We already covered the first great "weaning" I had to do with benzos (Xanax, Ativan, Valium) at our CBD for benzo withdrawal article.
Next, in lockstep, the doctors decided SSRI's would be the best course of treatment for my rolling anxiety.
It nearly killed me.
More accurately, I suddenly didn't want to live any longer.
It seems to be the go-to remedy for women entering a rough perimenopause as I did.
Lexapro.
According to the doctor, it takes a few weeks to start working (not true...see CBD and SSRI's to learn how they initially increase anxiety/depression).
About two weeks in, I was a mess.
Total flatline response.
No appetite...lost 10 pounds in 1 week. My stomach was a wreck.
Then I started to feel nothing.
No taste. No feeling. Just flat affect. (the technical term).
Negative thoughts crept up and even suicidal thoughts.
I ended up in the ER after I couldn't sleep for 3 days straight.
The ER doctor there prescribed an anti-nausea drug (did I mention my gut was wrecked??) which has a strong warning against taking with SSRI's.
Psychotic break, please.
As I mentioned in my story here, this was the lowest point of my life and I really was negotiating with "someone" as to whether I wanted to stay on this Earth any longer.
I had to stop the SSRI's.
Apparently, I'm in good company if you check out the stats at the CBD versus SSRI's page or CBD versus anxiety medications here.
They generally work for about 30% of patients until the body builds tolerance.
We're going to really look at how CBD affects the same serotonin pathways but without tolerance below!
More importantly, we'll address the real star of the show..BDNF! Our brain's fertilizer!
Coming off of the benzos was brutal but this would turn out to be worse.
SSRIs don't have the clinical addiction connection with dopamine but that doesn't mean they're easier to come off of.
You shouldn't drop them cold turkey.
The focus of this article is how CBD might help with the process.
Research is shedding light on the pathways shared by both but in very different ways.
We'll look at the following topics:
- A quick introduction to the pathways of SSRIs and how CBD affects them
- Can CBD help with SSRI withdrawal
- Can CBD be taken with SSRI's
- Can CBD replace SSRI's
- My process using CBD to replace SSRI
- Best CBD for SSRI withdrawal and replacement
Lots to cover and as with all our articles, we're going to lean heavily on NIH research.
Let's get started.
First, a lay of the land.
A quick introduction to the pathways of SSRIs and how CBD affects them
It's important to get some background on what SSRI's do in the body.
Our focus here is on anxiety (since that's our current run of investigation) but SSRIs are actually more relevant for depression.
Either way, they affect the same pathway.
Serotonin.
Serotonin is a powerful workhorse neurotransmitter in the brain.
And gut!
In fact, 70% of our serotonin is actually made in the gut (see CBD and gut biome here).
SSRI's primary lever is to boost the amount of serotonin available to neurons.
It turns out that the real effect of serotonin on the pathways of anxiety and depression deal with neurogenesis.
That's why it takes so long to work.
Neurogenesis is the process of rebuilding and replenishing neurons.
Learn all about it at our CBD and neurogenesis article.
In fact, you can't deplete serotonin or its precursor (tryptophan) and cause healthy people to suddenly display anxiety and depression:
Tryptophan depletion studies in never-depressed individuals are variable, with no or little overall effect on lowering of mood
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728667/
Read that back over again. It's really important.
Where they see an effect is in healthy people with a family member that has depression or people with past depression issues.
There appear to be other systems that influence this.
In fact, the gut microbiome's role is coming to light:
Influence of gut microbiota on behavior is becoming increasingly evident
Check out CBD and gut bacteria for anxiety here.
We digress!
As we stated above, serotonin's real effect on anxiety and depression appears to be in its ability to rebuild or repair specific brain areas under duress.
Many things can cause damage to these brain areas in the anxiety circuit:
- Chronic inflammation
- Chronic stress
- Infection at specific times of brain development
- THC (yes, CBD's cousin in cannabis)
- Gut bacteria dysregulation and gut permeability
- Immune system response to weakened gut barrier
- Trauma/Infection
The last one is critically important.
