Once bitten, twice shy.
Many people who have had a bad reaction (to put it mildly) to SSRIs and other medications that boost serotonin in one direction are wary of anything that might lead that way again.
CBD has shown powerful effects along the serotonin pathways for anxiety, depression, and a host of issues.
This begs the question.
Does CBD cause serotonin syndrome?
A secondary question is on the backside...can CBD help with serotonin syndrome?
Let's look at what research shows but understand, I can attest to how bad serotonin syndrome is first hand.
I was (mis) prescribed Lexapro for what turns out to be a significant flux in hormones due to perimenopause (that story is here).
The SSRIs like Lexapro, Zoloft, and Effexor are the go-to medications now for roughly 25% of women who will have a brutal perimenopause.
If you're in that boat, check out why some women get hit so bad here.
Within 30 days of the Lexapro, I was starting to display the tell-tale signs.
Flat effect. Nothing tastes, feels or looks good. I lost weight (because food had no taste!!).
Then the weird body movements and finally, 3 nights of no sleep. Crash in an ER.
It was around that time that I decided to get off of everything (benzos, SSRIs, heart meds, etc) and figure out what was going on.
Again, in the end, it was estradiol and progesterone (see estrogen review) but I had gone through the worst thing ever in my life...serotonin syndrome.
We've now done pretty extensive research on the serotonin pathway but let's zero in on what happens when you have too much serotonin.
Wait till you see the effect of histamine on this process! We can actually affect that piece.
More importantly, how does CBD affect that pathway.
We'll cover these:
- What is serotonin syndrome
- The Histamine and serotonin syndrome connection
- Why do SSRIs cause serotonin syndrome
- Can CBD cause serotonin syndrome
- Can CBD help with serotonin syndrome
- How much CBD for serotonin pathway support
- What's the best CBD for serotonin pathway support
Let's get started.
One final note...serotonin syndrome is a very dangerous condition. You must get immediate medical help - ER or hospital. It can be serious!
What is serotonin syndrome
Simply put, serotonin syndrome is a build-up of too much serotonin.
Like most neurotransmitters, the body is desperately trying to fine-tune a balance of serotonin.
Too little serotonin:
- depressed mood.
- impulsive behavior.
- low self-esteem.
- poor appetite.
You'll notice anxiety and depressed mood but many things can cause those and this is part of the issue with SSRIs.
They are generally effective (temporarily) for 30% of patients with depression and there's a question on even that.
See CBD versus SSRI here.
Those conditions make up the vast majority of SSRI prescriptions.
Again, serotonin has its fingers in so many pies (basically all human behavior) that we covered it in detail at our CBD and serotonin function here.
It's really important to understand its role as a master regulator and promoter of brain plasticity (see how SSRIs really work).
What about too much serotonin?
Now we're getting into serotonin syndrome...caution!
The first round of symptoms:
- Agitation or restlessness
- Rapid heart rate and high blood pressure
- Dilated pupils
- Loss of muscle coordination or twitching muscles
- Muscle rigidity
- Heavy sweating
Just take a look at those...so varied. Goosebumps? Diarrhea? Confusion?
Really, restless legs and "shocks" in the nervous system is what told me something was wrong.
It can then progress to seizures, high fever, irregular heartbeat, and unconsciousness.
Again, it can be deadly if not immediately addressed.
The usual suspects for serotonin syndrome (especially taken together) can be found here:
My particular instance is when they gave me Zofran (anti-nausea med - serotonin is huge player in the gut) while already on Lexapro (a known no-no in the medical world).
It led to a psychotic break for the evening.
Thanks, ER doctor!
Watch out for migraine meds, SSRIs, SNRIs, MAOs, pain meds, anti-nausea meds, herbal supplements like St John's Wart, Ginseng, and nutmeg, plus others.
Like we said, with serotonin, it's all about balance.
The histamine connection with serotonin syndrome
Here's the interesting piece.
Medications that block the breakdown of histamine are known causes of...serotonin syndrome!
We have a massive review of the issue with SSRIs (coming soon) but the mechanism by which SSRIs boost serotonin is partially via a big histamine hit!
The two are intimately linked and one of the key antidotes for serotonin syndrome is an anti-histamine!
CBD is a powerful calming agent for histamine and immune function when imbalanced which we'll see below. The type of CBD really matters though (more below).
SSRIs are definitely the main culprit since they're so widely prescribed these days.
What's the mechanism there?
Why do SSRIs cause serotonin syndrome
SSRIs have one powerful effect.
They block the reabsorption of serotonin back into the neuron.
It's literally in the name...selective serotonin reuptake inhibitor.
This makes much more serotonin available for use.
The net effect is that we have more serotonin.
Here's the deal….it works in one direction….up up up and away.
If you don't already have low serotonin, that's an issue.
Of course, during the 10-minute visit your GP (likely the prescribing doctor) will test your serotonin levels to make sure there's even a problem there.
There's no good way to test serotonin levels in the brain barring an autopsy which seems medically excessive.
They're just going based on symptoms and what their pharma rep told them about effectiveness.
