Psilocybin Safety Beyond Psychotropics: Understanding Medication Interactions

This article recaps the Psychedelic Support webinar “Psilocybin Pharmacologic Safety and Interactions: Psychotropics and Beyond,” presented by pharmacist and psychedelic safety expert Kristin Speer, PharmD, BCPS. In this session, Dr Speer expands the conversation on psilocybin safety beyond psychotropic medications, offering a clear, evidence-informed framework for understanding interactions across the broader medication landscape.

Drawing on clinical pharmacology, risk reduction, and real-world case examples, Dr Speer challenges oversimplified narratives about psilocybin risk and equips clinicians, facilitators, and individuals with practical strategies to assess safety without defaulting to fear or prohibition.

🎥 Watch the Webinar Replay: Psilocybin Pharmacologic Safety & Interactions — Psychotropics and Beyond with Kristin Speer, PharmD, BCPS

Why Psilocybin Safety Requires a Broader Lens

As psilocybin use expands across therapeutic, ceremonial, and personal contexts, questions about safety are becoming more urgent—and more complex. Much of the existing discussion has focused narrowly on antidepressants and other psychotropic medications. According to Dr Speer, this framing misses the bigger picture.

Psilocybin does not enter the body in isolation. It interacts with existing medications, physiological systems, and individual health conditions. Overlapping mechanisms, additive effects, and pre-existing risks can quietly accumulate until they cross a threshold.

Safety, in this context, isn’t about identifying a single “dangerous” combination. It’s about understanding how multiple variables stack together—and how small risks can compound.

Clarifying Psilocybin Metabolism and CYP450 Claims

One of the central topics Dr Speer addressed was a recent systematic review that suggested psilocybin carries a significant risk through CYP450-mediated drug interactions. While this claim has circulated widely, she urged readers to interpret it with caution.

Dr Speer walked participants through what is actually known about psilocybin metabolism, distinguishing between theoretical enzyme interactions and clinically meaningful risk. She emphasized that overstating metabolic dangers can lead to unnecessary exclusion, stigma, or overly restrictive policies—primarily when the evidence does not support such conclusions.

Rather than dismissing interaction concerns altogether, she modeled a more nuanced approach: careful evaluation grounded in pharmacology, context, and dose.

Revisiting Lithium, Seizures, and Psychedelic Risk

In this webinar, Dr Speer revisited the original data behind these claims and highlighted the need for precision.

She explained how historical case reports, dosage ambiguity, and confounding variables have shaped current assumptions—and why those assumptions deserve careful re-examination. Significantly, she did not minimize potential risks. Instead, she argued that risk should be studied rigorously rather than treated as settled science.

This distinction matters. When clinicians and facilitators understand why certain risks exist, they are better equipped to assess real-world safety rather than rely on blanket prohibitions.

When Medication Profiles Cross the Safety Threshold

One of the most instructive moments of the webinar came through a detailed case example. Dr Speer illustrated how introducing psilocybin made a participant’s existing medication regimen—safe on its own—problematic.

This case highlighted a key principle: psilocybin can act as the final variable that pushes a complex system beyond its safety threshold. The risk did not come from a single drug, but from cumulative burden.

By mapping out overlapping mechanisms and physiological stressors, Dr Speer demonstrated how clinicians can identify these tipping points before harm occurs.

Beyond Psychotropics: Common Medications That Matter

The webinar also explored medications not typically associated with psychedelic risk, including:

• Semaglutide
• Omeprazole
• Immunomodulators

Dr Speer explained how these agents can influence absorption, metabolism, immune response, or physiological resilience—altering how psilocybin is experienced and tolerated.

This broader view of interactions is especially critical as more people approach psychedelics while managing chronic conditions or complex medication profiles. Safety, here, becomes an exercise in systems thinking rather than checklist compliance.

What Evidence-Informed Harm Reduction Looks Like

Throughout the session, Dr Speer returned to a central theme: harm reduction is not about restricting access—it’s about supporting informed choice.

Participants were encouraged to:

• Critically evaluate the strengths and limitations of existing evidence
• Distinguish theoretical risk from clinically meaningful risk
• Anticipate changes in onset, intensity, or safety based on pharmacology
• Use transparency and education as safety tools

Rather than positioning herself as an authority who dictates rules, Dr Speer modeled a collaborative approach—one that respects autonomy while prioritizing care.

