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

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 (VAS0-100) 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.