Read up on the real research at our CBD versus SSRIs here where we really dive into the research around them. It's not so black and white and especially for mild or moderate depression.
A little side note….a large percentage of prescribed patients are women and women in their 40's and older.
It turns out that estradiol, our main hormone, is a key driver of serotonin levels.
It plummets in permenopause around the mid to late '40s, dropping to almost nothing into menopause.
We just lost our major proponent of serotonin! Check out perimenopause versus menopause here.
We would love to see the data on how many new SSRI patients are age 47!
So...if you have relatively normal serotonin levels or a spike due to hormone fluctuation AND you're on SSRIs...that can lead to serotonin syndrome.
Throw in another med that also boosts serotonin and now we're in trouble.
Also, keep in mind that SSRIs normalize….we build a tolerance to their effects.
The brain is trying to find balance and there's this outside juicing of a key component...a master regulator.
It goes the other way!
Suppressing serotonin function and even receptors.
This is why there's generally an increase in dose or layering/changing SSRIs over time.
The result of this... you can have serotonin discontinuation syndrome (a fancy, Orwellian way to say withdrawals) if coming off of SSRIs.
In fact, it can be dangerous and brutal to come off of them as I found out the hard way (check out CBD to wean off of SSRIs).
Okay...so we have a lay of the land...let's look at CBD specifically.
We don't want to trade one bad apple for another.
Can CBD cause serotonin syndrome
Now we're going to get into it.
First, let's introduce the endocannabinoid system.
It's a system of naturally occurring cannabinoids (2-AG and anandamide being the big players) that is tasked with balancing other downstream systems:
- Immune system - inflammatory agents
- Endocrine system - hormones like estradiol
- Nervous system - neurotransmitters like….Serotonin!!
Let's look at research on CBD and serotonin directly.
First, does CBD even affect serotonin in the research.
Our results suggest that the antidepressant-like effect induced by CBD in the FST is dependent on serotonin levels in the central nervous system (CNS).
They were able to block its effects with a known serotonin blocker to verify this was the correct pathway.
Probably our favorite study for serotonin specifically is this one.
They caused an injury to mice (that part, we don't like) which resulted in pain, anxiety, and an imbalanced serotonin level.
They then treated one group of mice with CBD.
Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity.
Allodynia is reduced pain sensitivity. 5-HT is none other than serotonin!
Acute or chronic pain is known to exhaust serotonin levels.
So does trauma, infection, stress, and hyperactive immune response.
CBD, in this case, helped to bring serotonin back to balance.
The most important word in that whole sentence is "normalized".
Not boosted. Not dropped. Normalize.
You see this quite often with CBD and serotonin. Words in NIH research like modulate, normalize, etc.
What exactly did it do when serotonin was low?
Repeated treatment with CBD (5 mg/kg/day, subcutaneously [s.c.], for 7 days) increased 5-HT firing through desensitization of 5-HT1A receptors
Newer research is showing an effect downstream from serotonin at the crux of tryptophan processing:
In contrast, micromolar doses of these cannabinoids strongly down-regulated mitogen-stimulated tryptophan degradation, independent of either cannabinoid receptor. Notably, CBD was about 2-4 times more active than THC to suppress IDO enzyme activity.
Tryptophan is worth looking at if you're coming off of SSRIs. It's the precursor to serotonin and we covered it extensively for this reason here:
Basically, CBD helped to make it more available to be put in production for serotonin AS needed by the brain.
Pumping up tryptophan does not juice serotonin levels to the point of serotonin syndrome.
The body has natural mechanisms to monitor this conversion.
Here's the important piece...can increasing doses of CBD by itself cause serotonin syndrome?
There's no documented case of it with millions of users.
We just need to look at the side effect profile.
As we mentioned above, serotonin syndrome has very specific and unique signs.
The common side effects for CBD are:
- Drowsiness (opposite of insomnia and not applicable during the day - see Can I take CBD in the middle of the day)
- Lower blood pressure
- Lightheadedness (from the blood pressure effect - see CBD and heart palpitations)
- Dry mouth
Researchers have tested CBD up to 1.5 grams (1500 mgs) with the same safety profile.
We'll look at the research below on the ideal dosage for neurogenesis or building new brain pathways.
Again, none of the telltale signs of serotonin syndrome show up in the profile.
Regardless of the dose (from 50mg to 1500mg)!
Keep in mind, we're only discussing CBD isolate or CBD by itself.
This doesn't go for all the full spectrum or junk CBD on the market without 3rd party testing.
We see very different side effects from responders who take full spectrum which usually arises from a histamine response.
Here's the takeaway and there's no better example than with CBD and cancer.
The endocannabinoid system is about balance and CBD supports this effort.
Research on cancer bares this out:
- Health cells with low information - CBD has little effect
- Healthy cell with high inflammation - CBD reduces inflammation
- Cancerous or pre-cancerous cell - CBD INCREASES inflammation!
Read that back again and see that CBD has a tri-phasic effect. Three different outcomes depending on the state of the system.
Inflammation is the natural way our immune system kills cancerous or pre-cancerous cells.
