This question usually revolves around two different separate types of medications.
- CBD and hormone replacement therapy (estradiol, progesterone, etc)
- CBD and SSRI's or Benzos during perimenopause
The first makes total sense.
The latter speaks to how current medicine basically deals with perimenopause.
There are about 1 million women entering perimenopause each year.
Of those, it's estimated that roughly 25% will have brutal transitions.
Many of those women will display signs of significant anxiety and/or panic attacks.
Rolling panic attacks and almost 24/7 anxiety.
Of course, 3 different doctors rolled out the benzo carpet and then switch to Lexapro, an SSRI.
The side effects and getting off of those was one of the hardest things I ever had to go through.
Of course, always work with a trusted doctor (who will work with you) or naturopath with any transition as it can be dangerous to do it quickly.
Let's look at these specific questions on CBD and perimenopause medications.
We'll cover these topics:
- Can you take CBD with HRT (hormone replacement therapy)
- Can you take CBD with benzo's for perimenopause
- Can you take CBD with SSRI's for perimenopause
- Other perimenopause medications and CBD
Let's dig deeper on these but again, work with a trusted naturopath like I eventually found.
Especially, if you're prescribed medications already.
This is true for any supplement.
Can you take CBD with HRT (hormone replacement therapy)
This is such a common question that we wrote an entire review on CBD and HRT here.
It's really a question of whether CBD will interfere with hormones.
From our research, there is little interaction with CBD and estradiol at the levels that CBD is administered.
Oral progesterone (or oral estrogen) may be a different situation.
Oral progesterone (a popular way to take it) derives its effect from the metabolizes rather than the raw substance.
This means that the liver breaks down the medication form of progesterone and the leftover metabolites are where the real effect comes from.
This is not uncommon and occurs with roughly 60% of medications.
Scientists call this "first pass" as it speaks to how much of a medication's effect is dictated by interaction with the gut and liver.
Oral progesterone (usually micronized and in oil) relies heavily on this first pass processing.
In fact, some powerful agents come out of this process:
Progesterone is metabolized into allopregnanolone and pregnenolone, which are neurosteroids and potent potentiators of the GABAA receptor.
Allopregnanolone is the basis for the new post-partum depression medication.
Of course, GABA is the star of the anxiety show not to mention the benzo #%*% show. (see CBD versus benzos and anxiety)
This is a very different course than when applied topically (via the skin for progesterone cream):
However, compared to oral progesterone, the levels of these neurosteroids have been found to be very low with parenteral routes like vaginal and intramuscular progesterone.
Why does this matter with CBD?
CBD uses the same pathway (partially) called Cytochrome P450.
It's known that pregnancy affects the absorption of medications due to these hormone effects on the liver.
The results showed that estradiol enhances CYP2A6, CYP2B6, and CYP3A4 expression, whereas progesterone induces CYP2A6, CYP2B6, CYP2C8, CYP3A4, and CYP3A5 expression.
The topical use of either hormone largely avoids this processing.
What does this mean with CBD?
If you do take CBD with HRT, take it at least 4 hours apart.
Oral progesterone peaks at about 4 hours. It then starts to go down from there.
I found this out directly.
I take 100 mg of progesterone right before bed and it helps significantly with sleep.
I was taking CBD with the progesterone and I found that I was losing the effects of my progesterone.
I spaced those two out (one before dinner and one before bed) and that issue went away.
Again, work with a naturopath who's current on how this all works.
The oral means of either estradiol or progesterone with their liver processing is the key constraint with CBD (or most medications for that matter).
Remember how progesterone and its metabolite had powerful effects on GABA, our brain's "brake" pedal?
Let's go there now.
Can you take CBD with benzo's for perimenopause
Benzo's (valium, Ativan, Xanax, Klonopin, etc) also use that same liver pathway.
Among benzodiazepines, alprazolam, triazolam, brotizolam and midazolam are mainly metabolized by CYP3A4, and quazepam, diazepam, and flunitrazepam are partly metabolized by this enzyme.
CYP is part of that P450 liver pathway we spoke of above.
CBD also uses the P450 pathway (with a shared focus on CYP3A4).
For this reason, CBD and benzos may affect how long each stays in the system.
In fact, we've had customers who say they can reduce their benzo dosage with CBD and have the same effect.
That being said, the same rule of taking CBD and benzos apart from each other applies.
The general rule is at least 4 hours but the farther the better.
Does CBD boost GABA the same way that benzos do?
Research is showing a different effect altogether.
As mentioned above, CBD does not work on the benzodiazepine receptor on GABA neurons.
We also know from studies on seizures that CBD helps to balance GABA Glutamate activity:
Preclinical evidence suggests that one aspect of the polypharmacy of CBD is that it modulates brain excitatory glutamate and inhibitory γ-aminobutyric acid (GABA) levels.
Here's the important piece.
Long term benzo use can down-regulate our entire, natural GABA system.
This is how the brain responds to an artificial boost:
- Acetylcholine for nicotine
- anandamide for THC
- GABA for benzos
Pick your drug and the brain has an opposing effect.
