CBD and the Pathways of PSSD

It's finally hitting the front pages. Post SSRI Sexual Dysfunction.


We've been covering the issues around tampering with the all-powerful serotonin pathways at our problem with SSRIs review or how we tapered off of SSRIs.


Lexapro was prescribed for our founder and it almost ended her. Total lack of feeling of anything (including sex drive) which ended in 3 nights of no sleep and an ER visit.


We'll touch on exactly what's driving the flattening of feelings including libido below but more importantly, we'll look at tools to repair.


The focus will be on neurogenesis (literally building new brain connections) since it's at the heart of any possible repair.


There's also a question of steroidal hormones to address as SSRIs are prescribed earlier and earlier…during key periods of brain and body development.


This is tricky since research shows developmental changes in serotonin function with SSRI use during these periods (up to age 25 in the case of puberty-driven brain development).


Wait till you see big sexual wet blanket of prolactin below!


Green shoots are appearing and we'll look at them along these topics:

  • What drives PSSD
  • The clues were there for PSSD all along
  • Unwinding early trauma, infection, and stress
  • Steroidal hormones and serotonin
  • SSRI use during development - the wet cement problem
  • SSRIs and the pudendal nerve
  • SSRIs and prolactin (ding ding ding!)
  • Pathways to repair after PSSD
  • Balancing serotonin function (focus on histamine)
  • Supporting BDNF (key to repair/rewiring nervous system pathways)
  • Balancing/supporting steroidal hormones
  • Support repair of the pudendal nerve
  • Balance gut (where serotonin production dominates)
  • Balancing prolactin
  • CBD isolate and PSSD repair
  • Other tools to support serotonin rescue

Let's get started!

What drives PSSD

Serotonin is the master manager of ALL human behavior. We did a deep dive on serotonin specifically here or serotonin and self-esteem.


Fascinating research!


Libido is just one facet of that giant canopy of behaviors.


The problem is that SSRIs build tolerance.


This means that they are hitting the serotonin pathways and receptors too hard relative to our natural levels and that's assuming you had low serotonin function to begin with (they can't test brain levels).


As a result, the body/brain will start to push back and actually reduce serotonin receptor numbers and sensitivity longer term.

This is at the heart of the issue for short/mid-term serotonin dysfunction (or lack thereof).


Some people though are seeing flat affect (the technical term…not feeling anything) for years after!


Technically, the receptors should start to come online about 30 days after discontinuation.


The DNA that makes proteins to form the receptor literally needs to be turned back on.


With PSSD, this isn't happening. Why?


The best theories are a few-fold:

  • The serotonin pathway is exhausted by stress, infection, trauma (even early life)
  • Steroidal hormones are not supporting normal function and repair
  • SSRI use occurred during development thus being "baked-in" into future function
  • Clues from the Pudendal Nerve (which controls sensitivity to the pelvic floor)
  • The powerful prolactin pathway

We'll look at all of these and how to offset the effects.


The development piece is really driven by age of use (in utero, age 2ish, puberty through age 25).


This is a real issue and luckily, the brain is always changing and we'll look at how to boost that process.


So how prevalent is this?

Sexual dysfunction (SD) is commonly observed during SSRI therapy, occurring in approximately 20-70% of patients taking an SSRI

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034069/


Now magnify this by the # of prescriptions…especially for teens when serotonin is actually building out its future system!



https://psychnews.psychiatryonline.org/doi/full/10.1176/appi.pn.2017.pp9b2


That's pre-pandemic! It's only gotten worse and look at the teenage range (we'll explain why this is important below).


The brain doesn't stop developing until age 25 (with white tract matter continuing a decade beyond).



Okay…that's the bad news. Let's start to unravel the PSSD piece.


Let's first address each of the three items above.

Unwinding early trauma, infection, and stress

First, do no harm.


You can't bring serotonin back online without removing the ball and chain from prior trauma, infection, and stress. Especially in early life or in-utero.


Don't take our word for it…

Early life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits.

https://pubmed.ncbi.nlm.nih.gov/32981537/


Goodness…serotonin is behind the curtain in managing our response to future stress.


Other research shows serotonin function can actually be downregulated as a result:

These results suggest that early-life stress induces persistent changes in 5-HT1A receptor and SERT mRNA expression in key brain regions involved in the development of stress-related psychiatric disorders.

https://www.frontiersin.org/articles/10.3389/fnmol.2014.00024/full


Here's the key takeaway…serotonin is a powerful stress response buffer.


