Comparing CBD versus SSRI's for Serotonin

by Indigo Naturals April 24, 2019

There was a mad scramble to find an alternative to the benzos for anxiety.

Benzodiazepines (Valium, Ativan, Klonopin, Xanax, and others) have a known and severe addiction risk that comes along with their anti-anxiety effect.

You can read all about it at our CBD versus benzos article here.

Then came fluoxetine (Prozac) in 1987.

That really marks the beginning of the SSRI (Selective Serotonin Reuptake Inhibitors) revolution.

They basically increase the amount of serotonin that is available to neurons.

This was originally geared towards depression.

In fact, if you read through this massive history of SSRI's below (we did...it's fascinating) and search or instances of the word "anxiety", it comes up twice

MDD also has been found to have comorbidity with other DSM disorders such as anxiety disorder, substance abuse, and impulse control disorder
Symptoms of depression or depression mixed with anxiety

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428540/#R89

Okay...so in conjunction with depression.

You can try that same trick with many other articles on SSRI's across NIH research.

Check out CBD and depression to get deep into how that works separately.

Interestingly, anxiety does come up in one area for SSRI's.

Side effects.

It's clear that SSRIs are primarily a medication for depression so why are they the most prescribed option for anxiety?

Great question and we'll get into it below.

We're going to learn all about the serotonin pathway in anxiety and SSRIs specifically.

Interestingly, we're going to show research that points to an interesting fact…

The positives of SSRI's may be the result of their effects on endocannabinoids and BDNF (brain's fertilizer)!!

Finally, we'll look to see how CBD affects those same pathways according to research.

Always research!

Since serotonin is called the "feel good" neurotransmitter, let's see if that's the same thing as "feel calm".

We'll save the topic of SSRI's for depression versus CBD for a whole separate article.

See the article on the comprehensive guide to CBD and depression.

These are the key topics:

How do SSRI's work for anxiety
How do serotonin levels affect anxiety
The endocannabinoid system and serotonin
CBD versus SSRI's for anxiety according to research

We go into a powerful new tool for addiction and habit with our book here:

Let's get started.

How do SSRI's work

First, what is an SSRI?

See the article "How do SSRI's really work a deep dive into brain repair".

As we mentioned, it's short for Selective Serotonin Reuptake Inhibitor.

Goodness...what does that mean?

A quick history.

It all dates back to the "monoamine" theory.

Researchers stumbled on anti-depression effects through medications designed for anti-tuberculosis and other uses.

They found that these substances would allow more specific neurotransmitters (called amines) such as serotonin, dopamine, and norepinephrine to be made available to neurons.

"Selective" just means that a new class could target one neurotransmitter (such as serotonin) and leave dopamine alone (important for addiction).

And voila...Prozac!

It's was the first blockbuster SSRI that targeted serotonin. Side note...the original block buster drug was synthetic estrogen and here's the kicker...estrogen drives serotonin!!

Interestingly, when tryptophan or serotonin is depleted in people without depression, they do not then become depressed!

This has to lead many researchers to re-evaluate the role of serotonin in depression as more of an adjunct or knock-on cause.

As we mentioned before, serotonin is more a lever for a depression.

What about SSRI's for anxiety?

Let's look at studies.

Keep in mind the stat from above where there is a strong correlation between depression and anxiety in some people.

Lexapro (Escitalopram)

Mean changes from baseline to Week 8 on the HAMA total score using a last-observation-carried-forward (LOCF) approach were -11.3 for escitalopram and -7.4 for placebo (P<.001)

The HAMA test is up to 56 points. The difference between Lexapro and placebo for anxiety was just under 4 points (roughly 7%).

The 11.3 point drop is roughly a 20% improvement over no treatment (placebo or otherwise).

https://www.ncbi.nlm.nih.gov/pubmed/15274172

Zoloft (sertraline) had a similar response with general anxiety disorder:

Hamilton anxiety scale between sertraline (mean=11.7) and placebo (mean=8.0).

