In this encore episode of the Psychedelic Medicine Podcast, psychedelic science researcher and educator Dr. Manesh Girn discusses his studies investigating psychedelic brain action. Manesh earned PhD in neuroscience at McGill University and is an author on over a dozen peer-reviewed articles on psychedelics and related topics. He is also chief research officer at EntheoTech Bioscience and runs the YouTube channel the Psychedelic Scientist.

In this conversation, Manesh discusses his recent article in Trends in Cognitive Sciences titled "A complex systems perspective on psychedelic brain action."He explains the complexity science approach used in the article, which emphasizes the brain is a holistic, interconnected system, rather than individual component networks that can be isolated. From this standpoint, Manesh critiques some simplistic explanations of the neural mechanisms of psychedelics which focus exclusively on interactions with the default mode network isolated from other brain systems.

He also explains how individual some of the neural effects of psychedelics are, citing different findings from different studies and observed variations between brain scans of different people. By better understanding these individual differences, and placing these different responses into a complexity science framework, Manesh believes that more individually-tailored psychedelic therapies are possible once the systems involved are more comprehensively understood.

Manesh closes this discussion by explaining the difference between genuine complexity and sheer chaos. Complexity, he explains, is a delicate balance of novelty and order, which is why psychedelic experiences can be both destabilizing and productive of novel insights and personal transformation.

In this episode:

• The research into psychedelics and the default mode network
• Using frameworks from complexity science in psychedelic research
• Measuring entropy in the brain
• Differences in neurological effects from taking between different studies and different individuals
• How a complexity science approach to neuroscience could better inform precision psychiatry

Quotes:

"You can't just look at a specific brain region or network [in psychedelic research], you've gotta talk about the brain as a whole, in this sense of seeing the brain as a system of interacting parts." [4:49]

"The core idea of this paper is that psychedelics put our brain into this state that is more dynamically flexible, it's more diverse in its activity patterns, and it's more sensitive to inputs that come in." [14:17]

"What we find in the brain imaging findings is that different studies disagree, but also if you look at individual people, they can have radically different effects on their brain—almost opposite." [21:37]

Links:

Manesh' recent article in Trends in Cognitive Sciences: "A complex systems perspective on psychedelic brain action"

​​Psilocybin vs Placebo Brain Connectivity Diagram from Dr. Robin Carhart-Harris

The Psychedelic Scientist YouTube Channel

The Psychedelic Scientist on Instagram

The Psychedelic Scientist on Twitter

Manesh on LinkedIn

EntheoTech website

Psychedelic Medicine Association

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In this episode, Will Van Derveer, MD joins to unpack what we know about which psychedelic medicines are best suited to particular mental health conditions. Dr. Van Derveer has trained several thousand mental health professionals in psychedelic-assisted psychotherapy, provided ketamine assisted therapy to hundreds of people, and has staffed MDMA therapy trials with MAPS. His book, Psychedelic Therapy: A Revolutionary Approach to Restoring Your Mental Health and Reclaiming Your Life, will be published by Shambala in the spring of 2026.

In this conversation, Dr. Van Derveer offers a clinician's framework for thinking through how different psychedelic medicines may align with different mental health conditions. He explores how factors such as anxiety levels, trauma history, prior psychedelic experience, and a person's orientation toward spiritual versus medical healing shape treatment decisions. Across discussions of anxiety, depression, PTSD, OCD, and eating disorders, Dr. Van Derveer reflects on the relative roles of ketamine, psilocybin, MDMA, and emerging short-acting psychedelics, while underscoring the importance of community, and integration. Throughout, he returns to a central theme: many conditions labeled as psychiatric may also reflect deeper forms of disconnection—social, existential, and spiritual—and psychedelic therapies can be powerful tools for restoring those lost connections when used thoughtfully.

