CBD Instead of Prozac?  Research on the Shared Serotonin Pathway

cbd and prozac

We've covered CBD versus SSRIs in general but let's look at the original player in the whole SSRI world….Prozac.


Interestingly, SSRIs (the class of medication) haven't changed too much in half a century aside from the cost.


The Effexors, Lexapros, and Paxils of the world all lead from the original discovery and offering of Prozac.



how does prozac work



It's still the most common SSRI on the market.


We'll dive into how Prozac (fluoxetine) works but more importantly, we'll look at questions around CBD and Prozac.


They share a powerful pathway but act on it in very different ways.


This difference is probably the most powerful effect of CBD when it comes to tolerance and long-term use. 


These are the topics we'll cover: 

  • A quick intro to the serotonin pathway
  • How Prozac works with serotonin
  • How CBD works with serotonin
  • The Tolerance difference between CBD and Prozac
  • Can you take CBD with Prozac
  • How Does CBD interact with Prozac
  • Can you use CBD instead of Prozac
  • The estrogen connection to serotonin
  • How much CBD to replace Prozac
  • What's the best CBD to use instead of Prozac


Let's get started!

A quick intro to the serotonin pathway 

We really need to understand the stage upon which these two play.


It may be the most powerful stage in terms of mood and emotional state.




It's commonly tasked as the "feel good" neurotransmitters but that's not entirely correct.


how does prozac affect serotonin


Really, it's a master regulator of all human behavior! 

  • Sleep
  • Sex
  • Appetite
  • Motivation
  • Self-esteem


Everything.  Check out our CBD and serotonin review to learn more.


There are fascinating studies where a person will reject bad offers if their serotonin is higher.


Our Serotonin and self-esteem review really gets into this.


The tie-in with depression (for which Prozac is generally prescribed) is more nuanced.


You can think of depression as a reduction in connectivity or communication across and within the brain.


This can be the result of a series of different insults: 

  • Chronic stress (eats up serotonin)
  • Trauma
  • Infection (even early infection in utero)
  • Excess glutamate (our brain's "gas pedal" - see CBD and glutamate)
  • Drugs and chemicals


prozac and depression


Here's the linchpin for serotonin.


What's fighting back against all this carnage in the brain is a family of chemicals with the biggest player being BDNF.


BDNF is short for brain-derived neurotrophic factors.  Basically the brain's fertilizer!


bdnf and prozac


Studies show that serotonin drives BDNF and BDNF drives re-engagement and growth in the brain.  The opposite of what causes depression.


This process is called neurogenesis (see CBD and brain repair).


We'll touch base on this below with how SSRIs like Prozac actually work.


Let's go there now.

How Prozac works with serotonin 

Prozac is an SSRI (selective serotonin reuptake inhibitor).


Basically, it makes more serotonin available to our neurons.


It juices serotonin levels!


Now, if this was the cause of any antidepressant effect, you would expect it to work pretty quickly.


After all, benzos juice up GABA, and their effect occurs in minutes.


Prozac actually takes a few weeks to kick in and in fact, anxiety and depression can actually INCREASE during that initial period.




Researchers found that when BDNF is blocked, SSRIs lose their neurogenesis and antidepressant effects!


BDNF is literally brain-building so that takes time.  A few weeks it turns out.


Check out CBD and BDNF or how SSRIs actually work to look at the research.


how does prozac work


SSRIs like Prozac work in about 30% of patients and studies show it was really skewed by people with serious depression.  


What about CBD?

How CBD works with serotonin 

CBD also works on the serotonin pathway along with others (GABA, glycine, etc).


Technically, it's called an allosteric positive modulator in that pathway.


This means that it works like a feedback mechanism!


  • If serotonin is low, it supports it
  • If serotonin is in range, it doesn't do anything
  • If serotonin is high, it may offset it


We see this effect across many different pathways with CBD.


Let's look at one big example following an injury (serotonin governs pain thresholds): 

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. 



Due to the injury, serotonin became exhausted.  As a result, pain and anxiety both went up.


CBD countered all these effects and primarily did so by "rescuing" serotonin (5HT).


You see words like normalize, rescue, and modulate all the time with CBD.  


It doesn't just continue to boost in one direction as Prozac does.


There is no example in research of serotonin syndrome (too much serotonin) from CBD like you have from Prozac.


Remember how we said that BDNF or neurogenesis is the key to how Prozac works?


Here's CBD's effect there: 

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



In our big review of CBD and depression, we look at how the prefrontal cortex is especially important and under assault with depression.


Synaptogenesis is literally the creation and growth of the connections between neurons that counters what drives depression.


