Welcome to PsychEd, the psychiatry podcast for medical learners, by medical learners.   In this episode, we begin to explore the neurobiology of the serotonin system — along with key pharmacological agents (SSRIs and classical psychedelics) that act on this system — with guest expert Dr. Robin Carhart-Harris, a neuroscientist and head of the Centre for Psychedelic Research at Imperial College London.   Our discussion is more theoretical than directly clinically relevant, striving to provide a mechanistic understanding of how serotonin functions within the brain and how serotonin-modulating drugs influence this system. The episode was inspired by a review published by our guest expert and Dr. David Nutt called “Serotonin and brain function: a tale of two receptors” (cited below). If you are interested in the topic, you might consider reading this review in full! Please note that the figures referenced during this episode can be accessed at https://journals.sagepub.com/doi/figure/10.1177/0269881117725915.   The learning objectives for this episode are as follows:    By the end of this episode, you should be able to…   Understand the general anatomy and function of the serotonin system, with a focus on the purported activity of the more common serotonin receptors and transporters. Describe the effects of serotonin reuptake inhibitors and how they lead to symptom improvement in mood and anxiety disorders, in addition to the mechanism of action of other serotonergic medications. Consider the two-pronged serotonin system conceptualized by Dr. Carhart-Harris, and understand how serotonergic agents (including SSRIs and classic psychedelics) and the concepts of active and passive coping fit within this theory.   Guest: Dr. Robin Carhart-Harris, a neuroscientist and head of the Centre for Psychedelic Research at Imperial College London.   Produced and hosted by: Dr. Chase Thompson (PGY3), Dr. Lucy Chen (Psychiatrist), Dr. Nikhita Singhal (PGY2)   Audio editing by: Dr. Chase Thompson   Infographic by: Dr Chase Thompson, Dr Nikhita Singhal   Interview Content:   00:18 - Introductions 3:00 - Learning objectives 4:10 - Introduction to serotonin 10:30 - 5HT1A receptors 24:30 - 5HT2A receptors 30:20 - Serotonin system operation under normal conditions 35:00 - Introduction of bipartite model / two divergent methods for addressing depression 42:20 - Parallels between psychological destabilization (through therapy) and the psychedelic effect  46:20 - Who should not have a psychedelic experience? Are psychedelics intrinsically psychotherapeutic or facilitative in nature? 50:20 - Brief discussion of the neuroimaging correlates of psychotherapeutic benefits from psychedelic experiences 58:40 - Discussion of why 2A agonists cause psychedelic effects but high serotonin release does not   Resources:   Carhart-Harris RL, Nutt DJ. Serotonin and brain function: a tale of two receptors. J Psychopharmacol. 2017;31(9):1091-1120. https://doi.org/10.1177/0269881117725915 Artigas F, Nutt DJ, Shelton R. Mechanism of action of antidepressants. Psychopharmacol Bull. 2002;36 Suppl 2:123-132. Antidepressants. In: Stahl SM. Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 4th ed. Cambridge University Press; 2013:284-369. Beliveau V, Ganz M, Feng L, et al. A High-Resolution In Vivo Atlas of the Human Brain's Serotonin System. J Neurosci. 2017;37(1):120-128. https://doi.org/10.1523/JNEUROSCI.2830-16.2016 Carhart-Harris RL, Bolstridge M, Rucker J, et al. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. 2016;3(7):619-627. https://doi.org/10.1016/S2215-0366(16)30065-7 Carhart-Harris RL, Leech R, Hellyer PJ, et al. The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Front Hum Neurosci. 2014;8:20. https://doi.org/10.3389/fnhum.2014.00020 Carhart-Harris RL, Friston KJ. REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics. Pharmacol Rev. 2019;71(3):316-344. https://doi.org/10.1124/pr.118.017160 Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016;30(12):1181-1197. https://doi.org/10.1177/0269881116675513 Griffiths RR, Richards WA, McCann U, Jesse R. Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology (Berl). 2006;187(3):268-292. https://doi.org/10.1007/s00213-006-0457-5   CPA Note: The views expressed in this podcast do not necessarily reflect those of the Canadian Psychiatric Association. For more PsychEd, follow us on Twitter (@psychedpodcast), Facebook (PsychEd Podcast), and Instagram (@psyched.podcast). You can provide feedback by email at psychedpodcast@gmail.com. For more information, visit our website at psychedpodcast.org.