 in 800 patients who are prescribed methylphenidate for ADHD develop psychosis, and the rate for amphetamines is about double that – around 1 in 400. Those rates may be an underestimation, because they are based on cases identified by the physician in the medical record – from a 2019 New England Journal study of 220,000 teens and young adults. But when we move to higher doses, like above 120 mg/day, the rates of psychosis are at least 12 times higher – around 1 in 25 people – and that’s based on a study of a non-psychiatric population that looked at high-dose stimulant use in narcolepsy. 

KELLIE NEWSOME: Those are rough estimates, but let’s recap. At clinical doses, the rate of psychosis is 1 in 800 for methylphenidate, 1 in 400 for amphetamine, and at high doses it jumps to 1 in 25. Moving on to actual methamphetamine abuse, the rate of psychosis is even higher: around 1 in 3 (the official number is 25-50%). The mechanism of psychosis in schizophrenia is pretty similar to the mechanism of action for amphetamine and methamphetamine – excess release of dopamine – and the more potent the dose, the higher the rate of psychosis.

CHRIS AIKEN: Methamphetamine was once prescribed to treat ADHD – strangely it is still available as a class-II controlled substance – but rarely prescribed because many of the problems we’ll talk about today showed up in clinical doses, including direct neurotoxicity on the brain. But even though it is FDA approved for ADHD, chronic meth abuse causes cognitive impairment as it gradually damages the dopamine tracts in the brain.

In the patients I’ve seen, these cognitive problems look very distinct from ADHD. They speak in short sentences and have trouble forming thoughts. They perseverate, they are less flexible in their thinking, and their problem-solving skills collapse. They are less aware of what’s going on around them and they are disorganized and forgetful in their everyday life. The closest way I can describe their mental status is to say that it resembles the negative symptoms of schizophrenia. They even have those soft neurologic signs so characteristic of schizophrenia, like stereotyped repetitive movements, muscle twitches and odd gestures, as well as psychomotor retardation. Some textbooks say that chronic methamphetamine users can develop, not only psychosis, but also the negative symptoms of schizophrenia, and I think this is what they’re talking about. It’s all dopamine dysregulation, whether through amphetamine abuse, schizophrenia, or the iatrogenic problem of ultra-high doses of stimulant prescriptions. Fortunately, there is evidence of recovery, both on PET scans and cognitive testing, and memory usually improves after a few months to a year of abstinence.

KELLIE NEWSOME: Psychosis and other symptoms of acute intoxication usually clear within a few days of stopping the drug. Unlike many drugs of abuse, withdrawal symptoms from methamphetamine are relatively mild. Usually the patients are tired, sleep a lot, and have a high appetite – the opposite of what stimulants do. More severe cases become depressed, dysphoric, irritable, anxious, and experience worse concentration and even worse paranoia. 

Those are the basics of methamphetamine use disorder, and the facts are pretty much the same for cocaine and amphetamine use disorders. But how did we get here? Let’s start at the beginning, in Japan, 1890. 

CHRIS AIKEN: Methamphetamine and amphetamine were both discovered within a few years of each other in Japan around 1890, but they weren’t widely used until the 1940’s. In World War II, both the allies and axis powers gave these drugs to their troops to increase their stamina, attention, and confidence. Ever wonder how Japanese Kamikaze pilots got up the nerve to fly their planes into enemy war ships? High doses of methamphetamine. 

In 2016, German author Norman Ohler wrote a best-selling book claiming that Adolph Hitler was given methamphetamine from 1937 onward. Methamphetamine was the preferred stimulant in Nazi Germany, where they were sold over-the-counter under the brand name Pervitin. 

Blitzed is a controversial book, but not because of its facts. Hitler’s use of methamphetamine has been documented for years, John F Kennedy also took prescription meth while in office. The book was controversial because attempts to explain the atrocities of the Third Reich as the work of mental illness are insulting to those who suffer psychiatric disorders, and run the risk of sounding like apologies for evil. Meth may have muddled Hitler’s mind, but the acts that brought him infamy began long before the routine injections.

KELLIE NEWSOME: As the world moved into the more domicile, civilian age of the 1950’s, both amphetamine and methamphetamine became popular in the US and abroad as antidepressants and diet aids; their use in ADHD came later in the 1960’s and 70’s. But methamphetamine fell out of favor though because of its high abuse and psychotogenic potential, not to mention its neurotoxic effects. The typical clinical doses were around 20-25 mg/day – but people turn that up 20 to 60-fold when they abuse methamphetamine, taking around 500 to 1400 mg in a single day. Besides destroying dopamine and serotonin tracks in the brain, high doses can also cause the blood-brain barrier to break down, leading to a serious risk of brain edema.

CHRIS AIKEN: Methamphetamine was a favorite of the 1950’s beat poets. Allen Ginsberg wrote of its manic and psychotic effects in his poem “Howl,” whose famous opening lines sum it up: “I saw the best minds of my generation destroyed by madness.” In the early 60’s, the counter-cultural Mods in London used it. In the song “Talking About My Generation,” The Who tried to imitate the stuttering vocal tics of Mod meth users.

