Introduction Close to 300 million people globally suffer from depression. Conventionalantidepressants likeSSRIs havetheirlimitations and side effects, such as decreased libido, gastrointestinal problems, and anxiety.In recentdecades, the interest in hallucinogens as a treatment for depression has grown.

AimThe primaryaim of this study wasto determine theeffects ofLSD and psilocybin on depression symptoms and co-occurringanxiety. Secondly,toinvestigate potential gender disparities in treatment outcomes.A study protocol was registered in PROSPERO (ID: CRD42024513128).

MethodA comprehensive literature search was conductedin PubMed, CINAHL,and PsycINFO,in February 2024.A Meta-analysis wasperformed with a random effects model calculating Standard mean differenceand Hedge’s g to measure the effect size.

Results14 studieswere included(n = 616).Of these,ninestudies wereincluded in the meta-analysis for depression, and sevenwere includedfor anxiety. Psilocybin had asignificantlarge effect on depressive symptoms (SMD:-1.1062,CI 95%[-1.55; -0.65], p<0.0001). The overall effects on anxiety favoured the intervention-0.97 (95% CI [-1.46; -0.47], p<0.01). LSD showed a decrease in symptoms in both the low BDI and high BDI groups compared to the placebo.

ConclusionPsilocybin demonstrates anantidepressant effect and a significant decrease in anxiety. Any conclusions about disparities in outcomes between men and women could not be made. Future well-designed phase two and three studies are necessary.Additionally,researchefforts should aimto explore the effects of psychological flexibility and psychotherapy in these treatments.