In fact, it's a buffer for pain, stress, infection, and more!


We've covered this in-depth in our trauma review on how the immune system is the future of mental health.


If your system has been "edited" by past stress (trauma and infection work the same way), this has to be addressed or your serotonin system will never function correctly.


Interestingly, this may be why you were prescribed SSRIs, to begin with.


The fascinating piece is that a great deal of this "markup" is done in the immune system and we'll look below at how to edit this out!


Newer studies on psilocybin are showing that the longer-term effects are due to DNA being turned on/off for….brain immune system genes!


Very exciting times.


Let's take a quick detour to what researchers have known for some time about SSRIs and libido.


You may get a little angry (at least we'll feel something, right??).

The clues were there for PSSD all along

Why the sudden explosion of media coverage around PSSD? Did they just find out about this effect?


No!


Two fascinating examples.


SSRIs have been used off-label for years now with premature ejaculation for males.


Specifically, delaying it and numbing the orgasm response.


Placebo, double-blind study looked at 100 men with premature ejaculation. The results?

All 100 (100%) patients experienced a significant increase in their AIPE total score after drug treatment.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374931/


AIPE is a score for PE.


Ummm…100%? You rarely see that number outside of election results from dictators.


We have a huge study on orgasm here and even premature ejaculation.


With SSRIs, it goes deeper.


SSRIs have been used in prisons to reduce the "activity" of sexual predators in their system.

Medications that affect libido through means other than via testosterone-suppression, include antipsychotics and serotonergic antidepressants (SSRI) (Baldwin 2003) and these medications are the most commonly used for this purpose. SSRIs have been associated with reduced libido and delayed orgasm in 60-70% of people taking them (Montejo 2001).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176659/


So…it's been known.


The fascinating piece is this.


When they're studying SSRI sexual dampening effects as a primary outcome (intended like above) versus a side-effect, roughly 70% of the people see a significant outcome.


Now…compare this with the estimate for people who see a benefit on SSRIs…


30%!


The mirror image. Mostly, people with severe depression.


We'll see below how the sexual effect may be due to too much serotonin which makes sense based on the 70/30 split.


For 70% of people taking SSRIs, serotonin was not the issue! Hence the hyper-serotonin PSSD effect.


We did a deep dive into the SSRIs research. They can't test your serotonin levels by the way. All guesswork is based on symptoms.


We'll assume you're not in prison…what's driving this with SSRIs and then we'll look at how to reverse it.


Let's first turn to a significant support system for serotonin.

Steroidal hormones and serotonin

We have to get past the thought that steroidal hormones are just about reproduction. Couldn't be further from the truth.

  • Estrogen directly supports serotonin function
  • Testosterone is converted in the mail brain to estrogen (lots of aromatase up there) to do the same
  • Progesterone supports GABA and calms immune response

Libido…for both men and women is driven by estrogen! Aggression is driven by testosterone.


In the brain, aromatase transforms testosterone, a hormone that drives sexual activity in males, into estradiol, which is a type of estrogen.

https://www.medicalnewstoday.com/articles/scientists-discover-key-brain-enzyme-controlling-sexual-desire-in-males


Either way, steroidal hormones are key to serotonin function.


Just look at estradiol's (our primary estrogen) effect:

  • Upregulates the expression of tryptophan hydroxylase, the enzyme in charge of the rate-limiting step in the serotonin biosynthesis pathway;
  • Helps augment serotonin receptor activation and subtype expression;
  • Blocks re-uptake; slows down degradation by suppressing monoamine oxidase expression – the enzyme that rapidly breaks down serotonin into inactive form. In other words, in order to have enough serotonin around, you need adequate estradiol levels.

https://www.zrtlab.com/blog/archive/mood-menopause-perimenopause/


We learned this the hard way during perimenopause (that story is here) which is how the SSRI prescription originally hit us.


Get your levels tested. There are lots of estrogenic signals in our food, environment, plastics, etc.


It's hard to get serotonin back in play without first balancing the supporting cast (estradiol or testosterone).


Look at the 2nd item.."helps augment serotonin receptor activation"


Hello! That's literally what we're trying to do. Undo the tolerance effect of SSRIs!


This is definitely part of how early life stress is "transmitted'"

It was hypothesized that the effects of early life CSS on OXT expression in dams is mediated by long-term changes in estradiol which are established during developmental exposure to early life CSS.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850073/


Essentially…early life stress can alter estradiol function long term.