Interestingly, with SSRI's, most of the positive benefit is on "psychic" aspects of anxiety versus "somatic" aspects.

psychic anxiety (mental agitation and psychological distress)
somatic anxiety (physical complaints related to anxiety)

https://dcf.psychiatry.ufl.edu/files/2011/05/HAMILTON-ANXIETY.pdf

Anxiety is highly influenced by placebo as you can see by the large improvement (8 versus 11 for the medication).

Effexor (Venlafaxine)

An actual clinical trial can be found here:

https://clinicaltrials.gov/ct2/show/results/NCT00183274

A study for Effexor with non-depressed people (very important) had similar results here:

These included a change of 1.7 (versus 1.3) from baseline on CGI severity item scores and a final score of 2.2 (versus 2.6) on the CGI global improvement item.

https://www.ncbi.nlm.nih.gov/pubmed/10831478

This ".4" improvement over placebo is about 20%. This mirrors the results for the SSRI's above.

There's a great meta-analysis (attempts to statistically summarize many different studies) here:

https://www.bmj.com/content/342/bmj.d1199

It really is what we've been searching for in terms of SSRI's as they deal with anxiety.

First, it's based on the HAMA score which is a well-accepted test for anxiety (not depression).

Secondly, all the major SSRI and SNRI's are listed.

Response means a drop in a score of 50%
Remission means a drop below 7 on the HAMA score (out of 56)
Drop out due to adverse reactions (side effects)

There are some interesting charts.

One shows the relative ranking of the different medications for the three attributes above.

Fluoxetine (Prozac) was ranked #1 for both response and remission.
Sertraline (Zoloft) was ranked #1 for adverse reactions.

This is very interesting.

Also, the improvement over placebo was high for all the listed drugs except for Lexapro (Escitalopram)

Just for *%#$ and giggles, let's compare that with top 11 "psychiatric" prescriptions in the US in 2016:

Zoloft (sertraline) – Depression
Xanax (alprazolam) – Anxiety
Lexapro (escitalopram) – Depression
Celexa (citalopram) – Depression
Wellbutrin (bupropion) – Depression
Desyrel (trazodone) – Anxiety, Depression
Prozac (fluoxetine) – Depression
Adderall (dextroamphetamine and amphetamine) – ADHD
Ativan (lorazepam) – Anxiety
Cymbalta (duloxetine) – Depression
Effexor (venlafaxine) – Depression

https://psychcentral.com/blog/top-25-psychiatric-medications-for-2016/

Okay, #1 is Zoloft which had the worse adverse reactions and low relative effectiveness.
#2 is Xanax, very short-acting and addictive benzo (more here on CBD versus benzos)
#3 is Lexapro which had the least improvement over placebo.
Then there's #11 (which is why we didn't stop at 10!) which is Effexor.

Notice how they're all listed for depression except for the benzo??

More importantly, where's Prozac?

It was ranked highest in both response (improvement) and remission (drop-in HAMA score below 7) with adverse reactions way below Zoloft.

Hmmm...if we were cynical. we'd say it's out of patent protection..we won't go there.

But the numbers do!

These results are good but not nearly as strong as for benzos since they directly affect GABA levels (much more relevant for anxiety).

The downside of benzos is plenty can be found at our CBD versus benzos for anxiety.

SSRI's were viewed as the least of two evils in terms of treating anxiety essentially.

One important note...SSRIs do build tolerance so your natural serotonin pathway will actually go down over time. Tolerance!

Don't get us started on the simple antihistamine hydroxyzine:

Efficacy was maintained throughout the 4 weeks of treatment and after abrupt discontinuation. In another controlled trial vs. lorazepam, hydroxyzine demonstrated greater and more rapid cognitive improvement.

https://www.ncbi.nlm.nih.gov/pubmed/9777055/

The average drop in the HAMA score was over 12 points (compared to best-case 11 above).

More importantly, it's not habit-forming like the benzos and doesn't carry the brutal (Serotonin withdrawal syndrome) effects when coming off.

That's a whole other article but just remember it when we talk about the type of CBD to look at (hint hint...histamines).

