The Effects of LSD and Psilocin on Anxiety-Related Behaviours in Zebrafish

Recently there has been a surge in interest in the research of hallucinogens, particularly serotonergic hallucinogens. While some preliminary research has shown some promising applications in the treatment of anxiety, these compounds are still poorly understood, and their reputation as drugs of abuse make clinical research challenging. Zebrafish, a popular model organism for neuropsychopharmacological research, are ideal for the pre-clinical testing needed to explore how serotonergic hallucinogens impact anxiety. LSD has demonstrated anxiolytic effects in zebrafish, however psilocybin has failed to demonstrate comparable effects. In this study we sought to determine if the dephosphorylated metabolite of psilocybin, psilocin, could produce an effect in zebrafish where psilocybin has previously failed. Using the novel tank diving test, fish treated with LSD (100µg/L and 250µg/L) displayed a significant increase in behaviours indicative of low anxiety compared to control fish and fish treated with psilocin, a result consistent with a reduction in anxiety. Fish in the psilocin treatment group (500µg/L and 1000µg/L) did not differ significantly from those in the control group, suggesting that at the doses used, psilocin does not impact zebrafish exploratory behaviour. Further research will be necessary to establish whether higher doses would be effective, or whether zebrafish are not sensitive to the psilocybin/psilocin compounds. While the study did demonstrate the effectiveness of LSD for reducing anxiety-related behaviour, fish treated with psilocin failed to differ significantly from control fish. Discipline: Psychology Honours Faculty Mentor: Dr. Melike Schalomon