A Comprehensive Look at CBD and the Pathways of Addiction
We've been working towards this point.
We also just wrapped up a 5000+ word review on NAC and mental health with a whole section on addiction.
It's time to turn our attention to the research on the broader topic.
What does research show for the broader field of CBD and addiction?
Are their shared pathways across different substances or is each unique in its means of action.
Looking at NAC and a shared connection with THC, we also want to look at the question of why some people are susceptible to addiction, to begin with.
Are the drugs filling some holes in various pathways?
These are the areas we'll touch on:
- An updated view of the addiction process
- A quick look at brain areas and addiction
- Addiction results in specific changes in brain function
- Neurotransmitters and addiction
- Compulsion and Risk-Taking behavior
- Neurogenesis and addiction
- Glutamate and Addiction, the New Kid on the Block in Research
- Can CBD help with addiction
- Studies on CBD and addiction
- Does CBD help with cravings
- CBD and THC or cannabis addiction
- CBD and alcohol addiction
- CBD and opioid addiction and withdrawal
- CBD and nicotine addiction
- CBD and amphetamine and cocaine addiction
- Can you become addicted to CBD
- CBD and drug withdrawal
- CBD and drug tolerance
- How much CBD to take for addiction
- What's the best CBD for addiction
An updated view of the addiction process
We're way past the point of calling drug addiction a lapse in self-control.
There's a great deal of research now underpinning the actual biology of not only the process of addiction but why some people may be more prone to it.
Drugs or alcohol can hijack the pleasure/reward circuits in your brain and hook you into wanting more and more.
Don't worry, we'll drill down into those brain areas (not literally, mind you!).
Let's first sketch these broad views of addiction:
- Addiction is a form of learning
- Risk for addiction can be due to genetics, mental health, environment, and trauma
- Addiction results in specific changes in brain function
First the learning part.
Our brain is wired to learn new things. The primary carrot of this system is dopamine.
Dopamine is the main neurotransmitter for our reward system.
Interestingly, there isn't pleasure associated with dopamine (that's the opioid system and even anandamide, an endocannabinoid named after the Hindu word for "bliss").
It's simply "do that again".
What does this have to with drugs that lead to addiction as opposed to broccoli?
They have a side trick of rewiring the dopamine pathway to make them the subject of most reward.
Above all other things!
Step back and think about what reward circuits in the brain really are there for.
They're to encourage learning.
Go back a few million years. This spot is good for food...remember it.
This berry tastes good...lock that into memory.
The reward circuit is generally a nudge towards something that's good for our survival.
We'll look at the specific pathway (dopamine) and area of the brain (nucleus accumbens) later but addictive drugs are able to push on this button.
THAT'S their secret! We'll look at how to unwind this effect later.
Some of them even have the ability to downregulate our ability to "unlearn" or rewire the brain.
The term for rewiring is called neurogenesis and figures big into CBD's effect.
Just remember, you can learn bad things as well as good.
It's why teenagers are so at risk for the initial stages of drug addiction.
Their brain's learning systems are hyperactivated while their impulse control unit (prefrontal cortex) is down for remodeling.
A potential bonanza for drug addiction.
What about risks associated with drug addiction?
Risk for addiction can be due to genetics, mental health, environment, and trauma.
Why can one person pick up a drink and that's the end of it while another is facing a lifetime of a fight?
Let's start with the biology...genetics.
There are specific genes now showing ties to risk for addiction in research.
Needless to say, this is early years for genetics but there are clear ties with risk which point to downstream pathways we can discuss below.
Just one example of many.
COMT and addiction
This is a great clue we can use below.
COMT, simply put, is a gene that governs the removal of various neurotransmitters with the big one for our discussion being dopamine!
Too little activity and dopamine might build up. Too much and we might have reduced levels of dopamine.
Both situations are bad as can be said with any of the master-regulator neurotransmitters (serotonin comes to mind).
The tie in with addiction is linked with early adolescent stress:
When looking at the COMT gene Lovallo discovered there is an interplay between a person’s genes and addiction because of adversity during childhood.
This makes sense as genes are highly influenced by the environment, the so-called epigenetic markers that our history has on our actual genes!
People with this mutation are susceptible to early-life stress.
There are other genes tied to GABA, glutamate, serotonin, how we process alcohol, etc that all influence addiction risk.
Downstream, we'll see these same players in our neurotransmitter section so just know that there's some biology preset (genetics) which is molded over time (environment).
It's estimated that a good half of the risk is tied to genetics:
A person’s genes play an important role in addiction and might account for 40-60 percent of addiction risk
The rest being the environment of course.
Genes tied to impulsivity, risk-taking, and stress response all figure prominently.
They also share a great deal in common...serotonin function and genes have been found in that pathway tied to addiction.
Let's look at that "molding piece now".
Environment, trauma, and addiction
As we saw with the COMT gene example, it required early life adversity to really bring out its addiction risk component.
Exposure to traumatic experiences, especially those occurring in childhood, has been linked to substance use disorders (SUDs), including abuse and dependence.
This is the epigenetic piece where the layer just above genes changes over time.
It doesn't have to just be trauma, however.
Peer influence can affect addiction outcomes as well:
Studies suggest that an animal's drug use can be affected by that of its cage mate,4, 5 showing that some social influences can enhance risk or protection.
