Research on CBD and Nicotine Addiction, Withdrawals, and Tolerance

CBD and nicotine addiction withdrawals and recovery


It's a rivalry.


Which is the oldest addiction...alcohol or tobacco?


Either way, they both share the dubious distinction of being the most common addictions in the world.


Interestingly, there's a hidden pathway behind how nicotine works in the brain which helps to shed a lot of light on why people may be drawn to nicotine, to begin with.


Hints from mental health issues such as schizophrenia also point to this pathway.


We'll get into all of that but more importantly, what does research show for CBD's effect on tobacco addiction, withdrawals, and tolerance?


We already did a master review on CBD and addiction pathways here.


We're not going to cover basic facts...we're diving deep to the heart of what drives nicotine addiction.


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Let's zoom into these areas specifically: 

  • Nicotine and the brain
  • Nicotine and acetylcholine
  • Nicotine and dopamine
  • Nicotine and glutamate
  • Nicotine and tolerance
  • What causes nicotine withdrawals
  • Research on CBD and nicotine addiction, withdrawals, and tolerance
  • How much CBD for nicotine addiction recovery
  • What's the best CBD for nicotine addiction recovery


Let's get started!

Nicotine and the brain 

Before we jump into the players involved, let's introduce the stage.


We have critical pathways in the brain that allow us to function correctly when at a balanced level.


It's very complicated and they're all interwoven.


That doesn't mean we can't piece out how addiction to nicotine works in the brain.


There are two critical steps to look at: 

  • Initial response to imbalances in a pathway
  • Repetitive "learning" process of addiction due to dopamine


Most people have tried a cigarette.


Why do the mass majority never really go back while a percentage fight quitting for years or decades?


In fact, most people quit using addictive drugs.  Interestingly, nicotine users have the longest durations before being able to quit.


The fascinating point is that all the addictive drugs usually hit one of these key pathways PLUS dopamine (we'll explain later).


For example: 

  • Benzos - boost GABA, our brain's "brake" pedal
  • SSRIs - boost serotonin, our master orchestrator - the so-called "feel good" neurotransmitter
  • Alcohol - boosts GABA and serotonin (no wonder it's so prevalent)
  • Opioids - boosts our natural opioid system
  • THC - boosts anandamide, our stress response buffer
  • Cocaine - boosts dopamine and downstream norepinephrine


What about nicotine?


Hello, acetylcholine!


You probably haven't heard of that one but it's a big deal in the brain.


We'll dive into later but if a person has low acetylcholine due to genes, environment, diet, etc may feel like nicotine is filling a hole in perfectly.


Like a great meal when you're really hungry.


That's the first piece.  Essentially, self-medication.


The second piece occurs with repetition.  


Let's introduce dopamine!


It's our "do that again" chemical which guides the reward circuit.


This circuit is exactly what you would think...encourage behavior that improves our chances of survival and thriving.


It's usually tied with food, water, and sex...remembering where a great watering hole is, etc.


Memory figures into this and it guides the process of learning.


This "learning" is key to relapse and recovery!


We have to "unwind" or unlearn the addiction pathway which is built up from repetition literally into the structure of the brain.


The key here is a term called neurogenesis which literally means to build new pathways and overwrite old ones.


That's the stage of nicotine addiction...let's jump into the players.

Nicotine and acetylcholine 

It doesn't roll off the tongue.  GABA is so much easier to wrap around!


So, what is acetylcholine?


Oh, just this: 

The brain contains a number of cholinergic areas, each with distinct functions; such as playing an important role in arousal, attention, memory, and motivation.


So, just arousal, attention, memory, and motivation.


See why someone running low might be drawn to nicotine?'s the process of being engaged with right now!


Nicotine happens to imitate the neurotransmitter acetylcholine and binds to those receptors (specifically those known as the nicotinic receptors).


Research is here.


In fact, genes tied to these receptors are directly implicated in risk of nicotine addiction: 

Human genetic studies have identified polymorphisms in nAChR genes, which predict vulnerability to risk for tobacco dependence.