Early life stress actually increases testosterone (and aggression) and stress hormones.


Interestingly, flux in estrogen is what feels so bad (anxiety, depression,etc). Remember…serotonin likes to be range-bound. Too high is almost worse (see serotonin syndrome) than too low.


Flux in estrogen directly affects our ability to handle…stress:

These data suggest estradiol variability may enhance emotional sensitivity to psychosocial stress, particularly sensitivity to social rejection.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764412/


Is there a gender connection between these estrogen flux effects and SSRI prescriptions during puberty (teenagers)?



https://www.statista.com/statistics/1133612/antidepressant-use-teenagers-by-gender-us/


Goodness…what are we doing to our girls??


It's better to evaluate hormone flux than try to monkey-hammer the manager of ALL human behavior.


PSSD can affect people of all ages but starting SSRIs early definitely carries some risk.


Let's look at that piece now.

SSRI use during development - the wet cement problem

Studies on mice who are exposed to SSRIs are fascinating.


Remember…the gut has its own "brain" - the enteric nervous system with the most neurons outside of the brain.


Over 90% of serotonin is actually made in the gut!


Here's the fascinating piece…serotonin during development directly manages the build-out of…our serotonin system!

Serotonin regulates both the development of serotonergic neurons (termed autoregulation of development) and the development of target tissues.

https://pubmed.ncbi.nlm.nih.gov/11750793/


So what happens when those mice are exposed to SSRIs?


Their gut nervous system doesn't develop fully. Reduced receptor numbers and function.


As a result, you see a slew of gut and brain-related issues. Dr. Attia has a great podcast on these effects here.

Although SSRI exposure during development leads to acute increases in serotonergic tone, it inhibits the development of the serotonin system and leads to reduced serotonin tone later in life

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963518/


This system's version of insulin tolerance.


Remember…the brain is being wholly remodeled during puberty…the prefrontal cortex (what makes us human) is being built out and "adultified".


Serotonin is front and center as the architect.


"Reduced serotonin tone later in life"


This is a real issue since development is an explosion of gene-directed growth. We'll look to see if we can crank up the brain-building machinery below.


Other signals are there for the brain as well:

Since SSRIs cross the placenta the unborn child is exposed to the maternal SSRI medication, resulting in, amongst others, increased risk for autism in offspring. This likely results from developmental changes in brain function

https://www.nature.com/articles/s41598-021-81327-z


Let's now turn south…to the local player.

Clues from the Pudendal Nerve (which controls sensitivity to the pelvic floor)

Serotonin is a huge systemic player in the brain, gut, and nervous system.


With PSSD, there's also a local aspect as well. Apathy may reside in the brain but "profound genital anesthesia" is local.


There's an important nerve structure that supports our entire pelvic floor in either gender which directly governs sensation including sexual touch.


So….to set the stage.


Imagine an oncoming bus barely misses hitting you. You jump out of the way thanks to your fight-or-flight autonomic nervous system.


The last thing on your mind…is sex. In fact, good luck while jumping out of the way thinking about anything remotely sexual.


The current theory on the pudendal nerve and SSRIs is that this system is blunting activity in the nerve trunk which manages sexual arousal locally.


How to make sense of this since the goal of SSRIs is to go the other way (rest and digest)?


Let's look at the key player in our "rest and digest" system. Acetylcholine (guide here).


This is your calm and focused player. The Vagus nerve is a major site of production.


So…SSRIs effect there??:

SSRIs inhibit the most important neuronal AChRs with potencies and affinities that are clinically relevant by binding to a luminal site that is shared with tricyclic antidepressants.

https://www.researchgate.net/publication/44653848


Okay…this is bad news. Acetylcholine is key to dementia and ADHD risk among others.


Does that bare out with SSRIs?

SSRI use is significantly associated with an increased risk of dementia when compared with nonuse.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079596/


And ADHD (along with autism):

We found an association between SSRIs/SNRIs prenatal use and the risk for ASD and ADHD (OR=1.42, 95% CI: 1.23–1.65, I2=58%; OR=1.26, 95% CI: 1.07-1.49, I2=48%, respectively).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686301/


Acetylcholine (sympathetic nervous system) directly opposes Adrenaline (parasympathetic nervous system - jump away from bus).


Could we be chronically stuck in a fight-flight pattern that is just hammering sexual function?


Interestingly, it's hard to find research on SSRIs and pudendal nerve activity. Go figure.


We do however have research on another powerful player. Prolactin!


