我曾了解但不喜欢的尼古丁类似物:6-甲基尼古丁
A Nicotine Analogue I Had Known and Didn't Love: 6-Methylnicotine

原始链接: https://psychotechnology.substack.com/p/a-nicotine-analogue-i-had-known-and

## 6-甲基尼古丁:一种有前景但有缺陷的认知增强剂 6-甲基尼古丁 (6-MN) 是一种最近被推广为认知增强剂的尼古丁类似物,承诺提供更平稳、更持久的效果,并可能减少成瘾性。作者是一位尼古丁含片用户,为了在写作挑战中提高效率,测试了两种剂型:口含袋 (Sett 公司的 Ceretine) 和口香糖 (Chewbizz 公司的 Nixodine-S),两者都含有 6-MN *和* 80 毫克 L-茶氨酸。 虽然 6-MN 提供了刺激作用,但作者发现它不如常规尼古丁对专注工作有效,描述为一种精神上的空转感,却没有实际产出。它确实减少了肌肉紧张等身体副作用。体验各不相同——一位同伴作家感到躁狂和欣快,而一位 Reddit 用户则成功利用它来减少大量的 Zyn 习惯。 一个关键问题是缺乏独立研究;数据主要来自制造商。作者推测 6-MN 可能在某些受体上是部分激动剂,即使在较高剂量下也会限制其有效性。尽管有前景,作者得出结论,6-MN 并非尼古丁类认知增强剂的“圣杯”,而是提倡对尼古丁类似物进行进一步研究。

一个黑客新闻的讨论围绕着一篇Substack文章,标题为“一种我曾经了解但不喜欢的尼古丁类似物:6-甲基尼古丁”。最初的帖子引发了一段关于类似化合物的简短交流,一位用户指出标题提到了研究化学品TiKHAL和PiKHAL。 对话很快转移到加兰他敏,这是一种天然补充剂,因其促进清醒梦和认知增强而日益流行。一位用户报告称,服用加兰他敏后,记忆力、注意力得到提高,并且梦境体验增强,并指出其效果类似于尼古丁,*但*没有相关的紧张感,且持续时间更长。目前它在美国作为膳食补充剂销售。另一位用户询问了加兰他敏的使用体验,从而引出了详细的回应。
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原文

6-Methylnicotine is a sketchy analogue of the good old nicotine: a slight tweak of its structure, somewhat worse toxicity data, and very little public research. In the last few years, some US companies started making and marketing products containing the (S)-enantiomer.

I’m a big fan of sublingual nicotine as a nootropic — I wrote about two years of using nicotine lozenges in my post “A Love Song to Nicotine”. 6-Methylnicotine is marketed as “smooth, long-lasting cognitive enhancement without the peaks and valleys” and “less addiction potential compared to traditional nicotine products.”

I am very much attracted to the allure for increasing brainpower to better serve the global technocapital the readers of this blog — I am currently on Day 22 of Inkhaven, a 30-day workshop for writers where you must publish a blog post a day or you get kicked out. So of course I had to try it, for science™ and for writing productivity.

There are two companies that sell and market oral products with 6-methylnicotine:

  • Sett sells Zyn/Velo-style pouches with either 3mg or 6mg, branding it as Ceretine™

  • Chewbizz sells gum with either 2 or 4.7 mg, under Nixodine-S branding.

I tried both. As expected both have very similar effects.

Annoyingly, both products also contain 80 mg L-theanine — an amino-acid from tea that’s often sold as a standalone calming / anti-anxiety supplement. It’s the main reason tea hits smoother than coffee: counteracting the jitteriness of caffeine. People who take caffeine in pills sometimes stack with L-theanine.

Somehow both companies settled on the same exact dose to add to their products to sand down the rough edges of this new stimulant — to prevent anxiety and overstimulation.

80mg is not a huge dose. A typical supplement capsule contains 200 mg. Its oral bioavailability is ≈50%. We don’t have good data on whether sublingual/buccal use changes much, but at least we have a higher bound of 100%.

I still wish I could evaluate the pure compound. Some readers of this blog are thinking: “Bro, stop complaining about L-theanine already, just acquire tolerance to it over a few weeks, and then report back”. I got you, my brothers, sisters, and non-binary siblings in Christ. This is exactly what I’ve been doing over the last 3 weeks of Inkhaven.

I’ve been taking 600-1200 mg of L-theanine every night to calm down from using 2-3 different stimulants:

  • my ADHD prescription one, lisdexamfetamine (10-15mg daily)

  • caffeine (≈250 mg daily)

  • nicotine (5-12mg, 4.5 times a week)

A very sustainable lifestyle, I know.

