Tolerance, dependence, and cycling strategies

This is Part 2 of the Nicotine Masterclass. If you haven’t heard Part 1, start there for a full breakdown of nicotine’s mechanisms, myths, and the science behind its misunderstood role in longevity, nootropics, and human performance. 

Nicotine is one of the most misunderstood nootropics in the world—and one of the most powerful tools for brain optimization and longevity when used correctly. In this episode, Host Dave Asprey breaks down how to harness nicotine for cognitive enhancement, metabolism, and human performance without falling into addiction. You’ll learn the real science behind dosage, timing, and cycling, plus how nicotine interacts with mitochondria, acetylcholine, and neuroplasticity to boost focus, motivation, and mental energy. 

Watch this episode on YouTube for the full video experience: 

https://www.youtube.com/@DaveAspreyBPR 

This is Part 2 of the Nicotine Masterclass. If you haven’t heard Part 1, start there for a full breakdown of nicotine’s mechanisms, myths, and the science behind its misunderstood role in longevity, nootropics, and human performance. 

Host Dave Asprey reveals practical biohacking templates for using nicotine safely and effectively—covering metabolism genetics, stack combinations, and how nicotine fits into a smarter not harder lifestyle. You’ll discover how low-dose nicotine can support attention, memory, and even protect against neurodegenerative diseases like Alzheimer’s and Parkinson’s. Dave also shares his own five-year nicotine protocol, how he avoided dependence, and why nicotine can be a game-changer for brain and mitochondrial performance when used intelligently. 

You’ll Learn: 

• How to use nicotine as a safe, powerful nootropic for brain optimization and focus 

• The genetics of nicotine metabolism and why dose timing matters 

• How to stack nicotine with caffeine, theanine, and rhodiola for maximum energy and motivation 

• Why nicotine enhances mitochondria and PGC-1α for better metabolism and longevity 

• The truth about nicotine tolerance, cycling, and how to avoid addiction 

• How nicotine affects sleep, neuroplasticity, and dopamine signaling 

• What science says about nicotine’s protective effects against Alzheimer’s and Parkinson’s 

• How to integrate nicotine into a complete biohacking protocol with fasting, ketosis, and supplements 

This episode is essential for anyone exploring biohacking, functional medicine, fasting, ketosis, sleep optimization, and cognitive resilience. You’ll learn how nicotine stacks with caffeine, theanine, rhodiola, and supplements for sharper thinking and sustained focus—plus the key mistakes to avoid so you don’t wreck your sleep or metabolism. Whether you’re a seasoned biohacker or just beginning your journey, this episode gives you the science, tools, and protocols to elevate your mind and body safely. 

Dave Asprey is a four-time New York Times bestselling author, founder of Bulletproof Coffee, and the father of biohacking. With over 1,000 interviews and 1 million monthly listeners, The Human Upgrade brings you the knowledge to take control of your biology, extend your longevity, and optimize every system in your body and mind. Each episode delivers cutting-edge insights in health, performance, neuroscience, supplements, nutrition, biohacking, emotional intelligence, and conscious living. 

New episodes are released every Tuesday, Thursday, Friday, and Sunday (BONUS). Dave asks the questions no one else will and gives you real tools to become stronger, smarter, and more resilient. 

Keywords: nicotine biohacking, nicotine masterclass, Dave Asprey nicotine, nicotine nootropics, nicotine cognitive enhancement, nicotine mitochondria, nicotine and dopamine, nicotine addiction prevention, nicotine cycling, nicotine dosage, nicotine metabolism, nicotine tolerance, nicotine and longevity, nicotine patch benefits, nicotine for focus, nicotine and acetylcholine, nicotine and caffeine stack, nicotine sleep effects, nicotine and Parkinson’s, nicotine brain optimization 

** Listen to part 1 here: https://www.youtube.com/watch?v=WjehLsHaRnE&t=1063s** 

Thank you to our sponsors! 

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Resources:  

• Danger Coffee: https://dangercoffee.com/discount/dave15 

• Dave Asprey’s BEYOND Conference: https://beyondconference.com 

• Dave Asprey’s New Book – Heavily Meditated: https://daveasprey.com/heavily-meditated 

• Upgrade Collective: https://www.ourupgradecollective.com 

• Upgrade Labs: https://upgradelabs.com 

• 40 Years of Zen: https://40yearsofzen.com 

Timestamps: 

00:00 – Trailer 

01:25 – Review of Pt 1 

02:48 – Genetics & Metabolism 

06:05 – Stacking with Other Compounds 

09:23 – Tolerance & Dependence 

13:42 – Fertility & Contraindications 

17:05 – Real World Use Templates 

21:40 – Travel & Jet Lag Protocol 

24:29 – Biohacking Lifestyle Integration 

25:31 – Longevity & Neuroprotection 

28:24 – Medical Applications & Research 

31:51 – Final Thoughts & Summary 

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