Sussing out stimulants and other drugs

Learn the signs and symptoms of monoamine agonist abuse.


Expertise on addictive drugs can be helpful even when you're not working in the hospital. Charles Reznikoff, MD, FACP, was celebrating St. Patrick's Day at a distillery when a woman with large pupils and rapid speech accused him of stealing her friend's phone.

To Dr. Reznikoff, an addiction specialist at Hennepin Healthcare and assistant professor of medicine at the University of Minnesota in Minneapolis, it was clear the woman was in the midst of a stimulant binge, and he responded to her accordingly (more on that later). During his ACP CME 30 talk, “Monoamine Agonists of Abuse,” he offered tips to help hospitalists make similarly quick evaluations of their patients.

Photo courtesy of Dr Reznikoff
Photo courtesy of Dr. Reznikoff

Three very diverse classes of drugs activate the monoamine system, starting with stimulants, such as amphetamines. “Stimulants are highly dopaminergic, and therefore, they are highly addictive,” said Dr. Reznikoff. “They create these movement disorders and stereotyped behaviors. They're also highly adrenergic and therefore cause hypertension and tachycardia and sometimes hyperthermia and can cause ischemic events and cardiovascular events.”

On the other end of the spectrum are hallucinogens, which are largely serotonergic and only mildly adrenergic and dopaminergic. “They do raise your heart rate and your blood pressure, and they do have some pleasurable euphoric effects that are attributable to dopamine,” he said. However, this drug class, which includes LSD, is less addictive and carries less cardiovascular risk than stimulants.

Dr. Reznikoff called the third class, between the other two, the empathogens, although he noted others have described them as entactogens and entheogens. This class includes such drugs as 3,4-methylenedioxymethamphetamine (MDMA), also known as ecstasy. “They're more serotonergic than a stimulant, they're less addictive than a stimulant, they're less cardiovascularly challenging than a stimulant, but they're not all the way to a hallucinogen They're in this middle zone,” he said.

One of the main risks of using these drugs, particularly those in the third category, is that it's hard to know what one is taking. They're made in illegal labs that, of course, provide no guarantee of their ingredients. “Every single type of drug today has a synthetic analog that is sold online,” said Dr. Reznikoff. “If you grow an illegal drug in a field, drones can find it, and DEA [Drug Enforcement Agency] agents can intervene. The future is these clandestine labs creating synthetic drug analogs.”

Many synthetic drugs won't show up on toxicology screens and can be contaminated with all kinds of impurities. “Many of these are poorly categorized agents, so people are literally experimenting on themselves,” he said. “It's going to be on us not to just get a drug screen, but to recognize the toxidrome and . . . infer what types of drug they used.”

Know your toxidromes

One common example of this challenge is distinguishing whether a hallucinating patient is on a hallucinogen like LSD or a dissociative like ketamine. Taking a dissociative splits cognition from perception, explained Dr. Reznikoff. “You cannot interpret your perceptual inputs,” he said. “Everything you see, hear, and touch is a scary hallucination to you, and you lack insight. You don't understand what's happening, and it's all a confusing blur.”

A clinician, even one who tries to act very friendly, can seem like one of these frightening hallucinations to a patient who has taken a dissociative drug. “Our presence in the room could just make them escalate,” he said. “The best thing to do is to keep the stimulus low—low lighting, low noise, minimize the [measurement of] vitals, minimize the interruptions, and then keep your fingers crossed because if the person calms down, you can ride it out.”

Patients who don't calm down can be given sedatives, but, in some cases, more extreme measures are required when they are dangerous to themselves or others. “Unfortunately, we've had to paralyze and intubate people and just wait until the dissociative wears off and then we can extubate them, and that is not a good outcome,” he said.

Intoxication with a hallucinogen, on the other hand, is much more easily managed. “Cognition is intact, so these folks who take LSD get scared, but they retain their insight,” said Dr. Reznikoff. “Health care workers can and should go into the room and offer calm reassurance.” He did offer one caveat: Patients with underlying psychosis may become unstable on hallucinogens.

Reassurance would probably not work for another intimidating, intoxicated patient he described: a large aggressive man presenting with ventricular tachycardia at 280 beats per minute. “That's the fastest heart rate that I've ever seen live. He was successfully cardioverted. Then, he was promptly verbally abusive and rude to the staff, especially the female staff. This lasted for 24 hours,” Dr. Reznikoff said.

The patient tested positive for both methamphetamine and amphetamines. “Of course, meth is metabolized to amphetamines, so whenever you use meth, you usually have a positive screen for both,” he said.

Talking is not the therapy for such patients. A hospital in North Dakota once asked Dr. Reznikoff for ideas on how to reduce assaults on their ED nurses by patients on methamphetamines. The cause of the problem, he found, was that nurses carried out routine care unaware that a patient was intoxicated on methamphetamines so the solution was to make the very first step in seeing patients a determination of whether they are on the drugs.