Early trauma or infection (even in utero -especially third trimester) can downregulate serotonin later in life (along with many other key pathways like GABA).
We have a monster review on it here.
Regardless of the cause, brain loss can feed into the pathway for anxiety and depression.
A good synopsis of it is here:
Pathological anxiety and chronic stress are associated with structural degeneration and impaired functioning of the hippocampus and the prefrontal cortex (PFC), which may account for the increased risk of developing neuropsychiatric disorders, including depression and dementia,"
https://www.sciencedaily.com/releases/2016/01/160121121818.htm
This is why we wrote extensively on the three researched ways to repair hippocampus brain tissues here.
So back to SSRI and serotonin.
A study looked at sertraline, an SSRI commonly used (brand name is Zoloft).
Their results:
Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121947/
Why is this important for SSRI's which boost serotonin?
Similarly, we discuss the possibility that adult hippocampal neurogenesis mediates antidepressant effects via the ventral (in rodents; anterior in humans) hippocampus' influence on the HPA axis, and mechanisms by which antidepressants may reverse chronic stress-induced 5-HT and neurogenic changes.
https://www.ncbi.nlm.nih.gov/pubmed/24300695
To decipher a bit…
5-HT is our serotonin pathway.
Neurogenesis (building and repairing brain tissue) in the hippocampus appears to be very important for longer-term anxiety and depression.
Again, learn all about neurogenesis CBD and the hippocampus here.
So...that's the primary lever by which SSRI's might affect anxiety and depression (till they don't due to tolerance).
Of course, serotonin levels alone can also have an effect.
IF you have reduced serotonin levels.
There's no good way to test for this so it's a guess by the doctor.
Usually, they infer...anxiety or depression = low serotonin.
Here's the important take away:
Chronic treatment with fluoxetine and imipramine induced anxiolytic-like effects in the novelty suppressed feeding test in control mice but not in animals that were submitted to x-ray-irradiation of the SGZ (SGZ-x-irradiation), a procedure that blunts neurogenesis by killing cells undergoing proliferation.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648779/
We'll translate because this is the smoking gun of our whole discussion.
Long term administration of an SSRI (fluoxetine is Prozac) reduced anxiety in mice.
However, when the area of the hippocampus where neurogenesis was essentially turned off (via radiation), the anti-anxiety effects went away!
What about CBD and this serotonin pathway?
Turns out that CBD directly affects and serotonin function but without the nasty side effects.
The eCB-induced modulation of stress-related behaviors appears to be mediated, at least in part, through the regulation of the serotoninergic system
https://www.ncbi.nlm.nih.gov/pubmed/21354188
eCB is short for the endocannabinoid system in which CBD operates in.
More importantly, CBD directly bolsters the endocannabinoid system which is involved across the entire anxiety circuit...not just serotonin.
Let's start with stress response (see CBD and stress or CBD and performance anxiety).
A great study on CBD and public speaking for people with social anxiety reflected this change in stress response:
Pretreatment with CBD significantly reduced anxiety, cognitive impairment and discomfort in their speech performance, and significantly decreased alert in their anticipatory speech
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079847/
It even reduces the physiological responses (heart rate, blood pressure, skin conductance) to stress:
this result suggests that CBD also protects the patients from their subjective physiological abnormalities induced by the SPST
This is important because remember that chronic stress and inflammation is what can do damage to brain areas such as the hippocampus which leads to long term anxiety and depressive states.
The long term stress is chemically displayed by cortisol.
See CBD, cortisol, and anxiety here.
The very thing - the "plasticity" or ability to change - of the hippocampus is what also makes it vulnerable to stress hormones like cortisol:
Imaging studies of the human hippocampus have suggested a negative relationship between cortisol levels and hippocampal volume.
https://www.sciencedirect.com/science/article/pii/S1044576584710311
As for cortisol, our stress hormone:
The present results suggest that CBD interferes with cortisol secretion.
https://www.ncbi.nlm.nih.gov/pubmed/8257923
Finally, as we saw with the mice and radiated hippocampus above, what about CBD and neurogenesis?:
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 proneurogenic action in the adult hippocampus by facilitating endocannabinoid-mediated signaling
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648779/
Voila! (my mother's French so I get the pass).
