Cholinergic agonists as a means to increase digestive drug absorption.

[Lightning-Nl]

Recently, I've noticed that after I take my Temazepam, or Xanax; if I have a cigarette or chew Nicotine gum, the effects of the benzo's will come on noticeably faster. Being that Nicotinic receptors are responsible for communicating muscular movement - it would stand to reason that the reason why I feel the drugs effect come on quicker is due to the fact that my digestive muscles are working more quickly due to increased Nicotinic activity. (If you don't agree, please explain).

So I started wondering if this same stimulation could be used as a possible means of increasing the absorption of a drug? Now, this is hard claim to make since both Nicotine and Methylphenidate are simulants. However, I've noticed that after taking a Ritalin IR, it's effects come on much quicker as well with Nicotine ingestion. Okay - this could easily be attributed to synergistic effects. However, if I smoke BEFORE immediately after I swallow the pills, the effects of the Ritalin can be felt for amuch longer period of time, and have a much higher peak.

Again, this could all be do to synergy of two stimulants. But, since I experienced the same effect with a drug (benzo) that has nearly the opposite effect of Nicotine (in fact, there's some evidence to suggest that Benzodiazepines may be direct Nicotinic antagonists - but that's not proven) it might stand to reason that Nicotine and therefore, any other Nicotinic agonist, would increase drug absorption.

What are other people's thoughts on this?

 

[St3ve]

I've noticed this with cannabis edibles... About 45min-1hour after ingesting them I can start feeling the high creeping in, I then usually feel an urge to smoke a cigarette. Within minutes from smoking that the effects of the edible kick in at full throttle.

Nicotine increases the resting metabolic rate by stimulating the digestive system, this is why you sometimes might suddenly need to use the toilet after smoking. I don't think nicotine would necessarily increase (total) drug absorption, but may help speed up the process by moving the compound through your intestines more quickly.

 

[endotropic]

Nicotine doesn't really do anything to affect gastric emptying, and might actually slow gastric emptying at high enough doses: Acute effect of nicotine patch on gastric emptying of liquid and solid contents in healthy subjects.

This study shows nicotine doesn't affect gastric parameters related to l-dopa absorption (although it inhibits absorption through a non-related mechanism): Effect of nicotine on the pharmacokinetics of levodopa.

Nicotine also reduces intestinal muscle tone, contrary to what you might have heard: Intra-luminal nicotine reduces smooth muscle tone activity in the distal large bowel.


So in my opinion it's unlikely that nicotine increases the absorption of oral drugs by affecting stomach emptying/intestinal motility. My guess for the interaction is that nicotine's stimulant effects make you more aware/attuned to the other drug effects.

 

[sekio]

Nicotine is also known to synergize with many other drugs by promoting dopamine release in the nucleus accumbens. I think this is partly why you'll see polydrug users often want a cigarette after imbibing their drug of choice. (Just smoke a joint? Need a cig. Coming up on E? Need a cig. Just did some lines of coke? Better have a smoke. etc)

 

[chicken hoagie]

This is easy discussion...Nicotine sensitizes the reward system in the brain in general..Meaning, anything you take, even food or a bike ride, intaking niicotine afterwards will result in increased satisfaction (increased extracellular dopamine release). Accompanying compounds in tobacco are Harmaline and Harmala - MAO inhibitors that also increase extracellular levels of neurotransmitters (dopamime, acetylcholine, nor-epinephrine, modestly serotonin, etc.). Together, all of these alkaloids in tobacco make it for a very potent drug-enhancer for all types of drugs that raise these neurotransmitters as well..As well as any life activity. BUT, the withdrawal from addiction is the kicker as always...So you will of course, experience the opposite when withdrawing.


I also speak for myself when I say that chewing tobacco is the ultimate shit-inducer by FAR.

 

[Seppi]

It's actually muscarinic agonists that will increase gastrointestinal motility. There's an unusual link between muscarinic receptors and a calcium-activated chloride channel called anoctamin 1 throughout the GI tract; anoctamin 1 is paired with and modulates the gastrointestinal pacemaker cells called the "interstitial cells of Cajal." In a nutshell, if you take enough Carbachol down the hatch, you should be prepared to explosively squirt liquid shit out of your ass.

 

[Lightning-Nl]

It's actually muscarinic agonists that will increase gastrointestinal motility. There's an unusual link between muscarinic receptors and a calcium-activated chloride channel called anoctamin 1 throughout the GI tract; anoctamin 1 is paired with and modulates the gastrointestinal pacemaker cells called the "interstitial cells of Cajal." In a nutshell, if you take enough Carbachol down the hatch, you should be prepared to explosively squirt liquid shit out of your ass.

That explains why smoking acts as an excellent laxative (at least I've found it has) since it induces massive ACh release through Nicotinic agonism.

 

[ebola?]

since it induces massive ACh release

No it doesn't. Rather, nicotine mimics ACh at the receptor subtypes it agonizes.

ebola

 

[Lightning-Nl]

No it doesn't. Rather, nicotine mimics ACh at the receptor subtypes it agonizes.

ebola

Actually it does. Beyond that - it causes a massive increase in Glutamate release, Dopamine Release, Epinephrine/Norepinephrine release, a bit of Serotonin release, enkephalin release, endorphin release, etc.

C'mon ebloa. I know that you're just using common sense - but common sense isn't always correct. Especially since ACh is the mediator of many functions in the body. Such as positive feedback looping Dopamine release and ACh release - and directly causing the release of adrenaline from the kidneys through Nicotinic Agonism.

 

[ebola?]

Interesting. I stand corrected. It's also intriguing that this release is physiologically localized to the hippocampus and mediated by at least two mechanisms (one dopaminergic, one not).

ebola

 

[Lightning-Nl]

I've noticed this with cannabis edibles... About 45min-1hour after ingesting them I can start feeling the high creeping in, I then usually feel an urge to smoke a cigarette. Within minutes from smoking that the effects of the edible kick in at full throttle.

I've noticed this as well. However, personally, I believe that the craving for a cigarette when you've smoked weed is due to the fact that CBD inhibits Acetylcholinesterase. Which causes a massive increase in ACh neurotransmission. It's also the reason why your heart rate soars when smoking weed, why you feel dizzy, and why your muscles become very jittery.

 

[Zilpe]

I've noticed this as well. However, personally, I believe that the craving for a cigarette when you've smoked weed is due to the fact that CBD inhibits Acetylcholinesterase. Which causes a massive increase in ACh neurotransmission. It's also the reason why your heart rate soars when smoking weed, why you feel dizzy, and why your muscles become very jittery.

Either that or it's your brain remembering that smoking a cigarette while high feels really good for the reasons discussed above.

 

[Lightning-Nl]

Either that or it's your brain remembering that smoking a cigarette while high feels really good for the reasons discussed above.

I should have mentioned that. Increased cholinergic activity would result in the remembrance of heighten Nicotinic activity produced by Nicotine. Which would, therefore, cause you to feel the impulse to smoke.

 

[AlphaMethylPhenyl]

But of course, nicotine and cigarettes are two different animals.

 

[Lightning-Nl]

But of course, nicotine and cigarettes are two different animals.

Very true. Cigarettes contain hundreds of active chemicals, while Nicotine... is just Nicotine. That's what people don't understand. Sure Nicotine in itself, is addicting. But the fact that people say it's 'highly' addicting is just ridiculous. Nicotine, in itself is not very addicting at all. Cigarettes on the other hand... are.