From Pharmacology to Practice

What makes this webinar especially valuable is its translation of complex science into real-world applications. Dr Speer consistently bridged molecular mechanisms with clinical decision-making, helping participants understand not just what the risks are, but also how to work with them responsibly.

For clinicians, this means moving beyond rigid contraindication lists toward individualized assessment. For facilitators and individuals, it means asking better questions and seeking qualified guidance when needed.

A Personal Path to Psychedelic Safety

Both professional expertise and lived experience shape Dr Speer’s approach to this work. On April 20, 1999, she was in lockdown at Chatfield Senior High School during the Columbine massacre. Witnessing trauma, grief, and resilience at a young age profoundly influenced her lifelong commitment to mental health and safe access to care.

Over more than 13 years as a pharmacist, her work has spanned hospice and palliative care, pain management, pharmacy benefits, and psychedelic medicines. Today, she operates at the intersection of clinical practice, consulting, and policy, with a focus on harm reduction in psychedelic therapies.

She is a co-founder of the Psychedelic Pharmacists Association, served as a pharmacology expert for Colorado’s Department of Regulatory Agencies (DORA) and the Healing Advocacy Fund, and helped develop screening criteria for Colorado’s Natural Medicine Health Act—now used in Oregon and beyond.

As creator of the Psilocybin Interaction Checker, she also provides consultations to help individuals and facilitators navigate safety without sacrificing autonomy or access.

Why This Conversation Matters

As psychedelic therapies continue to enter mainstream healthcare, the stakes around safety are rising. Oversimplified narratives—whether alarmist or dismissive—don’t serve patients, practitioners, or the field as a whole.

Dr Speer’s work reminds us that responsible psychedelic care requires literacy, humility, and context. Safety is not static. It evolves alongside evidence, policy, and practice.

By expanding the conversation beyond psychotropics, this webinar offers a grounded, ethical framework for navigating psilocybin use with clarity rather than fear.

Watch the full replay: https://youtu.be/QyI2tsBxOp8

About Dr Speer, PharmD, BCPS

Kristin Speer, PharmD, BCPS, is a pharmacist and nationally recognized expert in psychedelic pharmacologic safety and harm reduction. With more than 13 years of experience across hospice and palliative care, pain management, pharmacy benefits, and psychedelic medicine, her work bridges clinical pharmacology with real-world psychedelic use.

Dr Speer is a co-founder of the Psychedelic Pharmacists Association and has served as a pharmacology expert for Colorado’s Department of Regulatory Agencies (DORA) and the Healing Advocacy Fund. She also contributed to the development of screening criteria for Colorado’s Natural Medicine Health Act, now informing regulatory frameworks in Oregon and beyond.

Her approach is shaped not only by professional expertise but by lived experience. In 1999, she was in lockdown at Chatfield Senior High School during the Columbine massacre—an event that profoundly influenced her lifelong commitment to mental health, ethical care, and informed access.

As the creator of the Psilocybin Interaction Checker, Dr Speer provides consultation and education that help clinicians, facilitators, and individuals assess risk with nuance—supporting safety without fear-based exclusion.

Resources from the Webinar

🌐 Connect with Dr Speer

• Connect and consult with Dr Speer on LinkedIn
• Find Dr Speer on Instagram: @kristinspeer_pharmd
• Explore the Psilocybin Interaction Checker

📚 Books & Links from the Webinar

• Get the Slides from the Webinar
• Learn About or Join the Psychedelic Pharmacists Association
• See Colorado Department of Regulatory Agencies (DORA)
• Learn About the Healing Advocacy Fund
• Reference Colorado’s Natural Medicine Health Act

🎓 Courses & Continuing Education

• Understanding Psilocybin: Effects, Neurobiology, and Therapeutic Approaches
• Microdosing Psilocybin & LSD: What We Know So Far
• Free Harm Reduction Course: Riding the Wave
• All CE/CME Courses: Psychedelic Therapy Education & Training Programs
• Earn CE/CME Credits through Psychedelic Support’s Continuing Education Series

👀 Further Reading on Psilocybin

• Psilocybin Assisted Therapy Guide (Substance Guide)
• Unlocking the Magic: A Guide to Safe Psilocybin Use
• Articles tagged “Psilocybin” and “Psilocybin Therapy”