A range of risk factors are present including:
- Age of initial use
- Family life
- Early life trauma and stress
- Peer use
There's a good review here:
Finally, the big one that needs addressing. Mental health issues.
Interestingly, genetics and early life trauma both figure into mental health issues as well!
In many ways, addiction and mental health issues may be co-conspiring from the same well of genetics + environmental effects.
Aggregate analyses demonstrated significant prospective risks posed by baseline mental disorders for the onset of nicotine, alcohol, and illicit drug dependence with abuse over the follow-up period.
In the end, there may be risks associated with genes and the environment but not all drugs are addictive.
The ones that generally share certain traits that make them especially confounding.
They can actually prime the brain for wanting more of them?
Let's go there now.
A quick look at brain areas and addiction
We're going to try to make this simple since these areas will pop up later in very important sections.
Here's the basic circuit:
- Nucleus Accumbens - the seat of dopamine release to create a push to action
- Striatum - focuses and narrows attention after stimulation from nucleus accumbens
- Prefrontal Cortex - the rational control which should moderates the impulses
- Hippocampus - seat of memory and emotional focus
Of course, the brain is complex and nothing ever works as an island but these are key players in the addiction circuit.
Initially, with drug exposure, there's a surge in dopamine (way above naturals pops in dopamine) from the nucleus accumbens.
This pumps the striatum to decide what caused that and focus on it for action.
The prefrontal cortex generally adds a voice of reason...is this reaction justified? Is it helpful to our wellbeing?
The hippocampus catalogs the scenario in which this pulse occurred (feeling, location, people, etc - essentially the drug cues).
As this "circuit" gets primed over and over, it grows stronger (remember, it's a form of learning).
With enough exposure, it becomes a dominant circuit in our motivation but something every interesting happens on the crossover to addiction.
The connection between the prefrontal cortex (our rational counterforce) and the striatum becomes impaired. Weakened.
Welcome to full-blown addiction.
This check on compulsion is cut-off:
Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviors that are associated with addiction and the erosion of free will.
Below, we're going to look at exciting new research on a key player here and an actual supplement that may help.
Also, keep in mind that neurogenesis (building new pathways) is key and that's another section below we can actually affect.
Let's dig deeper into changes within the brain from addiction.
Addiction results in specific changes in brain function
There are four major effects:
- Priming of the dopamine system to respond to the drug more strongly
- Suppressing or damaged area of the brain designed to analyze risks and rational thought
- Suppressing the rewiring capability of the brain to "unlearn" the addiction
- Reduction in the underlying neurotransmitter pathway causing withdrawals (see CBD and tolerance).
Interestingly, CBD may have effects on each of these changes.
Let's look at each in more detail now. On to the brain!
Brain changes and addiction
Let's dig a little deeper into each of those brain changes above. It will help explain why it's so hard for an addict to quit.
Priming of the dopamine system to respond to the drug more strongly
Remember that dopamine is the major player in our reward circuit.
It's the "do that again" neurotransmitter.
All the addictive drugs have some entanglement with this system and generally in a specific brain area called the nucleus accumbens.
For example with benzos (highly addictive), yes they boost GABA levels (hence the calm or sleep...temporarily) but they also directly stoke dopamine release.
It goes beyond just stoking the reward system through:
Their findings strongly suggest that this juncture occurs when dopamine surges in response to drug-taking initiate a change in synaptic plasticity in dopamine-producing cells.
Goodness...synaptic plasticity. Basically, the neurons that make dopamine actually physically change to be ready for future waves of dopamine rushes.
Benzos actually go in and weaken a set of neurons that are tasked with controlling dopamine release in an area called the VTA.
Two negatives make a positive, so when benzodiazepines limit the interneurons’ restraining influence, the dopamine-producing neurons release more dopamine.
When this dopamine circuit isn't stoked, the withdrawal effects can be brutal of course.
Remember, that's the whole purpose of the reward circuit (but usually for eating good food, sex, etc).
It can take time to re-wire these changes but that's the brutal part of addiction.
What about the area of the brain designed to moderate impulse control?
The "choose job, family, health over drug" thing?
Suppressing or damaged area of the brain designed to analyze risks and rational thought
So the prefrontal cortex is your rational side of the brain. It's last to develop (both during puberty and for humans in terms of evolution).
It's the part that's shut down for remodeling during puberty (explains a lot, right??).
The net-net is this:
Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviors that are associated with addiction and the erosion of free will.
That review looks at how changes in the Prefrontal cortex start to shift salience (a fancy word for what you choose to focus on) to drug reward over your other life concerns (money, family, job, etc).
It does with neuroplasticity...basically changing the physical structure of the brain.
Remember that process (neuroplasticity) because it's key to some tools we have against addiction including CBD.
It's the subject of our next section.
Suppressing the rewiring capability of the brain to "unlearn" the addiction
Our brain, when functioning correctly, has a robust system to constantly rewire itself in the face of changes in our life and environment.
Part of the issue with addiction (and PTSD by the way) is a suppression of this system from regular drug use.
It makes it nearly impossible to "forget" the cues and addiction itself.
Remember, addiction is a form of learning (habits, cues, reward!!).
Studies looked at the mechanism specifically for addiction:
Suppression of adult hippocampal neurogenesis via cranial irradiation before drug-taking significantly increased cocaine self-administration on both fixed-ratio and progressive-ratio schedules, as well as induced a vertical shift in the dose-response curve.
