This is a common question that comes up and a logical extension to the article we just completed on whether you can build a tolerance to CBD.
Tolerance is really the enemy with most medications and supplements!
- The benzos for anxiety have a warning beyond a few weeks (check out CBD versus benzos).
- SSRIs or antidepressants will start to normalize after a period of time and lose effectiveness (see CBD versus SSRIs).
We'll get into why this happens below with long term use (separate from addiction) but the key question is this…
Can you take CBD long term?
There are two considerations to look at:
- CBD toxicity with long term use
- Can you build a tolerance to CBD with long term use
As for the question of too much CBD, we addressed that in our Can you overdose on CBD here.
Back to the long term. Here are the questions we'll address:
- How does CBD work in the body long term
- CBD toxicity and long term use
- Does CBD build tolerance with long term use
- Studies on long term CBD use
- Can you have CBD withdrawals
- Can you drop CBD cold turkey
- Should you cycle CBD use
- How much CBD for long term use
- The best type of CBD for long term use
Let's get started.
How does CBD work in the body long term
Before we get to the two questions for long term CBD use, we need to understand how it works.
It's critical to the question of both tolerance and toxicity for extended periods of time.
First, we have multiple pathways in our body and brain that usually have opposing forces.
Think of a tug of war where there's a movement back and forth but usually, the middle flag stays pretty centered (in the beginning anyway).
You can all apply this framework to 100's if not 1000's of sublevel chemical systems.
Just one example (albeit a big one), GABA and Glutamate.
GABA is like the "Brake" pedal of the nervous system. It slows activity down both within neurons and between them.
Benzos directly pump levels of GABA activity in the brain.
Hence the calming and sedative effect (temporarily).
Glutamate is on the other side of that equation and it works like the "gas" pedal for nervous system activity.
Caffeine can cause a release of glutamate and histamine which makes you more alert.
Where the goal in a tug of war is for one side to win, the goal in our body is a stalemate. Balance or "homeostasis".
Sure, you need more GABA when sleeping and more Glutamate when driving a car, but always back to baseline.
If one goes too strong you end up with bad effects.
Overdosing on benzos can lead to being sedated and even death. Too much glutamate can lead to seizures.
The system tasked with this balance is the endocannabinoid system. The very system where CBD works.
Research shows its primary role is homeostasis (a fancy word for balancing) of other key systems:
- Nervous system - neurotransmitters such as GABA, glutamate, serotonin and a myriad more
- Endocrine system - hormones both of the steroidal type and for metabolism, energy, etc
- Immune system - inflammatory responders and cellular controls over cell birth/death
Okay...we just listed off the three most critical, complicated, and interconnected systems that govern just about everything you feel.
So the endocannabinoid system is everywhere!
What about CBD?
Here's the interesting piece that sets CBD off from not only the medications we're used to (benzos, SSRIs, pain relievers, etc) but also the other cannabinoids (like THC).
CBD does NOT push these pathways in one direction.
That may sound unreal but that's the beauty behind it works.
Check out this chart (we'll decipher below):
Let's get into this because it's really important.
In all these pathways, substances can have different effects.
The big ones are:
- Agonist - increases activity
- Antagonist - reduces activity
- Inhibitor - blocks activity
- allosteric modulator - wait..what??
If you look at CBD, it has the last effect on very important pathways like serotonin (5HT).
This is a really important piece to the long term puzzle.
Most of the other effects are one-directional. Boost activity. Agonist.
The more of the substance, the more boosting. That's why you can overdose have serious health issues with many substances and medications.
- With benzos, everything slows down till it stops
- With SSRIs, it's serotonin syndrome which is life-threatening
- With alcohol, slows down till system shuts down
Again, almost everything we take works this way.
A signal goes from one neuron to another.
With CBD, the message goes the other way...from the receiving neuron to the sending.
It's a feedback system!
- That's enough, stop sending.
- We're low over here, send some more.
It's a constraint that operates within the endocannabinoid system which, if you think about it, is a constraint itself!
Keep the flag in the middle of the tug of war.
This leads to very interesting effects that pertain to our long term question.
First, CBD can have different effects depending on the state of the system.
No better explanation of this than CBD and cancer:
- Healthy cell with no inflammation - CBD has no effect
- Healthy cell with high inflammation - CBD reduces inflammation
- Cancerous or faulty cell (such as virally infected) - CBD INCREASES inflammation
Three different effects based on the state of the cell.