Let's talk about how Prozac and CBD are very different from each other in one crucial element.

The Tolerance difference between CBD and Prozac 

This is it.  The big difference.


There's a fascinating effect with any chemical or medication that pushes a key pathway up or down in one direction like Prozac.


The body pushes back!


We see this for almost every medication out there including Prozac.


does prozac build tolerance


Essentially, the brain will start to reduce the number and sensitivity of serotonin receptors to offset the external boosting of serotonin.


With time, Prozac will have less and less effect.  This is why doses and even other SSRIs are layered on with time.


It's the basis for tolerance.


Here's the issue….your natural serotonin level is slowly being suppressed as a result of this.


This can make coming off of Prozac brutal (see how to wean off SSRIs with CBD).


Technically, it's not called addiction because dopamine isn't spiked by Prozac but the withdrawal is some of the worst out there.


It was harder for our founder to come off Lexapro than off of Xanax (see CBD versus benzos), a known highly addictive substance.


Serotonin is just so integral to how we feel and SSRIs like Prozac really integrate into that system.


We did a deep dive on all the repercussions of this at our Problem with SSRIs review.


To get around the nasty word "addiction", it's classified as "serotonin withdrawal syndrome".


Great.  Feels just as horribly regardless of the name.


Keep in mind that DNA that controls the making of your serotonin receptors has to actually be turned back on. 


This can take 30 days or more depending on how long you were on it.


We have a whole section of how we weaned off of SSRIs.


best tools to taper prozac


There's a warning not to stop cold turkey which speaks to your underlying serotonin function's state after use.




What about CBD?  Does it build tolerance like Prozac?




We have a whole review on CBD and tolerance.


Since it only supports serotonin when it's low, it doesn't trigger the push back from our brain to downregulate natural function.


  • CBD does not build tolerance
  • CBD is not addictive
  • CBD is not hedonic (causes pleasure)
  • CBD does not spike dopamine (key to addiction)


This really is CBD's greatest strength and we see it throughout the research and across pathways.


In fact, CBD has been shown to help with withdrawal from other powerful drugs such as opioids and alcohol (see CBD and opioid addiction or CBD and alcohol addiction).


This again speaks to its re-balancing effect when key pathways are skewed (opioid system with opioids and GABA/serotonin with alcohol).


Let's look at some more practical questions.

Can you take CBD with Prozac? 

Usually, people are looking at CBD to wean off of Prozac for the reason above.


In terms of casually taking the two together, there's one key aspect to look at.


Prozac or fluoxetine has a very long half-life which means it stays in the system for a long time.


Its peak level is about 6-8 hours after use.


Both CBD and fluoxetine use the same pathway in the liver for processing...in fact, 60% of medications use this same pathway.


For this reason, we want to take them away from each other.


The general rule is 4 hours but based on the peak level of 6-8 hours, longer is better.


If the liver is busy processing CBD, fluoxetine may remain in the blood longer.


Test how you feel and word accordingly but the 4-hour separation is a good rule.


We have a whole review on Top Tips to Taper SSRIs


Along the same lines…

How Does CBD interact with Prozac? 

The main interaction is that CBD may slow the metabolism of Prozac since they both use the same liver pathway for processing.


This means that Prozac may remain in your system for a longer period of time.


Essentially, it correlates to being stronger for longer.


As we mentioned above, CBD shouldn't boost serotonin further into serotonin syndrome like other medications (anti-nausea, etc) can do with Prozac.


That being said, everyone is different so pay attention to how you feel and use small amounts to start.


With Prozac, it's very important that the time and dose are the same.  


Again, with longer-term use, your natural serotonin safety net has been reduced and it can feel pretty horribly to miss the daily dosage.


Adhere to the 4+ hours separate between the two and work with your doctor naturopath!

Can you use CBD instead of Prozac? 

Based on the research a.nd how they both work, it's hard to argue against using CBD instead of Prozac.  Work with your doctor (or naturopath who didn't prescribe Prozac to start)


CBD supports serotonin when low but doesn't build tolerance


It also affects many other pathways tied to depression such as: 


Prozac can't do those things!


These are some of the "insults" that are causing depression to begin with.


If you don't address those, we're not addressing what's drawing down serotonin, to begin with.  


Water (serotonin) is flowing out as fast as we put it in (Prozac).


Along with CBD, there's interesting research on the following: 

  • NAC - fascinating research - addresses excess glutamate and oxidative stress
  • Magnesium glycinate - supports GABA and calms excess glutamate
  • Vitamin D - get your numbers checked and see our review 
  • Berberine - addresses gut inflammation which sets the barometer for the brain as well
  • Steroidal hormones - estrogen and testosterone directly drive serotonin!