When they blunted the neurogenesis in the hippocampus (key area for memory and emotional "direction" processing), there was more self-admin of the drug!
Finally, the brain is a complicated chemical soup and it reacts when a drug starts tinkering with different ingredients in this mix
Reduction in the underlying neurotransmitter pathway causing withdrawals (see CBD and tolerance).
Aside from the "push" of dopamine, we have the "pull" of tolerance.
We'll use Benzos and GABA as a perfect example.
Initially, benzos pump up GABA levels along with a sidekick to dopamine as we described above.
If this is done long term, the brain will actually start to counter this artificial and much higher than a natural boost to GABA.
It will downregulate GABA function and even boost glutamate (the opposing "gas" pedal force).
After a few weeks, this goes all the way down to the genes for GABA receptor proteins (remember the epigenetics from above!!).
Fewer GABA receptors to try and thwart the onslaught of GABA flow by benzos.
So...when the drug wears off, your baseline (called tonic) GABA level is even lower than when you started.
This brings on even worse versions of what you were probably prescribed the benzos for, to begin with.
Anxiety. Panic attacks. Insomnia.
In fact, cold turkey dropping of benzos after long term use can result in seizures (too much glutamate without the GABA safety net).
We covered this in our How I used CBD to wean off benzos.
Worse yet, the new generation of benzos come on fast and hard, last a short duration, and drop off fast.
This makes the above cycle earlier, faster, and more severe. We looked at that in our CBD versus Ativan and Xanax review.
This whole process of offsetting the drug's effect is called tolerance.
Basically, it's why you need more and more to get the same effect (eventually just reducing a negative).
It's also a big part of the underlying effect of withdrawals which is the enemy to anyone dealing with addiction.
Now you know why they happen!
We mentioned the GABA effect with benzos but if you dig deeper, each drug has its preferred pathway and they all share something in common.
Let's go there now.
Neurotransmitters and addiction
We've talked about how dopamine is a key player in addiction since it's intimately wired into our reward system.
That's only part of the equation though.
Each drug boosts certain neurotransmitters, to begin with, which is fascinating in terms of why people use them chronically, to begin with.
Before we get to that, here are the "pairings":
- THC - boosts CB1 activity like Anandamide
- Benzos - boost GABA function
- Amphetamines (including ADHD meds) - boost glutamate function at the NMDA receptor
- Alcohol - boosts GABA, Serotonin, and a range of pathways
- SSRIs - boost serotonin function (just don't call it addition...Serotonin Discontinuation Syndrome)
- Opioids - boost opioid system
- Nicotine/caffeine - boost acetylcholine and glutamate function at the NMDA receptor
Of course, they all carry a whollop to the dopamine system for that extra addiction punch but looking above, it begs the question.
Are people who chronically use drugs self-medicating to supplement poorly functioning pathways?
The question came to mind with THC addiction and NAC (N-acetylcysteine).
We'll get into it below but CB1 activity helps to calm glutamate function. NAC does the same (See NAC and mental health).
Are people who chronically use THC (cannabis) using it to bring down excessive glutamate activity?
We're not talking about the 1-off joint but daily usage.
Of course, excess or detriments in any of these pathways would also mirror mental health issues.
- Too little GABA - anxiety and/or depression
- Too much glutamate - ADHD, autism, schizophrenia
Nicotine is another one. It's estimated that the vast majority of cigarettes are smoked by someone with diagnosed mental health issues.
It isn't that you are mentally ill if you smoke...more that people with mental illness are smoking vast numbers of cigarettes.
Self-medicating. The tie with schizophrenia is particularly present.
Nicotines boost glutamate activity at the NMDA receptor. And the connection with schizophrenia?
Thus, NMDAR hypofunction in prefrontal and cortical excitatory neurons may recapitulate only a cognitive aspect of human schizophrenia symptoms.
So...are people with schizophrenia chain-smoking to try and compensate for low glutamate levels in the area of the brain tied to planning, organization, and executive function?
Keep in mind that addiction is a function of learning. The more a person uses a drug, the more likely they are to become addicted (dopamine cycle).
Why a person starts to use a drug chronically may be more tied to key pathways not functioning at full speed.
We'll look at both NAC and psilocybin below to come at this from a different direction (resetting these pathways).
All of a sudden, the context of why a person is drinking changes if their serotonin/GABA systems are impaired.
Of course, dopamine will seal the deal over time.
Compulsion and Risk-Taking behavior with addiction
This figures highly into the teenage and early adulthood years.
We all operate on a spectrum of risk-taking and risk-averse behavior.
You probably have that friend or family member who pushes all the bounds.
What is that? "Oh, it's just who they are".
That "who you are" is shaped by experience and genetics.
Let's introduce serotonin. People mistake it for the "feel good" neurotransmitter but that's a slight to its full raw power (I sound like the emperor geeking out on the Deathstar).
But seriously….is it nothing less than the shaper of all human behavior.
Crazy studies and right smack in the middle of it is compulsion and risk-taking.
Check out just some of the studies.
First, a study on the monkey's where they suppressed serotonin by depleting tryptophan:
Reducing brain serotonin synthesis decreased preference for the safe option in a gambling task.
Gambling...a potential type of addiction (it doesn't just have to be a substance...it's learning after all).
Of course, these figures into the onset of addiction.
