Effects of LSD and Psilocybin on Heart Rate in Patients Receiving Psychedelic Treatment for Depressive and Anxiety Disorders: A Retrospective Observational Study

This retrospective observational study (n=30) of patients with treatment-resistant depression or anxiety disorders receiving LSD (100–200 mcg) or psilocybin (15–30 mg) under compassionate use found distinct cardiovascular patterns between substances, with LSD producing a delayed but sustained heart rate increase peaking at 3–4 hours while psilocybin showed an earlier decline, though no serious cardiovascular adverse events occurred.

“Classic psychedelics such as lysergic acid diethylamide (LSD) and psilocybin induce mild cardiovascular activation in addition to their psychological effects. While these effects are well described in healthy adults, little is known about their dynamics in clinical populations undergoing psychedelic-assisted psychotherapy.

This retrospective, observational, single-center study analyzed routinely collected data from 30 patients (mean age = 51.56 ± 12.19 years; 15/30 female) treated under compassionate use for treatment-resistant depression or anxiety disorders. Participants received either LSD (100–200 mcg) or psilocybin (15–30 mg) in supervised outpatient sessions. Heart rate and self-rated anxiety (VAS 0–100) were recorded at seven intervals from 30 to 300 min post-administration.

Linear mixed models examined heart rate trajectories over time × substance, controlling for age and, in a second model, perceived anxiety. Linear mixed models revealed no significant main effect of time (F(6, 77.25) = 0.76, p = 0.60) or substance (F(1, 30.82) = 0.66, p = 0.42), but a significant time × substance interaction (F(6, 77.25) = 3.03, p = 0.01). LSD was associated with a delayed but sustained increase in heart rate peaking at 3–4 h, whereas psilocybin showed an earlier decline.

These patterns persisted after adjustment for age and anxiety, and anxiety did not significantly modify the relationship between time and substance. No serious cardiovascular adverse events occurred.

These preliminary findings suggest that LSD and psilocybin may produce distinct temporal patterns of cardiovascular activation in clinical settings. However, interpretation should be cautious due to the retrospective design, small sample size, and dose imbalance between substances.”

Notes

Physiological differences between LSD and psilocybin likely underlie the different heart rate trajectories. LSD has a longer duration of action and broader receptor activity (including at cardiac serotonin receptor subtypes), which may explain its more sustained effect on heart rate. Psilocybin’s effects tend to be shorter and more selective.

These patterns match what’s known about the pharmacokinetics (how long the substances act) of the two drugs in both lab and clinical settings

No participants experienced tachycardia (>120 bpm) or any clinically significant heart problems during or after the sessions. Minor, transient effects (e.g., dizziness, nausea) were noted but resolved without issues.

This study suggests that in real-world clinical settings, LSD and psilocybin can produce mild, distinct patterns of heart rate elevation during psychedelic-assisted psychotherapy, with LSD’s effects lasting longer into the session than psilocybin’s. Importantly, no serious cardiovascular risks were observed in this small sample under supervised conditions.

Cheng, M.; Aboulafia-Brakha, T.; Buchard, A.; Boyanova Anastasova, R.; Girani, L.; Breitenmoser, A.; Alaux, S.; Mabilais, C.; Amberger, C.; Seragnoli, F.; et al. Effects of LSD and Psilocybin on Heart Rate in Patients Receiving Psychedelic Treatment for Depressive and Anxiety Disorders: A Retrospective Observational Study. Psychol. Int. 2026, 8, 1. Read Paper

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