This disproves my suggestion that 2 mg might increase HRV, but I was looking for 1 mg rather than 2. The 2 mg gum is still plausibly a higher dose than a 7 mg patch. I'm struggling to find studies in the lower doses. This may be because everyone wants to prove the harm of nicotine. There may even be publication bias (especially if there's no effect).

This was with a 14 mg patch. A 21 mg patch would probably reduce HRV given that a 4 mg lozenge does so.

I still expect to find enhance HRV with 7 mg. This study supports that hypothesis to an extent. That it, it shows that 14 mg may be the tipping point between increased or decreased HRV from nicotine.

Assuming a half life of two hours, I calculated a 7 mg per day patch delivers a peak dosage of around 0.8 mg. Given that a 4mg lozenge has a bioavailability of 79%, this is equivalent to a 21 mg patch.

Given that we know anything above a 7 mg patch disrupts sleep (while 7 mg enhances sleep), it's unsurprising that HRV was reduced. I expect that a 1 mg lozenge or gum would increase HRV. Given that the above citation lists the bioavailability of a 2 mg lozenge at 50%, 2 mg may also increase HRV.

I'll need to review this later. This is a more precise figure than I was familiar with. I think I read somewhere between 20% and 50%; I believe I cited that figure in one of my college papers.

As expected. This study was placebo controlled, too.

This is supported by a single-blind study on nicotine for akathisia.

I'd be interested to see the effect of a 7 mg patch. 14 mg is too high for sleep, so I wonder if it is also too high for akathisia.

Data like this seems to be definitive proof that nicotine is nothing like tobacco. I'm not aware of any evidence that nicotine itself is addictive, save for a few anecdotes. I don't put much stock in these anecdotes because people also report habit-withdrawal symptoms when they quit zero nicotine e-juice. That is to say, without placebo controls we cannot conclude drug withdrawal is the cause because it can also be explained by psychology.

That said, I'm reasonably certain that nicotine contributes to tobacco addiction. While I think nicotine is fairly non-addictive, I believe it enhances the addictiveness of other drugs. I think this is partly due to an entourage effect that alters the high, and also a memory-enhancing effect so one remembers the high more vividly.

Sounds like withdrawal. Why is information like this so hard to find?

This is what I'd expect for tobacco, but it tells me little about nicotine. Most of the subjective effects are not from tobacco, so It's still plausible that nicotine does not develop tolerance. Indeed, the effects that don't go away are the effects expected from nicotine.

They mention abstainers below. It appears that they are saying that there is memory improvement compared to complete non-smokers. Will need to check actual study. Note that my interest in nicotine is confounded by the use of tobacco.

Edit: eyeballing the graphs, it appears that the tobacco group did the best, while the marijuana plus tobacco group did the worst. Given the small sample size and high variability, these are not statistically significant. Nonetheless, that suggests that marijuana never benefits memory. Edit: eyeballing the graphs, it appears the tobacco group did the best, while the marijuana plus tobacco group performed worst. Given the small sample size and high variability, these results are not statistically significant. Nonetheless, it suggests that marijuana is never a benefit to memory.

Note that nicotine by itself had minimal impact on the microbiome. Nicotine speeds up transit through the intestine. Thus, the reason nicotine plus a high fat diet was detrimental is likely that nicotine is increasing the throughput of harmful prebiotics (e.g. protein in particular). When lots of fiber and resistant starch is present (will need to see if they provide this info for their diets), then nicotine mostly just carries it to the small intestine faster (and possibly reduces fermentation time).

Given that opioids have a negative effect on the microbiome, I was expecting nicotine to have a positive effect. Perhaps it would have a positive effect were there more resistant starch in the diet.

This is interesting!