To put the pieces together, look at the connection people found between risk-taking, serotonin genes, and alcoholism:
Significantly higher novelty-seeking scores were obtained in dissocial alcoholics carrying the S allele relative to those lacking it.
To translate, high novelty seeking and low hard-avoidance were tied to high serotonin levels.
Interestingly, there's a gender difference between men and women (anger versus crying). Fascinating. Read the review on tryptophan and stress response!
Remember how stress and stress response shared both genetic and environmental cues for addiction from above!
Finally, one last but very important section. Neurogenesis.
Neurogenesis and addiction
This may be the most important piece because it underlies learning.
Essentially, it's the process of building new pathways in the brain.
Keep in mind, the connections between seeing a bar, craving a drink, getting a drink, and feeling the relief is all a circuit.
It's been "hard-wired" into the brain after many similar such examples.
It has preferential treatment now in the brain as the physical connections are strengthened...like a ball rolling downhill.
That's also a process of neurogenesis...building out that pathway and it's partially why it's so hard to stop.
That being said, this pathway will wither if we're not drinking. The longer we don't drink, the weaker the pathway.
The trick is to "re-write" new pathways and that requires neurogenesis.
This is why exercise, mindful meditation, and even CBD can help.
They all boost neurogenesis. In fact, the studies on psilocybin show an explosion in neurogenesis.
Here's the deal...when we're teenagers, our brains are hyperactive in terms of this process.
That's why it's so much easier to learn a new language before a certain age.
This partially centers around BDNF, our brain's fertilizer (check out CBD and BDNF).
As we get older, this process slows down unless we really work to boost it (stay mentally engaged, avoid damaging things like bad sleep and drugs!).
If the brain's ability to re-write...or better yet, over-write existing addiction pathways, it can feel impossible to change.
In fact, chronic drug use can disable neurogenesis in a key area of the brain:
Reinforcing doses of drugs self-administered by rodents decrease DG neurogenesis
DG is an area of the hippocampus, our seat of memory, and emotional context.
The net effect of this downregulation:
Thus, the reduction in spontaneous neurogenesis (i.e., a reduction in neuronal turnover) that is observed after self-administration of various drugs of abuse may result in a more robust and long-lasting memory of drug-taking and seeking or decrease extinction learning.
Goodness...the drugs are making is so that they are the only thing remembered and thought of.
This points to effects by psilocybin which are massive explosions of neurogenesis (see psilocybin) and of course, CBD, the more gradual (and legal) option.
Exercise and mindful meditation also factor in here (see Meditation and exercise for neurogenesis)
Another study looked at blocking neurogenesis and the effects on recovery. Their statement:
Additionally, treatments that increase adult neurogenesis during abstinence might prevent relapse
This rebuilding of the brain is not just important for addiction but maybe the mental health deficits that lead to addiction.
There's a constant battle between damage (trauma, excess chemicals like glutamate, infection, genetic imbalances, drugs, etc) and repair (neurogenesis and BDNF).
It's all intertwined and there's an intriguing (till recently, overlooked) player.
Let's reintroduce him (her), shall we? Glutamate.
Glutamate and Addiction, the New Kid on the Block in Research
The review of NAC was fascinating. How could this simple precursor to our detox system called glutathione (see CBD and glutathione) have an impact across a range of addictions?
After all, they have different neurotransmitter affinities as we saw above.
Remember who we discussed where the prefrontal cortex (a rational constraint on compulsion, etc) is cut off from the more impulsive dopamine-sensitive sections?
New studies are pointing to glutamate imbalance:
The imbalance in glutamate homeostasis engenders changes in neuroplasticity that impair communication between the prefrontal cortex and the nucleus accumbens.
That study looked at how glutamate function was impaired following addiction:
Data exist showing that all three of these processes are altered by chronic treatment with cocaine, and to some extent by chronic treatment with heroin and nicotine.
The paper gets really technical but here's the net takeaway.
Following addiction, glutamate levels get impaired in certain areas (prefrontal cortex and the connections between it and the striatum/nucleus accumbens) AND glutamate levels get boosted in the nucleus accumbens.
This last bit is a turbo boost to "do that again" in the seat of habit-forming.
That's where NAC (N-acetylcysteine), a safe supplement you can buy right now comes in:
Activating cystine–glutamate exchange with N-acetylcysteine restores basal extracellular levels of glutamate and prevents the reinstatement of cocaine and heroin seeking
Goodness. Read the full NAC review here.
There's another supplement that has been shown to help balance glutamate systems.
So….let's look at CBD in light of everything we just discussed.
Can CBD help with addiction
We've covered a lot. Let's focus on the following before looking at studies:
- CBD and neurogenesis
- CBD and serotonin balance
- CBD and glutamate balance
- CBD and dopamine balance
- CBD and withdrawals
First, the key to learning new tricks (and erasing old ones) in the brain...neurogenesis.
It's been a long review so just to trigger your memory.
The key to learning and un-learning is the ability to build new brain pathways. Neurogenesis.
The heavy lifter in this process is BDNF, our brain's fertilizer (see CBD and BDNF).
Interesting information came out of studies on SSRIs to show that they actually worked (temporarily) by stimulating neurogenesis.
The fascinating piece is that when researchers cut off CB1 receptors, the neurogenesis and anti-depressant effects went away.
CB1 is our primary endocannabinoid receptor.
What about CBD specifically?
