CBD versus SSRIs for Perimenopause
It's so reminiscent of the '60s and '70s.
Valium was the goto medication for women around their mid to late 40's.
At the peak of Valium's popularity in 1978, Americans consumed more than two billion units stamped with the trademark "V."
Of course, they quickly learned of the terrible addiction issue with benzos.
If you're one of the 25% of women who can expect debilitating perimenopause or even the 50% that will have severe symptoms, you're probably going to get a script for an SSRI.
Lexapro. Zoloft. Celexa. Prozac.
We know women are prescribed at twice the clip as men and take a look at this age distribution for any clues:
These medications are used by 16.6 percent of people ages 40 to 59, 7.8 percent of those ages 20 to 39, and 3.4 percent of adolescents ages 12 to 19.
16.6% in our target age group but that's for both genders!
Just check out this chart here:
Look at the jump with women and more specifically, women age 40-59.
That's 22% of the total population in that age band and this was in 2011!
SSRI use has only grown since then so the numbers are probably closer to 30% of women during perimenopause and menopause.
Goodness. It's a giant science experiment.
Yes and no.
There's lots of research we've covered here:
That last one may be new to you but it's really the star behind the curtain with SSRIs.
But back to ladies in perimenopause….what is going on there?
Why do the doctors offer up benzos and SSRI's so quickly with very little discussion on the repercussions?
That's for another article.
Let's dive into SSRI's for perimenopause and see if there are other options.
Lexapro almost ended me. Yes, that sounds dramatic but it's true. My perimenopause hell story is here.
Let's go deep into this question:
- A quick intro to perimenopause
- Estrogen and Serotonin during perimenopause
- How do SSRI's work for perimenopause
- Perimenopause symptoms under the control of serotonin
- CBD versus SSRI for perimenopause
- CBD versus SSRI safety for perimenopause
- Other tools besides SSRI's for perimenopause
- Can you take CBD with SSRI's
- How much CBD to take for perimenopause
- What's the best CBD for perimenopause
Let's get started. If you're already on SSRIs, check out our full review of how I used CBD to get off of SSRI's, an otherwise brutal experience.
A quick intro to perimenopause
Let's understand why SSRI's even come about.
Perimenopause is all about the flux of key hormones:
- Estradiol - our primary estrogen - see estradiol review here
- Progesterone - powerful offset to estradiol in the body
Progesterone starts dropping late 30's and really takes a nosedive in perimenopause when period's start.
Most women don't realize that progesterone is at about 50% of its peak level by age 40.
Many "symptoms" will actually start the early to mid-'40s but we're just too busy to notice.
Estradiol is the real star of this perimenopause tragedy.
Your average doctor thinks it just glides gradually into menopause.
Not for the lucky ones!
It can go through an extreme roller-coaster ride of ups and downs during the few years prior to the loss of period.
Here's the problem…. Estradiol is a powerful player in many pathways across your body and brain.
It's not just for making babies!
One of those key pathways is serotonin.
Estrogen and Serotonin during perimenopause
No wonder we go sideways during perimenopause and menopause without HRT.
Estradiol has direct control over serotonin levels and balance:
Estradiol is especially nurturing towards serotonin – it stimulates TRPH expression to ensure that enough serotonin is made and suppresses MAO A levels to prolong the longevity of the neurotransmitter.
Their take away which we already know??:
This relationship between estradiol and serotonin is prominently featured in perimenopause when estradiol levels eventually plummet.
Serotonin is called the "feel good" neurotransmitter but that does it a disservice.
Serotonin has its fingers in so many pies within the body that it's hard to really capture its effect.
There's one way to actually see the effect...just look at the side effects of Lexapro, a favorite SSRI for perimenopause here:
How about these two...
- Very common (10% or more): Insomnia (up to 14%)
- Common (1% to 10%): Abnormal dreams, agitation, anxiety, nervousness, restlessness
I actually had the latter from Lexapro which so surprising considering the other 47 years of my life.
The point is this...serotonin is EVERYWHERE...a master regulator and messenger in the nervous system and gut.
And estradiol controls both its creation and removal.
Estradiol is in full disarray during perimenopause and then dropping to nothing during menopause.