Here's a good review of medications for anxiety:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181684/

We know that SSRIs directly increase the levels of serotonin.

Let's focus there for anxiety now.

How do serotonin levels affect anxiety

Serotonin is a powerful workhorse in the brain and body. Master regulator of ALL human behavior. So there's that.

If you look at the side effects of SSRI's, you're stuck with just how many pies serotonin has its fingers in!

What about Serotonin and anxiety?

We know that GABA is the primary pathway for anxiety and serotonin is primary for depression (in terms of standard medical practice).

Really, new research is pointing more to inflammation, stress response, and gut health and even early trauma but that doesn't sell billions of dollars of medications.

The real future of mental health is the immune system (que psilocybin). So...how do SSRI's (which drive serotonin levels) help with anxiety?

If you research "Gaba and anxiety" at NIH, you get lots of studies.

Try this with Serotonin and anxiety.

It's really thin.

Let's look at some of the better-delineated pathways.

Serotonin required for stress response
Serotonin required for neural plasticity (ding ding ding)
Serotonin as a modulator of Glutamate and GABA

See the article on glutamate and mental health.

Remember that fear and anxious emotional reactions primarily reside in the Amygdala.

There's a review of this avenue but as the author states, the role of serotonin remains poorly understood:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820447/

The brain plasticity piece might reflect more of a root cause.

SSRI's have been shown to remodel brain networks.

For good and bad.

The good. (again, tied to depression).

Stress, inflammation, and depression can cause certain parts of the brain to atrophy .

Neurons can shrink, retrench, and even die under constant depression/stress.

By affecting the pathways for depression, SSRI's may help to stop and reverse the brain loss.

Chronic stress and depression reduce serotonin levels:

https://www.ncbi.nlm.nih.gov/pubmed/24300695

The key items jump out in this research:

Specifically, chronic stress significantly attenuates 5-HT neurotransmission and 5-HT1A autoreceptor sensitivity, and this effect could represent an endophenotypic hallmark for mood disorders.

So chronic and even acute stress or depression affects serotonin.

This shrinks the ability of the brain to make new connections (neurogenesis) which results in a reduced ability to handle stress:

In addition, by decreasing neurogenesis, CUS decreases hippocampal inhibition of the hypothalamic-pituitary-adrenal (HPA) axis, exacerbating stress axis overactivity

To translates, the brain is less able to keep the fight or flight system under control. Panic. Anxiety! Resilience goes down.

Finally...in terms of why SSRI's which affect serotonin might have an impact:

Similarly, we discuss the possibility that adult hippocampal neurogenesis mediates antidepressant effects via the ventral (in rodents; anterior in humans) hippocampus' influence on the HPA axis, and mechanisms by which antidepressants may reverse chronic stress-induced 5-HT and neurogenic changes.

To translate, 5HT is the chemical name for serotonin.

This study is showing that serotonin's very ability to affect anxiety and depression may result from boosting repair of brain tissue damaged from stress.

This may be the most important take-away. In fact we did a massive review of how SSRI's actually work and it mainly came down to BDNF, our brain's fertilizer. More here.

This partially explains why it can generally take weeks to months in order to have an effect.

We're remodeling the brain!

The bad.

Some of the side effects associated with Prozac in humans, such as anxiety and behavioral switching patterns, maybe due to excessive denaturation of granule cells in the hippocampus

https://www.sciencedaily.com/releases/2011/03/110316084425.htm

Basically, you're monkeying with a powerful pathway in one direction. It's too much...like redlining an engine.

Speaking to some of the side effects…

These changes to the cell's plasticity were associated with increased anxiety and alternating between periods of hyper or hypoactivity.

That's going the wrong way.

We're messing with the master regulator of all human behavior.

Finally, since serotonin is everywhere in the brain, does it affect levels of Glutamate (gas pedal) and GABA (brake pedal) which are intimately tied to anxiety?

Yes.

In several brain regions, 5-HT is diffusely released by volume transmission and behaves as a neuromodulator rather than as a “classical” neurotransmitter.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430669/

Again, 5-HT is the scientific name for serotonin.