More recently, a study conducted with transgenic mice (GFAP-TK mice) showed that the anxiolytic effect of chronic CBD administration (14 days) in stressed mice depends on its pro neurogenic action in the adult hippocampus by facilitating endocannabinoid-mediated signaling
That's a mouthful but basically, CBD spurred neurogenesis in the seat of memory and emotional control...the hippocampus.
It's key to anxiety and depression (See CBD and neurogenesis for anxiety).
Another study found similar effects were through the CB1 receptors:
CBD induced a substantial increase in net neurogenesis by a CB1 receptor-dependent mechanism (Wolf et al.,
What about the white matter tracts (the highway of information between brain areas) that get damaged between the prefrontal cortex and the striatum or nucleus accumbens?
A study found that THC can diminish these same white matter connectors but that CBD has opposite effects:
It is important to note that the two major components of marijuana, Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have opposite effects behaviorally, symptomatically, and in terms of functional activation of all of the regions-of-interest for the current study
We'll cover more of that in the cannabis addiction section.
Next up, serotonin.
CBD and serotonin balance
Before we get to the heavy hitter (dopamine and glutamate), let's touch base on serotonin.
After all, it governs compulsion, risk-taking, and just about every human behavior.
Might be relevant to addiction.
First, understand that serotonin function is directly impacted by addiction:
Furthermore, serotonergic neurotransmission changes across the addiction cycle from initial to chronic drug exposure, the development of dependence, withdrawal, abstinence and relapse.
Mice who have genetically inhibited dopamine function still respond to stimulants like cocaine and serotonin was part of net craving.
The drugs that really impact this system are alcohol, stimulants, and THC but serotonin is critical for another reason.
It's the primary booster of BDNF (neurogenesis). By the way, Estradiol (our primary estrogen) is as well ladies. Check out CBD and estrogen here.
Helping to balance this system may be CBD's greatest card to play.
Our favorite in terms of balancing serotonin levels (remember, too high or too low is bad):
Overall, repeated treatment with low-dose CBD induces analgesia predominantly through TRPV1 activation, reduces anxiety through 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.
Let's decipher the Klingon, please.
They basically caused an injury to mice which depleted their serotonin (due to stress of the injury).
Serotonin is a key player in pain sensitivity (which obviously factors into behavior!).
CBD was able to offset the pain threshold changes but the key part is…" rescues impaired 5-HT neurotransmission". 5-HT is short for serotonin (the "t" being for tryptophan..see CBD and tryptophan for stress response).
As we discussed in our CBD versus SSRIs, serotonin balance is the key because an extreme either way is bad news.
Really check out the CBD and serotonin pathway for more on this.
Next up, the new kid on the block.
CBD and glutamate balance
First, understand that all the big neurotransmitters are intimately linked...almost inscrutably so.
5-HT differently modifies glutamate- and GABA- mediated effects, acting on distinct 5-HT receptor subtypes.
5-HT is serotonin. Goodness...what a mess.
What can CBD possibly do with such a complicated system?
First, CBD was originally found due to its effects on seizures which are primarily an imbalance of glutamate and GABA.
Then there's this from a study of autism (also can have a glutamate imbalance element):
Preclinical evidence suggests that one aspect of the polypharmacy of CBD is that it modulates brain excitatory glutamate and inhibitory γ-aminobutyric acid (GABA) levels, including in brain regions linked to ASD, such as the basal ganglia (BG) and the dorsomedial prefrontal cortex (DMPFC).
"Modulates". Music to our ears.
This balancing of glutamate/GABA speaks to its powerful effects on schizophrenia, possibly the most complicated of our mental health issues. Read it...it's fascinating.
Interestingly, NAC is also showing interesting research there and we discussed in our NAC review how it's primary effect is to boost glutathione (our natural detox system).
Why does this matter?
We show here that the glutathione cycle molds the activity of synaptic glutamate, the major excitatory neurotransmitter in the central nervous system.
It's a manager of glutamate levels!
CBD also boosts glutathione (hence the effects on fatty liver from alcohol) except in one place….cancer cells!
It selectively increases oxidation (the enemy of glutathione) in cancer or virally infected cells in research mirroring our immune's natural way to kill cancer.
Now on to the big hitter with dopamine.
CBD and dopamine balance
Dopamine spikes with drug use are a signature piece.
It's a key part of learning and addiction is just learning something bad which is accelerated due to the dopamine effects.
Dopamine is also a master regulator so trying to pump or drop it will likely not end well.
Interestingly, research is pointing to CBD's direct effect on dopamine function and balance.
First (and we'll decipher afterward...we promise):
Our findings demonstrate a novel NAC→VTA circuit responsible for the behavioral and neuronal effects of CBD within the mesolimbic system via functional interactions with serotonergic 5-HT1A receptor signaling.
Okay...the NAc is nothing other than the Nucleus Accumbens we've discussed so much in terms of addiction.
There's serotonin, another master regulator intertwined with dopamine.
Another study on CBD for the effects of the amphetamine's effects through the dopamine system:
Cannabidiol Counteracts Amphetamine-Induced Neuronal and Behavioral Sensitization of the Mesolimbic Dopamine Pathway through a Novel mTOR/p70S6 Kinase Signaling Pathway
"Mesolimbic" dopamine is exactly the locations we're interested in for addiction as it's dubbed the "reward pathway".
Essentially, CBD reduced the hyperactivation of dopamine neurons that usually occurs with amphetamine use.