Is it really that surprising that women are getting slammed during this period of time?
We're actually very frustrated (angry more like it) that women get short shrift during this period of life.
Benzos, SSRIs, and a slew of heart, BP, etc meds are what we get from our 10-minute doctor visit.
So...benzos are only supposed to be prescribed for 1-2 weeks max. Why are SSRI's the new goto med for perimenopause?
How do SSRI's work for perimenopause
We saw how serotonin's main supporter in the female body (men actually work differently here) is estradiol.
It's left the station and ran the train into the side of a mountain.
What do SSRI's do in this situation?
Simply put, SSRI's boost the availability of serotonin.
They essentially block is reabsorption so it hangs around for longer.
There may be some gut microbiome modulation but research has pointed to serotonin pathways being the key driver.
So how do they work?
Interestingly, doctors will usually prescribe benzos for the first few weeks.
This is usually casted a period needed for the SSRIs to start working but that's not correct (or true).
Remember how serotonin is all over the place? It's also in an area that released Corticotropin-Releasing Hormone, a key stress initiator.
SSRI's can actually cause an INCREASE in anxiety and depression during the first few years due to this effect.
There's no real way to test serotonin levels accurately in our nervous system so doctors are going based on symptoms.
Most of the research is actually on depression for SSRI's but anxiety has quickly gained ground as a basis for prescription since benzos are so fraught with problems.
That's where most doctors stop. SSRI's boost serotonin. Serotonin makes you feel better.
It's so much more interesting than that!
Newer research is showing that serotonin drives pro-growth chemicals in our brain and the nervous system called neurotrophins.
The biggest one is BDNF...our brain's fertilizer.
All roads are pointing to this effect for depression and even anxiety.
If estradiol's "pro-growth" support is pulling away, BDNF levels drop.
Check out CBD for BDNF and how do SSRI's really work to get into the hard research.
When they blocked BDNF's precursor, the anti-depressant effects of SSRI's go away!
We review accumulating evidence that the neurotrophin brain-derived neurotrophic factor (BDNF) serves as a transducer, acting as the link between the antidepressant drug and the neuroplastic changes that result in the improvement of the depressive symptoms.
It's not just SSRI's though.
Exercise. Meditation. Ketamine. Psilocybin (watch how this explodes over the next decade) all point to...BDNF (and its cousins).
Basically, the brain is like a garden with constant growth and pruning.
The growth drops out with estrogen and the pruning (our immune system) continues or speeds up due to systemic inflammation.
That garden drives you to feel and interact with the world.
When we researched CBD and various symptoms, serotonin kept popping up in the strangest of places.
Perimenopause symptoms under the control of serotonin
The nervous system in all it's glory really depends on serotonin.
It has a popular image as a contributor to feelings of well-being and happiness, though its actual biological function is complex and multifaceted, modulating cognition, reward, learning, memory, and numerous physiological processes.
Serotonin isn't a feel-good neurotransmitter. It's more that you'll feel really bad without it!
Or with too much of it (called Serotonin syndrome).
Here are symptoms we covered which leaned heavily on serotonin function (not complete by any measure):
- CBD and perimenopause anxiety
- CBD and perimenopause depression
- CBD and perimenopause brain fog
- CBD and perimenopause anger and irritability
- CBD and perimenopause mood changes
- CBD and perimenopause sleep
- CBD and perimenopause aches and pains
- CBD and perimenopause fatigue
- CBD and perimenopause weight
We could go on but each of those are in-depth.
You'll also see these different areas covered in the side-effect profile of SSRI's.
Again, it's tough to tinker with such a master-regulator without knock-on effects.
So let's jump to the main course...CBD versus SSRIs for perimenopause (and even menopause).
CBD versus SSRI for perimenopause
SSRI's boost serotonin levels in one direction.
This is of course until the brain offsets this addition of serotonin and "normalizes" the other way.
We'll get into this below for the side effects of both.
How does CBD work?
This is really interesting.
We all have an endocannabinoid system which is aged at about 600 million years old evolutionarily speaking.
It's tasked with balancing other key systems in response to stress:
- Immune system - our response to inflammation and infection
- Endocrine system - our complicated system of hormones
- Neurotransmitters - like….serotonin!!