If you've read our comprehensive look at CBD and anxiety, the Amygdala is all over it!

The effects on Glutamate and GABA are varied depending on where you are in the brain.

As we said, serotonin is a workhorse of brain signaling!

Here's the deal.

No doctor can test if you're "low" in serotonin.

They just go based on symptoms (depression).

For anxiety, it's not even a good proxy but they're trying to avoid the serious side effects of benzos.

Too much serotonin has actually been tied to social anxiety.
Increasing serotonin can cause anxiety during the first few weeks (by boosting CFR - the stress cascade).
An excess of serotonin can cause a host of nasty side effects and worse (serotonin syndrome).

So the question begs…

Can we get neuroplasticity, serotonin balancing, and anti-stress and inflammation a different way?

We're almost there.

One more stop.

The endocannabinoid system and serotonin

Before jumping into CBD, let's look at the system it operates in….the endocannabinoid system.

Every living animal has one and recent research are showing it's critical to balancing other key systems:

Nervous system - including neurotransmitters like serotonin, GABA, and Glutamate
Endocrine system - hormones including histamine and others
Immune system - inflammatory responders like cytokines and microglia (in the brain)

Since SSRI's are primarily concerned with boosting serotonin, our question is how does serotonin and the endocannabinoid system interact.

Do they at all?

Yes!

Remember that the basic role of the endocannabinoid system that researchers have teased out is that a regulator.

Finding balance in other systems.

Serotonin is a neurotransmitter and under the same governance as any other player in that system.

To put a point to it…

Ample evidence from behavioral studies also suggests that eCBs are important regulators of stress responses and a deficit in eCB signaling contributes to stress-related disorders such as anxiety and depression.

"eCB's" is short for endocannabinoids which we have naturally in our brain and body.

How does it exert its effect on stress response?

The eCB-induced modulation of stress-related behaviors appears to be mediated, at least in part, through the regulation of the serotoninergic system

Via our serotonin pathway!

https://www.ncbi.nlm.nih.gov/pubmed/21354188

Remember that the role of serotonin for anxiety is more tangential than for depression.

Most of the effect appears to be reversing the loss of critical brain mass as a result of stress, inflammation, and/or depression (which research is saying may just be another variant of inflammation).

The effects of the endocannabinoid system are all over this process!

First, researchers deleted CB1 receptor genes or blocked the receptors themselves...

CB1 is the primary endocannabinoid receptor found primarily in the nervous system:

Similarly, genetic deletion of CB1 receptor profoundly enhances the secretion of stress hormones (i.e. ACTH and corticosterone) elicited by an array of stressors

The direct effect was an increase in the very chemicals that drive anxiety.

When they enhanced signaling at those receptors...

It has been shown to reduce the behavioral responses to stress

https://www.ncbi.nlm.nih.gov/pubmed/12461523/

Goodness...a resilience switch!

Serotonin is directly involved in our stress response.

For instance, activation of the 5-HT1A receptors has been shown to reduce the secretion of ACTH and corticosterone induced by an array of stressors

Those are the primary chemicals released by the nervous system tied to anxiety and stress response!

5-HT is just serotonin.

Now...to put it all together…

eCBs have been shown to attenuate the response of the HPA axis to acute restraint stress by facilitating 5-HT mediated neurotransmission

https://www.ncbi.nlm.nih.gov/pubmed/20571484/

Let's decipher that because it's the final piece tying serotonin to the endocannabinoid system and anxiety.

Basically, when they increase the levels of an endocannabinoid called Anandamide, it increased serotonin signaling and reduced stress response tied to anxiety.

Anandamide is named after Anand, the Hindu goddess of "bliss".

Aptly named!

So increasing Anandamide levels (or reducing FAAH levels...another endocannabinoid) reduce anxiety/depression and stress effects.

Let's get right to the point...what's the effect of SSRI's on Anandamide.

We thought you would never ask!

Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in the activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase.

https://www.nature.com/articles/npp2015318

What's the BLA?