Keep in mind that our body's natural system to remove the cancer is via the immune system and basically involves jacking up oxidative stress (ROS) to kill the cell (called apoptosis).
Chemo and radiation are essentially surges in ROS that kills indiscriminately.
It's this feedback effect in the body that makes CBD so different.
Compare that to THC, its cousin.
THC is an agonist of CB1 activity. It basically mimics a naturally occurring endocannabinoid called Anandamide in our brain.
Anandamide is the so-called "bliss" molecule named after the Hindu deity of bliss, Anand.
Unfortunately, it's in one direction. Up, up, up!
That's why you can have bad effects from too much THC (anxiety, psychosis, nausea, etc).
Check out CBD versus THC to really understand the difference.
Why does this conditional response versus one-direction effect matter for long term use?
Let's go there now!
Does CBD build tolerance with long term use
There's a reason we dragged you through the explanation above.
Now you're perfectly prepared to understand tolerance, the enemy of long term use of almost everything.
Our body is constantly trying to balance out 100's (if not 1000's) of key pathways and we know the endocannabinoid system is the heavyweight in this endeavor.
Now, from nowhere, Ativan (benzo - see CBD versus Ativan) explodes on the scene and it boosts GABA levels in an artificial way and at levels not found naturally in this pathway.
Okay...if it happens once or twice, no problem.
The tug of war (GABA and glutamate) eventually comes back to the middle after overshooting (hangover or rebound anxiety).
If it keeps happening (long term use), the body tries to compensate.
This is really fascinating.
The body will actually start to suppress GABA activity and even boost glutamate to compensate.
It will reduce natural levels of GABA by reducing the number and sensitivity of receptors after a period of time.
This goes all the way down to the very DNA that makes the proteins that form the GABA receptors!
That can occur after a few weeks of use.
The drug (Ativan in our case) will have less and less effect.
Or, another way to say it...
You'll need more and more to get the same effect.
This just confirms the body's panic and it suppresses more and more natural GABA function.
You can see that this eventually ends in a total collapse. It's a living hell.
In fact, if people stop cold turkey at this point, they can actually get seizures (glutamate's been ramped up and GABA function is basically offline).
Not to mention, terrible withdrawal effects and overwhelming anxiety or insomnia (probably the very things that the Ativan was prescribed for).
So...cut to the chase. Does CBD cause tolerance with long term use?
We covered this in-depth at our CBD and tolerance here.
The short answer:
CBD does not seem to induce tolerance.
And a large scale review of many studies:
They also conclude from their survey, that none of the studies reported tolerance to CBD
This question of tolerance also goes to the heart of the second question…
Will CBD remain effective long term?
The very reason substances lose effectiveness over time is due to tolerance.
The body's knee-jerk response to something that pushes a pathway in one direction.
Cheating at the tug of war.
You now have a look behind the curtain as to why some things can be used long term while MOST can't.
In the latter category, you have most of us use in today's world:
- THC (cannabis with high THC)
- Sugar (insulin response is suppressed with too much sugar resulting in diabetes)
Did we just list off 1-2 of your vices?
We're all guilty but CBD's unique (even among its cousins in the cannabis plant) feedback effect does not lead to tolerance, withdrawals, or lessening effectiveness long term.
We compared CBD to CBG, CGN to see the same differences (albeit, slower).
Now you know why we focus on cbd isolate!
Check out deeper dives into these mechanisms with NIH research here:
Next up, the other question for long term CBD use.
CBD toxicity and long term use
The second question for long term CBD use deals with toxicity.
Essentially, does CBD build up over time in certain tissues?
There are substances that are safe in lower amounts but will gradually build over time.
Even taking iron and certain vitamins can have this effect depending on your genetics and health situation.
There's a good review of many CBD studies and they found the following:
Moreover, psychological and psychomotor functions are not adversely affected. The same holds true for gastrointestinal transit, food intake, and the absence of toxicity for nontransformed cells.
They even listed the max dosage that they tested up to:
Chronic use and high doses of up to 1500 mg per day have been repeatedly shown to be well tolerated by humans
1500 mg is way above the levels we've seen in research for more serious issues.
300 mg is the peak level for neurogenesis which is key to anxiety, depression, and a host of mental health issues on a LONG TERM basis
We're talking about building new pathways and connections in the brain.