We're hearing from many women who have been on benzos for years!
This is completely negligent of the doctors.
Can CBD help to normalize this new deficit (on top of whatever was drawing down GABA, to begin with...hint hint...progesterone and estradiol loss during perimenopause)?
Let's look at schizophrenia studies.
Okay..that may sound extreme but bear with us (and my perimenopause hell was only slightly removed!)
A great deal of studies are pointing to early exposure to virus as a trigger for schizophrenia.
Our immune response is "primed" to over-react and it attacks the brain itself.
This can cause imbalances in GABA systems as a result.
CBD's effects on this dysfunctions GABA system?:
Overall, these findings show that CBD can restore cannabinoid/GABAergic signaling deficits in regions of the brain implicated in schizophrenia pathophysiology following maternal poly I:C exposure.
"Restore signaling deficits".
By the way, the areas of the brain they're looking at are the prefrontal cortex which is intimately tied to our primary anxiety circuit.
This is probably one of the most fascinating studies we've seen in terms of CBD's effects in very very complicated systems.
Just a head's up...there are studies on how benzo's rip choline from the body and brain.
It just may be the most important variable to prevent dementia and Alzheimer's.
In our CBD and perimenopause brain fog guide, we look at how estradiol directly supports choline function.
Combining a loss of estrogen and benzos may be a 1-2 punch for dementia according to research.
Next up...the other class of medications commonly given to women in perimenopause.
Can you take CBD with SSRI's for perimenopause
Lexapro, Effexor, Prozac, Zoloft, Paxil, Celexa, etc
GABA is a line worker.
Serotonin is more of a boss with control over so many systems, it's amazing we even tinker with it.
That's what SSRI's do.
They boost the availability (essentially the level) of serotonin.
This appears to be the goto medications given during perimenopause.
It's usually anxiety or depression that triggers the prescription but we're seeing a hodge-podge of symptoms being used to write the script.
After a 10 minute visit.
God forbid you check out the hormones which are driving the entire train wreck but that's where our health system is these days.
Fascinating deep dives into one of the blockbuster drugs of all time.
We'll zero in on whether you can take CBD and SSRI's.
Many people are looking to use CBD to wean off of SSRI's which we covered separately.
What about together?
We don't have good studies yet on CBD taken with SSRI's which is pretty fascinating considering the sheer numbers of people using SSRI's (not to mention women in perimenopause).
What do we know about the shared pathways?
SSRI's increase the availability of serotonin in the brain. They also have been shown to remodel the gut a bit which isn't surprising when you consider how important serotonin is to gut function.
SSRIs have been shown to normalize which is why for the roughly 30% of people that they help, doses and/or medications will have to change.
This speaks to the long term prospects of SSRIs:
However, a review of 14 naturalistic studies of long-term treatment for depression over 10 years found that outcomes for depressed patients were poor, with multiple relapses and large variability, both within and between individuals.
They went on to find:
Patients in nondrug-treated samples did not show worse outcomes, while some had superior outcomes.
In that study, 73% described withdrawal effects.
If you need to understand just how powerful and wide-spread serotonin effects can be, looks at these effects here:
Participants also reported a number of other emotional effects, including “feeling not like myself ” (54.4%), “reduced positive feelings” (45.6%), “caring less about others” (36.4%), and “suicidality” (36%).
I personally felt this with Lexapro. We wrote an entire article on SSRI's and homicidal or suicidal thoughts.
Craziest period of my entire life.
There's a great NIH review of SSRI's true effectiveness here.
There are two theories as to why they normalize or lose their effectiveness.
- Some people are true responders to the medication and therefore, the placebo effect goes away
- Receptors in the brain become insensitive to increased serotonin as a rebound reaction
First, the placebo effect:
Similarly, in a meta-analysis of 19 randomized, clinical trials for MDD, Kirsch and Sapirstein calculated that the placebo response and other nonspecific factors accounted for nearly 75 percent of the observed symptomatic improvement observed in drug-treated groups.
So basically, these people probably did not have a lowered serotonin level to begin with.
Again...you can't test serotonin levels in the brain.
Let's look at the second one since we can't do much about placebo effects.
Like with all things SSRI's, the terms are cloaked in techno-speak (withdrawal becomes serotonin discontinuation syndrome, etc).
Tolerance is called 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.
The effectiveness of recurrent treatments also figures in here:
The number of prior antidepressant drug exposures was negatively associated with response to initial sertraline therapy (odds ratio=0.81, p=0.0035) and noted that this odds ratio conveyed a 19.9-percent reduced likelihood of response in the current episode with each prior antidepressant treatment trial.
So with every additional treatment, the effectiveness drops by 20%.
This is a perfect example of tolerance.
Remember how this worked with benzos and GABA?
In this regard, prolonged antidepressant treatment may induce sensitization changes, not unlike the tolerance/dependence issues induced by chronic benzodiazepine exposure.
And finally...the drill-down further:
For instance, downregulation of five HT1a receptors might be responsible for the loss of antidepressant effects in some patients.