The bilateral Amgydala (ding ding ding if you've read our CBD for anxiety article).

The amygdala is the seat of our fear and emotional response and intimately tied to anxiety.

Wow.

Fluoxetine is Prozac...the first of all SSRI's.

To make it easier for the rest of us to understand...

There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs.

The mechanism for this brain alteration is via the endocannabinoid system.

One final piece from this fascinating study:

electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA.

Let's translate, please.

The SSRI fluoxetine increases anandamide (an endocannabinoid) which causes a calming effect of the Amygdala where anxiety is driven.

We could literally stop right there.

But we won't!

What does any of this have to do with CBD?

CBD versus SSRI's for anxiety according to research

First, does CBD even operate on the same pathways as SSRI?:

Neurogenesis in the hippocampus
Serotonin pathways
GABA and Glutamate levels

Yes. Yes. and resoundingly Yes!

Let's look at research (always).

We mentioned neurogenesis or the remodeling of brain pathways and circuits being a primary effect of SSRI's (which is why they take so long).

Remember that benzos can affect anxiety almost immediately (which is part of the problem...see CBD versus Benzos for anxiety).

SSRI can actually INCREASE anxiety and depression in the first 2 weeks.

We explain why this happens in our CBD for anxiety article but it speaks to Serotonin being such a multifaceted taskmaster of neurotransmission.

What about CBD?

There's an entire article on CBD and neurogenesis here.

The net net…

The cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898685/

Interestingly, THC had the opposite effect and negatively affected learning in that study.

Another study showed this effect plays a direct part in CBD's effect on anxiety:

The anxiolytic effect of cannabidiol on chronically stressed mice depends on hippocampal neurogenesis: involvement of the endocannabinoid system.

https://www.ncbi.nlm.nih.gov/pubmed/23298518

Anxiolytic just means anti-anxiety. Cannabidiol is long-form for CBD.

Anandamide figured into this process.

SSRIs affect serotonin signaling. Does CBD?

Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain.

https://www.ncbi.nlm.nih.gov/pubmed/3015713

Furthermore…

Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity.

"Normalize" is the keyword.

Not boost (like SSRI). That's where SSRI's can get into trouble...Serotonin Syndrome and tolerance.

More research shows that CBD's effect on depression (since that's its primary pathway) comes from serotonin "normalizing".

The antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels.

https://www.ncbi.nlm.nih.gov/pubmed/29885468

By boosting serotonin (as opposed to norepinephrine), the effects on depression by CBD were reduced.

This points to serotonin as a key pathway.

Serotonin has been shown to have a key role in neurogenesis in the hippocampus so the two may be intertwined:

https://www.ncbi.nlm.nih.gov/pubmed/25125239

The study speaks to the "homeostasis" or balance...of the hippocampus to support mood.

Next, CBD versus SSRI's for GABA levels.

SSRI's primary pathway is serotonin.

We know that the more immediate lever for anxiety is actually GABA (the target of benzos).

How does CBD affect GABA levels?

The results demonstrated that both cannabinoids are able to modulate electrical currents via changes in GABA receptor activity.

The net effect of this "modulation" (there's that word again)...

This latter aspect draws CBD closer to other GABA drugs that are able to reduce symptoms of anxiety without generating sedation or ataxia.

https://lift.co/magazine/discovery-cannabidiol-acts-gaba-neurons-explain-antiepileptic-properties/

What really stands out in that study is this part...

In fact, the cannabinoids did not alter the responses to maximal GABA concentrations, a phenomenon that is also observed with benzodiazepines and which confers them a highly safe profile.

This means that CBD only had an effect with low GABA...it didn't keep driving GABA levels once they were higher!

Benzos will drive GABA right to the point of passing out and even death!

That's a great segue into comparing the safety of SSRIs and CBD for anxiety.

CBD and SSRI safety for anxiety

In that same article above, the researchers found that the effects of CBD on GABA were most pronounced when GABA levels were low and then tailed-off when GABA levels increased.

This is the Holy Grail of anxiety relief.