If we were betting people, we would wager here.

SSRIs and prolactin for PSSD

Prolactin has many roles but one of them is to just hammer sexual desire, function, and activity.


It's the basis for the "refractory" period after orgasm during which a male is unable to get an erection.


The effect is not just for men though..

Most women (like most men) with elevated prolactin levels and well-defined hypothalamo-pituitary disease developed a lack of or a marked decrease in sexual desire, and many of them complained of problems with lubrication or orgasm

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4901097/


Sound familiar?


So…what about SSRIs' effect on prolactin?

Selective serotonin-reuptake inhibitors (SSRIs) have been reported as the most common cause of drug-induced hyperprolactinemia.1

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440440/


Ding ding ding!


We can drop the mic now. "Hyperprolactinemia".


Prolactin levels so high as to be associated with a disease state.


This speaks to why SSRIs can have a pretty immediate effect on sexual desire and function.


This level of prolactin may also indicate too much serotonin!


After all, they can't test your serotonin levels during that 10-minute visit they prescribe the SSRIs (sorry…jaded).


Either way, too much prolactin is a giant wet blanket on libido and sexual function not to mention orgasm.


Just a final wrap…

Serotonin also increases prolactin release, and selective serotonin reuptake inhibitors (SSRIs) can cause hyperprolactinemia. This may contribute to the sexual side effects commonly associated with SSRI use.

https://www.jneurosci.org/content/jneuro/36/28/i.full.pdf


Okay…that's all the bad news. Let's change course.

Pathways to repair after PSSD

We're going to focus on a few key areas with a focus on CBD and other tools:

  • Balancing serotonin function (focus on histamine)
  • Supporting BDNF (key to repair/rewiring nervous system pathways)
  • Balancing/supporting steroidal hormones
  • Support repair of the pudendal nerve
  • Balance gut (where serotonin production dominates)
  • Balancing prolactin

This is the best-known approach to healing after drug tolerance effects such as with SSRIs, MDMA, ecstasy, and finasteride (yes…issues like PSSD as well).


Why CBD?


It hits all of these key pathways but a fascinating review on PEA (another endocannabinoid) sets the stage (more on that in the pudendal nerve area).


Let's get started!

Balancing serotonin function (focus on histamine)

Long-term SSRI use leads to reduced serotonin function. This is tolerance and it's the enemy.


Keep in mind that serotonin can be exhausted or downregulated by the usual suspects:

  • Stress
  • Pain
  • Trauma
  • Infection

We've looked at this at our CBD and stress or serotonin and infection reviews.


So…check this out!

repeated treatment with low-dose CBD induces analgesia predominantly through TRPV1 activation, reduces anxiety through 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319597/


To translate…an injury caused exhaustion of serotonin which led to pain and anxiety.


CBD countered this by "rescue" of the serotonin (5ht) pathway!


Here's the critical piece...CBD is a positive modulator of serotonin.


It supports when low!


We don't see serotonin syndrome or the bizarre symptoms that come along with SSRIs or too much serotonin (insomnia, etc).


In fact, serotonin syndrome is a result of the hyperactivation of histamine!


You can actually get serotonin syndrome from drugs that block the breakdown of histamine (no direct serotonin effect needed).


CBD doesn't display this even at very high doses tested (1500mg daily and higher).


Check out CBD versus SSRIs to learn all about powerful differences.


In our how SSRIs really work review, we dug deep into the process and BDNF and neurogenesis was the key driver!


Let's go there now with CBD.

Supporting BDNF (key to repair/rewiring nervous system pathways)

First, some good news.

Serotonin nerve pathways can repair but it takes time (assuming we've taken the burden off the existing system from the above insults):


Following a lesion of serotonin axons in the rat neocortex with a high dose of amphetamine, there is a gradual reappearance of serotonin-immunoreactive axons over many months

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990493/


A key piece of this is BDNF, our brain's fertilizer:

BDNF treatment promoted the regrowth of 5-HT axons when initiated up to a month after PCA administration.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6772430/

5-HT is code for serotonin!


CBD's effect on BDNF and neurogenesis:

Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex

https://pubmed.ncbi.nlm.nih.gov/29869197/


Goodness. CBD directly supports BDNF and brain repair…in this case, the prefrontal cortex (a hangout for serotonin), the key hub that keeps fear at bay and makes us human.


Check out CBD and BDNF.


Other powerful BDNF players:


You're going to see this list over and over.


Let's turn south to steroidal hormones.

