Longevity/Neurowellness Episode 2 — Nootropics and Cognition with Yanni and Juubilan
This podcast brings together Julian, Sean, and Yanni for an informal but wide-ranging discussion about neuroplasticity, nootropics, psychiatric risks, stimulant medication, sleep, exercise, and performance-enhancing drugs. Their central message is that there is no universal "Limitless pill" or perfect stack: cognition, mental health, training, and drug responses are highly individual. Although they discuss many compounds and personal experiences, much of the conversation is anecdotal or based on early research, so their claims should not be treated as medical advice.
1. Introductions and the Goal of Better Wellness
The episode opens with Yanni introducing his guests, Julian and Sean, who are both active online in neuroscience, pharmacology, wellness, and performance-enhancing-drug discussions.
Julian says he has independently studied neurology, pharmacology, and performance-enhancing drug pharmacology for around five years. Sean, who had recently started college neuroscience studies, says his main interests are nootropics, neuroscience, and improving quality of life. He distances himself somewhat from the fashionable label "biohacking," preferring to talk about practical wellness and cognitive improvement.
"I mainly talk about nootropics, neuroscience… and just enhancing your quality of life."
Their goal is not merely to list supplements or drugs. They want to explore the underlying principles—how the brain learns, how habits form, what sleep does for cognition, and why people should be careful with compounds that alter the brain.
2. Neuroplasticity Is Powerful—but It Reinforces Bad Habits Too
The first major topic is neuroplasticity, meaning the brain's ability to adapt, reorganize, and form or strengthen connections. The speakers describe it as central to learning, recovery from difficult experiences, and adapting to one's environment.
"The brain's natural ability to rewire and reorganize itself… is the reason why we learn things [and] adapt to our environment."
They also mention neurogenesis—the formation of new neurons—as a related but more controversial topic in neuroscience. Julian notes that there is debate over exactly how much adult neurogenesis occurs in humans and how important it is in different brain regions.
Sean emphasizes that neuroplasticity is not automatically good. The brain can become more flexible in either a constructive or destructive direction. If someone uses a compound believed to increase plasticity but spends their time compulsively scrolling, gaming, using drugs, or reinforcing another harmful behavior, they may simply become better conditioned to do that behavior.
"The brain is in this plastic state able to go backwards or… go forwards."
"There's not going to be one compound… that is going to boost your plasticity high enough to where you're going to become a genius out of nowhere."
They compare this process to training in the gym: repeating a movement develops muscle, while repeating a thought pattern or behavior strengthens that mental pathway. In their view, any attempt to increase learning capacity should be paired with intentional practice, such as reading, studying, exercising, developing a skill, or building a healthier routine.
The speakers share personal examples of inadvertently reinforcing unhelpful habits. One describes becoming heavily absorbed in a video game while taking compounds intended to support plasticity. Another describes using cannabis while experimenting with nootropics, later realizing that he might have been strengthening an unhealthy routine rather than "fixing brain fog."
Their broader warning is simple:
"If you're not actively focusing on good habits… you will get addicted to the most [unhelpful] things ever."
3. Habits, Withdrawal, and the Risks of Research Chemicals
Sean describes a difficult experience after being admitted to a psychiatric ward. He says that he had been using multiple substances and routines he associated with productivity, learning, editing videos, and research. In the ward, he suddenly lost access to his supplements, devices, online activity, and usual rituals.
The experience made him recognize how deeply habits can become wired into daily life. Even without normal obligations, he felt distressed by not being able to check his phone, work on content, read, or follow his familiar routine.
"Having all of my habits, all of my routines… completely stripped from me… felt like hell."
"Once you have a habit wired in, it is not easy to get off."
The others distinguish between ordinary habits and dependence on psychoactive drugs. Cannabis, benzodiazepines, opioids, stimulants, and other substances can alter mood and perception directly, so stopping them may be more difficult than simply changing a behavior. Still, the participants see both as examples of how repeated experiences can condition the brain.
Julian adds an important caution: many "research chemicals" and experimental nootropics have very limited human safety data. People may know one or two possible mechanisms from animal studies or patents, but that does not mean they know the full effects, interactions, long-term risks, or psychiatric consequences.
"We don't know what half of these things do down to their core."
"Once you're in psychosis, once you reach mania, your chance of developing mania or psychosis in the future is enhanced."
This is one of the episode's most valuable themes: a mechanism that sounds promising online does not equal a proven treatment. The speakers repeatedly criticize the belief that someone can find a perfectly "science-based stack" that instantly makes them smarter, more motivated, or more neuroplastic.
