This is a critical question for long term use of CBD.
Many people we hear from are trying to get off of benzos or SSRIs which can definitely build up a tolerance.
The last thing we want to do is trade one bad for another.
We'll get into all the research and really understand what tolerance is.
We can then look at specific questions we have like CBD for tolerance to THC and other drugs.
We covered the whole process of CBD and withdrawals here which is intimately tied to tolerance but let's dive in deeper to how the body adjusts to CBD.
Here are the topics we'll get into:
- What is tolerance to outside drugs
- Does CBD build tolerance over time
- Are there withdrawal symptoms if you stop CBD
- Is there CBD tolerance anxiety rebound
- Do you need a CBD tolerance break
- Can you have CBD reverse tolerance
- Can you use CBD long term
- How much CBD for long term CBD
- The best type of CBD to avoid tolerance (histamine issue)
Let's get started.
What is tolerance to outside drugs
It's a very interesting process and the book Never Enough is one of the best descriptions we've seen across the range of different drugs that cause tolerance.
At a 30,000 foot view, tolerance is the effect where a drug stops having the same effect.
This generally leads to needing more and more of the same drug to have the same (or lower) effect.
What's going on closer to the ground is so much more interesting though.
Essentially, the body's primary focus is summed up in a term…
Homeostasis.
This is a word to describe a constant strive towards balance.
Yes, there can be moves up or down in a given pathway, but always back to balance (if able).
Each of the different drugs directly boosts certain pathways...powerful pathways of key neurotransmitters.
- Benzos - GABA (our nervous system's "brake pedal". See CBD and GABA pathway
- SSRIs or antidepressants - primarily our serotonin or "feel good" (so much more really) neurotransmitter. See CBD and serotonin pathway to really understand what's going on there.
- Nicotine and caffeine - Acetylcholine - our alert or focus neurotransmitter. Key to protecting from dementia by the way
- Cocaine - NMDA and glutamate - "gas pedals" of the nervous system
- Opioids - directly boost the opioid system - a complex web of pain and reward chemicals
- THC (CBD's cousin) - boosts anandamide, our "bliss' molecule (see CBD and THC)
- Alcohol - a little bit of everything (very small molecule) but definitely GABA and serotonin (See CBD and alcohol)
Again, find a drug that causes tolerance and you'll generally dig down further to find a key pathway that it's directly increasing (volume, availability, etc).
The problem is that is an artificial increase in a sudden amount that's very uncharacteristic of the levels our brain will dole out.
It's a spike to the system!
The nervous system detects this spike and tries to counter it.
If you're using a substance once, the push back may be short and transitory.
Think of a "hangover" effect.
Feeling "frazzled" after a night of drinking is essentially a depletion of GABA (calming effect) and serotonin. Also, the poison (acetaldehyde) removal process is falling behind.
The issue is when we use these substances for a longer period of time.
The brain keeps trying to offset the boost by going the other way.
We looked at CBD and GABA specifically and the telltale signs were there.
Not only would GABA drop but glutamate (it's opposing force) would be increased and DNA that made the GABA receptor proteins would be shut down.
All in an effort to downregulate GABA to offset the benzo boost.
The DNA piece can take weeks to turn off and weeks more to normalize when the benzo stops (see how I used CBD to wean off benzos).
Keep in mind that tolerance is a separate function from addiction where dopamine, our reward neurotransmitter (the "do that again" chemical) is also boosted by the drugs above.
Interestingly in our discussion, the system in charge of balancing all these pathways is critical to our discussion.
The endocannabinoid system.
This is across three main systems:
- Immune system - see CBD and antiviral effects for coronavirus
- Endocrine system - hormones - see CBD and PMS
- Nervous system - Neurotransmitters! All the players we discussed above!
As researchers put it:
Many of the former relate to stress-recovery systems and to the maintenance of homeostatic balance.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481537/
Their use of the word "stress" is different than being late for a meeting.
It has a more general meaning for anything that pushes on a system one way or the other.
As we drill down, see more specific examples:
Among other functions, the ECS is involved in neuroprotection, modulation of nociception, regulation of motor activity, neurogenesis, synaptic plasticity and the control of certain phases of memory processing.
Goodness. "Among others".
Okay, neurogenesis and synaptic plasticity there are key to tolerance as they involve making changes in the brain.
We'll look at that below for helping with tolerance to other drugs.
Now, to the question at hand.
Does CBD build tolerance over time
So...does CBD cause this same push back effect known painfully as tolerance?
No.
Research is showing no signs of tolerance which isn't surprising when you drill down.
If CBD has documented research on GABA and serotonin pathways (as examples), how is it able to positively affect these without building tolerance?