Benzos will just keep pushing in one direction…

Anxiety relief to drowsiness to amnesia to anesthesia to death if you keep increasing levels.

What about the safety of SSRIs?

We've written extensively on the drawbacks there at our CBD versus Anxiety medications page.

A quick summary:

Masking increased anxiety/depression for the first few weeks of use with benzos
A significant list of side effects
Serotonin Syndrome for people who already have higher levels of serotonin
Serotonin Discontinuation Syndrome - can we call it what it is??

Let's look at these and then compare them with safety research on CBD.

Research shows no initial increase in anxiety/depression when initially taken.
Remember, it does not "juice up" the levels of serotonin-like SSRI's.
If too low, it boosts serotonin levels. If too high, it actually works with the endocannabinoid system to rein in the level.

That's the role of the endocannabinoid system.

How many times have we've seen "modulate", "balance", "homeostasis" in the research?

There has not been a known overdose of CBD. Research has tested it up to 1500 mg with a strong safety profile.

For anxiety, the top range is probably up to 300 mg according to research (we'll explain why below).

What about side effects?

CBD's common side effects are:

Drowsiness
Lowered blood pressure
Lightheadedness
Dry mouth

What about SSRI's side effects?

Thirty-eight percent of the approximately 700 patients surveyed reported having experienced a side effect as a result of taking a selective serotonin reuptake inhibitor antidepressant; the most common side effects mentioned were sexual functioning, sleepiness, and weight gain.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719451/

Those are the common ones.

For a full list for Lexapro, go here:

https://www.webmd.com/drugs/2/drug-63990/lexapro-oral/details/list-sideeffects

What you're struck by is just how many systems are affected by serotonin.

It truly spans the entire body and brain with so many functions.

When we look at an actual clinical trial of Effexor, it showed 81% had some side effect from use:

https://clinicaltrials.gov/ct2/show/results/NCT00183274?view=results

Part of the problem is that there's no real way to see if a person really has low serotonin.

Serotonin is also key to gut functions which, if you read any of our articles, is key to health!

Most of our serotonin is actually made in the gut.

Let's look at what happens on SSRI's with too much serotonin.

Serotonin Syndrome

This is a rare but serious consequence of having too much serotonin.

It can be fatal.

https://en.wikipedia.org/wiki/Serotonin_syndrome

Make sure to get medical help immediately if you suspect any of the symptoms listed.

Again...SSRI's only push in one direction...more serotonin.

Finally, the Orwellian Serotonin Discontinuation Syndrome.

Serotonin isn't said to have the classic withdrawal and addiction symptoms like benzos for anxiety.

It doesn't directly hit the dopamine or reward system and avoids the habit-forming results of doing so.

That doesn't mean they're easy to come off.

For the same reason, they're hard to go on and have such a list of side effects.

You've been tinkering with a master transmitter in the brain and body.

The body adjusts accordingly.

Now, you take it away!

SSRI's can be brutal to come off of depending on dosage, how long you took it, and the state of anxiety.

There's a whole process of weaning off of SSRI's which inevitably must happen since they normalize anyway (lose their effect in the serotonin system).

Approximately 20% of people who stop SSRI experience SSRI discontinuation syndrome.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449237/

Other studies have shown the percentage of those affected up to 56% with roughly half of them having severe symptoms

https://www.psychiatrictimes.com/couch-crisis/sorting-out-antidepressant-withdrawal-controversy/page/0/1

Most people are totally unaware of this potential back-end repercussion from their doctor.

Effexor and Paxil had the most issues with symptoms due to half-life.

Just like benzos, the shorter the half-life, the more severe the "discontinuation" symptoms.

In this regard, Effexor is suspect with a half-life of 5 hours (much lower than other SSRI's):

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024727/

Paroxetine (Paxil) had one of the highest "discontinuation" results in comparison to other SSRI's.

The rate of discontinuation with paroxetine has been reported at 34.5% compared to placebo at 13.5% in a 12-week double-blind placebo-controlled study

The numbers may be higher than the quoted 20% depending on the SSRI:

A randomized controlled trial comparing 3 SSRIs found the highest incidence with paroxetine (66%) followed by sertraline - Zoloft (60%) and the lowest incidence (14%) was with fluoxetine (Prozac).