In this episode, you'll hear:

• Why safety, medication interactions, and psychiatric history must come before all other considerations
• The difference between clinical and ceremonial approaches to psychedelic healing
• Considering when group versus individual approaches to psychedelic therapy may be best suited for a particular patient
• How ketamine, psilocybin, and MDMA may play distinct roles in treating anxiety and depression
• Considerations of dose, tolerance, and maintenance sessions for ketamine treatments
• Why MDMA-assisted therapy stands out for chronic and severe PTSD
• Dr. Van Derveer's perspective on emerging psychedelic medicines and the future of treatment

Quotes:

"As time wears on, I lean more toward the group dynamic [for psychedelic therapy] because of the power of community and healing in community. And also, of course, it can help mitigate the cost of access for people." [8:24]

"There's a lot of conversation about ibogaine right now, and I think it's an incredibly powerful, beautiful, sacred, ancient medicine that has a role. But it has a lot more porcupine quills on it than, say, ketamine or MDMA." [27:16]

"In acute suicidality, I think ketamine is the treatment of choice. There's nothing like it. … it can be quite impressive how quickly suicidal thoughts melt away. But it is a short game because often it doesn't stick for people. And that's a huge drawback." [28:39]

"We know that there are clear associations between chronic depression and high levels of inflammation in the body and also in the brain. Ketamine and psilocybin both have strong anti-inflammatory effects. But it seems like somehow the pathways that psilocybin is working on… tends to produce longer term benefits." [30:10]

"I tend to think that spiritual connection—in whatever your language is, whatever your metaphors are, however you think about it—is something that we need to think about for health overall." [40:21]

Links:

Dr. Van Derveer on LinkedIn

Dr. Van Derveer on Instagram

Dr. Van Derveer on X

Dr. Van Derveer's forthcoming book, Psychedelic Therapy: A Revolutionary Approach to Restoring Your Mental Health and Reclaiming Your Life

Integrative Psychiatry Institution website

Previous episode: Is Psilocybin Safe for Me? with Seth Mehr, MD

Psychedelic Medicine Association

Porangui

In this episode, Alicia Bigelow, ND joins to discuss the potential of psychedelic medicine to support the menopause transition. Dr. Ali Bigelow is a naturopathic physician, ketamine provider and licensed psilocybin facilitator in Portland, OR. She leads individual and group retreats, enjoys incorporating live music into her sessions when desired, and is passionate about supporting those navigating life transitions, such as end of life and menopause, through her low dose group, Menomorphosis. Dr. Bigelow will be doing retreats in 2026 with Rise Up Journeys at RiseUpJourneys.com

In this conversation, Dr. Bigelow explores the emerging intersection between psychedelics and the menopausal transition, framing perimenopause and menopause as profound neuroendocrine, psychological, and existential shifts rather than merely clinical syndromes. She also discusses how hormonal changes—particularly declining estrogen—interact with serotonin, inflammation, and neuroplasticity, potentially shaping psychedelic experiences and outcomes. Throughout the discussion, Dr. Bigelow emphasizes the unique capacity of psychedelics to support self-actualization, identity reformation, and meaning-making during midlife, especially when combined with hormone therapy, intentional integration practices, and strong community support.

In this episode, you'll hear:

• Why perimenopause and menopause represent a major but under-recognized neurobiological life transition
• How estrogen, serotonin receptors, and psychedelics like psilocybin may interact in midlife
• What we know (and don't yet know) about hormone replacement therapy and psychedelic efficacy
• The potential anti-inflammatory effects of psychedelics and their relevance to menopausal symptoms
• How ketamine may function differently from classic psychedelics during hormonal transitions
• Why psychedelics can support identity reorientation, self-actualization, and "not caring" in generative ways
• The critical role of community, creativity, and nervous system regulation in integration during midlife

Quotes:

"We don't honor and celebrate aging and elderhood overall in our culture. … What I do feel is really vital is that we gather and support each other in all of life's transitions, and [menopause has] not only been underrepresented, but also just under honored." [3:29]

"As [estrogen] levels decrease, there's a decrease in serotonin receptors—which is the 5-HT2A receptor. And so that reduces our sensitivity to, and activity of serotonin. And psilocybin and LSD and other 5-HT2A agonists—they can enhance their receptors and the activity of those receptors." [13:20]

"The understanding is that with [estrogen] hormone replacement therapy you would then, theoretically, see a replenishment of [serotonin] receptors, and then the psilocybin would have more ability to act on those receptors." [15:37]

"Psilocybin—and psychedelics in general—and the menopausal transition are just really beautiful complements to each other and they become even more potent when used together." [19:48]

Links:

Dr. Bigelow on LinkedIn

Dr. Bigelow on Instagram

Dr. Bigelow's website

Synaptic Institute website

Rise Up Journeys website

Psychedelic Medicine Association

Porangui