Podcast Summary: The Human Upgrade with Dave Asprey

Episode 1399 – “The Superbrain Drug Politicians Use to Outsmart Everyone”
Date: January 16, 2026
Host: Dave Asprey
Guest: David Renteln (co-founder of Lucy, oral nicotine company)

Overview

In this episode, Dave Asprey explores the controversial yet potentially transformative cognitive and performance-boosting effects of nicotine, specifically through smokeless oral delivery systems like gum and pouches. Joined by David Renteln from Lucy, the conversation delves into the neurological mechanisms of nicotine, its history, the regulatory landscape, harm reduction, strategies for safe use, and its popularity among high performers—including U.S. politicians.

Key Discussion Points & Insights

1. Nicotine: Reconsidered as a Cognitive Enhancer

• Topic: The evolving stigma around nicotine and its use among professionals and politicians.
  • Example: RFK (Robert F. Kennedy Jr.) using nicotine pouches during Senate confirmation hearings (00:00, 32:28).
  • Dave remarks on increasing use in government:
    “You see a lot of people in government using nicotine pouches now... they don't come with the same kind of stigma [as vaping].” (32:59)

2. Biochemical Mechanisms & Research

• Acetylcholine & NAD+:
  • Nicotine increases brain acetylcholine—a neurotransmitter critical for memory and learning—by downstream release (00:25, 05:09).
  • New research shows nicotine can upregulate NAD+ in brain and tissue, potentially supporting cellular energy and longevity (03:33, 18:15).
• Learning & Performance:
  • Dave: “It basically makes you smarter, helps you learn faster, is pleasurable, and is also... behavior reinforcing.” (05:09)
  • Referenced studies (e.g., Dr. Paul Newhouse, Vanderbilt, on nicotine in Alzheimer’s patients) show promising results for cognitive preservation (18:15).
  • Caution around stacking nicotine with acetylcholine-boosting drugs (e.g., Aricept, Huperzine A):
    “You might want to be careful with nicotine because you’re doubling down on acetylcholine.” (20:30)

3. Nicotine Delivery Methods: Risks, Benefits, and Regulatory Hurdles

• Smoking vs. Oral Nicotine:
  • Smoking and vaping deliver nicotine quickly—highest risk for addiction and health damage.
  • Oral absorption (gum, pouches) is slower, reduces euphoria, and is considered lower risk.
    “Use a form factor that releases nicotine... as slowly as possible, because that negatively correlates with the euphoria.” (11:57)
• Switching from Smoking:
  • Renteln describes moving from cigarettes to oral nicotine as replacing a high-risk habit with a much safer alternative.
    “You don’t get the lung irritation, but you still have to break the habit of it.” (10:45)
• Dosing and Addiction:
  • Under 5mg/day is generally considered to have low addiction risk.
  • Dave: “My recommendations are five on a normal day, 10 on a burst day, and don’t do what I do...” (16:08)
  • Renteln’s highest: 45 pouches/day (8mg strength), described as “mega dosing”—no apparent negative effects reported except potential for tolerance (16:28).

4. Protocols and Biohacking Approaches

• To Avoid Addiction:
  • Don’t use daily if you’re worried about dependence; choose slower delivery (patches lowest, pouches/gum moderate, vaping/smoking fastest) (11:52).
• Stacking:
  • Nicotine synergizes well with caffeine, modafinil, and most nootropics; caution urged with acetylcholine enhancers (24:06).
  • Enhances meditation and psychedelic therapies for some (27:37, 25:09).

5. Behavioral Reinforcement

• Contextual Use:
  • Nicotine can reinforce positive behaviors—Renteln uses it to boost learning and morning routines:
    “The dose... that is most effective, that I feel, is the first dose that I take in the morning. And so dialing in a morning routine is probably the most effective way...” (43:31)
  • Dave discusses Pavlok and the idea of pairing negative and positive reinforcement for behavioral change (41:43).

6. Harm Reduction, Regulation, and Politics

• Regulatory Success & Mistakes:
  • U.S. regulatory landscape has both improved quality control and handicapped innovation (29:31).
  • EU’s ban on Swedish snus cited as a cautionary tale—Swedians’ switch to oral tobacco dramatically lowered smoking rates (29:52).
  • Dave’s take: Regulation should focus on access control and innovation encouragement, and not be driven by legacy industries or puritan attitudes (35:59).
• Government Use and Policy:
  • Discussion around politicians adopting pouches—influencing shifts in public health policy and product acceptance (32:24).
  • Commentary on entrenched government-business connections and stock trading (33:36).

