Psilocibin, or “magic mushroom,” use increased among all age groups since decriminalization in 2019

Embargoed for release until 5:00 p.m. ET on Monday 21 April 2025   

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Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.   
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1. Psilocibin, or “magic mushroom,” use increased among all age groups since decriminalization in 2019

Past year psilocybin use increased by 44% among young adults (age 18 – 29) and 188% among older adults.

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-24-03145

URL goes live when the embargo lifts  

A multisource observational study aimed to quantify the change in prevalence and health care utilization of psilocybin users between 2014 and 2023. The study found that the prevalence of psilocybin use increased across all age groups, with those with mental or physical comorbidities among the most common users. The findings are published in Annals of Internal Medicine. 

Researchers from Rocky Mountain Poison and Drug Safety in Denver, CO and colleagues studied five nationally representative data sets - the National Survey on Drug Use and Health (NSDUH), the Survey of Non-Medical Use of Prescription Drugs (NMURx), Monitoring the Future (MTF), the National Poison Data System (NPDS), and the National Hospital Ambulatory Medical Care Survey (NHAMCS) - to calculate annual estimations of the prevalence of psilocybin use in the United States. Psilocybin is the first hallucinogenic substance to be decriminalized in some states. The researchers found that before 2019 (the first year psilocybin was decriminalized anywhere in the US), psilocybin use remained relatively stable. Since 2019, lifetime use among adults and adolescents increased. Additionally, past year use increased by 44% among young adults (age 18 – 29) and 188% among older adults. Past year use among 12^th graders increased 53% since 2019, and prevalence in 2023 was 2.5%. Adults with mental health or chronic pain comorbidities were more likely to use psilocybin. The rate of psilocybin exposures reported to U.S. poison centers increased 201% in adults, 317% in adolescents, and 723% in children. In 2023, past year adult psilocybin use was higher than estimates for cocaine, LSD, methamphetamine, or illicit opioid use. The results emphasize the need for public health and health care professionals to consider the elevated rates of psilocybin use in future policy and intervention development. 

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To contact corresponding author Joshua C. Black, PhD, please email Paula Cooper at Paula.Cooper@rmpds.org.  

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2. Medicaid enrollees with diabetes lack access to medications with cardiovascular health benefits

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-24-01449

URL goes live when the embargo lifts             

A national cross-sectional study evaluated the unrestricted availability of sodium–glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), the only two diabetes medications that reduce cardiovascular disease (CVD) and death, among Medicaid enrollees. The study found that many Medicaid enrollees have restricted access to cardioprotective medications, with tirzepatide almost entirely restricted. The authors note that formulary plan coverage is a potential lever to mitigate health inequities for low-income Medicaid enrollees with diabetes, warranting consideration of state policy changes to increase access to these medications while balancing pharmaceutical costs. The findings are published in Annals of Internal Medicine. 

Researchers from the University of California San Francisco studied data from enrollees with diabetes in all 50 Medicaid fee-for-service (FFS) plans and 273 managed care organization (MCO) plans as of March 2024 to assess the availability of SGLT2is and GLP-1 RAs. These medications are not only used to manage type 2 diabetes, but they have also been shown to significantly reduce atherosclerotic cardiovascular disease (ASCVD), renal events and deaths. People from lower income and racial/ethnic minority backgrounds experience higher rates of diabetes and its complications and are also more likely to be insured through Medicaid, so the researchers aimed to characterize the unrestricted availability of diabetes medications with cardiovascular (CV) benefits among Medicaid enrollees. The researchers used publicly available data to obtain plan-level formulary coverage information and enrollment size for all Medicaid plans included. The primary outcome was Medicaid plan unrestricted availability of each drug class studied. They used the availability of dipeptidyl peptidase-4 inhibitors (DPP4is) as a benchmark for their findings since these drugs are also expensive but lack the CV and mortality benefits of SGLT2i and GLP-1 RA drugs. They also did a secondary analysis of the availability of tirzepatide, a dual GLP-1 RA and glucose-dependent insulinotropic polypeptide receptor which has more potent effects on weight loss and glycemic control than other GLP-1 RA medications and potentially greater CV benefits. 

