pubmed.ncbi.nlm.nih.gov

Psilocybin, an Effective Treatment for Major Depressive Disorder in Adults - A Systematic Review - PubMed

  • ️Mon Jan 01 2024

Review

Psilocybin, an Effective Treatment for Major Depressive Disorder in Adults - A Systematic Review

Tessa Watford et al. Clin Psychopharmacol Neurosci. 2024.

Abstract

Psilocybin is a classical psychedelic which has been utilised for healing purposes for millenia. However, with its classification as a Schedule I substance, research into this compound is scarce with few FDA-approved clinical studies. Despite this, profound findings into its antidepressant effects (largely through its action on 5-HT1a receptors) in mental illnesses such as major depressive disorder have rapidly increased interest back into their potential therapeutic benefits. This systematic review provides an analysis of the studies examining the clinical use of psilocybin for major depressive disorder. In total 6 studies were selected, including 319 participants, with half being randomised controlled trials and half open label trials. In every study psychological support was included as an integral part of the treatment. It was found that every study significantly favoured the use of psilocybin in reducing depressive symptoms, with few side effects. This gives psilocybin an advantage over commonly prescribed selective serotonin reuptake inhibitors (SSRIs), which carry more risk and cause more adverse effects. This drug therefore shows promise for being used as a clinical treatment for major depressive disorder, however future research should develop a paradigm for its use, with the timing of sessions and type of psychological support specified to allow for more precise analysis of the clinical effects of the drug. Additionally, more studies into its clinical efficacy are needed for appropriate detection of any publication bias. With this, psilocybin could prove to be revolutionary in treating depression and become an alternative medication to SSRIs.

Keywords: Depression; Psilocybin.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1
Fig. 1

Synthesis of psilocybin [38]. L-Tryptophan is decarboxylated into tryptamine, to become methylated to form dimethyltryptamine (DMT). DMT is then oxidised forming psi-locin, which with the addition of a phosphate group forms psilocybin.

Fig. 2
Fig. 2

Structures of psilocybin and psilocin [2].

Fig. 3
Fig. 3

PRISMA flow diagram of the database search, selection of studies and articles to include in the sys-tematic review. PRISMA, Primary Reporting Items for Systematic Reviews and Meta-Analyses Statement.

Fig. 4
Fig. 4

Forest plot conducted using RevMan showing the MD between baseline and 5/6 weeks post intervention scores on QIDS. This illustrates how each study significantly favors psilocybin for reducing depressive symptoms. The squares represent the individual studies with the size representative of the weight of the study in the analysis. The diamond represents the overall/summary effect, and the lines represent the confidence intervals. MD, mean difference; CI, confidence interval; QIDS, Quick Inventory of Depressive Symptomatology.

Fig. 5
Fig. 5

Funnel plot conducted using RevMan to analyse publication bias, of which shows that there is a possibility of publication bias due to the asymmetry of the data points for the QIDS baseline and 5/6 weeks post intervention scores. The dotted lines represent the 95% confidence intervals while the middle vertical line is the overall effect. Each study is represented by a dot, with the standardised MD result plotted on the x-axis, and their precision/standard error (SE) on the y-axis. MD, mean difference; QIDS, Quick Inventory of Depressive Symptomatology.

Fig. 6
Fig. 6

Forest plot conducted using RevMan, showing the MD between baseline and up to 6 weeks post intervention BDI scores. Each study significantly favors psilocybin for reducing depressive symptoms. The squares represent the individual studies with the size representative of the weight of the study in the analysis. The diamond represents the overall/summary effect, and the lines represent the confidence intervals. MD, mean difference; CI, confidence interval; BDI, Beck Depression Inventory.

Fig. 7
Fig. 7

Funnel plot conducted using RevMan showing that pub-lication bias is unlikely in the BDI baseline and up to 6 weeks post intervention scores due to the symmetry of the plotted points shown. The dotted lines represent the 95% confidence intervals while the middle vertical line is the overall effect. Each study is represented by a dot, with the standardised MD result plotted on the x-axis, and their precision/standard error (SE) on the y-axis. MD, mean difference; BDI, Beck Depression Inventory.

Fig. 8
Fig. 8

Forest plot conducted using RevMan, showing the MD be-tween baseline and up to 6 weeks post intervention HAM-D scores. Each study in this analysis significantly favors psilocybin for reducing depressive symptoms at up to 6 weeks post intervention with the drug. The squares represent the individual studies with the size repre-sentative of the weight of the study in the analysis. The diamond represents the overall/summary effect, and the lines represent the confidence intervals. MD, mean difference; CI, confidence interval; HAM-D, Hamilton Depression Rating Scale.

Fig. 9
Fig. 9

Funnel plot conducted using RevMan showing asymmetry for the HAM-D baseline and up to 6 weeks post intervention scores meaning there is possibility of publication bias. The dotted lines represent the 95% confidence intervals while the middle vertical line is the overall effect. Each study is represented by a dot, with the standardised MD result plotted on the x-axis, and their precision/ standard error (SE) on the y-axis. MD, mean difference; HAM-D, Hamilton Depression Rating Scale.

Similar articles

Cited by

References

    1. Stamets P, Weil A. Psilocybin mushrooms of the world: An identification guide. Ten Speed Press; 1996.
    1. Nichols DE. Psilocybin: From ancient magic to modern medicine. J Antibiot (Tokyo) 2020;73:679–686. doi: 10.1038/s41429-020-0311-8. - DOI - PubMed
    1. Hofmann A, Heim R, Brack A, Kobel H. [Psilocybin, a psychotropic substance from the Mexican mushroom Psilicybe mexicana Heim] Experientia. 1958;14:107–109. doi: 10.1007/BF02159243. German. - DOI - PubMed
    1. Mahmood ZA. Natural Products, editor. Bioactive alkaloids from fungi: Psilocybin. In: Ramawat K, Mérillon JM, editors. Springer; 2013. pp. 523–552. German. - DOI
    1. Johnson MW, Griffiths RR, Hendricks PS, Henningfield JE. The abuse potential of medical psilocybin according to the 8 factors of the controlled substances act. Neuropharmacology. 2018;142:143–166. doi: 10.1016/j.neuropharm.2018.05.012. - DOI - PMC - PubMed

Publication types

Grants and funding