4. Nootropics, Cannabis, and NSI-189
The group next discusses nootropics that they have found notable, beginning with NSI-189, an experimental compound often discussed in online nootropic communities for possible effects on mood, cognition, and neurogenesis.
Sean describes NSI-189 as one of the more subjectively noticeable compounds he has encountered. He explains a proposed mechanism involving the TLX receptor, growth factors such as BDNF and EGF, and possible effects on neural stem cells in the hippocampus. In simple terms, the hippocampus is strongly involved in memory formation and is often studied in relation to stress and depression.
He says people he has spoken with report improved hopefulness and less depression while using it.
"Everybody that I've ever spoken to that's tried NSI-189 has said… it completely abolished any symptoms of depression that they may have."
However, Julian offers a major counterpoint: NSI-189 did not meet its primary endpoint in a Phase II clinical trial for depression. While some secondary cognitive measures appeared encouraging, the main standardized depression outcome did not show the hoped-for benefit.
"Mechanistically, everything can look beautiful. Anecdotally, everything can look amazing. But then we put it through an actual clinical trial and then it fails."
This exchange captures the podcast's tension between curiosity and skepticism. Sean remains interested in the cognitive findings, while Julian argues that clinical trial outcomes matter more than enthusiastic personal reports.
They also discuss the idea of a bell-shaped or U-shaped response curve. In many biological systems, too little can be ineffective, a moderate amount may be beneficial, and too much may become harmful or less effective. They apply this idea broadly to sleep, supplements, dopamine, norepinephrine, and performance-enhancing drugs.
"Everything you want is just like a ratio."
The group briefly discusses cannabis-related cognitive effects. Sean cites research he interprets as implicating the NMDA receptor, especially an NR2B-related pathway, in some THC-related cognitive impairment. He suggests that certain compounds may reduce these effects, but this part of the conversation is speculative and should not be interpreted as a safe method to combine substances. Cannabis can affect memory, attention, motivation, anxiety, and psychosis risk, particularly in vulnerable individuals.
5. Stimulants, Drug Metabolism, and Psychiatric Sensitivity
Julian describes himself as unusually sensitive to psychoactive drugs. He says that because of past substance use and possible genetic differences in drug metabolism, even low doses of stimulants, SSRIs, and other medications can affect him strongly.
"I'm hyper-responsive to everything… I take half the clinical dose of everything, sometimes a quarter."
He explains that this sensitivity is why he personally avoids many nootropics. Compounds that others find energizing or cognitively useful can leave him anxious, overstimulated, or unable to sleep.
The group then discusses drug metabolism, especially the enzyme CYP2D6. Enzymes like CYP2D6 help the body process many medications. Some drugs inhibit or induce these enzymes, potentially changing how long another substance stays active or how strongly someone feels its effects. They mention interactions involving stimulants, propranolol, bupropion, modafinil, and antidepressants.
The main practical lesson is not that people should self-manage complex drug combinations. Instead, it is that interactions can be real, unpredictable, and highly individual.
"A lot of these random lifestyle habits can induce or inhibit a lot of enzymes."
The participants also criticize long-term, casual use of amphetamine-based stimulants. Sean argues that stimulants may improve short-term attention and motivation but could have trade-offs for sleep, dependence, anxiety, and long-term neural adaptation. He discusses animal research involving NMDA receptor subunits, but these findings cannot be assumed to translate directly to people.
Sean recounts stopping multiple medications abruptly during his psychiatric hospitalization, including a long-acting stimulant. He describes severe fatigue, increased appetite, low motivation, and feeling unable to get out of bed. This reinforces an important real-world point: stopping psychiatric or stimulant medication suddenly can be difficult and should be managed by a qualified clinician whenever possible.
"I was stripped of the drug that made me a workaholic… and I was stripped of it entirely."
They also discuss bromantane as a compound of interest, but nootropic "replacement" strategies for prescription stimulants should be approached cautiously. Replacing, tapering, combining, or discontinuing psychiatric medications without medical supervision can carry significant risks.
6. Sleep, Memory Consolidation, and Circadian Rhythm 🌙
The conversation shifts to sleep, which all three participants treat as one of the foundations of cognition, mood, recovery, and longevity.
"Sleep is one of the most important facets of your day-to-day lifestyle that you really need to lock in."
They link poor sleep with worse cognitive performance, memory, hormonal health, inflammation, insulin sensitivity, and mental stability. Sean says severe sleep deprivation contributed to his psychiatric crisis and notes that while sleep deprivation can sometimes produce a very brief antidepressant-like effect, it can quickly lead to anxiety, instability, and worse functioning.
