Effects of Psilocybin and Select Pharmaceutical Interactions

Abstract

In Canada, the use of both prescription medications and psychedelics has become increasingly prevalent. As of 2022, approximately 16.5% of Canadians—about 6.3 million individuals—were prescribed at least one antidepressant, with fluoxetine remaining one of the most commonly used options (IQVIA, 2023). Benzodiazepine use, including drugs like alprazolam, ranges between 5% to 10% nationwide, with notably higher usage (15–20%) among older adults aged 65 and over (Davies et al., 2017). Psilocybin use, while less common, has shown steady presence in the population; in 2019, years hallucinogens such as psilocybin, LSD, and PCP were used by approximately 2% of Canadians—equating to roughly 587,000 people— and by approximately 6% of young adults aged 20 to 24 (Health Canada, 2023). Based on the statistical overlap between antidepressant and psychedelic users, it is estimated that over 126,000 Canadians may be experiencing interactions between these drug classes, a number that is expected to grow as both psychedelic therapy and recreational use become more culturally accepted. We investigated the chemical, physical, and psychological effects of psilocybin, fluoxetine, and alprazolam and their interactions with each other. In clinical contexts, benzodiazepines like midazolam are sometimes used to manage overwhelming psychedelic experiences, offering a pharmacological baseline for understanding how sedatives may interact with psilocybin. When taken concurrently, fluoxetine appears to attenuate the mind-altering effects typically induced by psilocybin, likely due to its modulation of serotonin receptor activity. This dampening effect suggests a pharmacological counteraction between the two substances. There is little direct research on the interaction between psilocybin and alprazolam, but from what is indicated, they may exhibit small interactive effects. Understanding these interactions may provide insight into more accurate harm-reduction strategies and clinical decision-making.