I’ve tried 6-MN three times so far in doses of 9-12 mg consumed over 1-2.5 hours. Unfortunately, my hopes of finding a better cognitive enhancer for writing didn’t come true. The compound has some merits, but it’s a worse tool overall.

I’m buzzed and stimulated, but it’s much harder to apply this to anything productive writing-wise. It’s as if my mental engine is just spinning in idle without transmitting it to the gears of actual work. I also feel somewhat dissociated, like I’m watching someone else move the cursor, type words, open tabs on my laptop.

As soon as I swap the gum or pouch for a regular 2 mg nicotine lozenge, my productivity starts to pick up.

The primary advantage of 6-MN is less physical side effects. It’s a smoother experience, with less muscle tension. I suspect my blood pressure and heart rate might also be lower, but I haven’t measured either.

Caveats

  • I have ADHD, it might be more useful for someone without it.

  • I’ve built ~3× tolerance to nicotine over the last 3 weeks.

  • L-theanine — my tolerance to it blunted its effects, but I could definitely feel some

  • The different delivery systems (pouch/gum vs lozenge) are also confounders.

I gifted a tube of pouches to Gwern, a writer whose post on sublingual nicotine led to me using nicotine as a cognitive enhancer. His opinion: hard to distinguish from nicotine, feels more mild, not worth using given that it’s more expensive and much less widely used than regular old nicotine.

, a fellow Inkhaven resident:

I feel manic, focused, and euphoric. I ran across E Hall second floor a few times. I feel hot, but this could just be my space heater.

I can’t tell if my writing output / quality is better or not, I suspect it’s equivalent but would have to assess when not high.

Writing certainly feels more fun.

A reddit user used it to quit 2 tubes of Zyn a day habit (30×6 mg pouches, 180 mg/day):

I’ve been a degenerate 2 can a day user of Zyn 6mg for quite some time. [...] I switched to 100% Sett pouches on 9/19 with relatively minimal withdrawals and now only use like 4-6 of their 6mg pouches. Which was a massive reduction from using the Zyns. My heart rate has gone down 6 points and my blood pressure is better than what it was on nicotine.

The chart above comes from Sett’s website, where it functions mainly as marketing: trust us, we did the science™.

The X-axis is labeled “Log – Nicotine Equivalent” but the actual units aren’t specified. We cannot, unfortunately, precisely say “a 3 mg pouch corresponds to the –6 point on this curve”.

I asked GPT-5.1 to do some guesstimating. It says that the units for FLIPR are typically mol/L, and that plasma nicotine in regular smokers during the day is about 10–50 ng/mL, which is between -7.2 and -6 after you convert ng to nmol and take log10. This is where the curve for α4 and α3 gets above 1.0 nicotine equivalent. If there was a properly labeled chart, I would’ve spent time verifying the math and the sources, but for now I’m leaving this analysis as is.

The interesting bit is the α6 plot. The curve tops clearly below the 1.0 nicotine line, which suggests that it’s a partial agonist at this receptor. Can we “fix” worse α6 binding by taking a larger dose?

In On Trying Two Dozen Different Psychedelics I described how I liked to stare at receptor binding affinity tables for psychedelics. With psychedelics, you can’t really compensate for weaker 5-HT2a agonism by taking a higher dose: you might get a more intense experience, but it still lacks “depth.” My very speculative hypothesis is that something similar might be happening here — 6-MN just feels “flatter” and less effective than nicotine, even when the stimulation starts to get uncomfortable.

Take this section with a grain of salt. I wish we had proper data on this compound — this is only a single proprietary study by the company making a product with 6-MN.

In the same On Trying Two Dozen Different Psychedelics I described how I tried two dozen psychedelic. Most were Sasha Shulgin’s discoveries. Shulgin would modify existing known chemicals and then test the compounds on himself and his friends.

I wish there were a Shulgin-style research program for nicotine analogues. Nicotine clearly works as a cognitive enhancer for some people, but it’s also just the first nicotinic drug we stumbled on in nature. It seems likely that in the vast space of “things that hit nicotinic receptors” there are very interesting compounds.

Big Pharma unfortunately explores these compounds for smoking cessation and some neuropsychiatric conditions. Still, there are already compounds that could be interesting for cognitive enhancement, e.g. Varenicline, Cytisine and GTS-21.

I’m sure the nicotinic “holy grail” is out there. But it’s definitely not 6-methyl-nicotine.

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