This really is the beauty of CBD.
We have to first introduce 3 different "actions" that chemicals can have on a given pathway:
- Agonist - boosts activity
- Antagonist - reduces activity
- Inhibitor - blocks activity
- Negative Allosteric modulator - what???
That last one is where CBD operates. Let's explain.
If you look at all the pathways that cannabinoids affect in this link, you'll notice something interesting:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345356/table/T1/
For example, THC is an agonist of CB1 receptors. It essentially mimics anandamide and boosts in one direction.
The nervous system will respond in kind but in the opposite direction.
This is why long term THC use can lead to depression/anxiety.
CBD is never an agonist. Its effect is not one-directional.
IT works like a feedback system between neurons.
Where the "agonist" that cause tolerance above send their message in one direction, CBD boosts the signal from receiving neuron backwards to say:
- "We're all good here...no more GABA please"
- "We're low on GABA...increase potential".
This is why you can see different effects depending on the state of the system.
The effects on inflammation and cancer are perfect examples of this.
CBD can actually have a tri-phasic effect (three different outcomes):
- Healthy cell, low inflammation - CBD has minimal effect
- Healthy cell, high inflammation - CBD reduces inflammation
- Cancerous or pre-cancerous cell - CBD INCREASES inflammation
That last piece is fascinating for this reason.
Boosting inflammation is our natural immune system's response to faulty cells to kill them.
It's call apoptosis.
Chemo and radiations are essentially giant spikes in inflammation but they inflict this on all cells.
So the net effect of this nuanced effect in these pathways in terms of triggering a reaction?:
CBD does not seem to induce tolerance.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958190/
This goes for long term use tested with epeliodex, the CBD analog for seizures.
What about withdrawal symptoms from stopping CBD?
Are there withdrawal symptoms if you stop CBD
The knock-on effect of tolerance build-up are withdrawal symptoms when you stop or when the drug drops in level within our bloodstream.
Let's take benzos for an example with GABA.
- Benzos will spike GABA levels
- Our body responds by lowering our natural GABA production
- The drug wears off
We're now worse than when we started.
If this occurs long term, you get a vicious cycle where you need much more drugs to have an ever decreasing effect.
When it wears off, you have brutal withdrawal effects (See CBD and Ativan or Xanax withdrawal).
What about CBD?
If it built tolerance, you would expect similar withdrawal effects (a symptom really).
We would expect to see withdrawals symptoms if there was tolerance since our natural pathways have been diminished:
In healthy volunteers, no evidence of withdrawal syndrome was found with abrupt discontinuation of short-term treatment with CBD.
https://www.ncbi.nlm.nih.gov/pubmed/32036242
In a review of multiple studies for CBD safety, the following was found:
They also conclude from their survey, that none of the studies reported tolerance to CBD.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569602/
Let's get into some specific questions people have.
Is there CBD tolerance anxiety rebound
We partially covered this in our Can CBD cause rebound anxiety or Can CBD increase anxiety articles.
Basically, anxiety is probably the most popular reason people use CBD (thanks a lot coronavirus).
Many people got stuck with benzos (our story is here - also see CBD versus benzos) and know all too well how the rebound anxiety can whollop you when the drug wears off.
As we showed below, you're actually in a worse place than before you started the benzo.
That could take weeks if not longer for the body to readjust but we'll discuss how CBD might speed that process.
The key question is this...does CBD cause this same rebound anxiety?
No. Since CBD doesn't cause withdrawals and tolerance, it does not cause a rebound effect.
That being said, if the underlying reason for the anxiety (if chemical and not situational) is still unbalanced, the original anxiety will likely come back.
That's short term.
Longer-term, CBD use is much more interesting as we'll cover below.
Take a look at CBD and long term anxiety to see how we can actually "rewire" the pathways of anxiety.
Neurogenesis is our keyword there and we'll talk about it below since it's key to reversing tolerance.
Another targeted question.
Do you need a CBD tolerance break
This is common with any drug that causes tolerance.
Essentially, it means taking a break from the drug so that the body's opposite response can calm down and even reverse.
Depending on the drug and how long it was used, this can take weeks or even longer.
Remember, DNA was turned off for GABA receptors after long term benzo use.
Signals have to flow downstream that it's safe to make our own GABA again.
Since CBD does not cause tolerance, it also doesn't require a tolerance break.
In fact, in many studies, CBD was shown to normalize these pathways by itself.
You can read all about it in the CBD and GABA function review as a powerful example (since benzos are becoming the next opioid epidemic).
Let's touch on how CBD is doing that next.
Can you have CBD reverse tolerance
We're finally going to speak to the process of bouncing back after tolerance.