CBD works as a constraint on the naturally occurring endocannabinoids we have in our system.
This is why it's everywhere in the news.
Too much or too little of a critical chemical can be bad.
Remember that too much serotonin can cause very serious issues (it's called serotonin syndrome).
That's a known possible side effect from SSRI's.
Let's look at CBD's effect on serotonin directly.
There's lots of new research on this front.
We'll start with the newest:
Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity.
Allodynia is heightened pain sensitivity. We all know anxiety (unfortunately).
The 5HT is what we're interested in here.
That's the pathway for serotonin.
The most important word in that whole statement??? Normalized.
Not increase. Not reduce. Normalize.
Music to our ears.
You'll see this throughout NIH studies with words like "modulate", "normalize" and "balance".
Another study used a separate agent to block serotonin function and the effects of CBD went away.
Prior to that…
Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors.
Look at this little snippet in the description:
In vivo microdialysis revealed that the administration of CBD significantly enhanced serotonin and glutamate levels in vmPFCx in a different manner depending on the emotional state and the duration of the treatment.
The PFC is the prefrontal cortex... the key to both anxiety and depression.
What's fascinating is the different effects depending on the "emotional state".
SSRI's can't do that. It's up up and away.
There's a constraining effect from CBD. If it gets too high, the effect starts to drop.
This is all due to the endocannabinoid system itself. It's about balance.
CBD even showed the same effect as a popular SSRI, fluoxetine (Prozac):
Results showed that CBD (10 mg/kg), FLX (10 mg/kg) and DES (5 mg/kg) induced antidepressant-like effects in mice submitted to FST.
Again, a serotonin blocker eliminated the anti-depressant effect of CBD.
Here's the fascinating piece...newer researcher is pointing to effects on the endocannabinoid system as being the way that SSRI's actually work.
It mainly comes down to neurogenesis or building new neurons and connections.
Like this piece:
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.
Let's translate because it's pretty fascinating.
When they block neurogenesis, the SSRI's lose their effectiveness.
The whole new scope of research is on how chronic stressors (stress, immune response, chemicals, etc) reduce the brain's ability to rebuild and replenish.
Serotonin directly drives BDNF and other agents responsible for this growth.
Estrogen drives serotonin. Till it doesn't.
Just for baby-making though.
See how this all works? Pretty fascinating.
The net effect:
Already an acute i.p. administration of 3 mg/kg was anxiolytic to a degree comparable to 20 mg/kg imipramine (a selective serotonin reuptake inhibitor [SSRI] commonly prescribed for anxiety and depression).
What about safety?
CBD versus SSRI safety for perimenopause
This is night and day.
Here's a list of side effects for Zoloft, a very popular option for women in perimenopause.
The more common ones:
- Acid or sour stomach
- decreased appetite or weight loss
- diarrhea or loose stools
- sleepiness or unusual drowsiness
- stomach or abdominal cramps, gas, or pain
- trouble sleeping
Zoloft is considered one of the better ones in terms of adverse reactions.
A Japanese study looked at Zoloft for PTSD.
About 44% of the participants had bad reactions associated with the drug itself.
Here's the fascinating one we discussed in our SSRI's and suicidal or homicidal though review:
Discontinuation syndrome, self-injury or violence towards others, and activation syndrome, which are events of concern during treatment with SSRIs, were observed in one patient (0.8%), nine patients (7.4%), and one patient (0.8%), respectively.
7.4% of the participants had issues with self-injury or violence.
That's higher than we expected (generally quotes as very rare).
Here's the bigger issue for us.
The brain normalizes. When an outside chemical increases a given substance, the brain will either drop the naturally made level of that substance or reduce the receptivity of it.
What about with serotonin?
Most antidepressant drugs increase the concentration of 5-HT in the extracellular brain space by preventing its reuptake. However, this increase is offset by a negative feedback operating at the 5-HT cell-body level.
The term for when SSRI's stop working is tachyphylaxis.
Fava et al found that 26 of 77 depressed patients (33.7%) who had achieved full remission of symptoms on fluoxetine 20mg daily experienced a recurrence of symptoms (ADT tachyphylaxis) between 14 and 54 weeks despite maintenance treatment.