Balancing/supporting steroidal hormones

There's no workaround for testosterone, estradiol, and progesterone.


We have massive reviews on the health effects here:


Bioidentical is critical and testing is required. If you're older, beware of the "your levels are fine for your age" dismissal.


Find a good naturopath who wants to actually understands the power of steroids.


Vitamin D is a steroid that governs about 1000 transactions and helps to manage the other steroids.


So many people are deficient and endocrinologists want us up to 60ng/ml.


Then, there's the question of hormone flux. Remember, it's the change in estradiol that causes so much suffering.


Berberine shows interesting effects for balancing hormones such as with cases of PCOS (polycystic ovarian syndrome). An issue with pretty intense hormone imbalance and a new bacteria angle from recent research.


Check out the review of berberine.


B vitamins and Omega 3's are also crucial to hormone balance and of course, a constant stream of estrogen from our food and environment isn't helping:

  • Seed oils
  • Plastics (BPA, PFOAs, etc)
  • Hormones in food stock (used to fatten them up quickly or as a screen, for "infection")
  • Cosmetics, hygiene products
  • Birth control (progestins are tough on the body…sorry in advance)

Get your levels tested (not sure why this isn't part of the annual anyway) and for men, T has dropped at every age range by roughly ½ in the last 20 years!


See the testosterone review….just crazy data!


Let's turn specifically to the pudendal nerve.

Support repair of the pudendal nerve

Okay…this is both fascinating and a great excuse to introduce the endocannabinoid system in which CBD operates.


First, the endocannabinoid system is tasked with balancing other key systems in our body…maybe every system:

  • Nervous system - including serotonin, and more
  • Endocrine system - hormones!
  • Immune system - inflammation and cellular birth/death cycles (which feature BDNF!)

Alright…so right in the wheelhouse of repairing our systems.


CBD works like a feedback mechanism unlike THC (its plant-based cousin) which pushes in one direction (hence the "high", side effects, and tolerance longer term).


So…let's introduce a distant cousin…PEA. Short for palmitoylethanolamide (thank goodness).


Studies are starting to look at PEA for pudendal neuralgia:

Mechanical hyperalgesia caused by chronic inflammation was significantly reduced by both intraperitoneal and intra-articular injections of PEA.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645590/

This speaks to to endocannabinoid system being front and center in...repair!


Another study looked at CBD and neuropathy (essentially…damage nerve tissue usually from too much glutamate):

There was a statistically significant reduction in intense pain, sharp pain, cold and itchy sensations in the CBD group when compared to the placebo group.

https://pubmed.ncbi.nlm.nih.gov/31793418/


So between nerve repair (BDNF) and nerve recovery (neuropathy), there's exciting research towards pudendal nerve function IF the issue is mechanical and not upstream signals like serotonin and prolactin.

We'll touch on that below. Big review on PEA.


Next stop..north to the gut.

Balance gut (where serotonin production dominates)

We can't really discuss serotonin without looking at the gut.


Inflammation there is a huge hit to serotonin function thus the diarrhea, nausea, or constripation, etc which result from serotonin imbalance.


CBD has a powerful effect to counter imbalance there!


Since the endocannabinoid system is varied and far-reaching, CBD's interaction in balancing gut states is as well:

The underlying mechanisms of CBD action are complex but include GPR12, and GPR3 and GPR6 (Brown et al., 2017; Morales et al., 2018; Laun et al., 2019), besides many others, such as GPR55, TRPV1, and serotonin 5-HT1A receptor (Silvestro et al., 2020).

https://www.frontiersin.org/articles/10.3389/fncel.2022.867267/full


Okay…catch the last one! Serotonin.


We have massive reviews on CBD and gut inflammation.


Also, berberine, Vitamin D, steroidal hormones, and medicinal mushrooms are powerful players.


Let's turn to that prolactin piece (that's where our bet is).

Balancing prolactin

First, do no harm. Does CBD drive prolactin?

Basal prolactin (11.5 +/- 4.3 ng/ml) and growth hormone (1.5 +/- 0.7 ng/ml) levels were unchanged after placebo and CBD.

https://pubmed.ncbi.nlm.nih.gov/8257923/


Just a head's up…can't say the same for THC (cannabis):

Marijuana use had the broader hormonal changes since it influences estradiol (P = 0.000; B = −11.616), prolactin (P = 0.000; B = 3.211), SHBG levels (P = 0.017; B = 7.489), and T/E2 (P = 0.004; B = 14.030). Sedentary lifestyle (P = 0.028; B = 1.279) and tobacco smoking (P = 0.031; B = −2.401) influenced the prolactin levels.

https://www.frontiersin.org/articles/10.3389/frph.2022.820451/full


An increase in prolactin (wrong direction for libido). Cannabis smoke is estrogenic but blocks aromatase (which drives male libido in the brain).