As we mentioned, tolerance is a chemical and even physical process in the nervous system….primarily the brain if we're dealing with neurotransmitters (which we are).
The brain has an elaborate system to repair, replenish, and rewire.
In fact, there's a robust system of cell birth and death happening every second.
The can be neurons or even the various architectures that link them.
This is generally called neurogenesis.
It's the basis behind how SSRIs work (temporarily since they build tolerance).
Most people point to serotonin as the taskmaster in that pathway but the real star is further down.
BDNF!
You probably don't know it by heart but it's the brain's fertilizer.
It's also key to reshaping, rewiring, and redirection brain!
Literally, the key to brain "plasticity" or the ability to change.
We've gone into detail at our CBD and serotonin and even CBD and BDNF to see how CBD affects this pathway.
Here's the interesting piece...this is completely under the pervue of the endocannabinoid system where CBD works.
In fact:
Genetic or pharmacological manipulations of cannabinoid receptors (CB1 and CB2) or enzymes responsible for endocannabinoid-metabolism have also been shown to control proliferation and neurogenesis in the hippocampus.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648779/
The net effect of blocking CB1 activity was to also block the antidepressant or antianxiety effects of the SSRI medication.
Back to tolerance.
The goal is to reduce short term withdrawal symptoms (anxiety, insomnia, etc) while "rescuing" the downregulated pathway as fast as possible.
That's where neurogenesis comes in!
In fact, our review of psilocybin (the active ingredient in magic mushrooms) points to an explosion in BDNF as the key to its immediate and long term effects on anxiety and depression.
CBD is just a more gradual process (and a legal one at that).
Also, check out CBD and neurogenesis here.
Mindful meditation and exercise also positively affect this pathway.
What about long term use?
Can you use CBD long term
There are generally two concerns with long term use of any chemical:
- Build up of toxic effects
- Build up of tolerance
Let's look at the first one.
Administration of CBD via different routes and long-term use of 10 mg/d to 400 mg/d did not create a toxic effect on patients.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326553/
In fact, CBD boosts glutathione, our body's primary toxin removal system.
Check out CBD and glutathione or CBD and oxidation.
We already addressed the tolerance piece.
In the dozens of safety studies we have looked at, there has not been any indication of long term use issues.
Let's look at the dosage with a focus on the neurogenesis aspect.
How much CBD for long term CBD
We actually have some pretty good research on this piece.
First, a test dosage is around 25-30 mg (about 1 dropper at the 1000mg bottle level).
That's a small amount and just to see how it feels on your system.
Studies point to the maximum dose for neurogenesis at 300 mg per day.
Beyond that, even if other aspects continue (anxiety or antipsychotic effect), the brain-remodeling effect goes down.
For that reason, 300 mg is generally the high level for opposing the "entrenchment" of tolerance.
We would love to see studies looking at with and without CBD for tolerance reversal or even cognitive behavioral therapy (a very slow form of neurogenesis if you think about it).
Most people may see relief at lower amounts as this is driven by weight, liver processing, genetics, etc.
Play with the levels based on how you feel but 300 mg is generally the peak level for neurogenesis.
Another important piece.
The best type of CBD to avoid or recover from tolerance (histamine issue)
There are some basic requirements:
- Organically grown in US at an FDA registered farm
- CO2 processed
- 3rd party tested (ours is available at top of every page)
- No THC (THC can increase anxiety and has addiction issues itself)
- No Solvents
- No Heavy Metals
- No Pesticides
- No Bacteria
We actually test ours twice since our whole family uses it.
What about the whole full spectrum versus CBD isolate question?
First, all the research we reference on this site (over 100 NIH studies) are on CBD isolate. CBD by itself.
There's no real research on full spectrum.
We've gone through the whole comparison of CBD isolate and full spectrum here.
The bigger issue is histamines...the culprit behind allergic responses.
Roughly 40-60% of the population has histamine issues.
This number goes up if you're older or female (see CBD and perimenopause allergies).
We see so many people who try full-spectrum and have side effects that go away with CBD isolate.
Read the reviews...it's a battlefield of histamine sufferers finding that CBD isolate works for them.
The other big issue is cost.
CBD is still expensive (probably won't be for long).
We did a whole CBD cost comparison here to show how many brands are just plain ripping people off even if their product is legit.
At 300 mg doses for neurogenesis and tolerance, we have to be able to afford this stuff.
That's why we priced our 6000 mg bottle at 3 cents per mg of CBD.
That's roughly 30 doses at the 300 mg level. It's the cheapest we can find on the market for verified CBD levels that's 3rd party tested.
If you read our story here, you'll understand why we do this. This is personal for us.
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.