🫠 Psychonaut POV

Welcome to Tricycle Day. We’re the psychedelics newsletter that resists the urge to label things ‘good’ or ‘bad.’ Except pineapple on pizza, which is objectively great. (We will not be hearing counterarguments at this time.) 🍕

Manesh Girn, aka The Psychedelic Scientist, has been working with the sharpest minds in the field for years. But while most researchers are focused on psychedelics' utility in mental health, Manesh has his sights set higher. He sees these molecules as tools to enhance human potential.

We spoke to Manesh about the ways his own mind and research have surprised him, a dangerous misconception he’s noticed among psychedelic enthusiasts, and how he’d bring scientific rigor to the study psychedelics as catalysts for spiritual growth.

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How did you become interested in psychedelics, neuroscience, and the default mode network specifically?

I entered this world through my exploration of spirituality and meditation as a teenager. It started when a high school counselor gave me a copy of Three Pillars of Zen by Philip Kapleau, which got me fascinated with the idea of meditation for greater insight and enlightenment. After reading that book, I started thinking about ways to expand consciousness in general.

My first psychedelic experience came at 16 or 17 when I tried psilocybin mushrooms at the beach. It was a profound, introspective experience where I felt distinct from my usual self and had an expansive view of the world. It really opened my eyes to how our brains construct reality and how easily it can be altered. That realization made me want to study the brain to understand how this all works.

In college, I volunteered at a cognitive neuroscience lab doing mind wandering and meditation research with fMRI. This position led to a collaboration with Robin Carhart-Harris, who was just starting to do brain imaging studies with psychedelics. For grad school, I focused on the default mode network to inform psychedelic research. After my PhD, I moved to San Francisco to work with Robin on psychedelic brain imaging full-time, as a postdoctoral scholar at the University of California, San Francisco. It's been a journey of personal experiences, meeting brilliant people, and being in the right places at the right time.

So far, what have you found in your own psychedelic research that has surprised you the most?

What's surprised me most is realizing how little we actually know, despite popular narratives suggesting otherwise. Back when How to Change Your Mind came out in 2018, there was this idea that we understood how psychedelics work, and that it was all about the default mode network. But six years later, we're still far from a comprehensive understanding.

I've come to see the brain effects of psychedelics as much more holistic and complex. It's not just about specific networks changing; it's about the entire brain shifting how it processes information. This is a more nuanced view than the reductionist explanation of "psychedelics turn off the default mode network." That simplistic model doesn't account for the wide range of experiences people have on psychedelics, spanning a variety of distinct and dynamically changing alterations to our perception, thinking, emotions, and sense of self.

The reality is that psychedelic experiences are incredibly multifaceted. Someone can take a substantial dose and have a profound psychological and visionary experience without ego dissolution, while another person might be extremely sensitive and merge with everything on a lower dose. We're only beginning to tackle this complexity scientifically, by mapping how brain changes interact with context (i.e., set and setting) to produce unique experiences. It's still a young field with so much room for expanding our models.

Unlike many academics, you devote substantial time and energy into educating the public. What do most people—even enthusiasts and industry insiders—get wrong about psychedelics?

People often misunderstand psychedelics as inherently positive. This view is naive and overlooks the pivotal role of context—that is, set and setting. Psychedelics are essentially context amplifiers. That means they can potentially make someone a worse person, exacerbate depression, or cause harm if not used properly.

The idea that putting psychedelics in the water supply or dosing authoritarian dictators would make the world better is, unfortunately, misguided. Psychedelics and the neuroplasticity they induce are intrinsically neutral. Their effects depend heavily on how they're administered; the intention of the journeyer; and the preparation, support, and integration provided.

Regarding neuroplasticity, it's important to understand that while psychedelics increase the brain's ability to form new connections, they don't specifically increase "positive" neuroplasticity. The brain doesn't distinguish between connections that serve helpful or unhelpful behaviors; it simply encodes what's activated together. This increased plasticity could support positive changes like being more present or compassionate, but it could equally reinforce negative patterns like deeper rumination or anxiety.

This is why integration is so critical. If someone takes psychedelics to break out of negative thought patterns but continues with critical self-talk during the neuroplastic period, they might end up back where they started or even more entrenched in those patterns. The potential for transformation exists, but the direction of that transformation isn't guaranteed to be positive without proper care and attention.

Most of the research on psychedelics today is focused on mental health applications. What do we know about psychedelics' effects on creativity and human potential?

The research on psychedelics' effects on creativity and human potential is still pretty limited. We're mostly focused on mental health right now, for good reason—that's how regulations will change. But there's definitely interest in how psychedelics can expand people beyond just a healthy baseline, towards greater meaning, purpose, and fulfillment.

Studies on psychedelics and creativity have shown mixed results. The tricky part is mimicking true creativity in a lab context. There are plenty of artists and visionaries we can point to, who were inspired by psychedelics—people like Steve Jobs, and even Kary Mullis who attributed his idea for PCR to an LSD vision. But the actual studies so far aren't showing that strong or reliable of an effect.

I’m currently working closely with an exciting new organization, The Center for MINDS, to try to come up with ways to study this relationship more naturalistically. The challenge is, creativity is such a loose concept and often comes unexpectedly in daily life. The tasks used in existing studies, like finding novel associations between pictures or listing all the things you can do with a household object, seem super contrived—probably even more so when you're tripping.

There's some promising work suggesting psychedelics synergize with meditation, helping people reach deeper, more unitive states. We're also seeing evidence that psychedelics act as meaning-enhancing molecules. They tend to help people feel greater personal significance in their lives.

I think there's potential for psychedelics to enhance skill acquisition, too. The plasticity and other benefits, if you get the dosage right, could potentially help with any kind of skill you want to learn—things like chess, skiing, languages, or anything that involves dropping into flow states. There's so much there that's barely been tapped into. I think that's the future of this research.

If resources weren’t a constraint and you could run any psychedelic study, what would it be?

I'm really excited about exploring how psychedelics can help people grow in their spiritual maturity or level of awareness. I'd love to investigate what the brain signatures of that kind of growth look like.

If I had all the resources in the world, I'd put together a think tank of experts to develop measures and frameworks for studying this area. We'd need to conceptualize how psychedelics affect healthy people's relationships with themselves and determine the physiological and neural states associated with greater internal integration and internal harmony.

I envision a longitudinal study where we assess people's baseline level using these measures, and then put them through a sequence of psychedelic experiences with different molecules over time. We'd track how their neurophysiology changes, providing empirical evidence for the idea that psychedelics expand consciousness and promote spiritual growth.

We'd need to create new scales first that go beyond standard clinical measures to assess "supra-health" dimensions. We could draw from concepts like Maslow's hierarchy, transpersonal psychology, and various stage development theories to create a quantifiable assessment of growth.

That’s the exciting frontier in my opinion. The mental health applications of psychedelics are undoubtedly important, but I’m convinced that treating illness is just scratching the surface. The next step is using psychedelics to explore and enhance human potential. Health is the baseline. With these molecules, we can pursue self-actualization.

Want more from Manesh?

Check out his free ‘5-Steps to Re-Wiring your Brain with Psychedelics’ pdf, and dive deeper into the essentials of psychedelic science in his brand new Psychedelic Medicine Masterclass.

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DISCLAIMER: This newsletter is for educational and informational purposes only and is not intended as a substitute for professional medical advice. The use, possession, and distribution of psychedelic drugs are illegal in most countries and may result in criminal prosecution.