Remember the mention of schizophrenia above where many sufferers are chronic chain-smokers?


That disease is marked by a significant deficit in acetylcholine function in the prefrontal cortex which is tasked with cognition - planning, organizing, etc.


They are essentially self-medicating.


Interestingly, why do people both alert and calm with nicotine?


Acetylcholine is the neurotransmitter for our parasympathetic nervous system.


This is the rest and digest part which generally speaks to a relaxed state.


That's just the tip of the iceberg.


Memory directly relies on choline.  There's a huge swath of studies on choline and Alzheimers.


By the say, estrogen directly drives acetylcholine which is why women start to see a decline in memory and Alzheimers after they lose their estrogen (See estradiol review or CBD and estrogen).


Muscle movement also relies on acetylcholine.  Your entire vascular tone does as well (via nitric oxide release).


We could go on and on but we're really focused on the brain and nervous system.


How you feel!  That's where nicotine has its immediate effect via acetylcholine.


Not only does acetylcholine govern your background operation (heart rate, blood pressure, digestive movement, etc) but it's directly tied to the other end of the spectrum.


Higher executive function!


This is what makes us humans and not apes.  The area behind the forehead called the prefrontal cortex where we plan, strategize, organize, and all the things people generally get a cigarette before doing.


See how it's all coming together.


Proper acetylcholine function leads to calm, cool, and collected.


No wonder some people might self-medicate if running low.


As we said before: 

The primary addictive component identified in tobacco smoke is nicotine, which exerts its behavioral effects via interaction with nicotinic acetylcholine receptors (nAChRs).


Goodness.  Now we've peeled back the curtain on what starts the love affair.


Let's bring in the sex now.  Dopamine.

Nicotine and dopamine 

That last statement on sex was not just tongue and cheek.


Dopamine governs the reward for food, water, and


Anything that moves towards genetic survival.


It's net effect is.."Do that again".


Dopamine guides learning as a result of this.  Learn what works for survival and do it again.


Rinse repeat.


Here's the deal...any addictive drug has to also hit this pathway.


Broccoli isn't addictive because it doesn't really ping the dopamine system that hard.  


Sugar and fat, much more.


Nicotine?  Through the roof.


You can't really have addiction without dopamine and reward circuit.


Interestingly, this is where the hard-wired, long term effects of addiction operate.


This is why you can feel the need for a cigarette years or decades after quitting.


We're talking about literally structural changes in the brain.  Think of a river established by running water (dopamine).


If the water goes away, the river bed is still there and if water runs, it flows right back along the same path.


Check out our review on CBD and dopamine for addiction.


As for nicotine and dopamine, does the pattern hold?


Nicotine was found to markedly increase the firing rate of both groups, although the dopamine neuronal response pattern was considerably different and more vigorous than that in the non-dopamine neurons.


Here's the, water, and sex cause a dopamine rush but nothing close to what addictive drugs like nicotine cause.


They supercharge this response!  Also, the brain isn't able to quickly breakdown nicotine the way it's able to with acetylcholine.


Many neurotransmitters are made as needed and quickly broken down.


The brain doesn't know how to do this with nicotine so it lasts longer and at a higher level.


Hello, addiction!


One final stop you may not have heard of.


Where new research is pointing.

Nicotine and glutamate 

Glutamate is our brain's "gas" pedal.


That seems appropriate when considering nicotine but it's also key to addiction.


This is based on the newest research which coming to this conclusion.


We did a full review on CBD and glutamate as well as NAC (n-acetyl cysteine) and addiction.


NAC is showing impressive results for mental health and addiction (they're both intertwined as we showed above with deficient pathways).


To put a point to it: 

Evidence suggests that blockade of glutamatergic neurotransmission attenuates both nicotine intake and nicotine seeking.,(Mansvelder%20and%20McGehee%202002).&text=In%20summary%2C%20acute%20nicotine%20administration,located%20on%20presynaptic%20glutamatergic%20terminals. balancing glutamate activity, both consumption and craving of nicotine goes down.


