Published in the June 2016 issue of Today’s Hospitalist
YOUR PATIENT is young, feverish and crazy agitated. He is clearly on drugs, but his urine screen is clean. What’s going on?
It’s possible that he has taken some of the new drugs of abuse that are popular with high school- and college-age patients but alien to almost everyone else. “A lot of these drugs are legal and widely available,” University of California, San Diego toxicologist and emergency physician Alicia B. Minns, MD, told hospitalists at this spring’s Society of Hospital Medicine meeting. “It’s a cat-and-mouse game. The government can’t keep up with all the different derivations of these products that become available.”
It’s also possible that if your patient has abused one or more of these drugs, he is experiencing “excited delirium,” a life-threatening condition most clinicians are unfamiliar with. Excited delirium comes on suddenly and is marked by symptoms of bizarre or aggressive behavior, shouting, paranoia, agitation, violence toward others, unexpected physical strength and dangerous hyperthermia.
“We see profound tachycardia and hyperthermia and a lot of agitation.”
~ Alicia B. Minns, MD University of California, San Diego
“Most doctors feel uncomfortable managing these patients because they are not quite sure about the presentation, how long the effects last or how to treat them,” said Dr. Minns. “But these drugs are out there, and they are used a lot.”
Most newer drugs being abused are psychostimulants, which act like cocaine or methamphetamine—only they are more potent, she said. “You need to take these patients very seriously.” Treatment has to be “very aggressive” so otherwise healthy young patients don’t develop multisystem organ failure.
“A lot of times, we are paralyzing them and putting them on a ventilator,” she explained. “And we are sending a lot of these patients to the ICU.”
Known commonly as “Spice” or “K2” and sold under hundreds of names including “Bombay Blue,” “Bliss,” “Black Mamba,” “Aztec Fire” and “Kush,” synthetic cannabinoids are inexpensive alternatives to marijuana. They are also more dangerous than pot because they are much more potent.
More than 11% of 12th-graders report that they currently use them or have in the past, making them more popular than ecstasy or cocaine. Currently, U.S. poison control centers field between 500 and 700 calls a month about these drugs.
“We don’t see a lot of poison center calls about marijuana, but we are seeing it with these,” Dr. Minns said. “That’s because these drugs produce more severe effects than traditional cannabis.”
Part of the popularity of these drugs comes from the fact that they don’t show up on urine tests. As a result, she noted, these substances are favored the military or in jobs that require regular drug testing. The drugs are usually sold in small foil packets containing dried, shredded plant material, with one or several synthetic cannabinoids sprayed on. The material can be smoked, or the drugs come in a liquid form that can be vaporized and inhaled through e-cigarettes.
Although these man-made chemicals can produce many of the “same reported euphoric effects” as marijuana, she explained, they are structurally dissimilar to Δ9THC. The packets usually contain a number of different synthetic cannabinoid chemicals that can be anywhere from “10 to 800 times more potent in terms of cannabinoid-binding receptors as traditional marijuana” and tend to produce more dysphoric effects.
“We see a lot of agitation, and we have seen seizures,” Dr. Minns said. “Many of these patients have hallucinations and paranoia, while some are somnolent.” Case reports have detailed young people with ST and troponin elevations, and some need dialysis.
“Unless you get a history of synthetic cannabinoid use,” she noted, “these patients often look similar to someone on amphetamines.”
Complicating doctors’ decision-making: A lot of these patients are using other abuse substances. “It’s hard to tease out what is caused by what,” she said.
The bottom line, however, is that it probably doesn’t matter if the patient is using other drugs. In terms of treatment, there is no antidote, and treatment mainstays are benzodiazepines for agitation as well as fluids and other forms of goal-directed, supportive care to address other symptoms.
Commonly known as “bath salts,” synthetic cathinones have nothing to do with the Epsom salts that people use to bathe.
Instead, these compounds are synthetic versions of the stimulant cathinone that is found naturally in the khat plant, which has been chewed in East Africa and parts of the Middle East for centuries. Some synthetic cathinones are legal, including the antidepressant bupropion. But the ones that Dr. Minns said are being abused are marketed as cheap substitutes for methamphetamine, cocaine and Molly (MDMA). Some of the street names include “MeowMeow,” “Ivory Wave,” “Vanilla Sky” and “MCAT.”
Bath salts are not as popular as synthetic cannabinoids. According to Dr. Minns, surveys find that only between 1% and 2% of high-school seniors in the U.S. abuse them, with higher rates documented in Europe. However, these drugs tend to be more dangerous.