That's why doctors will change SSRI's, increase the dose, or layer on other SSRI's.
We see the same thing with THC and CB1 receptors.
Heavy THC users see their CB (endocannabinoid) receptors actually decrease in numbers as an offset.
The rate for SSRI "tolerance" is estimated at about 33%.
Here's the bigger issue...regardless of where your serotonin level was before SSRI treatment, the natural base level may be lower after use.
Trying to come off of SSRI's can be brutal!! My story is here.
It's not technically "withdrawal" since dopamine is generally not affected but the net effect is the same.
Your "feel good" master regulator is dropped into a hole.
What about CBD's safety?
The four most common side effects:
- Dry mouth
- Dizziness (drops blood pressure)
- Lightheadedness (the blood pressure drop)
There's a full review of safety here:
It's important to understand that CBD uses the same liver pathways as other medications including SSRIs.
Work with your doctor or naturopath with any supplement.
Let's look at other interesting tools for perimenopause anxiety and depression.
Other tools besides SSRI's for perimenopause
- Tryptophan - interesting research on serotonin's raw material Buy Here
- Siberian Rhubarb - extensively studies for primary symptoms (review here; Buy here)
- Fisetin - powerful anti-inflammatory to take a load off serotonin Buy here
- Berberine - powerful gut remodeler where serotonin dominates Buy here
- B complex - critical rate-limiting vitamin for serotonin Buy here
- Exercise and meditation - see their effects on neurogenesis here
The big question people have.
Can you take CBD with SSRI's
This is tricky. When I came off of Lexapro, I did it very gradually.
Doctors will warn you not to come off SSIR cold-turkey (it can be dangerous) but they don't really tell you how tough it's going to be.
Worst than benzos!
We've had clients who gradually reduce their SSRI with a pill splitter...a sliver at a time and use CBD to remodel the serotonin pathway as described above.
The general rule is at least 4 hours apart but I took my at separate times completely.
If I could do it all over again, I would have taken 150 mg of CBD in the morning and 150 mg at night and reduce the SSRI over a period of 1-2 months monitoring how I felt the whole way.
Again, work with a naturopath to make this transition.
CBD may make SSRI's last longer and at a higher level if they both use the same liver pathway.
This is good in that some customers claim they can bring down their SSRI level but at the beginning, we don't want to spike SSRI's effect.
This brings us to dose.
How much CBD to take for perimenopause
I started at very low levels - 25-30 mg of CBD to test how I felt.
I slowly (very slowly) brought those levels up to 300 mg a day, split in two.
Research is showing that 300 mg of CBD is the peak level for neurogenesis (the ultimate goal with SSRI's anyway).
Beyond 300 mg, the neurogenesis effect actually goes down.
BDNF and neurogenesis is our ultimate goal (in terms of the serotonin pathway that is).
Slow and steady with the assistance of a naturopath or trusted doctor.
Think of Indiana Jones when he replaces the golden statue with the bag of sand.
What's the best CBD for perimenopause
We've linked to 100's of NIH studies on CBD and the various pathways it affects.
It's all based on CBD isolate.
Not CBD full-spectrum or hemp oil or whatever marketing lingo the latest brand is pushing.
There's another reason that's important for women in perimenopause.
Allergies and histamines!
Roughly 40-60% of the population has histamine issues.
This gets worse as we get older and for women.
Just look at the relationship between allergic reactions and serotonin:
Serotonin serum concentrations were higher in AR patients out of pollen season than in.
AR is short for allergic rhinitis (sinus allergies to pollen).
We don't want any other plant material (all the flavonoids and terpenes they're pitching) to cause a histamine response.
Some of those are used by the plant to fight off pests!!
Of course, the other basic requirements hold true:
- Organically grown in the US at an FDA registered farm
- CO2 processed
- 3rd party tested
- No THC
- No heavy metals
- No solvents
- No bacteria
- No mold
We test our twice since our whole family uses it and we've been in perimenopause hell.
Be well. Be informed. Take care of each other.
Get specific links for CBD and Perimenopause symptoms and questions here.
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.