It's the effect directly on serotonin receptors that may cause tolerance:
Extensive data reported a number of cellular and molecular adaptive changes of the 5-HT system both at pre- (i.e. autoreceptor desensitization) and postsynaptic levels (i.e. stimulation of hippocampal neurogenesis and normalization of neurotrophins levels) following long-term treatment with various classes of ADs.
Classic tolerance as the brain tries to blunt the effect of outside chemical intruders.
What does CBD for serotonin function when it's skewed high or low?
This is one of our favorite pathways for CBD since serotonin is so critical to "feeling good".
Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity.
Allodynia is a heightened pain threshold. Anxiety...many of know that (see CBD and perimenopause anxiety).
The last bit is what we're interested in.
"Normalize 5-HT activity".
5HT is shorthand for serotonin.
"Normalize" is the most important word you'll read in this whole article.
It goes to the heart of the endocannabinoid system that CBD supports.
It has been shown to balance other key systems in the body:
- Immune system - inflammatory response
- Endocrine system - hormones
- Nervous system - neurotransmitters including….GABA and serotonin
It reminds of low dose naltrexone and the opioid system where it allows the system to recalibrate and function correctly (full review on low dose naltrexone here).
And the 5HT1A receptor specifically?:
Repeated treatment with CBD (5 mg/kg/day, subcutaneously [s.c.], for 7 days) increased 5-HT firing through desensitization of 5-HT1A receptors.
Another study compared CBD and fluoxetine (SSRI' - Prozac) had similar effects:
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).
Depression is one thing but we see the effects on anxiety as well:
The results suggest that CBD can attenuate acute autonomic responses to stress and its delayed emotional consequences by facilitating 5-HT1A receptor-mediated neurotransmission.
What about the long term use of CBD?
Moreover, adaptive changes in pre- and post-synaptic 5-HT1A receptor functionality were also found after chronic CBD.
You read through the research and it becomes very questionable to use SSRIs before CBD!
In our humble opinion of course.
CBD has not shown tolerance or addictive qualities in all the studies.
What about taking them together?
Back to the liver.
SSRI's also use the P450 pathways to metabolize and they even use different avenues there depending on the SSRI prescribed.
We want to be very careful not to spike serotonin or it can lead to serotonin syndrome...a potentially dangerous spike in serotonin.
Others have used it to reduce the SSRI levels.
Always work with a trusted doctor or naturopath.
When I used CBD to wean off of Lexapro, I took them at opposite times and I ramped up very very slowly.
Starting at about 30 mg, I increased to 100 mg of CBD after 1 month.
I'm now at 150 mg in the morning and 150 mg at night since research is pointing to 300 mg as the ideal dose for peak neurogenesis (building new research).
Of course, for women in perimenopause, this is all Fiddling While Rome Burns without hormones.
Check out our CBD and perimenopause review or estradiol guide.
You can't replace the critical role these hormones occupy with CBD or SSRI's.
My doctor was like many others and immediately went to benzos and SSRI's for what was a hormone issue.
If you're reading this...you're in the same sinking boat.
Some SSRI's are showing the same risk profile for dementia due to their effects on choline.
Since these medications appear to be the go-to with many doctors for women in perimenopause in lieu of hormones, we're really sending women into the abyss.
Very frustrating considering that the research is all there.
What about all the other meds they put me on (blood pressure meds, heart meds, cholesterol meds, etc)?
Other perimenopause medications and CBD
Here's the deal.
Roughly 60% of medications on the market use that same P450 liver pathways to metabolize.
Some get reduced as a result while others actually have their effect (like progesterone) from this metabolism.
Anything that "occupies" this pathway will affect how the other traffic gets through.
There are many common medications that women in perimenopause find themselves on.
Always work with a doctor but the general rule it at least 4 hours away from other medications.
The fact that these drugs are all interacting with each other (and other bodily systems) is a whole other matter but doctors rarely get into that.
We looked at the whole pain pathway here:
- CBD and Tylenol and Ibuprofen
- Low dose naltrexone
We've covered the hormones here:
- Can I take CBD with HRT (hormone replacement therapy)
- Can I take CBD during my period for PMS
CBD and Vitamin D
We can't find any research on the impacts of CBD on vitamin absorption.
The only reference is how CBD is a more powerful antioxidant than Vitamin C or E (see CBD and oxidative stress).
CBD and Benadryl
Check our CBD and perimenopause sleep to understand why Benadryl or Tylenol PM are not long term options for sleeping issues.
They rip choline from you and have been tied to dementia as a result.
CBD and blood pressure meds like Losartan, Valsartan, and others
This is tricky as the common blood pressure meds can be very entrenched in key systems.
CBD and Allery meds
This glimpse into perimenopause is just the beginning. 'Dre's Story' offers our complete, research-rich journey into hormones, tools to feel better, and safety. The full Perimenopause Toolkit with new additions can be found Here. Please review so other can learn. Feeling better starts with understanding what is happening.
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.