The Impact of Psychedelic Drugs on Anxiety and Depression in Advanced Cancer or other Life-threatening Disease: A Systematic Review With Meta-analysis

Objectives: Life-threatening cancer or other diseases can induce anxiety and depressive symptoms. We performed a systematic review with meta-analyses of randomized controlled trials assessing patients with cancer or other life-threatening diseases using validated anxiety and depression scales. Methods: PubMed was searched up to November 15, 2022 and citations were applied to prespecified inclusion criteria. Disease rating scales for anxiety or depression included the State-Trait Anxiety Inventory (STAI) (STAI Trait [STAI-T], STAI-State [STAI-S]), Beck Depression Inventory (BDI), Hospital Anxiety and Depression Scale (HADS) (HADS-Anxiety [HADS-A]; HADS-Depression [HADS-D]), Profile of Mood States (POMS), and the Hamilton Rating Scale for Depression (HAM-D or GRID-HAM-D-17). Safety outcomes included assessments of blood pressure and heart rate. Results: Five trials, predominantly in cancer patients, had data assessing anxiety and depressive symptoms. These trials found promising results for psychedelics versus placebo in several anxiety and depression scales but increases in blood pressure and heart rate also occurred. There were some concerns of risk of bias because it is difficult to truly randomize a psychedelic trial and there was a high percentage of patients in the trials who had used psychedelics in the past. There was high heterogeneity for all analyses that we could not explain. Conclusions: Although the results are promising, future trials are needed to assess the optimal psychedelic, dose, number of sessions required, and how psychedelic naïve patients would respond both psychologically and hemodynamically before this therapy can be considered for widescale clinical use.