There are ties with this system and schizophrenia as well.
We've looked at root pathways in the brain for addiction and CBD.
Let's get to more practical questions in terms of trying to stop addiction.
CBD and withdrawals
We covered this quite a bit in our CBD and withdrawals review.
There's research showing that CBD can directly counter the nasty effects of withdrawals.
First opiate withdrawal and CBD.
This is one of the worst addictions out there but we're all too familiar.
The effects with CBD on the cravings were striking:
Acute CBD administration, in contrast to placebo, significantly reduced both craving and anxiety induced by the presentation of salient drug cues compared with neutral cues.
It even affects the aspects we're not in direct control of such as heart rate and cortisol levels.
Maybe the more interesting result was this:
CBD also showed significant protracted effects on these measures 7 days after the final short-term (3-day) CBD exposure.
This would speak to more long term effects or neuroplasticity since the peak CBD is about 4-6 hours after use.
Again...remodeling the circuit of addiction.
And alcohol, our oldest and most popular addiction?:
Experimental studies found that CBD reduces the overall level of alcohol drinking in animal models of AUD by reducing ethanol intake, motivation for ethanol, relapse, anxiety, and impulsivity.
We've covered CBD and anxiety (a key withdrawal symptom) but the more relevant reviews are How I used CBD wean off benzos or How I used CBD to wean off SSRIs in terms of withdrawals and process.
Let's get into some of the actual studies (above opioid withdrawal study was placebo, double-blind by the way).
Studies on CBD and addiction by type of drug
We're going to break this up by drug type to see if we have studies on CBD since they share common pathways but have unique neurotransmitters as a basis.
We'll start with CBD's cousin, THC.
CBD and THC or cannabis addiction
It's surprising to many people that CBD and THC have opposite effects across many pathways.
Despite the bogus buzz of needing THC to activate CBD.
We also dived deep into THC including addiction at our why you need CBD if you smoke cannabis.
So...what does research show for CBD and THC addiction (and it is THC...not the cannabis per se).
Animal studies first showed CBD's ability to reverse the effects of THC addiction:
In combination, low doses of CBD (1, 10 mg/kg) reversed the conditioned place aversion induced by THC (10 mg/kg).
Anecdotal studies in humans with chronic, relapsing, cannabis addiction also reflect this effect:
With the use of the CBD oil, the patient reported being less anxious, as well as settling into a regular pattern of sleep. He also indicated that he had not used any marijuana since starting the CBD oil.
Another individual study looking specifically at withdrawal symptoms:
Daily assessments using the Withdrawal Discomfort Score, Marijuana Withdrawal Symptom Checklist, Beck Anxiety Inventory, and Beck Depression Inventory showed a rapid decrease in withdrawal symptoms, leading to a score of zero in all tests by day 6.
We look forward to more research but what's going on?
THC spikes CB1 (our main endocannabinoid receptor) activity just like anandamide (our most prominent endocannabinoid).
Yes, this gives a feeling of bliss but stay with us here.
Why do some people smoke every once in a while while others, only occasionally?
It turns out that CB1 activity calms glutamate! Read the review of NAC to understand why this is so important for mental health (anxiety, depression, schizophrenia, bipolar, autism, negative thoughts, and more).
Chronic use may just be a way to reign in glutamate imbalance.
CBD and NAC could be powerful allies with cannabis addiction and we'll break it out separately.
Next up, alcohol.
CBD and alcohol addiction
Just like THC might be self-medicating for anandamide (stress response) and glutamate balancing (via CB1 receptors), alcohol pumps GABA and serotonin (along with just about everything).
No wonder it's everywhere!
Let's start with the animal studies specifically focused on a mouse strain designed to become addicted to alcohol:
Increasing doses of CDB (30, 60, and 120 mg/kg) administered intraperitoneally (i.p.) progressively decreased both ethanol preference (from 75% to 55%) and intake (from about 6 g of pure ethanol/kg body weight/day to 3.5 g/kg/day) in a two-bottle choice paradigm (water versus 8% ethanol solution).
So, CBD reduces the intake and preference for alcohol.
More importantly, the reduction was tied to the dose of CBD!
You may ask...how are these mice bred to crave alcohol?
There are specific genes tied to alcohol addiction risk and look at the effects of CBD there:
CBD treatment was associated with changes in gene expression of key targets closely related to AUD.
Another study looked at CBD in conjunction with naltrexone:
They found that combining CBD and naltrexone reduces ethanol consumption and motivation to drink ethanol more efficiently than either drug administered alone.
Yet, another study looked at CBD's effects on reinstatement (mice version of relapse) based on cues:
CBD reduced the number of responses during context-induced reinstatement (∼50% decrease) on sessions (days) 1, 4, and 7 of the treatment phase.
Most interestingly were the duration of CBD's effect:
CBD effect was long-lasting since the 50% reduction was still visible 3, 18, 48, and even 138 days (sessions) after the CBD treatment phase.
That points to neurogenesis...rewiring the brain!
There's a lot of research on the protective effects of CBD for the liver and brain with alcohol.
We look forward to large-scale studies for alcohol abuse. Also, check out CBD and alcohol here to understand how they interact.
Next up, from the front-page headlines. Opioids.
CBD and opioid addiction and withdrawal
The opioid system is a complex and bewildering system that's interwoven into pathways you wouldn't expect.