7. Addiction: Nuance and Harm Reduction Philosophy

• Physical vs Psychological:
  • Nicotine’s primary risk is physiological dependence. Comparison to AA/NA cultures, where cigarette and coffee use is tolerated (39:04).
  • Renteln: “AA, NA... smoking appears to be tolerated and coffee appears to be tolerated... those two substances don’t cause behavioral changes that are problematic.” (39:04)
  • Discussion on using addiction positively—for example, replacing smoking with a less harmful addiction like nicotine pouches or even exercise (38:15).
  • Public health concerns around limiting access to less harmful alternatives for vulnerable populations (37:51).

Notable Quotes & Memorable Moments

• On government and politicians using nicotine:
  “If I was going to sit there and be just asked the most asinine questions by all those senators and congresspeople and all, I would be absolutely using nicotine and modafinil...” – Dave (32:40)

• On stacking and threshold doses:
  “If you’re keeping it to under 5mg per day... you’re unlikely to get addicted... You go above 10, you’re probably going to fall into addiction land.” – Dave (15:46)

• On reframing nicotine’s place in biohacking/longevity:
  “If you were addicted to crack and you could be addicted to exercise instead, the exercise addiction is better, but it’s still addiction. In the case of smoking... nicotine is probably good for you and way less bad for you.” – Dave (38:15)

• On oral nicotine as a competitive, enjoyable alternative:
  “What we designed it for was to be a product that could actually compete on a brand, an enjoyment level with cigarettes. So better flavor, texture, an approachable brand.” – Renteln (28:37)

• On regulation and innovation:
  “If people do this, it’s better than smoking. Allow innovation here because it doesn’t say in the constitution that the government can limit innovation or that they have any say over what you put in your body... You did a long time ago. I know Big Pharma made you do it, but you need to chill out.” – Dave (35:59)

• On advice for those considering nicotine:
  “If it’s not a substance that you’re familiar with, there’s no reason to start. I would say also that the continuum of risk is extremely important to know about... if you’re going to use nicotine, you should use it with a product that won’t kill you.” – Renteln (47:27)

Important Segment Timestamps

• [00:00] – Opening: Politicians & nicotine, societal stigma.
• [02:20] – Guest intro (David) & origin story of Lucy.
• [03:33] – Delivery methods: pouches, gum, safety/ingredients.
• [05:09] – Nicotine’s effects on learning & reinforcement.
• [10:45] – Transition from smoking to oral nicotine, breaking habits.
• [11:52] – Safe protocols for non-smokers / minimizing addiction.
• [16:08] – Dosing advice, addiction thresholds.
• [18:15] – Academic studies: nicotine & Alzheimer’s.
• [20:30] – Stacking with acetylcholine enhancers.
• [24:06] – Nootropics/nicotine stacking.
• [29:31] – Regulatory landscape, harm reduction, EU comparisons.
• [32:28] – Politicians/policy, stigma differences.
• [35:14] – International innovation/testing due to regulation.
• [37:07] – Addiction theory: physical vs. psychological, harm reduction.
• [41:43] – Behavior reinforcement, Pavlok, pairing with habits.
• [43:31] – Renteln’s routine: using nicotine to reinforce positive habits.
• [47:27] – Summary advice on nicotine for new users.

Flow, Tone, and Takeaway

The conversation is candid, science-based, and occasionally irreverent, reflecting Dave Asprey’s style: practical, biohacker-friendly, and a bit rebellious against overregulation and anti-innovation biases. The tone is open-minded but cautious, promoting informed, moderate, and individualized use of oral nicotine as a legitimate, lower-risk nootropic for those seeking cognitive enhancement or switching off cigarettes.

Bottom Line Recommendations

• Nicotine can be a powerful cognitive enhancer and habit reinforcement tool—if used in oral, slow-acting forms and with mindfulness to dose and frequency.
• For non-users, there’s little reason to start; for smokers, replacing cigarettes with oral products is a massive health benefit.
• Regulatory bodies should support, not hinder, safer alternatives and innovation, especially given the shifting cultural and governmental reality.
• Above all, make personal risk-benefit decisions without undue moralism or social stigma.

For more biohacking, performance, and longevity insights, listen to The Human Upgrade with Dave Asprey.