“There is less central nervous system (CNS) penetration than with amphetamines, so we find that people need to re-dose and re-dose and re-dose to obtain the CNS effects they want,” Dr. Minns noted. “They are getting a drug-stacking effect, which is why we see profound tachycardia and hyperthermia and a lot of agitation.” Because it’s never clear which particular chemicals and doses are present in any given product, “the onset of action and duration varies, and those are hard to predict. We have seen people with prolonged delirium for days.”
In addition, studies have reported tolerance and withdrawal with these drugs. “There is a potential risk for long-term neuropsychiatric problems,” she said. “In PET scans of chronic users of bath salt products, the brain almost looks like a Parkinson’s patient’s brain. No one knows how much you need to use and for how long to develop those adverse effects.”
As is the case with synthetic cannabinoids, physicians have no antidote, and treatment consists of benzodiazepines to control agitation. If a patient has hyperthermia— and Dr. Minns has seen patients come to the hospital with temperatures of 106 degrees or higher—they need to be rapidly cooled, and sometimes paralyzed and intubated. They can also end up with long ICU stays.
Originally invented and promoted by chemist Alexander Shulgin, PhD, whose 1991 book “PiHKAL: A Chemical Love Story” continues to inspire people to use these hallucinogens, 2C drugs at higher doses can cause tachycardia, hypertension, hyperthermia, seizure and death.
“Clinically, think about your worst methamphetamine addiction combined with your worst serotonin syndrome, and this is your patient,” Dr. Minns told hospitalists. “These patients are very sick, and unfortunately, there are numerous case reports of young healthy people dying from these products and the excited delirium they cause.”
The drugs are sold as tablets or powder, and people typically snort them. Many who use them think they are ingesting something else, like ecstasy. There are no national statistics on their prevalence and use.
How should you treat these patients? Similar to those who have intoxication from other psychostimulants, with a focus on sedation and rapid cooling if the patient is hyperthermic.
Unlike the other drug groups, this naturally occurring, inexpensive hallucinogen causes short-term, intense LSD-like psychedelic effects when smoked, inhaled or brewed as tea. It is also called “Magic mint,” “Diviner’s sage,” “Sally-D” or “Mystic sage,” and it can be legally bought for gardening purposes.
The rate of use among high-schoolers is higher than that of cocaine or ecstasy, and hundreds of YouTube videos have been posted by people documenting their Salvia trips. Although such experiences tend to be intense, they last only five or 10 minutes. Poison control centers receive very few calls about these drugs, and these patients rarely show up in emergency departments.
When they do, they usually have recovered by the time a physician sees them, said Dr. Minns. The patients she does see are the ones who have had “an overwhelming sense of loss of control.” She recommends treating this anxiety with benzodiazepines.
Salvinorin A, the active ingredient in Salvia divinorum, is the most potent naturally occurring hallucinogen, and it works differently in the body than other hallucinogens. It does not affect serotonin receptors, but instead acts on the kappa opioid receptor.
Deborah Gesensway is a freelance writer who covers U.S. health care from Toronto.
What should you do?
FOR HOSPITALISTS treating patients who have used any of the latest generation of drugs of abuse, Alicia B. Minns, MD, a University of California, San Diego toxicologist and emergency physician, offers the following tips:
Call the poison control center. In addition to having toxicologists available who can help you devise a management plan, poison control centers “typically have the most up-to-date information,” particularly about these constantly-evolving drugs. “Even within the ED community,” said Dr. Minns, “there is a knowledge deficit.”
Don’t test. Except in rare cases, such as when it’s needed forensically, don’t bother sending out samples. GC-MS or LC-MS testing will detect the drugs but will not help guide decision-making.
Don’t rely on urine drug screens. Not only will urine screening not detect these new drugs of abuse, but just because a patient tests positive for cocaine or methamphetamine doesn’t mean other drugs weren’t ingested too. “There is a tendency to over-rely on urine drug screens,” she noted, “and you have to interpret screens with caution because they don’t give you the whole picture. Just because a drug screen is positive for meth, that doesn’t mean that’s why the person is sick.”
Err on the side of over-sedating. “Be aggressive about sedating these patients,” she said. “The sooner they are sedated, the safer it will be for staff and the patients as well.”
Consider comanaging these patients with the ED doctors. “Usually when patients first come in, that’s when they are the sickest,” Dr. Minns said. “It is not uncommon for the ED to sedate the patient and call the hospitalist to admit them, then have patients awake, calm and ready for discharge even before they are moved to a bed.” Typically, she added, once patients are stabilized, “they continue to do well.”