Chemo and radiation essentially create an explosion in inflammation.
Serotonin function is the same way as the endocannabinoid system is clearly intertwined with its levels.
Again, we don't see any of the initial symptoms or signs of serotonin syndrome even at very high doses of CBD despite research above showing it "rescues" serotonin function.
See why we're excited?
What about if we're already on SSRIs and experiencing serotonin syndrome.
Can CBD help with serotonin syndrome
Again, you can't play around with this. If you have some of the symptoms above, you must get medical attention immediately.
It's very serious.
Typically, the course of treatment is a benzo (like Ativan or Xanax - see CBD versus Ativan and Xanax) and/or a medication that blocks serotonin.
This keeps the situation from becoming deadly.
The benzos are a short term fix as we go through in our CBD versus benzos review (GABA pathway in that case).
We don't have research on CBD for serotonin syndrome specifically but based on the research for how it "modulates" or "normalizes" serotonin function, it's an interesting avenue for researchers to explore.
We definitely want CBD isolate to avoid any stoking of histamine. Huge review on how CBD isolate calms mast cell (where histamine comes from) activation.
In fact, histamine may be the target to right the ship and to that effect:
We went into detail on how we used CBD to taper off Lexapro (SSRI) here.
It was a slow...very slow process.
Again, serotonin is tied into almost everything you feel.
Definitely, don't bypass doctor's advice for initial stages of serotonin syndrome.
Watch out for the Ativan or Xanax as they are short term (1-2 weeks) at best or addiction and withdrawal becomes an issue as documented in research and by the black box FDA warning.
Let's look at the information dosages.
How much CBD for serotonin pathway support
A test dosage is usually around 25-30 mg but that's very low. Just to see how your body responds.
Again, with CBD isolate and an organic base oil, the safety profile is very strong in research.
There's a range of dosages out in NIH research for various issues.
- Sleep is showing help at 160 mg.
- More serious issues like schizophrenia are generally around 600 - 800 mg.
The most telling for us is on neurogenesis (see CBD and neurogenesis).
This is a fancy term for the brain's ability to change. Plasticity is the technical word.
Any long term change whether making a memory, learning something, or losing an addiction is heavily leaning on this plasticity.
Meditation and exercise or even cognitive behavioral therapy get there slowly by forcing new pathways by practice (and/or BDNF - see CBD and BDNF).
Psilocybin (from magic mushrooms) gets there with an explosion of BDNF. See our psilocybin review.
CBD has shown a powerful effect on this pathway and it maxes out at 300 mg doses per day.
That's why I take 150 mg in the morning and 150 mg before bed.
This is key to the long term rewiring of the brain and support of brain repair/growth.
Most people prescribed SSRIs are doing so for anxiety or depression.
It's important to get at the root of cause the prescription to begin with and neurogenesis is key to long term change in the brain.
Everyone's body and chemistry is different (weight, genetics, liver processing, etc) so this is just a benchmark.
There's really interesting research on early trauma/infection and serotonin levels later in life (more here). The immune system is the future of mental health.
Always go based on how you feel.
CBD should be taken as far away from the SSRI (at least 4 hours) and consult with a naturopath.
An important few points on the best type of CBD.
What's the best CBD for serotonin pathway support
The basic requirements are following with any CBD you're putting in your body:
- Organically grown in the USA at an FDA registered farm
- CO2 processed (cleanest option)
- 3rd party tested free of:
- No THC
- No Pesticides
- No Bacteria
- No Mold
- No Heavy Metals
- No Solvents
We actually test our twice as our entire family uses it daily.
Test results are available at top of every page to make it easy to find.
Then there's the whole full spectrum versus CBD isolate question.
A great of the market is full-spectrum and we're not sure why.
All the research (100's of NIH studies) are on CBD by itself.
The other cannabinoids are either not researched as extensively or in such low amounts as to just be marketing.
We covered this in our CBD isolate versus full spectrum.
The bigger issue is this:
40-60% of the population has allergy or histamine issues and full spectrum is not a great fit there.
This is why we see so many reviews of people who have bad experiences with other CBD only to see those go away with CBD isolate.
That's exactly why we started Indigo Naturals to begin with!
Allergic reactions to 3-4 of the biggest CBD brands on the market.
Histamine (chemical behind allergic reactions) is also a powerful neurotransmitter of its own right.
Histamine eats up GABA (target of benzos) which is our primary calming agent in the brain. If exhausted, glutamate (the brain's gas pedal) is highly destructive and directly tied to anxiety and...depression!
Combining histamine release (because of plant material or other substances in full spectrum) and serotonin syndrome is a potential nightmare.
We don't want to rock that apple cart with plant material (hemp oil) and/or all the lovely plant substances (terpenes, flavones, etc) that are usually touted with full spectrum.
Just a head's up...though they may have health benefits, many are used by the plant to protect (histamine response) from potential attackers!
We use CBD isolate (3rd party tested) and MCT oil (a simpler extract of coconut oil) for IndigoNaturals to match what's found in research.
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.