CRF-1 receptors and nicotine withdrawal

[ProducedRaw]

This paper states that during nicotine withdrawal, CRF-1 receptors are agonised and lead to increased stress levels which in turn lead to relapse:

George et al. (3) report that (i) precipitated nicotine withdrawal in rats increases CRF levels in the central nucleus of the amygdala; (ii) precipitated withdrawal increases anxiety-like behavior through activation of CRF1 receptors; (iii) cessation of nicotine exposure in rats previously exposed to nicotine increases nicotine self-administration; and (iv) antagonism of CRF1 receptors prevents “abstinence”-induced increases in nicotine intake. This series of experiments provides strong support for the idea that CRF1 is involved in the biology and behavior of nicotine withdrawal, including negative reinforcement (i.e., offsetting the unpleasantness of cessation) and relapse (i.e., a return to self-administration). In other words, nicotine withdrawal is indeed a stressor that acts via the CRF–CRF1 system, which in turn results in increased nicotine self-administration to offset stress. This finding also suggests that pharmaceutical interventions should be developed to intervene in the stress system, to attenuate withdrawal-induced smoking relapse.

I've found three CRF-1 antagonists - Antalarmin, CP-154,526 and Pexacerfont. Has anyone tried using these to combat nicotine withdrawal or am I going to have to be the guinea pig?

 

[sekio]

Unless you're working for a university or under FDA supervision, I wouldn't advise eating almost totally untested chemicals.

 

[ProducedRaw]

Fair enough, I'll wait until more testing has been done. This does seem to have the potential to be a silver bullet for nicotine addiction though, which is an exciting prospect.

 

[ProducedRaw]

Might aswell lump this into the same thread -

I was exploring the feelings brought on by nicotine withdrawal last night and noticed that it reminded me a lot of Salvia, namely the uncomfortable anxiety and sweat. After some googling, I found this study which confirms that kappa-opioid receptors are activated during withdrawal and that antagonising them will help with smoking cessation. Unlike CRF-1, this receptor isn't so novel so the antagonists (Norbinaltorphimine, 5'-Guanidinonaltrindole, JDTic) should be safer to use. Has anyone tried this and will I be OK, health-wise, taking any of those antagonists?

 

[Hammilton]

shouldn't be any major problems, but obtaining them won't be easy- or cheap.

I'm not aware of any major issues associated with kappa antagonists. In fact, buprenorphine is a kappa antagonist.

 

[ProducedRaw]

In fact, buprenorphine is a kappa antagonist.

I noticed that too but I have some qualms about using a mu agonist to quit smoking since I don't want to exchange one addiction for another.

 

[Limpet_Chicken]

Isn't the primary metabolite of buprenorphine, norbuprenorphine a KOR agonist, though? seems that would make bupe less effective for that purpose.

 

[Coolwhip]

I wouldn't worry much about norbupe's kappa agonism at any dosage he would be taking bupe at.

If you really wanted to try, you could take a large dose of naltrexone, followed by a small dose of buprenorphine, and kappa antagonism should be what is left.

Although I really don't think it is going to help as much as you hope.

 

[ProducedRaw]

Unfortunately I'm too broke to order exotic antagonists at the moment but I finally found some cheap and effective nicotine withdrawal aids. Bupropion is a norepinephrine-dopamine reuptake inhibitor and is used as a quitting smoking aid with decent levels of success - so how can we reproduce those effects with minimal side effects, no script and at a low cost? The answers are L-Dopa (for increasing dopamine levels) and Rhodiola Rosea (for stimulating serotonin, norepinephrine and dopamine activity). I've been smoke free for 10 days now and while the first 5 were difficult to weather due to the physical symptoms, I've hardly had any cravings! Normally, I'm one of those types of people who break down and buy a pack on the second day so this has been a pleasant surprise. I'm using 1.5g of Rhodiola Rosea per day and as much L-Dopa as needed (initially up to 120mg/day, now 45mg/day), in the form of Mucuna Pruriens tablets. To address the CRF-1 activity, I've been supplementing with magnesium (up to 1g/day for the first few days, now down to ~300mg/day) since that is known to stave off stress related symptoms. I also found 5-HTP to be very effective in combatting the irritability that comes with the withdrawal.