The speakers emphasize that sleep is not just about spending a certain number of hours in bed. They encourage sleeping until one wakes naturally when possible, creating a regular schedule, avoiding phone scrolling in bed, and treating sleep as a deliberate recovery period rather than an inconvenience.
"Knocking the [hell] out and staying the [hell] out is important."
Slow-Wave Sleep and Long-Term Memory
They explain that slow-wave sleep, often called deep non-REM sleep, is important for memory consolidation. The simplified idea is that the hippocampus temporarily holds newly learned information, then repeatedly "replays" it during sleep so that it can become more stable and distributed across the cortex.
"Your hippocampus will basically replay all the memories you learned during that day… into your cortex."
This is why they argue that cramming information and barely sleeping is ineffective for long-term learning. Studying is only part of learning; sleep helps preserve what was studied.
"If you want to remember it long term… you sleep."
They also mention research in rodents showing that neural activity patterns related to movement and exploration can be replayed during sleep, sometimes in reverse sequence. While the technical details are still being studied, the speakers are fascinated by the idea that the sleeping brain actively reorganizes experience rather than simply "switching off."
REM Sleep and Sleep Timing
They also stress REM sleep, the stage often associated with vivid dreaming. They suggest that deep sleep and REM sleep serve different but complementary roles: deep sleep is strongly tied to restoration and consolidation, while REM may help with emotional processing, integrating memories, and creative association.
Yanni argues that timing matters because the first portion of sleep tends to include more deep sleep, while later portions contain relatively more REM sleep. His broader claim is that a consistent, earlier sleep schedule may support a more stable circadian rhythm than sleeping very late, even if total sleep time appears similar.
The speakers recommend treating melatonin primarily as a circadian signal rather than a high-dose sedative. They criticize the trend of taking very large doses simply to force sleep.
"People treat melatonin like it just gets you to sleep… it's directly attacking your circadian rhythm."
They also discuss basic sleep-environment strategies:
- Keep the bedroom dark.
- Keep it cool.
- Reduce bright light and phone use before sleep.
- Consider a warm shower before bed, followed by a cooler sleep environment.
- Maintain a regular wake-up and bedtime routine.
- Avoid late-day stimulant use and intense late-night training when it disrupts sleep.
7. Psychiatry, Genetic Tests, and Why "Stacks" Are Not Universal
The podcast returns to psychiatric vulnerability. Julian makes one of the strongest cautionary statements in the episode: people with moderate-to-severe susceptibility to conditions such as mania, psychosis, severe anxiety, bipolar disorder, or schizophrenia should be extremely careful with nootropics and experimental psychoactive compounds.
"Anybody with any sort of… moderate to severe psychiatric susceptibility has no place using nootropics."
Even Sean, despite being highly interested in nootropics, agrees with the underlying message. He says that what works for one person may be disastrous for another. Someone may share symptoms such as anxiety, brain fog, poor focus, or depression, yet have a completely different neurochemical and medical situation.
"All of the neurochemical environments are so vastly different."
They criticize online users who ask creators for a generic "stack" and promise to copy it exactly. Sean rejects the idea that viewers should trust his personal routine simply because he discusses pharmacology online.
"My stack is literally mine… tailored to my needs."
"I am not this holy grail of which you can just instantly follow me."
The group also discusses GeneSight-style pharmacogenetic testing. Julian explains that such tests can provide information about metabolic enzymes—such as whether someone may process a medication more quickly or slowly—but they do not reliably reveal which psychiatric medication will work best for a person.
"It does not tell you your neurochemical makeup."
"The GeneSight test is [about] how you metabolize a drug. That's all."
He criticizes clinicians who oversell these tests as definitive guides to medication selection. In his view, psychiatry remains heavily dependent on trial and error, although the future may bring better tools, perhaps involving more direct biological measures.
The speakers acknowledge that psychiatric treatment often focuses on reducing suffering and improving function rather than providing a permanent cure.
"The goal is to treat and attenuate the symptoms so we're not suffering."
8. The "Magic Bullet" Mindset in Fitness and Nootropics
The participants complain humorously about the online culture of asking strangers for personalized meal plans, training splits, physique ratings, drug stacks, and coaching—often while expecting comprehensive advice for free.
They see the same mistake across bodybuilding, cognitive enhancement, and wellness: people want a quick, universal answer rather than understanding their own circumstances and doing consistent work.
"People are always looking for some sort of magic bullet that doesn't exist."
"There's no one-size-fits-all for any skill or trade."
They argue that even apparently simple questions—such as "What is your meal plan?" or "What is your workout split?"—cannot be answered meaningfully without context. Genetics, current fitness level, goals, schedule, injury history, food preferences, sleep, stress, medications, and many other variables matter.