The opposite is true for GABA, the brain's "brake" pedal which is directly opposed to glutamate.


The net net...balance of these key pathways is essential for recovery.


After all, when they try to work on nicotine addiction by just addressing acetylcholine, the results are very poor.


It turns out that acetylcholine receptors are all over the pathways of glutamate and GABA which makes sense if you look at acetylcholine's effects (learning, arousal, focus, etc). 


Nicotine and tolerance


Why addiction?  Why not just casual use and you're done?


A big part of this equation is tolerance.


Tolerance is the process of the brain offsetting an outside chemical by pushing back in the opposite direction.


One cigarette won't do it (really) but a few months of chronic smoking definitely will.


To recap...nicotine juices both acetylcholine and dopamine.


This can feel good especially if you're already low.


Dopamine's going to feel good no matter what.


With repeated use, the brain starts to downregulate both pathways.


After all, those are naturally occurring chemicals in the brain.


Eventually, a cigarette just makes you feel average (as before you ever smoked).


With enough smoking, you're just trying not to feel bad since your natural systems have been ratcheted down.


The 100th cigarette won't feel as good as the first but much better than the 1000th.


This is the process of tolerance and all addictive drugs have this effect.


Interestingly, studies show the effects go right down to the DNA where proteins for these receptors are turned down or off.


The key to reversing this and rescuing these pathways is neurogenesis which we'll discuss below.


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It makes it very tough to get off of nicotine and leads to our next section...withdrawals.

What causes nicotine withdrawals

Remember how we looked at why some people might be so drawn to nicotine...reduced acetylcholine function.


Now imagine it's even lower than that point due to tolerance!


This gives nicotine powerful control over how we feel.


More importantly, nicotine withdrawal is dopamine.


Remember, it's the "do that again" neurotransmitter.


Dopamine is a master of learning and it has modified the brain to look for, get, and reward nicotine.


This is now hardwired into the brain itself.  Physical structures and connection.


Natural dopamine levels are also downregulated since the body is constantly juiced with unnatural levels from nicotine.


The withdrawal effects come from both a reduced level of both acetylcholine and dopamine as well as the reward circuit not being stoked by nicotine.


The key here is "salience".


That's a technical term for what the brain feels is important for all the competing things before you.


Dopamine drives this focus and it's been primed for nicotine now.


Dealing with withdrawals requires both a short term and long term approach.


We'll touch on that below in the recovery piece but we have calm down initial symptoms of withdrawal which come from lowered acetylcholine and dopamine while juicing up the ability of the brain to "unwind" the nicotine reward pathway.


That last part is neurogenesis!


Let's get to the reason you actually came here.

Research on CBD and nicotine addiction, withdrawals, and tolerance 

Let's first look at research specific to CBD and nicotine and then we'll drill into the pathways mentioned above.


We'll cut to the chase.


A double-blind, placebo, and randomized study of smokers looked specifically at nicotine: 

In contrast, those treated with CBD significantly reduced the number of cigarettes smoked by ~40% during treatment.


Interestingly, the effects continued at follow-up 2 weeks later after the original study.


What is driving this long term effect?  We'll get to that in the neurogenesis piece below.


Another study looked at nicotine cravings when presented with cues between placebo and CBD: 

However, CBD reversed this effect, such that automatic AB was directed away from cigarette cues (P = 0.007, d = 0.704) and no longer differed from satiety (P = 0.82).


Okay, let's break this down.


Basically, they looked at the power of various cues (the start of the reward circuit from above) after a period of abstinence or not smoking.


Cravings would increase for people with the placebo but not with people who had the CBD.


In fact, the desirability was the same after abstinence as with right after smoking (sanity).


CBD also decreased the pleasantness of cigarette images.


This speaks to salience...where dopamine is guiding our focus.