More acute (short term) effects were generally tested between 300 mg and 800 mg for:
1500 mg being the max level they tested for toxicity is way above those levels.
By the way, these are daily amounts.
Keep in mind that CBD uses a very common pathway in the liver for the processing which many meds (estimated at about 60%) also use.
For this reason, work with your naturopath or doctor regarding interactions if you're on other medications.
What studies do we have for long term CBD use to buttress these claims?
Studies on long term CBD use
Originally, CBD gained fame for its effect on seizures.
The first FDA synthetic version of CBD (Epeliodex) was actually prescribed for that condition.
Needless to say, they have to go through lots of long term safety testing for FDA approval.
They looked at daily panels to see if there were changes from long term use of CBD:
Epileptic patients were treated for 135 days with 200–300 mg oral CBD daily and evaluated every week for changes in urine and blood.
Moreover, neurological and physiological examinations were performed, which neither showed signs of CBD toxicity nor severe side effects. The study also illustrated that CBD was well tolerated
That's the longest study to date but there's a good review of many longer-term studies (weeks to months) here:
Keep in mind that Epeliodex is synthetic and if we've learned anything, synthetic never works as well as the original.
- Progestins versus progesterone (NIH review here)
- Hydrogenated oils versus natural oils
- Fake sugars versus real sugar
We should know by now but there's not much money to be made in the real stuff!
The safety profile of CBD Isolate (key difference versus full-spectrum - see here) is even better than the synthetic version.
Let's look at some questions that pop up around long term use of CBD.
Can you have CBD withdrawals
Once you understand the process above (body pushes back), withdrawals make perfect sense.
Let's look at our Ativan and GABA example.
Ativan spikes GABA hard, for a short duration (compared to older benzos), and then drops off hard.
Long term use will cause a reduction in the GABA pathway a result.
So what happens when the Ativan drops off and you have no safety net of natural GABA function?
Whatever you were taking it for (anxiety and insomnia are primary reasons) just got magnified.
Much worse than before you started.
This is why it's so hard to come off of benzos and other drugs that "normalize"... another way to say build a tolerance.
Then there's the nasty little dopamine side-kick.
Dopamine is our "do that again" neurotransmitter...key to our reward system.
It's front and center in almost any addiction as these drugs tend to "tickle" or prime dopamine release.
It's why you can get addicted to Ativan but not relish.
So tolerance and dopamine drive nasty withdrawals. What about CBD?
First, we established that CBD doesn't build a tolerance. What about dopamine?
Here's where it gets interesting.
Dopamine is a neurotransmitter so it's part of the nervous system that's under the endocannabinoid's balancing act.
So...does CBD have it's "constraining" effect there as well?
Goodness….this is exciting:
evidence has demonstrated that CBD strongly modulates the mesolimbic dopamine (DA) system and may possess promising antipsychotic properties.
The keyword there is "modulates". Not boosts or blocks. It manages!
This is actually exciting information for mental health issues (see CBD and schizophrenia) as well as….addiction!
Check out CBD and addiction.
Not only is CBD showing promise (also check out psilocybin and addiction) for addiction, its effect on withdrawals to other drugs such as opioids and wait for it...THC...are very intriguing.
We did a full analysis of CBD and withdrawals here.
Can you drop CBD cold turkey
If you've been taking many medications long term and try to just drop them, it can be dangerous and even deadly.
- Long term benzo use can cause seizures
- Doctors will warn you not to come off of SSRI's cold turkey.
- Even common blood pressure meds have to be slowly weaned off.
ACE inhibitors and ARB's block ACE2 activity (our body makes angiotensin to increase blood pressure when needed - these drugs interfere with that at the ACE2 receptor).
What does the body do when this activity is blocked?
It makes more ACE2 receptors!
Same process as above!
Needless to say, if you suddenly cut off blood pressure meds (ACE2 inhibitors and ARB's) and the body's been ramping up angiotensin function to offset or compensate...cold turkey's not going to be good.
What about CBD?
Again, there's no indication of issues with cold turkey as the body doesn't build a tolerance to CBD.
We covered this from another direction which is...can you have rebound anxiety from CBD if you stop it.
Here's the interesting piece about long term CBD use.
One of the primary effects is to boost neurogenesis.
Neurogenesis is literally the building of new pathways in the brain.