This statement just means that CBD's "long term" effect on anxiety are due to the same neurogenesis in the hippocampus that SSRI's affect.
Again, check out CBD and neurogenesis or CBD versus SSRI's for anxiety (and depression).
We've covered all these topics in detail but felt it was important to at least look at the shared pathways.
The interesting factor is that CBD doesn't just boost serotonin levels regardless of baseline.
It supports the endocannabinoid system which balances serotonin levels.
You see this all over the research such as:
Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain
https://www.ncbi.nlm.nih.gov/pubmed/30157131
We have to translate that....it's too important.
Essentially, they injured mice and which depleted serotonin and increased pain sensitivity and anxiety.
CBD reverses these effects and primary through the serotonin pathway!
The key work is "modulate". Not boost like SSRIs.
Let's get to more specific questions that originally brought us here.
Can CBD help with SSRI withdrawal
So...they don't officially call it SSRI withdrawal.
They don't officially say it's "addictive".
Personally, I can tell you it's was one of the hardest things to come off of...ever!
Even rougher than the benzos (see CBD and benzo withdrawal) and they have a black box warning on the package!
Since SSRI's don't directly juice the dopamine system in the usual suspect region of the nucleus accumbens, they're not classed as technically "addictive" or habit-forming.
They also don't create euphoria (pleasure) or have the technical term of "hedonic".
For this reason, problems with coming off of SSRI's are grouped under the term Serotonin Discontinuation Syndrome.
George Orwell would be proud (and probably medicated).
Here's the deal...serotonin is a master neurotransmitter in the nervous system (and gut).
Yes, it governs gut function, sleep, and sex drive but it's real tour de force is on mood.
Sometimes called the "feel good" neurotransmitter, it can loosely be associated with feeling...right, grounded, whole. "Good in our own skin".
Yes, those sound like cheesy catchphrases from a 60's Woodstock song but nevertheless, this speaks to how widespread serotonin's effect in the brain.
Many neurotransmitters are one-trick ponies.
GABA slows things down. Glutamate speeds them up. Cortisol is a stress response.
Serotonin is a blanket of activity across the brain.
This is obvious from the crazy catch-all of side effects from SSRI's found here:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021323s047lbl.pdf
It's an impressive list of bodily functions gone awry.
I can personally attest to a few of them including suicidal thoughts and total flat affect.
Check out some of the research on SSRI's and suicidal or homicidal thoughts:
With age stratification, there was a significant association between SSRIs and violent crime convictions for individuals aged 15 to 24 y
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570770/
By the way, CBD does not show any of these effects which aren't surprising given the role of the endocannabinoid system and neurotransmitters.
The keyword there is "modulates". Not increases. Not reduces.
The endocannabinoid system is shown to balance the key system in the body:
- Nervous system - neurotransmitters such as serotonin and GABA
- Endocrine system - hormones such as cortisol and histamine
- Immune system - such as inflammatory agents which can damage brain areas
So...given the many pies that serotonin has its finger in, what do you think will happen when you take it away!
Unlike the benzos, at least the doctor warned me in advance not to stop it cold turkey.
I was prescribed Lexapro for rolling panic attacks and 24-7 anxiety (from perimenopause hormone drop and serum sickness from oral typhoid vaccine...story here).
After everything we learned, a high dose of CBD (300 - 600 mg) in the beginning would have been ideal.
I would wean that down to 300 mg for the long term effect of neurogenesis (see how many mg of CBD for anxiety here) which research shows on a bell curve...peaking about 300 mg.
I personally, take 150 mg in the morning and 150 mg before bed.
Before, my anxiety would race at night and interfere with my sleep.
It's best to hold the CBD oil under your tongue for up to 60 seconds (see how to increase CBD by 4xs here).
Ideally, you want to take it after a meal so more can get into the bloodstream.
It's important to take CBD at least 4 hours away from any medication including SSRIs.
