Effects of Psilocybin and Select Pharmaceutical Interactions
MacEwan University Student eJournal – February 18, 2026
Source: OpenAlex
Summary
In Canada, approximately 16.5% of the population, or about 6.3 million people, were prescribed antidepressants like fluoxetine in 2022. Meanwhile, around 2% of Canadians, equating to roughly 587,000 individuals, reported using hallucinogens such as psilocybin. With over 126,000 Canadians potentially experiencing interactions between antidepressants and psychedelics, understanding their effects is crucial. Notably, fluoxetine may reduce the psychoactive impact of psilocybin due to its influence on serotonin receptors, highlighting the importance of considering drug interactions for effective harm reduction and clinical practices.
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.