What's important right now!


So...reduction in actual cigarettes consumed, pleasure from the triggers for smoking, and focus on smoking.


These effects were long term.


What's going on here?


Let's drill down since you were so patient with the pathways of nicotine addiction above. 

  • CBD and acetylcholine for nicotine addiction
  • CBD and dopamine for nicotine addiction
  • CBD and glutamate for nicotine addiction
  • CBD and neurogenesis for nicotine addiction
  • CBD and salience for nicotine addiction


First, the neurotransmitters.


CBD and acetylcholine for nicotine addiction.


We looked at how acetylcholine comes in play above with nicotine addiction and even the genes tied to risk.


So...what's CBD effect there?


First this one: 

Here, we demonstrate that systemic injections of CBD (0, 5, 10 or 30 mg/kg, i.p.) at the beginning of the lights-on period, increase the extracellular levels of ACh collected from the basal forebrain and measured by microdialysis and HPLC means.


Did you notice the "during light on" part?  


Acetylcholine is tied to arousal, focus, and….day time!


We wrote about this in our "Can I Take CBD in the middle of the day" review.


Interestingly, the effects of CBD differ depending on the time of day.


It can also support sleep (see CBD and sleep) at night.


How does CBD have this effect?


We have to go upstream to serotonin for that.


Studies are showing that serotonin (our master regulator) governs acetylcholine.  It can boost or inhibit acetylcholine depending on brain area and situation.


CBD's effect on balancing serotonin is well established and maybe it's the greatest trick.


Check out CBD and serotonin to learn more.  


Tied into this whole process and addiction itself is dopamine.

CBD and dopamine for nicotine addiction 

Balancing and even rescuing dopamine is critical with nicotine addiction.


Remember, this is the linchpin for our reward circuit and it's been severely turned to rewarding nicotine intake.


We have a whole review on CBD and dopamine since it's so important.


The studies on CBD and schizophrenia (with dopamine being a major player) are fascinating but we have more targeted info for addiction.


We need to dig a little deeper into the endocannabinoid system.


One of our primary endocannabinoids called anandamide.  It generally acts as a stress responder.


Studies are showing it's intimately tied to various aspects of addiction.  An enzyme called FAAH breaks down anandamide.  


Look what happens when you block it: 

FAAH inhibitors have been shown to reduce nicotine self‐administration and conditioned place preference (CPP) in rats and monkeys as well as nicotine‐induced dopamine release in the nucleus accumbens


Guess what acts in this fashion?




CBD also inhibits FAAH, which results in increased anandamide levels.


Check out FAAH and the woman who can't feel, pain, anxiety, or depression.


This speaks to the study above where nicotine lost it's preferred status among smokers even when craving it.


Again, check out CBD and dopamine for more detail.


Next up...glutamate.

CBD and glutamate for nicotine addiction 

This is where all the new research is going for both addiction and mental health.


It's intimately tied in with than none-other-than...acetylcholine: 

In summary, acute nicotine administration increases the release of glutamate via excitatory nACh receptors located on presynaptic glutamatergic terminals.,(Mansvelder%20and%20McGehee%202002).&text=In%20summary%2C%20acute%20nicotine%20administration,located%20on%20presynaptic%20glutamatergic%20terminals.


We wrote about how CBD has a powerful effect on glutamate and GABA balance.


In summary: 

CBD has multiple targets, but one aspect of its polypharmacy may be to help regulate excitatory glutamate (E) and inhibitory γ-aminobutyric acid (GABA) (I) transmission, which may influence the activity of excitatory and inhibitory signaling pathways.,facilitates%20glutamate%20and%20GABA%20neurotransmission


"Regulate" - that's the keyword.


Let's finally get into what we can do about it.  Why might CBD help?

CBD and neurogenesis for nicotine addiction 

This is the most important section you'll read.


It's the key to unwinding anything.