They both can use the same pathway in the liver (p450) for processing which might boost or reduce levels of the SSRI in the bloodstream.
Work with a naturopath.
Remember how we said that CBD "modulates" serotonin function.
Here's the critical piece of that study:
Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity.
https://www.ncbi.nlm.nih.gov/pubmed/30157131
Rather than just increase serotonin available in the brain and body, CBD worked through the endocannabinoid system to affect receptor sensitivity.
- Too much serotonin is bad (See Serotonin syndrome below).
- Too little serotonin (function) is bad (anxiety, depression, and a host of mood disorders).
The most important word in that statement is "normalize".
Balance is our goal.
There's interesting research on how CBD does this by influencing our brain's own conversion of tryptophan to serotonin:
these cannabinoids in the modulation of serotonergic signaling by their capacity to increase the availability of circulating tryptophan, the precursor necessary for the biosynthesis of the neurotransmitter 5-hydroxytryptamine (5-HT; serotonin)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033942/
We wrote an entire article on CBD, tryptophan, and inflammation for anxiety.
It's fascinating and could be a key between inflammation/infection and mood disorders.
The closest direct study we have for withdrawal is brand new with opioid withdrawal.
It's even more difficult than SSRI withdrawal since the dopamine and naturally occurring opioid systems in the brain are hit hard!
The results from a double-blind study:
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.
https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2019.18101191
Big review on CBD and opioid withdrawal here.
More interestingly to us is the long term effect it had:
CBD also showed significant protracted effects on these measures 7 days after the final short-term (3-day) CBD exposure.
We're not sure why this isn't on every broadcast across the country given the opioid (and soon to be benzo) epidemic.
Learn all about CBD and addiction here.
SSRI's are different in that it's more a function of serotonin balancing but the opioid study is a powerful example.
Here's an interesting point.
SSRI's eventually build tolerance.
This is a technical term for the brain's reaction to boosting serotonin by making less serotonin itself to offset the outside influence.
The brain will literally reduce the number and sensitivity of serotonin receptors.
That's why doctors will change SSRI's after a period of time or increase dosages.
Eventually, the SSRI will be ineffectual aside from long term neurogenesis effects we mentioned above.
Of course, if you still have the chronic stress, inflammation, or immune response, the damage to the hippocampus continues unabated.
Here's the issue.
When you come off the SSRI...even slowly...you'll definitely have a reduced baseline serotonin level even if you didn't actually have one before.
A great book called Never Enough by Judith Gisel explains this reaction in the brain very poignantly. A must-read!
Let's look at another question we see regularly.
Can CBD help with Serotonin Syndrome
First of all, serotonin syndrome is a very serious, life-threatening condition.
Essentially, it's the result of too much serotonin.
A general explanation and list of symptoms is below but seek medical help immediately if present:
https://en.wikipedia.org/wiki/Serotonin_syndrome
It can start with shivering and diarrhea.
More severe symptoms can follow. Even deadly outcomes.
One note...a common approach to treating Serotonin syndrome in the medical field is the administration of benzos which have their own issues.
See CBD and benzo withdrawal here.
Short term, they may be fine but addiction issues can crop up pretty quickly.
In terms of CBD for Serotonin syndrome, we have to be careful since they both use the same P450 pathway in the liver.
Anything that taxes this metabolism pathway can increase levels of SSRI's.
Some people actually use CBD to reduce the dosages of SSRIs due to this effect.
Usually, your doctor will recommend reducing the SSRI right away (work with your doctor) if they suspect Serotonin Syndrome.
You can check the half-life of the various SSRI's here at our CBD versus SSRI's articles.
Here's the issue.
The common practice for Serotonin syndrome is to stop the SSRI.
This may then lead to SSRI Withdrawal Syndrome which we described above.
Work with your doctor on this. It can be very serious and very fast.
Learn all about the SSRI Syndrome treatment commonly prescribed here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865832/
Just a head's up...watch out for opioids and SSRI's combined as there's a known additive effect between the two of them.