Needless to say, addiction opioids (prescription or street) is a horrifying situation in the US.
There's some new and interesting research on CBD and opioids with larger study settings.
Let's start with a newer study:
Over half of chronic pain patients (53%) reduced or eliminated their opioids within 8 weeks after adding CBD-rich hemp extract to their regimens. Almost all CBD users (94%) reported quality of life improvements. The results indicated a significant relationship between CBD and PSQI
Digging deeper into the research, scientists are showing exactly how CBD is affecting the pathways and some old friends should be familiar:
initial data suggest that CBD normalizes heroin-induced impairment on the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid glutamate receptor (AMPA) GluR1, as well as the CB1R expression within the nucleus accumbens
GLUR1 is a key processor in the glutamate pathways. CB1 is our main endocannabinoid receptor and guess where they found the effect:
Nucleus accumbens...the seat of dopamine reward signaling fo addiction.
The most important word there is "normalizes". This is the beauty of CBD...it doesn't boost or drop..it's like a feedback substance in a critical system (endocannabinoid) designed to balance other key systems.
The hardest part of opioid addiction is the withdrawal and there's research on that now.
CBD reduces morphine withdrawal symptoms (e.g., wet shakes, diarrhea, abnormal posture, ptosis, chewing, or teeth chattering)
We mentioned above regarding the big study on opioid withdrawals but a quick reminder:
Acute CBD administration, in contrast to placebo, significantly reduced both craving and anxiety induced by the presentation of salient drug cues compared with neutral cues.
We'll do a full break out of CBD and opioid addiction before too long.
Next up, nicotine.
CBD and nicotine addiction
Nicotine pumps acetylcholine (the "alert" and focus neurotransmitter). Also, glutamate, our brain's gas pedal.
Riding on our self-medicating wagon, there's a huge connection between chronic tobacco use and mental health.
As for studies, they're promising and speak towards the need for larger ones.
First, the cues of nicotine which are so critical to quitting.
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).
This basically says that after CBD, smokers who had not smoked were not as drawn to nicotine cues (pictures of smoking, etc) and even compared their cravings to someone who had just smoked.
A study of smokers looking to quit were also given CBD:
In contrast, those treated with CBD significantly reduced the number of cigarettes smoked by ~40% during treatment.
Make sure to check out our review on NAC for addiction as well. CBD and NAC together could be powerful allies here.
Next, an addiction different from most others.
CBD and amphetamine and cocaine
Amphetamines can exhibit psychotic effects and are therefore used in studies of schizophrenia.
In a study on CBD, they looked specifically at the nucleus accumbens after CBD and amphetamine use:
Specifically, we report that CBD can attenuate both behavioral and dopaminergic neuronal correlates of mesolimbic dopaminergic sensitization, via direct interaction with mTOR/p70S6 kinase signaling within the mesolimbic pathway.
Basically, it normalized dopamine function in the reward circuit!
Another study looked at how CBD protected the brain from the tremendous rush of damage caused by amphetamine:
In conclusion, we could not observe effects on locomotion, but CBD protects against d-AMPH-induced oxidative protein damage and increased BDNF levels in the reversal model and these effects vary depending on the brain regions evaluated and doses of CBD administered.
Let's decipher that...it's interesting!
First, if you look at the scans of brains after amphetamine use, you see large holes inactivity after a pretty short duration.
This is literally brain loss from running neurons at full speed (think of redlining an engine).
BDNF (our brain's fertilizer) is losing the battle of repair and growth with this onslaught.
Look at what CBD did!
It reduced the oxidative damage and supported the repair mechanism (BDNF - see CBD and BDNF).
There's a good review of CBD and amphetamines and cocaine.
CBD also potentiated the extinction of cocaine- and amphetamine-induced conditioned place preference (CPP), impaired the reconsolidation of cocaine CPP, and prevented priming-induced reinstatement of METH CPP.
Those are technical terms for pathways that lead to craving, relapse, and use.
Basically, putting the drug first!
The interesting piece is this:
It is important to note that following the cessation of treatment with CBD, reinstatement remained attenuated for a long time (≈5 months) despite plasma and brain CBD levels remaining detectable only for 3 days
Essentially, this would have to point to neurogenesis to have such long term effects.
Think of a sped-up "un-learning" process.
CBT but with turbo!
We'll do a full review of the psycho-stimulants as they're called.
One note...amphetamines are known to be neurotoxic so supporting the brain's system of repair is critical. See Exercise, mindful meditation, and CBD for neurogenesis.
CBD for benzo addiction
We've covered this in detail at the following reviews:
- CBD versus benzos for anxiety
- CBD versus Ativan and Xanax
- How I used CBD to wean off benzos
- CBD versus benzo for GABA function
There's a great deal of research on how CBD helps to balance the GABA systems which benzo directly target.
Some practical questions next.
Can you become addicted to CBD
Studies have shown that CBD is not addictive.
- It does not normalize (lose effect over time)
- It is not hedonic (cause pleasure or self-administering)
- It does not cause withdrawals
The studies across the board, including those on safety, mirror these.
How is this possible if it directly affects key systems like dopamine, GABA, and serotonin, etc.
CBD's effect on oxidative stress and Cancer is a perfect example:
- Healthy cell, low inflammation - CBD has no impact
- Healthy cell, high inflammation - CBD reduces inflammation
- Cancerous (or virally infected cell) - CBD INCREASES inflammation
Read that back over! It's really fascinating.