The researchers found that among 50 state FFS plans, 80% had availability of an SGLT2i and 60% of a GLP-1 RA. This compares to 84% of FFS states having unrestricted availability of a DPP4i. Tirzepatide was restricted in all but one state. Availability of these medications was significantly lower among 273 MCO plans studied, which covered 83% of all adult Medicaid enrollees, with 66.7% having availability of an SGLT2I and 48% of a GLP-1RA compared with 74.7% of MCO plans having availability of a DPP4i. Tirzepatide was restricted nationwide in these plans. The researchers estimate that 1.7 million adult enrollees with diabetes (25%) had restricted availability of an SGLT2i and 2.7 million (40%) had restricted availability of a GLP-1 RA, which is driven by the more restrictive policies of MCO plans. They also concluded that there is significant variation in availability of these medications among states. Finally, medication availability has improved for all classes since 2020, but to a much lesser extent for GLP-1 RAs in the MCO program, where rates have remained under 60% since 2022. The results call attention to the need for continuous monitoring of unrestricted availability for these medications in Medicaid plans, particularly tirzepatide given its effectiveness for treating diabetes and related complications.  

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To contact corresponding author Anil N. Makam, MD, MAS, please email Elizabeth Fernandez at Elizabeth.Fernandez@ucsf.edu.

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3. Despite its efficacy, efanesoctocog alfa not a cost-effective choice in treating severe hemophilia A

Price of efanesoctocog alfa would need to decrease by at least 53% to meet cost-effectiveness thresholds

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-24-02749

Summary for Patients: https://www.acpjournals.org/doi/10.7326/ANNALS-24-02749-PS

URL goes live when the embargo lifts                   

A cost-effectiveness analysis evaluated whether a newer and more efficacious treatment to prevent bleeding in those with severe hemophilia A, efanesoctocog alfa (Altuviiio), improves outcomes enough to justify its higher cost compared to standard-care factor VIII prophylaxis. The study found that efanesoctocog alfa is not cost-effective for severe hemophilia A, suggesting that patients and doctors continue to discuss the best treatment options for bleeding prevention. According to the researchers, this is the first study to examine the conventional and distributional cost-effectiveness of an efanesoctocog alfa prophylactic strategy compared with standard-care factor VIII prophylaxis in patients with severe hemophilia A. The study is published in Annals of Internal Medicine.  

Researchers from Yale School of Medicine and colleagues used data from the recent phase 3 XTEND-1 study of prophylactic once-weekly dosing of efanesoctocog alfa in patients with severe hemophilia A to build a Markov cohort model to project the quality-adjusted life expectancy and costs of severe hemophilia A. In the XTEND-1 study, efanesoctocog alfa showed a 77% improvement in annualized bleeding rate compared with standard-care factor VIII prophylaxis. However, it costs about $900,000 annually in the United States and its cost-effectiveness is unknown. As such, the researchers assessed both the conventional and distributional cost-effectiveness of prophylaxis with efanesoctocog alfa compared with standard-care factor VIII prophylaxis in patients with severe hemophilia A. The researchers used the results of the XTEND-1 study to build a Markov cohort model that imitated the costs and outcomes of people living with severe hemophilia A. The patient cohort included males with severe hemophilia A who had been treated previously with standard products and whose average age was 34 years. Each cohort was assigned to one of two treatment groups: efanesoctocog alfa prophylaxis or standard-care factor VIII prophylaxis. The model conservatively assumed that chronic arthropathy is eliminated with efanesoctocog alfa use, efanesoctocog alfa reduces the incidence of intracranial hemorrhage (ICH), and standard-care treatment is with octocog alfa (Advate), one of the most expensive products in the U.S. Health outcomes were quantified in quality-adjusted life years (QALYs). Costs were estimated in 2023 U.S. dollars using the medical care component of the Consumer Price Index. The researchers performed a conventional cost-effectiveness analysis by estimating the incremental cost-effectiveness ratio (ICER) per QALY and determined cost-effectiveness using a willingness-to-pay threshold of $100,000 per QALY. The researchers also conducted a distributional cost-effectiveness analysis (DCEA) to account for health inequities associated with hemophilia A. The model was validated, as the projected annual bleeding rates with efanesoctocog alfa and standard-care factor VIII were similar to those found in the XTEND-1 study. Despite conservative assumptions that favored efanesoctocog alfa prophylaxis, compared with standard-care factor VIII, prophylaxis with efanesoctocog alfa accrued 5.11 additional lifetime discounted QALYs and $10.9 million in additional lifetime discounted costs, resulting in an ICER of $2.13 million per QALY, well-above cost-effectiveness thresholds of $50 000 to $150 000 per QALY used in the U.S. To meet these thresholds, the cost would have to decrease to less than 53% of its current price.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To contact corresponding author George Goshua, MD, MSc, please email george.goshua@yale.edu.