More on that here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865832/
Can CBD be taken with SSRI's
There isn't specific research yet on SSRI and CBD taken at the same time.
Yes, we want to take it at least 4 hours apart if taking together. We explained that in our CBD and medications here.
CBD uses the same liver pathway (P450) as most SSRI's so it may cause their levels to increase in the bloodstream.
There are some reports on Reddit boards where people can reduce their SSRI levels or stop completely (slowly of course) due to CBD's effect.
This is what we know.
SSRI's boost serotonin in one direction...up up up and away (until the brain catches up and offsets the increase).
CBD works in the endocannabinoid system to balance serotonin function.
In theory, CBD should help to exercise a check and balance on serotonin functioning.
CBD can boost serotonin when levels are low. (see CBD and serotonin here).
It doesn't have the side effect profile of SSRI's (Serotonin Syndrome) even at much higher levels (tested up to 1500 mg in studies).
This points to the fact that it doesn't boost in one direction.
We want to see hard research on it but you're not going to get that from pharmaceutical companies where billion-dollar markets are jeopardized.
We can only look at shared pathways at this point.
Again, at least 4 hours apart.
See below for CBD levels to help offset this drop-off.
Can CBD replace SSRI's
Based on the shared pathways for both (serotonin), replacing SSRI's with CBD might be an option.
Ideally, you start with CBD before getting entangled in SSRI's but that's another article on our health care delivery system!
Make sure to work with your naturopath and know that it is strongly advised not to stop SSRI's quickly.
A quick review of how I replaced Lexapro:
- Gradually reduced Lexapro dose over 30 days with pill cutter
- Tested CBD for 50mg first day to test; opposite time from SSRI
- Quickly increased to 300mg daily (3 x 100mg after meals)
After this period, I reduced CBD to 100mg daily but some people see much longer periods for serotonin pathways to find grounding.
One note..estrogen and testosterone drive serotonin and there's no bandaiding the loss of these! See estrogen and mental health as an example.
Best CBD for SSRI withdrawal and replacement
In our experience based on both research of the market and personal trial and error, there are a few considerations in choosing the best CBD for SSRI withdrawal and replacement.
First, the basics:
- Organically grown in the US
- CO2 processed (much cleaner end result)
- 3rd party tested
- No THC (see THC versus CBD for anxiety)
- No pesticides
- No solvents (speaks to the CO2 processing above)
- No bacteria
- No mold
- No heavy metals
Those are minimum requirements and we actually test IndigoNaturals twice to this effect.
Secondly, we need a sufficient level of CBD.
The ideal sweet spot for neurogenesis (which is the basis for SSRI's effect) in the brain is 300 mg per research.
Beyond that, we still have a dose-dependent effect on anxiety but the neurogenesis effect actually decreases.
For this reason, a good 90% of the junk on the market isn't going to work.
A 1-ounce bottle with 300 mg is a complete rip-off.
We went through that same process when we originally started.
That's why we have 2000 and really 6000 mg bottles of CBD.
I personally use the 6000 mg bottle with 1 dropper in the morning and once at night.
One dropper is about 200 mg (6000 divided by 30).
Finally, all the research is on CBD by itself.
Not CBD full-spectrum, hemp oil, or anything else.
Just CBD.
For 40-60% of the population, histamine responses to all that plant material are going the wrong direction for anxiety due to serotonin withdrawal.
See CBD, Histamine, and anxiety here.
Histamine is a powerful excitatory chemical in the brain and directly opposes GABA.
It's simple….we based crafting of IndigoNaturals on research.
Just look at any of our articles (such as CBD and general anxiety disorder or CBD and depression as an example).
We don't mess around because we've suffered ourselves.
We're out of that now and we want others to understand what's happening and get relief.
If you've been there, you'll understand why.
One final piece...the real effect of SSRI's (downstream) may be something you've never heard of called BDNF.
See CBD's effects at our CBD and BDNF for neurogenesis.
Related Research:
How SSRIs really work
Can CBD help with withdrawals
Does CBD cause serotonin syndrome
The immune system and mental health
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.