This is long term, structural change, as opposed to short term, fixes to various pathways.
Guess what else does that...exercise and mindful medication (see here).
Cognitive-behavioral therapy is essentially neurogenesis via time, work, and effort.
This means that long term CBD use can actually lead to long term structural changes (see CBD and anxiety as a powerful example).
Again, we did the full review of psilocybin because it uses the same BDNF pathway.
Remodeling receptors (be it GABA or ACE2) is also part of this process!
It's very exciting and probably our favorite effect of CBD in the body.
Make sure to read those articles. Long term CBD use is a MUST for these structural changes.
It goes to the heart of addiction as well which may represent a "learned" pathway in the brain.
Unlearning those "habits" and rewiring new ones are literally blocked by some drugs.
Neurogenesis is the key to re-opening this toolkit for changing the brain (and our behavior).
Finally, what about cycling CBD use?
Should you cycle CBD use
Some supplements need a "cooling off" time.
This is generally a result of either tolerance and/or toxicity.
There are people with THC who will take a "cannabis break" because they no longer feel the effect.
Essentially, this is time for the body to stop pushing back via the opposing effect we described above.
It can take 4-6 weeks depending on the pathway, usage, and more.
The DNA changes take a while (new receptors, etc).
Since CBD doesn't cause this knee-jerk reaction from the body, cycling wouldn't be required.
What about toxicity?
Some supplements and drugs will build up over time.
The other concern is that the liver or kidney is constantly having to metabolize or break down the chemical.
Certain substances need the liver's process to even have their effect (THC is an example).
As we saw above, CBD doesn't build up in tissue over time.
What about the liver?
Studies looked at CBD and the liver in a few different scenarios.
First, they basically poisoned mice and studied the effects on the liver with or without CBD:
Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function.
5HT is serotonin...just a little important as our "feel good" neurotransmitter.
Then they looked at CBD for injury as a result of alcohol:
Cannabidiol attenuates alcohol-induced liver steatosis, metabolic dysregulation, inflammation, and neutrophil-mediated injury
So...across the board improvement function.
Again, we don't see studies with CBD dose ranges that people actually use which show toxicity or buildup.
This brings up a good question...how much CBD long term?
How much CBD for long term use
So we definitely know the upper limits from the study above.
They tested 1500 mg/daily.
There's actually other research that we can look at for a better guide.
The study on neurogenesis showed that it peaks at 300 mg.
After that point (to 600 mg), the neurogenesis effect starts to go down as other pathways come into play.
Since neurogenesis is the key to long term positive change, that's a good target.
For acute or short term effects, studies looked at 600 mg and even 800 mg but those dealt with immediate needs (public speaking with social anxiety or psychosis respectively).
300 mg is a good target for longer-term effects and brain plasticity remodeling.
Of course, a trial dosage is usually around 25-30 mg and it's dependent on each person's situation (genetics, weight, liver function, etc).
Depending on the situation, that puts the average range from about 80mg to 300mg for longer-term issues.
If you have specific questions on a given issue, let us know and we can send over research.
What about the type of CBD?
Best CBD for long term use
There are two concerns if we're going to use CBD long term.
- Quality and purity of the CBD
- CBD isolate versus full-spectrum
Taking bad CBD with contaminants or even minimal levels of THC is not good long term of course.
CBD must have the following 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
This is a must and a brand must post this directly on the website (ours is available at the top of every page).
Our whole family uses IndigoNaturals for years now (daily) so we're very serious about these requirements. We actually test twice (from the vendor and finished product).
Even our teenagers use is so it's very important.
The second piece is more nuanced.
All the research we've looked at (100's of NIH studies) is on CBD isolate. CBD by itself.
Most of what is sold out on the market is full-spectrum CBD which doesn't have the research backing it.
In fact, they can have up to .3% THC and other cannabinoids (CBC, CBG, CBN, etc).
Remember above how CBD was the ONLY cannabinoid that had the reverse modulator effect?
The others are generally agonists, antagonists, or inhibitors.
One direction. More importantly, we don't have the research on long term use of those.
CBD and THC have extensive research and THC has tolerance issues long term.
CBD isolate is the cleanest option to get the benefits of CBD. We add ours to MCT oil (an organic coconut oil extract) as a base.
Just two ingredients.
Anything long term needs to be very clean and very well researched.
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.