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4. Most patients with newly diagnosed atrial fibrillation during hospitalization not dispensed anticoagulants for stroke risk

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-24-01967

Editorial: https://www.acpjournals.org/doi/10.7326/ANNALS-25-01073

URL goes live when the embargo lifts            

A population-based retrospective cohort study described the use of anticoagulation and the risk for stroke after newly diagnosed atrial fibrillation (AF) during hospitalization for other causes among older patients. The study found that most patients with presumed provoked AF were not dispensed anticoagulants in the year after discharge from the hospital, and the stroke risk in patients with CHA₂DS₂-VA scores greater than 4 approximated the 2% threshold commonly used to initiate anticoagulation in AF. The findings are published in Annals of Internal Medicine. 

Researchers from the University of Toronto studied data from a cohort of 20,639 adults in Ontario, CA aged 66 and older who were discharged from a hospital between 1 April 2013 and 31 March 2023 with a first diagnosis of AF during care. Inclusion in the cohort was selective, with patients excluded for several factors including a discharge diagnosis of stroke, any AF diagnoses in the five years before discharge, and those who were dispensed a prescription for anticoagulants int he 180 days preceding the index date. Patients with newly diagnosed AF were categorized into the following groups: cardiac medical, cardiac surgical, noncardiac medical, and noncardiac surgical. Patients were followed for one year after discharge, and the primary outcome was hospitalization for stroke. Secondary outcomes included dispensation of anticoagulation, hospitalization or emergency department (ED) visits for bleeding, and death. The researchers used the category of hospitalization and the median CHA₂DS₂-VA score of 4 to complete their analysis. They also used the complement of the Kaplan-Meier survival function to estimate the incidence of all-cause mortality and the Aalen-Johansen estimator to estimate the risk for stroke in different categories of AF. Among the cohort, the mean age was 77.1 years and 40.4% were hospitalized for noncardiac medical. Those in the noncardiac surgical group were often younger and more likely male. The mean CHA₂DS₂-VA score was highest in the cardiac medical group and lowest in the noncardiac surgical group. After hospital discharge, the risk of death at one year following newly diagnosed AF was highest in the noncardiac medical group. Fewer than half of the patients were dispensed anticoagulants in the year after discharge, with the cardiac medical group having the highest incidence of anticoagulant dispense. Those dispensed anticoagulants often had a higher CHA₂DS₂-VA score, with 26.4% of patients with scores of one to four and 35.2% of those with scores of five to eight were receiving anticoagulation at one year. The one-year risk for both stroke and bleeding was highest in the cardiac medical group. The estimated stroke risk without anticoagulation for those in the cardiac surgical, noncardiac surgical, or noncardiac medical hospitalizations was below the 2% threshold used in clinical guidelines to initiate anticoagulation. Those with CHA₂DS₂-VA scores less than five had a lower incidence of stroke without anticoagulation.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To contact corresponding author Husam Abdel-Qadir, MD, PhD, please email h.abdel.qadir@utoronto.ca.  

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