How I Used CBD and Research to Get off SSRI's and avoid Serotonin Withdrawal Syndrome
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 lock step, 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 like I did.
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. 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 a 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.
Coming off of the benzos was brutal but this would turn out to be worse.
SSRI's don't have the 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 SSRI's are actually more relevant for depression.
Either way, they affect the same pathway.
Serotonin is a powerful workhorse neurotransmitter in the brain.
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
Where they see an effect was in healthy people with a family member that has depression or people with past depression issues.
There appears to be other systems that influence this.
In fact, the gut microbiome's role is coming to light:
An influence of gut microbiota on behaviour is becoming increasingly evident
Check out CBD and gut bacteria for anxiety here.
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
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,"
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.
Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor
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.
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.
Of course, serotonin levels alone can also have an effect.
IF you have reduced serotonin levels.
There's no good way to test to 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.
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
More importantly, CBD directly bolsters the endocannabinoid system which is involved across the entire anxiety circuit...not just serotonin.
A great study on CBD and public speaking 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
It even reduce 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.
Long term stress is chemically displayed by cortisol.
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.
As for cortisol, our stress hormone:
The present results suggest that CBD interferes with cortisol secretion.
Finally, as we saw with the mice and radiated hippocampus above, what about CBD and neurogenesis?:
More recently, a studied 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
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.
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
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).
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 is called 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 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 alright, grounded, whole.
Yes, those sound like cheesy catch phrases 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 stress response.
Serotonin is a blanket of activity across the brain.
This is obiviously from the crazy catch-all of side effects from SSRI's found here:
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
By the way, CBD does not show any of these effects which isn't surprising given the role of the endocannabinoid system and neurotransmitters.
Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain.
The key word there is "modulates". Not increases. Not reduces.
It's shown to balance 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 so 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 before bed.
Before, my anxiety would race at night and interfere with my sleep.
It's best to hold the CBD oil under you 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 2 hours away from any medication including SSRI's.
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.
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.
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 host of mood disorders).
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)
We wrote an entire article on CBD, trytophan 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.
More interestingly to us is the longer 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 the interesting point.
SSRI's eventually normalize.
This is a technical term for the brain's reaction to boosting serotonin by making less serotonin itself to offset the outside influence.
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 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:
It can start with shivering and diarrhea.
More severe symptoms can follow.
There's a good review here:
One note...a common approach to treating Serotonin syndrome in the medical field is the administration of benzos which have their own issues.
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 levels of SSRI's 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.
CBD may not make sense in the initial phase of drawing down the SSRI during the syndrome phase since it also uses the liver's system to break downSSRI's but check out the above section on CBD's effects for what follows that spike in serotonin.
Work with your doctor on this. It can be very serious and very fast.
Learn all about the SSRI Syndrome treatment commonly prescribed here:
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:
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 2 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's 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 checks 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 2 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 doctor and know that it is strongly advisable not to stop SSRI's quickly.
Read above on the slow process I took to wean off SSRI's if that is your goal.
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 (actually higher according to 3rd party testing results).
I personally use the 6000 mg bottle with 1 dropper in the morning and one 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.
For 40-60% of the population, histamine responses to all that plant material is going the wrong direction for anxiety due to serotonin withdrawal.
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 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.