“Quickly determine if this person is intoxicated on meth and if yes, do not spend unneeded time with them. Do not argue with this patient. They are going to be argumentative, [and] they're going to try to draw you into an argument.” Instead, offer the patient a sedative and return when he is calm.

It is important to determine if such a patient is at high risk for suicide, violence, or end-organ damage, including hypertensive emergency. “Suicide is a major, major risk in cocaine- and methamphetamine-using individuals. They're actually more at risk of suicide than people with depression. It is very rare that you find someone addicted to stimulants who has not contemplated or attempted suicide. They are incredibly dysphoric and yet also energetic. Dysphoria plus energy is a very, very dangerous mix,” said Dr. Reznikoff.

First-line treatment for stimulant toxicity is benzodiazepines. He recommended lorazepam if giving an IV, or diazepam as an oral medication because it has rapid onset. “Second, obviously, supportive care—everything you would normally do for these folks who are malnourished and hypertensive and dehydrated and just generally suffering.”

Don't give these patients selective beta-blockers to treat their hypertension. “Stimulants activate alpha and beta, so if you block beta, you leave alpha unblocked and you can worsen the hypertension, even trigger hypertensive crisis. If you have to use a beta-blocker, I would use labetalol, which is nonselective,” Dr. Reznikoff said.

Antipsychotics are a popular treatment choice, but they should be secondary to benzodiazepines, he advised. “Some docs these days are giving out ketamine in the emergency department to manage methamphetamine intoxication, and that can work as well. But I would urge everyone, benzos first.”

Recognizing stimulant addiction

It may take a long time for patients to come down from a stimulant binge. Stimulants vary in their timelines, Dr. Reznikoff explained. Crack cocaine binges are the fastest, with about 12 hours from first use to toxicity. “At that point, people crash, sleep it off, wake up the next day,” he said. Cocaine binges can go 36 hours, but patients on meth can continue using for as long as a week.

Dr. Reznikoff typically asks patients what's the longest they've stayed awake while on a stimulant. “It is shocking the answers you'll hear,” he said. “They could be minimizing, denying, and then you ask them that question and they'll say, ‘Well, doc, five nights.’ It's almost like asking an old-time doc, ‘What's the longest overnight shift you've ever worked?’”

Lengthy sleepless binges are an issue specific to stimulant addiction. “If you drink too much alcohol, you pass out. If you use too much opioid, you overdose,” he said. “Each drug, if used in an extreme, is self-limiting except for stimulants. If you use too much stimulants, you wake up and use more.”

As a stimulant binge continues, the effects of the drug get more intense and less pleasurable. While on a binge, those who use can go from confident to bold to aggressive, wide-awake to sleepless to insomniac. It was this spectrum of response that allowed Dr. Reznikoff to diagnose the woman who approached him on St. Patrick's Day. “I could tell you that she was vigilant or maybe paranoid. I could look at her and say that ‘You are on a stimulant, and you are at least mid-binge or perhaps past mid-binge.’”

Binges typically end in one of three ways. Patients get arrested, arrive at the ED, or are familiar enough with the process to treat themselves with a central nervous system depressant. “People that are using a lot of stimulants and are highly stimulated will sometimes use GHB [gamma-hydroxybutyric acid] to sedate themselves and come down from their high,” said Dr. Reznikoff.

That might also bring them to the hospital, however. “The classic GHB overdose would be a young individual who presents unarousable, intubated, and, 24 hours later, abruptly wakes up and possibly even self-extubates. This was a big problem 15 years ago or so. Many people who were clubgoers or exotic dancers who used GHB would write the letter G on their palm because if they happened to use too much, they would become comatose and nobody would know why,” he said.

A slightly newer trend, called “party and play,” is popular among young white men in urban areas, Dr. Reznikoff reported. “They will meet and have sex parties while on methamphetamines. This group tends to use IV methamphetamines as their mode of use. When they get very intoxicated on meth, they use a variety of drugs to bring themselves down, most commonly GHB,” he said.

Not surprisingly, this kind of stimulant use is also associated with risk for sexually transmitted infections. “I cannot tell you how important it is to screen these folks for sexually transmitted infections frequently and also sexual violence or exploitative relationships,” said Dr. Reznikoff.

Ideally, you'd also want to get them addiction treatment, but unfortunately, “There really are no good medical options for stimulant use disorder,” he said. “Of course, all the traditional treatments, like inpatient treatment, outpatient treatment, intensive outpatient treatment, all those behavioral treatments still apply and are good options.” But these efforts are often not successful for patients with stimulant use disorder, he noted.

Finally, clinicians should warn patients about the risk of poisoning from contamination of street drugs and illicit pharmaceuticals. “People are increasingly getting poisoned with psychostimulants,” said Dr. Reznikoff. “If you buy an Adderall pill on the street, it's quite likely it's not Adderall at all; it's methamphetamine. . . . Educate patients about impurities and unknowns when they use club drugs and the potential that they're using fake pharmaceuticals when they buy them on the street.”