Table 1.
Summary of Clinical Trials Assessing the Anxiolytic Effects of Ayahuasca, Ketamine, LSD, MDMA, and Psilocybin
| Study | N/Diagnosis | Study Design | Drug and Dose | Principal Findings |
|---|---|---|---|---|
| Dos Santos et al, 202170 | 17/SAD | Double-blind, placebo-controlled, randomized group trial | Ayahuasca 2 mL/kg | Significant reduction in the SSDPS scale with no effect of time; increased self-perception and speech performance at days 7, 14, and 21; anxiety scores via VAMS and BAI were not significantly decreased at days 7, 14, and 21 |
| Glue et al, 201762 | 12/Treatment-resistant GAD or SAD | Uncontrolled, open-label trial | Subcutaneous injection of ketamine 0.25 mg/kg, 0.5 mg/kg, and 1 mg/kg | 50% reduction in HAM-A and FQ scores within 1 hour after 0.5 or 1 mg/kg dose that persisted for up to 7 days |
| Glue et al, 202064 | 12/Treatment-resistant GAD or SAD | Double-blind, controlled trial | Subcutaneous injection of ketamine 0.25 mg/kg, 0.5 mg/kg, and 1 mg/kg | Majority of patients reported >50% decrease in HAM-A and FQ scores after 0.5 or 1 mg/kg dose |
| Glue et al, 201863 | 20/Treatment-resistant GAD or SAD | Uncontrolled, open-label trial | Subcutaneous injection of ketamine 1 mg/kg | 50% reduction of HAM-A and FQ scores within 1 hour of administration |
| Taylor et al, 201868 | 18/SAD | Double-blind, randomized, controlled crossover trial | IV ketamine 0.5 mg/kg | Significant reduction in LSAS scores compared to placebo at 2- and 10-day follow-up; no significant change from placebo on the VAS for anxiety symptoms |
| Gasser et al, 201467 | 12/Anxiety associated with life-threatening illness | Double-blind, randomized, placebo-controlled trial | LSD 200 μg | Significant reduction in STAI-S scores at the 2-month follow-up and sustained after 12 months; STAI-T scores were not significantly decreased |
| Gasser et al, 201566 | 10/Anxiety associated with life-threatening illness | Open-label, nonplacebo trial | LSD 200 μg | Significant reduction in STAI-S and STAI-T scores at 12-month follow-up, 77.8% reported sustained reduction in anxiety |
| Wolfson et al, 202065 | 18/Anxiety associated with life-threatening illness | Double-blind, randomized, placebo-controlled trial | MDMA 125 mg | Reduction in STAI-T scores by –23.5 at 1 month after second psychotherapy session; statistically significant reductions of STAI-T and STAI-S at 6- and 12-month follow-up |
| Grob et al, 201169 | 12/Anxiety associated with advanced-stage cancer, GAD | Double-blind, randomized, controlled trial | Psilocybin 0.2 mg/kg | Significant reduction in STAI-T scores for the entire 6-month follow-up |
BAI, Beck Anxiety Inventory; FQ, Fear Questionnaire; GAD, generalized anxiety disorder; HAM-A, Hamilton Anxiety Rating Scale; IV, intravenous; LSAS, Liebowitz Social Anxiety Scale; LSD, lysergic acid diethylamide; MDMA, 3,4-methylenedioxymethamphetamine; SAD, social anxiety disorder; SSDPS, Self-Statements During Public Speaking; STAI-S, State-Trait Anxiety Inventory-State; STAI-T, State-Trait Anxiety Inventory-Trait; VAMS, visual analog mood scale; VAS, visual analog scale.