Their conclusion is that individualized coaching can have value, but people should also respect experts' time and should not expect a stranger's exact routine to transform their own life.
9. Testosterone, Estrogen, and Performance-Enhancing Drugs
Later, the group talks about anabolic-androgenic steroids, often called "gear." This section is based mostly on personal experiences and should be viewed as a cautionary discussion rather than an endorsement of use.
Julian says he used anabolic drugs for years but eventually stopped because of psychological and neurological side effects. He describes a past cycle involving testosterone, nandrolone, and an aromatase inhibitor used to reduce estrogen. He believes that combining nandrolone with aggressive estrogen suppression may have changed how sensitive he felt to estrogenic effects afterward.
"My brain turned into mush from nandrolone."
He describes panic attacks, anxiety, sleep disruption, emotional instability, and recurring sensitivity when he later tried even small amounts of testosterone. Whether his interpretation of the hormonal mechanisms is correct cannot be determined from the discussion alone, but the story highlights the risks of experimenting with hormones without careful medical oversight.
Yanni shares his own experience of high estrogen-related symptoms while using testosterone. He describes rapid weight gain, water retention, puffy nipples, and intense emotional reactions. In a humorous example, he recalls becoming tearful while watching a motivational scene in The Karate Kid.
"That's what high E2 will do to a man."
The group agrees that more drug is not always better. They discuss the possibility of diminishing returns at high doses, along with increased risks such as elevated red blood cell counts, estrogen-related effects, cardiovascular strain, psychiatric side effects, and poorer overall well-being.
"For most people, they really, really, really don't need to be touching other drugs."
Their more restrained message is that fundamentals—food, sleep, training, recovery, and consistency—are more important than endlessly adding compounds. However, because anabolic steroid use can seriously affect cardiovascular health, fertility, mental health, liver function, blood pressure, and endocrine function, medical supervision is essential.
10. Walking, Exercise, and BDNF 🏃
Near the end, the speakers return to a safer and more practical cognitive-enhancement tool: physical exercise.
They describe walking as useful not only for calorie expenditure and cardiovascular health, but also for thinking. One speaker says that walking gives him some of his best ideas because it reduces external distractions and lets him think more freely.
"Your best ideas really come to you when you're walking."
They discuss BDNF, short for brain-derived neurotrophic factor. BDNF is a protein involved in the growth, survival, and adaptability of neurons. It is often described as supporting brain plasticity, although it is not a magical "brain fertilizer."
The speakers reference a 2021 systematic review and meta-analysis suggesting that a single session of high-intensity exercise can produce an immediate increase in circulating BDNF in healthy young adults.
"BDNF increases almost immediately in your bloodstream during and right after a single session of physical exercise."
Their broader takeaway is that exercise may offer an acute cognitive and mood benefit while also supporting long-term brain health. Unlike experimental drug stacks, walking and aerobic activity are accessible habits that can be built into ordinary life.
11. Circadian Habits and the Limits of Mechanistic Speculation
In the final technical discussion, they return to circadian rhythm and stress management. Yanni argues that demanding activities, especially intense exercise, may fit better earlier in the day because cortisol naturally rises in the morning and may be easier for the body to manage then.
He suggests that late-night training—especially when combined with caffeine or other stimulants—can interfere with sleep. Sean agrees that early exercise is often more sustainable, though individual schedules can vary.
They also discuss experimental compounds such as Selank, Semax, pinealon, and other Russian-developed peptides or drugs. The speakers are intrigued by claims that these substances may influence BDNF, stress pathways, dopamine, or gene expression. Yet they repeatedly admit that the mechanisms and human evidence are incomplete.
"For a lot of these Russian drugs and psychotropics, we literally just don't know anything about them."
"The issue isn't what they do; it's rather what they're doing to get there."
This is an important distinction. A compound may appear to produce a useful effect in an animal model or a small study, but researchers may not know all the downstream pathways, long-term changes, interactions, or risks. The speakers recognize that this uncertainty is exactly why enthusiasm should be balanced with caution.
12. Closing: Curiosity, Education, and Getting Smarter
The podcast ends on a positive note. The speakers express genuine excitement about neuroscience, pharmacology, research, and continuing to learn. They want to make more podcasts, improve their knowledge, and share educational content with their audiences.
One speaker says that while many people obsess over becoming bigger or more muscular, he is motivated by the idea of becoming more knowledgeable.
"For me, I want to be so much smarter, bro."
They thank each other for the conversation and hope to collaborate more frequently. The final message echoes the overall theme of the episode: stay curious, work on the fundamentals, question bold online claims, and keep striving to improve.
"Keep striving to be better."
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