PHILADELPHIA—When thinking about the effects of recreational substance use in patients undergoing anesthesia, some specific substances like cannabis may come to mind. Hallucinogens and psychedelics? Not so much, but perhaps they should.
Patients who use them may be at risk for serotonin syndrome if exposed to other serotonergic agents, whether a prescription antidepressant or postoperative opioids, according to a presentation at the 2024 annual meeting of the American Society of Anesthesiologists.
“We now know how important it is to ask if patients are using a cannabis product, which can alter different parts of the anesthetic. We also need to ask if they’ve recently used psychedelics or hallucinogens,” said Trent Emerick, MD, an associate professor of anesthesiology and perioperative medicine and bioengineering at the University of Pittsburgh.
“It’s a few extra words, but the answer could impact the anesthetic. Anesthesiologists need to know how prevalent hallucinogens and psychedelics are, and how their use may magnify serotonin syndrome risk,” Emerick told Anesthesiology News.
Prevalence of Use and Nonchalance
At present, Emerick guessed that less than 5% of anesthesiologists ask about hallucinogen and psychedelic use, for two main reasons. First, although now more than 8% of young adults and more than 4% of early midlife adults use these agents, this is a relatively recent development; just five or six years ago, their prevalence was only about 2%.
Second, whether due to increasing decriminalization or the way hallucinogens and psychedelics are portrayed in contemporary pop culture, patients may not think of them as substances of use or abuse, but more as herbal or home remedies, he noted.
“They think of these agents as benign substances with hallucinogenic properties they may benefit from. They don’t understand that ‘magic mushrooms’ might have some anesthetic implications in the intra- and postoperative period, and don’t even think to mention them to their anesthesiologist,” Emerick said.
Wording can be important during the preoperative drug screen, cautioned Antje Barreveld, MD, an associate professor of anesthesiology at Tufts School of Medicine, in Boston, and the chief of pain medicine at Newton-Wellesley Hospital, in Newton.
“If you ask if they use illicit or street drugs, here in Massachusetts, and in many states, marijuana is legal; that wouldn’t register as illicit. There’s clear evidence that someone can have a marijuana disorder, but if we don’t ask the question right, it gets muddled,” she said.
Also, anesthesiologists may be giving more weight to medications and substances that obviously impact the cardiovascular system or, in the case of alcohol, the central nervous system. “So, we tend to have an agenda when we’re assessing patients’ substance use,” Barreveld said.
Hallucinogens, Psychedelics And Serotonin
“Hallucinogenic” is a broad term, referring to anything that alters mood, thinking patterns, or creates auditory or visual perceptions that don’t exist. “Traditionally, most hallucinogens don’t cause long-term addiction or memory changes,” Emerick said.
There are a number of different molecules that could be considered hallucinogens. But the agents he’s most interested in and concerned about are hallucinogens that modulate the serotonin system. “These are the classic psychedelics. Unlike a regular selective serotonin reuptake inhibitor (SSRI), these increase serotonin globally, across many parts of your brain,” according to Emerick.
“What’s interesting about serotogenic hallucinogens is that they bind to serotonin through the 2A subreceptor, which is involved in changes in the brain’s neuroplasticity and its ability to rewire itself,” he said, noting that psychedelics don’t create new neurons, they just affect the way existing neurons interact with one another.
“That’s where the crux of the benefits—and side effects—of psychedelics may come from. The 2A subreceptor is also found in the visual cortex, which is why people get hallucinations,” Emerick said.
Of the three main categories of psychedelics—the lysergic acid diethylamide (LSD)-derived ergolines; tryptamines, which include psilocybin from mushrooms; and phenethylamines, which include mescaline from peyote, Emerick focused on the latter two, which have driven the spike in prevalence.
In the perioperative setting, the concern facing anesthesiologists is the risk for serotonin syndrome in patients who have recently used one of these agents. “The mechanism of action for classic psychedelics is largely through the serotonin 2A receptor, which can increase serotonergic effects on the body,” Emerick said.
The problem is that many of the anesthetic agents that anesthesiologists use, such as methadone in the OR, also increase serotonin. Problems can also arise in postoperative recovery, when patients might be exposed to fentanyl, or may simply be taking a serotonin-norepinephrine reuptake inhibitor or an SSRI.
“Patients may not realize that their antidepressant along with the psychedelic is increasing their serotonin,” Emerick said.
All this excess serotonin can lead to potentially life-threatening serotonin syndrome. “Patients can have cardiac issues—high blood pressure, palpitations—and flushing,” he said.
Early signs of serotonin syndrome include agitation and confusion. Patients experience what feels like a hot flash, and they can become hyperreflexic. Deterioration can happen rapidly; if the serotonin syndrome is severe enough, it can lead to cardiovascular collapse and significant cardiovascular problems.
“To prevent this, all an anesthesiologist would have to do in elective cases is ask a simple question: Any recent psychedelic or hallucinogen use? That three-second question may get a no from 80% to 90% of patients, but if you uncover a couple of patients a week, you can preemptively alter their anesthetic to avoid further agents that increase serotonin.”
Also important to mention is the cross-over class of entactogens/empathogens (e.g., MDMA, commonly known as ecstasy), which are both serotonergic and dopaminergic, interacting with both neurotransmitters to create a sensation of empathy and inward reflection.
“While the prevalence of those substances isn’t going through the roof, they do also interfere with serotonin and can cause serotonin syndrome,” Emerick said.
“These drugs are not evil, but we need to ask about use, and know how they affect our patients and our ability to care for them around surgery.”
By Monica J. Smith
Barreveld is an advisor for Lin Health and Noema Pharma, and serves on the speakers bureau and as a consultant for Vertex. Emerick reported no relevant financial disclosures.
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