Here's why this process is so important: 

  • Rescuing receptors and pathways for acetylcholine and dopamine
  • Unwinding existing "structure" tied to nicotine reward circuit
  • Creating new pathways for long term recovery


All new revolutionary research is pointing to this.


CBD's effect is pronounced here.


An interesting study on reversing the effects of THC point to this: 

Associations between greater right subicular complex and total hippocampal volume and higher plasma CBD concentration were evident, particularly in heavy users.


Notice the brain area...the hippocampus.


This is the intersection between memory and mood control.


In fact, it's anti-anxiety and anti-depression effects rests on this neuron repair and growth: 

preclinical studies have shown CBD to induce synaptic plasticity and facilitate hippocampal neurogenesis,29,30 with some evidence suggesting that the proneurogenic action of CBD via the hippocampus may underlie its anxiolytic effects.


We have a whole section on CBD and neurogenesis or brain repair.


The great news is that this points to how much CBD for nicotine addiction.

How much CBD for nicotine addiction recovery 

Let's break this down into two phases: 

  • Initial withdrawal symptom phase
  • Longer-term pathway rescue for dopamine and acetylcholine


These may be quite different.


Studies on more acute issues (public speaking, schizophrenia, etc) point to higher levels of 600-800 mg per day.


This might just be the first few days after quitting where withdrawal symptoms are the most extreme.


Remember that the acetylcholine and dopamine systems will be ratcheted down significantly.


That's what underlies withdrawal symptoms.


At this point, we're just trying to minimize the core symptoms which CBD has shown results on separately: 


Once the initial withdrawal symptoms start to subside, we can look at long term rewiring of the reward circuit carved out by nicotine use.


Research here points to 300 mg per day as the peak level for neurogenesis.


Exercise and mindful meditation (check out Calm app) also boost this pathway.


This is the key to rescuing the receptors (dopamine and acetylcholine), allowing the nicotine pathway to wither, and rewriting new pathways.


This may be 2-8 weeks depending on the length of use, state of your system, etc.


Check out CBD and BDNF or CBD and brain repair to dive deeper into this process.


It's popping up in research across mental health and addiction as THE key.


Also, check out our review on psilocybin (from magic mushrooms) which will probably throw the whole addiction arena.


50 years on hold!


What about the type of CBD?

What's the best CBD for nicotine addiction recovery 

We first have some basic requirements to avoid the junk out there (of which, there is plenty): 

  • Organically grown in the US at an FDA registered farm
  • 3rd party tested
  • CO2 processed
  • THC free - THC actually makes other drugs like nicotine or alcohol more pleasurable
  • No pesticides
  • No solvents
  • No heavy metals
  • No bacteria
  • No mold


We actually test our CBD twice since our whole family uses it daily (at the 300 mg level for long term brain support).


Then there's the question of CBD isolate versus full spectrum.


All the research including dozens of NIH studies referenced across our site is based on CBD isolate.


There's almost no research on full-spectrum that everyone's pushing online.


More importantly, roughly 40-60% of people have histamine issues and you see it our reviews.


People will try full-spectrum, have bad side effects, and then switch to isolate at which point they go away.


This number goes up for women and as we get older.


That's why we focus on CBD isolate - it actually matches the research and hopefully it's clear that we base everything on research!


Finally, there's the cost.


The dosages used in the studies above are generally around 400 mg per day.


The cost per mg of CBD is the key driver there and our 6000mg is priced at about 2-3 cents per mg BEFORE discounts.


It's the best pricing on the market for 3rd party tested CBD isolate.  


That's for a reason.


We found CBD when coming off of benzos and SSRI's following a brutal perimenopause (our story is here).


It was one of the toughest things we had to deal with and CBD got us through it.


We don't want cost to prevent people from getting off of nicotine as well.


Hopefully, now you see you have some powerful allies in this endeavor.


Also, check out NAC review for addiction here.


CBD and NAC combined could be powerful tools across all addiction and recovery!


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Always work with a doctor or naturopath with any supplement!

The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.



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