Oxidative stress is the immune system's primary way to naturally kill off faulty or cancerous cells.
CBD had three different effects (called triphasic) depending on the state of the system.
THAT is the beauty of how CBD works in the endocannabinoid system.
It's also why the research on CBD and key pathways like dopamine, serotonin, GABA/Glutamate is littered with words like "normalizes", "modulates", "resues".
It works like a feedback system for our primary balancing agent...the endocannabinoid system.
In order to not be addictive, we need to address the next two items as well.
CBD and drug withdrawal
Check out CBD and withdrawals for detailed information.
CBD doesn't cause tolerance (next up) and therefore, there is no withdrawal effect.
Withdrawal usually occurs when a natural pathway is drawn down after drug use (GABA, anandamide, etc).
We described above how CBD acts as a constraining agent rather than a one-directional one.
Not just up or down.
We also looked at CBD's effect on withdrawals from other drugs above by different drug classes.
The research shows that CBD actually normalizes dopamine function in the critical nucleus accumbens (seat of addiction).
CBD and drug tolerance
Tolerance is the long term crusher.
Your brain or nervous system will steadily work to counter the sledgehammer effects of the drug.
If you originally had low GABA function (and therefore anxiety and/or depression), you may end up with a benzo prescription which directly pumps up GABA.
The brain will actually start to downregulate the GABA function to offset this rush from the drug.
This is a viscious cycle where you eventually end up with very little tonic (means baseline) GABA.
When the drug runs off, you're in a very bad place.
In fact, long term benzo users who stop cold-turkey can risk seizures.
CBD does not build tolerance over time and may help to speed the repair of a given pathway affected by another drug.
This is the neurogenesis piece since there are physical changes as a result of tolerance (reduced receptors, etc).
Otherwise, the reversal of tolerance from another drug can take weeks or months.
Check out CBD and tolerance to really understand this.
Now let's get more practical.
How much CBD to take for addiction
The studies above were generally higher levels of CBD (300 - 600 mg on average).
As should be apparent, addiction is a kind of learning and we want to speed up the un-learning process.
Neurogenesis is key here and we actually have research on that for CBD dosage.
300 mg is the peak level of neurogenesis. As it goes higher, neurogenesis actually starts to go down even if these higher levels are better for specific withdrawal symptoms (anxiety, insomnia, etc).
300 mg/day is then the ideal long term dosage for addiction.
Earlier amounts may need to be higher depending on how you feel and withdrawals symptoms.
The opioid withdrawal study was based on 600 mg/day.
This points to two phases potentially:
- 1st phase - withdrawal symptoms relief
- 2nd phase - neurogenesis and repair
Work with your doctor or naturopath with any supplement especially in light of other medications or drugs.
CBD may interact with other drugs depending on liver metabolism, etc.
The general rule is 4 hours away from other substances but work with a naturopath.
What's the best CBD for addiction
There are basic requirements with any CBD:
- Organically grown in the US at an FDA registered farm
- CO2 processed
- 3rd party tested
- No THC (can increase the pleasure of other drugs)
- No pesticides
- No solvents
- No heavy metals
- No bacteria
- No mold
We test our CBD twice since our whole family uses it.
Next up, we have to be able to afford it.
After all, we're looking at 300 mg/day potentially.
The key there is the cost per mg of CBD. We price our 6000 mg bottles at about 3 cents per mg, the lowest on the market we find for legitimate CBD.
Check out our CBD cost comparison here.
Finally, the CBD isolate versus CBD full spectrum.
First, all the research on our site (100's of NIH studies) are based on CBD isolate.
There's just not much research on the full spectrum that everyone's selling.
More importantly, histamines.
Roughly 40-60% of people have histamine or allergy issues.
This gets more pronounced as we get older and for women (thanks progesterone).
We don't want all that plant material causing allergic responses when we're in the middle of withdrawals.
We know there's a strong correlation between mental health and addiction (after all, pathways are shared).
Allergic reactions also figure in:
Changes in allergy symptoms and depression scores are positively correlated in patients with recurrent mood disorders exposed to seasonal peaks in aeroallergens.
CBD isolate is the cleanest way to get the benefits of CBD. We have many people who have allergic reactions to full-spectrum which disappear when they try isolate.
Other tools showing promise in research (NAC, Psilocybin, etc)
Yes, we focus on CBD but if we come across research that's very interesting and might reduce suffering, we dive right in!
The goal is to help people after all.
Two big players of addiction are front and center.
- NAC - N-acetylcysteine
NAC is safe, available, and a no-brainer. We did a full review of NAC for mental health (including addiction).
Psilocybin, the core substance in psychedelic mushrooms is not yet legal (it's coming...slow and steady) but is also showing promise for addiction.
Read the review of psilocybin here. It's going to be a total game change within 5 years.
Of course, anything that supports neurogenesis and stress response is beneficial:
- Mindful meditation
- Forest bathing
- B vitamins (need for all your neurotransmitter)
- CBT (a slower process of re-learning)
Exercise and mindful meditation have pretty compelling research for neurogenesis.
Personally, CBD and NAC combined to offer a real strategy for offsetting the damage, withdrawals, and long term brain changes of addiction.
Both have strong safety profiles and are available right now!
Be well. Be informed. Take care of each other.
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.