Alright…so what about getting prolactin back in balance (too high with SSRIs)?


This is so interesting!


Let's introduce cortisol, our primary stress hormone.


First, cortisol and prolactin have a direct relationship.


To wit...

Stress is also a critical physiologic cause of hyperprolactinemia

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304861/


This makes sense…if you're under stress (discount danger basically), not a great time to reproduce.


Remember…hyperprolactinemia means too much…to a point where it's abnormal.


So…stress control is critical. CBD's effect there?


Check out the review of CBD and public speaking…for people with diagnosed social anxiety! A form of stress torture really.


The net effects of 600mg 1 hour before:

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/

Goodness.


Big review on CBD and performance anxiety or CBD and stress response but it goes deeper.


When SSRIs are first started, there can actually be an INCREASE in anxiety and depression.


What gives?


Turns out that serotonin being so far-reaching can increase corticotrophin-releasing factor, the initial trigger for stress (cortisol, etc).


SSRIs will actually boost our stress response initially!


CBD and corticotrophin-releasing factor?

Interestingly, cannabidiol at low (5 mg/kg) and intermediate doses (15 mg/kg) successfully blocked the effects induced by acute stress on corticotropin-releasing factor, pro-opiomelanocortin and glucocorticoid receptor gene expression.

https://journals.sagepub.com/doi/abs/10.1177/0269881118805495


Why interestingly?


Because it didn't have this effect under times of low stress!!! Remember…feedback mechanism when pathways are taxed.


Keeping prolactin under wraps requires balancing cortisol and stress pathways.


Some usual suspects on the stress response front:


Let's get practical now. How much? What type? Etc.

CBD isolate and PSSD repair

First, peak neurogenesis guides our dosing regimen for CBD.


300mg daily matches that level in research.


There are higher doses for more severe issues but brain repair peaks at 300mg.


Over time, this level can come down but check out our review for how to increase bioavailability by up to 4xs.


Next up is the type of CBD.


CBD isolate (CBD by itself) is very different from full-spectrum. Aside from all the research being based on CBD by itself, histamine is the big player with PSSD.


Remember that the excess of SSRIs can actually occur due to histamine being boosted!


CBD isolate calms histamine response when excessive (see CBD and histamine or CBD and brain inflammation) but full spectrum can actually trigger responses.


We see this all the time when people see their anxiety go up with full-spectrum.


More on CBD isolate versus full spectrum or check out product reviews to see people's actual histamine response.


Certain requirements are mandatory for CBD generally:

  • From organically grown hemp in the US at FDA-registered farms
  • 3rd party tested (available at top of every page)
  • Zero THC - can trigger histamine and affect prolactin/hormone levels
  • No solvents
  • No pesticides
  • No heavy metals
  • No mold
  • No bacteria


Then, there's cost.


We price our 6000mg bottle at 2-3 cents per mg of CBD before discounts of up to 50%.


We found CBD after a brutal experience with Lexapro and serotonin syndrome (that story is here) following perimenopause (when estrogen goes sideways! - go figure).


If we can help other people avoid what we went through, it's worth it.


To that end!

Other tools to support serotonin rescue

We've covered the big pathways and CBD's effect there.


It's not the only player! Here's our PSSD rescue toolkit:

  • CBD isolate
  • Vitamin D
  • B vitamins (key to hormonal balance)
  • Berberine
  • Steroidal hormone support
  • Medicinal mushrooms
  • Tryptophan (can't take while on SSRIs)
  • Psilocybin (when legal or available in your area)
  • Omega 3's (fish oil, etc) - avoid seed oils and processed foods
  • Turmeric
  • Exercise
  • Mindful meditation


We have giant reviews on most of these because they don't build tolerance (enemy #1 with many supplements) and address the key pathways mentioned above! You can search top of the page for any of these guides.


Look…our experience with Lexapro opened up an entirely new world to us regarding our health and wellness.


You have to use this horrible experience to learn and build back even stronger!


Be well. Heal. Get back to health.

Related Research:

The problem with SSRIs

CBD versus SSRIs

Top 10 Tips to Taper SSRIs

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.

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