Then the hippies took it over in 1967’s Haight-Ashbury San Francisco, a summer of love that ended in an autumn of angst. In the Spring of that year, young adults flocked to Haight-Ashbury to take part in a utopian community where meals were cooked together, possessions were shared, and love was free. Many in the community took methamphetamine, and by the Fall that idealism had descended into paranoia and violence. A documentary on PBS’s American Experience covers the decline in Summer of Love, Season 29 Episode 12.

Soon after, meth was picked up by biker gangs like Hell’s Angels, who transported it in the crankcases of their motorcycles, giving rise to the nickname “crank” and another violent incident that brought an end to 60’s idealism, the Altamont disaster. Held in the final month of the 1960’s, Altamont was planned as a sequel to Woodstock, but it suffered 3 fatal flaws. First, the stage was a low one set at the bottom of a slope, causing gravity to pull the large crowd onto the performers. To secure the stage, the Rolling Stones hired a Hell’s Angels to keep the audience off it – paying them with $500 worth of beer. Besides lacking in security training, many of the Hell’s Angels members were also high on methamphetamine, a drug that makes people overconfident, paranoid, and aggressive. Add to this the psychedelic antics of the youthful crowd, and the outcome was tragic: 4 people died and countless more were severely injured, including an 18 year old man who was stabbed to death by the Hell’s Angels. 

KELLIE NEWSOME: The 1980’s saw the spread of a new type of methamphetamine, methamphetamine hydrochloride, better known “crystal meth” and sometimes called “ice” for its resemblance to ice shards (not to be confused with “rock” which is a yellowish pebble sized chunk of meth that is usually ingested). Although the central ingredient was the same, this crystallized form allowed the drug to be smoked, resulting in a nearly instantaneous euphoria and a rapidly spreading epidemic that spread from Hawaii to California to the rest of the US.

Methamphetamine also has unique sexual effects. It increases sexual desire, and inhibits ejaculation, a combined effect that some people use to prolong sexual encounters. These “party and play” sexual gatherings are popular among homosexuals, where men meet – often on the internet – for meth-infused sexual encounters, often involving group sex, and ratcheting up the rate of HIV infections.

CHRIS AIKEN: So what is new with meth abuse? In the past few years we’ve seen new controlled trials to help people stay off meth. In addition to the bupropion-naltrexone combination we covered in this month’s issue, there is support for topiramate, mirtazapine, atomoxetine, and a natural CAM treatment called citicoline. Topiramate and citicoline may reverse some of the neurotoxic effects, and mirtazapine is particularly useful for easing the withdrawal symptoms. 

KELLIE NEWSOME: And then there’s P2P meth. If you understand the difference between Lexapro and Celexa; Ritalin and Focalin; or the 50/50 racemic amphetamine that recently re-entered the market as Evekeo, and the 100% dextro-isomer that is branded as Dexedrine and Vyvanse, then you’ll have no trouble grasping this concept.

Like the traditional stimulants amphetamine and methylphenidate, methamphetamine is a racemic, 50/50 mix of two mirror-image isomers: d-methylphenidate and l-methylphenidate. And as is true for the traditional stimulants, the d isomer is the more potent one; l-methamphetamine is relatively inert in the CNS. The pharmaceutical industry appreciates these d vs. L isomer differences, which is why we’ve seen a growth in d-isomer stimulants like Dexedrine, Vyvanse, Focalin, and the latest – Azstarys. And the illicit drug industry realizes it as well. In the past decade, black-market meth labs have figured out how to produce the purified d isomer, so today’s meth is often more potent than meth of yore. D-methamphetamine speeds up all the problems we’ve just described with methamphetamine.

If you’ve watched the Netflix series Breaking Bad, you probably recall the obsessional focus of Walter White as he tries to create his signature, purified methamphetamine. The series gets it right. Like real-life meth labs, Walt uses P2P to produce the d-isomer, which is why d-methamphetamine is called P2P meth.

CHRIS AIKEN: And now for the word of the day…. Alkermes

KELLIE NEWSOME: In the 1400s, a small Italian family came to wield outsized power across Europe by creating the modern banking system. Their wealth underwrote the Italian Renaissance, and their favorite drink was Alkermes liquor, a mix of sweet and bitter herbs that was soaked in the reddish skin of the Kermes bug, yes that’s right – an insect – which gave the drink its scarlet color. 

But that’s not the Alkermes we’re talking about. Today, Alkermes is better known as an Irish pharmaceutical company that is responsible for some of the psychiatric products now on the market. They brought us two long-acting injectable meds: Aristida for aripiprazole injectable; and Vivitrol, a long-acting naltrexone injectable. Indeed, the naltrexone-bupropion trial we covered today used the long-acting Vivitrol shot, which was donated by Alkermes, but the study we covered was independently funded by the NIMH.

But that’s not why we’ve chosen Alkermes as the word of the day. As you’ve probably guessed, that points to our next episode, because Alkermes has a new product: Lybalvi, a combination of samidorphan and olanzapine that is supposed to relieve some of the pounds this antipsychotic can pack on. Next week, we’ll see how well it works.

Learn more about addictions psychiatry in our CME journal, the Carlat Addiction Treatment Report. The latest issue has research updates on antipsychotics for methamphetamine psychosis, a review of meds for alcohol use disorders, and clinical updates on vaping and nicotine cessation. And to earn CME credits for your podcast listening, follow the link in our show notes.