There's that more positive result for Prozac, which isn't really prescribed anymore.

We'll leave our jaded comments there.

Can you take CBD with SSRI's

This a common question.

It's usually from people looking to transition off of SSRI's.

Some key points.

The P450 Pathway

Both CBD and SSRI's use a pathway in the liver called P450.

For this reason, we want to take them at least 2-4 hours away from each other.

One study showed that CBD could boost the effect of a particular SSRI.

This may help in the weaning process for those looking to get off or reduce levels.

The more gradual, the better and work with your doctor if you have one that's supportive (see our story here for the opposite).

Watch blood pressure as that can drop with CBD.

Based on the research above, CBD should help to balance excessive serotonin's effects on the body.

Make sure to work with your doctor before coming off of SSRI's.

SSRI and gut bacteria or microbiome

Every week, we get a study on how gut bacteria directly affect health.

Anxiety and depression are no different.

In fact, roughly 90% of our serotonin is made by our "second brain", the gut.

The microbiome or gut bacteria directly affect this process.

SSRI's directly affect gut bacteria.

The studies this as it pertains to pregnancy since the gut biome can transfer down to babies.

Their final takeaway:

Since maternal microbial metabolites contribute to health outcomes in offspring, insults to the maternal microbiome by SSRIs might have inter-generational consequences.

https://www.biorxiv.org/content/10.1101/501742v1?rss=1

On the general effects of SSRI's on serotonin and the gut biome, there's a great review here:

http://www.fitbrittnutrition.com/blog/2018/3/17/how-anti-depressants-ruin-digestive-health-guest-post-by-nick-kowalski-nicksfit

How much CBD to match the effects of SSRI

One study directly looked at this question.

They studied 3mg per kg of body weight and 30 mg per kg of body weight.

The 3mg per kg of body weight had the best effect on anxiety and neurogenesis:

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). Fifteen days of repeated i.p. administration of 3 mg/kg CBD also increased cell proliferation and neurogenesis (using three different markers) in the subventricular zone and the hippocampal dentate gyrus.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569602/

The 30 mg helped with anxiety but not with neurogenesis (which is key for longer-term correction of brain mass loss due to stress, depression, anxiety, etc).

To figure out dosage levels in pounds of body weight:

Multiply your weight by 1.45

For example, 120 pounds would be (120 x 1.45) or 174 mg

Of course, always start lower and work your way up to that level.

In introductory dosage is approx 20-30 mg.

The key number for neurogenesis (the real star behind serotonin) is 300mg daily.

The best CBD to help transition off of SSRI's

If you have decided to try CBD to come off of SSRI's, some basic requirements must be met.

See the article "How I used CBD to get off of SSRIs and Benzos".

The CBD needs to be organically grown in the US at FDA registered farm and 3rd party tested for:

No pesticides
No solvents
No mold
No bacteria
No THC (very important for anxiety)

That's a minimum and we designed IndigoNaturals to meet these requirements.

Our whole family uses the oil so we want it vetted.

Finally, there's the whole question of full-spectrum versus CBD Isolate.

How much of the research on CBD for anxiety is based on full-spectrum across the dozens of studies that we've researched?

Almost Zero.

It's all on CBD by itself.

THC can actually increase anxiety. It also builds tolerance (see CBD versus THC for anxiety)

Then there's the whole histamine and anxiety issue.

All the plant material that every other brand is pushing may not feel great for the 40-60% of the population that has histamine or allergy issues.

That number goes up for women and higher yet for people over 40.

For this reason, we want clean CBD isolate in MCT oil (coconut extract).

Look, histamine is excitatory and actually wears down GABA levels.

Learn all about histamine, CBD, and anxiety here.

Again, if you read our story here, you can see that we crafted IndigoNaturals for anxiety.

After getting walloped by Lexapro (an SSRI).

We have our personal review of how we used CBD to wean off of SSRIs here.