These tools along with CBD are powerful players.


Psilocybin will soon be a very powerful player for depression (especially treatment resistance) as it comes online.  The research there is nothing short of groundbreaking (albeit 60 years old now).


We compare CBD versus SSRIs but our CBD and depression is the fuller review.


Let's take a detour for ladies out there.

The estrogen connection with serotonin 

The lifetime risk of major depression in the United States is 21% in females versus 13% in males 



And for antidepressants like Prozac?

Women are nearly twice as likely as men to be taking the medications, the report found, with antidepressants used by 16.5 percent of females compared to just under 9 percent of males. 



What on earth is going here?


Hello, estrogen!


Many people (and doctors) think of estrogen as purely for reproduction.


Couldn't be further from the truth.


Check out our estrogen and mental health to learn more.


Here's the little secret: 

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.  



Goodness...Estradiol directly drives serotonin.


steroidal hormones and prozac


It drops off the map in our late 40's.  That's how we found CBD to begin with...a brutal perimenopause starting around age 47.  That story is here.


Most women who go into their GP or even OBGyn will be likely be prescribed a benzo first or jump right to an SSRI like Prozac.


Never...ever...looking at estrogen's effect.  It's infuriating really.  We looked at Estradiol safety here and more recent research on oral bioidentical here.


The Dutch Test is a great way to check the status of key steroidal hormones.  Don't discount progesterone either (see Progesterone review).


The two work together for mental health and serotonin function.


What about amounts of CBD to replace Prozac?

How much CBD to replace Prozac 

This partially depends on where you are on the Prozac roller coaster.


If you've been on it for a while, you may face pretty serious withdrawals, the so-called "serotonin withdrawal syndrome".


This can be brutal.


When we weaned off of Lexapro, we use a pill cutter to slowly reduce the level over 30 days and we had only been on it for a few months.


We hear from people that have been on Prozac for decades!


If we look at the studies on opioid withdrawal, it breaks down the dosages into two distinct periods: 

  • Initial withdrawal period - Day 1 - 10 on average
  • Rebuilding period - Day 11 - 30 (and beyond depending on the length of Prozac use)


The initial period, when withdrawal effects are brutal pointed to 600 mg daily.


This can be broken out into 3 doses after a meal but away from Prozac by at least 4 hours.


If you hold under your tongue for up to 60 seconds, this will boost the bioavailability.


Once the initial withdrawal period settles down, research then points to 300 mg of CBD daily for peak neurogenesis.


Remember, this is what we're after, to begin with!  It's the MEANS by which there is an antidepressant effect.


See CBD and BDNF or CBD and brain repair.


This can continue long term as needed.  Again, remember to address the root driver of depression such as immune hyperactivity, excess glutamate (brain's gas pedal), and systemic inflammation.


 There's fascinating research on how early trauma, infection, or stress (even in utero) can downregulate serotonin later in life and that requires addressing the immune system edits!

early trauma and prozac


What about the type of CBD?

What's the best CBD to use instead of Prozac 

First, basic requirements: 

  • From organically grown hemp in the USA at FDA registered farms
  • CO2 processed
  • 3rd party tested (ours is at top of every page)
  • No THC (we'll explain below)
  • No heavy metals
  • No solvents
  • No pesticides
  • No mold
  • No bacteria


best cbd to taper prozac

The THC part is important.  THC also builds tolerance with time on the anandamide pathway.


Anandamide is our "bliss" molecule so we don't want to slowly downregulate those receptors (called CB1).


See CBD versus THC to learn more.


We focus on CBD isolate because all the research is on CBD by itself.


Most of the market pushes full-spectrum (with little research) but there's a big issue there.


40-60% of the population has histamine issues and full-spectrum can have very different side effect profiles.



prozac and histamine



The last thing we want to do is trigger histamine since it's excitatory in the brain just like glutamate (gas pedal) and that causes inflammation.


One of the insults mentioned above for depression.


Histamine issues go up as we get older and for women (thanks for leaving progesterone!).


See CBD isolate versus full spectrum to learn more.


Then, there's cost.


The key measure is the cost per mg of CBD.


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


This is the cheapest price we can find for high-quality CBD isolate.


We do this because we originally found CBD isolate during a tailspin coming off of Lexapro (a newer SSRI like Prozac).


If we can help people avoid that situation, it's well worth it.


Be well. Take care of each other.  Take care of yourself.


Related Research:

The Problem with SSRIs

CBD versus SSRIs

Top 10 Tips to Taper SSRIs


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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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