Hallucinogens May Elevate Death Risk by More Than Twofold

Hallucinogens are associated with a 2.6-fold increased risk for premature death in some individuals seeking emergency care, according to a recent study. The risks are especially substantial in vulnerable patients who are suicidal, who are susceptible to severe mental illness, or have comorbid conditions such as respiratory disease or cancer.

The findings come at a time of renewed interest in the therapeutic potential of substances like psilocybin, lysergic acid diethylamide, methylenedioxymethamphetamine (MDMA), and ketamine for mood and substance use disorders. In 2023, the Canadian Institutes of Health Research allocated roughly $3 million to three clinical trials examining psilocybin-assisted psychotherapy in the treatment of alcohol use disorder, treatment-resistant depression, and end-of-life psychological distress in patients with advanced cancer.

“The use of hallucinogens and psychedelics is very rapidly increasing; 5.9% of Canadians used a hallucinogen last year,” said lead study author Daniel Myran, MD, Canada Research Chair in Social Accountability at the University of Ottawa and a scientist at the Bruyère Health Research Institute, the Institute for Clinical Evaluative Sciences (ICES), and the Ottawa Hospital.

“But there’s little information about some of the health consequences that might occur from using these substances, particularly outside of clinical or research settings,” he told Medscape Medical News.

The findings were published on March 3 in CMAJ.

Filling the Gaps

To address current gaps in the literature, the researchers conducted a retrospective, population-based study examining the association between hallucinogen use and mortality in Canadians seeking acute care through an emergency department (ED) visit or hospitalization.

The eligible individuals were 11,415,713 patients in Ontario, aged 15-105 years, with healthcare records held by ICES for ED visits, hospitalizations, and outpatient physician visits between January 2006 and December 2021. Deaths were categorized by cause, including alcohol; trauma; intentional self-harm; cancer; infections; or circulatory, respiratory, or gastrointestinal system diseases.

The primary analysis included 77,101 patients matched to the general population by age, sex, and index date and followed for a median of 7 years. Overall, 0.7% (n = 7953) of eligible patients had recorded hallucinogen-associated acute care events. More than a third of events (35.1%, n = 2778) were attributable to harmful use, followed by hallucinogen poisoning (20.9%, n = 1661), intoxication (18.8%, n = 1495), and dependence or withdrawal (13.0%, n = 1034).

Over 5 years, the risk of death in patients with hallucinogen-associated acute care was 9.7-fold times higher than that in members of the matched general population (6.1%, n = 482 vs 0.6%, n = 460). When the researchers accounted for sociodemographic factors, prior substance use or mental healthcare, and chronic conditions, the risk for death remained 2.57-fold greater than in the general population.

Findings Lack Granularity

“These sorts of studies are important as a benchmarking process. As we go further into the future and see psychedelics become more widely available, we could then see if that change in availability impacts the risks associated with them,” said Leah Mayo, PhD, Parker Chair in psychedelics at the University of Calgary and member of the Hotchkiss Brain Institute, both in Calgary, who was not involved in the study.

Mayo also pointed to several study limitations, which included a lack of data on patterns or types of hallucinogens used, as well as unmeasured confounders associated with risky behaviors.

“Hallucinogens are broadly defined as different classes of drugs that have different associated risk profiles. For example, MDMA, a stimulant, has a different risk profile than a classic serotonergic psychedelic or ketamine, a dissociative that can be used recreationally,” she explained.

The nuances of these substances and their effects, as well as the context in which they are used, are lost in a larger perspective such as this study, she added.

Although more research is needed, the study findings highlighted the shared characteristics of patients seeking acute care for hallucinogens, like comorbid conditions such as respiratory disease or cancer or having sought prior care for mental health or substance use. Elevated mortality risk was also linked to intentional self-harm, poisoning, or cancer. These factors must be analyzed further in future research, because “it’s people who have cancer who are at the end stages of life who might use psychedelics to alleviate their end-of-life distress,” said Mayo.

Nevertheless, these initial findings carry an important message for clinicians, Myran said.

“If you’re seeing an individual in an ED or in the hospital and there’s a feeling that hallucinogenic use is involved, that individual is at quite an elevated risk of death,” he said. “I’d highlight that there is other stuff going on that’s also causing them to be at risk, but they need care, follow-up, and support.”

The study was supported by a grant from the Canadian Institutes of Health Research. Myran reported no relevant financial relationships. Mayo is on the Scientific Advisory Board for PharmAla Biotech.

Liz Scherer is an independent health and medical journalist who frequently writes about cannabinoid therapeutics and psychedelics.