Can CBD Help With Weaning off Effexor (venlafaxine) or be Taken With It? Research on shared Serotonin pathway
This question usually comes from two very different angles.
Can CBD help me wean off Effexor?
Can you take CBD along with Effexor?
We'll cover all of this.
This includes Effexor.
We'll cover what makes Effexor different from the other SSRIs.
There are very specific differences with Effexor due to its half-life (we'll explain later).
This directly drives side effects.
It also affects a separate pathway called norepinephrine than the traditional SSRIs like Lexapro.
These are the questions we'll look at research for:
- A quick look at how Effexor works
- How is Effexor different from other SSRIs
- How does CBD work for serotonin versus Effexor
- How is CBD different from Effexor
- Can you wean off of Effexor with CBD
- Can CBD help with Effexor withdrawal symptoms
- Does CBD interact with Effexor
- The process we used to wean off Effexor
- How much CBD to wean off Effexor
- What's the best CBD to wean or use with Effexor
Let's get started.
A quick look at how Effexor works
We've already dived deep into this at our How SSRIs really work but a quick recap will really help.
Effexor actually operates on two separate pathways.
We've covered serotonin in detail at our CBD and serotonin.
Serotonin is a master regulator neurotransmitter.
It's mistakenly called the "feel good" neurotransmitter but that's misleading.
Basically, you'll feel really bad it's too high or low.
When spending a few dozen hours in NIH research on the matter, you find that the real trick for depression and to a lesser extend, anxiety is one specific component of serotonin's action in the brain.
It drives neurogenesis!
That's a fancy word for building new brain and connections within the brain.
This is will be the big push over the next decade since it figures heavily into every major mental health issue and addiction (the two are intimately tied).
Serotonin directly drives BDNF which is our brain's fertilizer.
In fact, the antidepressant activity was directly dependent on this effect.
When they blocked the neurogenesis (via a BDNF key enzyme called TRK), the antidepressant effect goes away.
Interestingly, it's dependent on CB1 receptors which it the key endocannabinoid receptor.
This is the system that CBD works in!
This neurogenesis effect explains why it takes a few weeks for Effexor to work.
In fact, depression or anxiety can worsen during this period (during which, they may prescribe benzos).
Norepinephrine is a different animal. You probably know it better as adrenaline.
It's the fight/flight chemical!
Why on earth would we want to increase adrenaline, our stress chemical?
Think of it as a gradient.
At full speed, norepinephrine will make your heart race, your blood pump, and your muscles ready for spring to (or away).
If you're running too low, it might just lead to...arousal. Focus.
The theory with Effexor is that this pathway is not functioning correctly and therefore a little shot will help.
After all, what's the opposite of arousal?
Flat affect. Disinterested. Depression even.
Interestingly, norepinephrine at these lower levels (not due to a bus about to hit you) is a direct reflection of your dopamine levels.
Dopamine drives norepinephrine to guide focus, attention, and activity.
They're cutting out the middle man essentially and going right to norepinephrine.
So...Effexor combines a boost to serotonin (behind the curtain is brain growth) and norepinephrine.
Sounds great? Let's put it in the water, right?
Here's the downside (skipping over side effects).
They can't really test what your serotonin levels are in the brain.
It's usually based on a 10-minute doctor visit with your GP no doubt.
Research is showing that SSRI's work for about 30% of people.
The problem is that the brain sees this unnatural boost in serotonin and norepinephrine and pushes back.
It actually starts to downregulate the natural pathways for serotonin and norepinephrine down to the genetic level!
This is the basis for tolerance and it's why people will have to increase doses or change (even layer) medications.
The net effect is that when the SSRI wears off, you may feel worse than when you started.
This is true for all SSRIs but Effexor is a bit different (besides the norepinephrine effect).
Let's go there.
How is Effexor different from other SSRIs
This is interesting.
We already noted one major difference with norepinephrine.
That's not the only difference.
SSRIs differ in two key ways:
- Half-life of effect
- Potency of effect
The first is really a big deal.
How long does it take for the body to break down the SSRI so it no longer is juicing serotonin (and norepinephrine with Effexor)?
In some way, Effexor is like the Xanax of the SSRI world.
Check out the chart here with half-lives:
You'll notice that Effexor has the lowest half-life of any of the SSRI/SNRI's.
The other SSRIs last many times longer...up to 80+ hours.
What does this mean?
It means that the rebound effect will occur faster and harder with Effexor.
Like a serotonin hangover.
You see this with SSRI discontinuation syndrome (a fancy way to say withdrawal symptoms).
The half-life of an SSRI directly figures into how quickly the symptoms of withdrawal come on.
Combine this with the fact that our serotonin and norepinephrine pathways are suppressed as a result of tolerance.
It's the opposite of extended-release.
It comes on quickly and goes away quickly.
This "shelf" is an issue and we've seen it with Xanax and Ativan (see CBD versus Xanax and Ativan).
The other issue is that too much serotonin (called serotonin syndrome) is a very serious issue.
Check out CBD and serotonin syndrome.
Remember that they can't really test how much serotonin you have...they're going by symptoms but if you look at our CBD and depression review, there are many aspects that figure into depression.
- Brain areas
- Gut microbiome
- Repair pathways (BDNF, etc)
So...too much serotonin is an issue.
So...how does CBD compare?
How does CBD work for serotonin versus Effexor
One of CBD's researched and primary effect is on the very same pathway.
We've covered it in detail at our CBD and serotonin article but some quick takeaways.
First, the studies on direct effect.
Serotonin wears many hats and one of them is pain sensitivity.
Researchers caused injuries in animal studies and then looked at CBD's effect.
Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity.
Let's break that down.
Allodynia is increased pain sensitivity. So CBD was able to calm this pain response driven by reduced (exhausted really) serotonin levels.
As for anxiety, we know it all too well (see CBD and anxiety).
The third part is what we're interested in.
"Normalized" 5-HT. 5-HT is serotonin!
They go on to say later that it "rescues impaired 5-HT neurotransmission".
Goodness. What about specifically for depression which is why most people are prescribed Effexor.
Another study looked at this specifically:
our findings indicate that CBD could represent a novel fast antidepressant drug, via enhancing both serotonergic and glutamate cortical signaling through a 5-HT1A receptor-dependent mechanism.
Ah, ha...glutamate. The "gas pedal" of the brain.
We covered it in detail at our CBD and glutamate review.
Glutamate is similar to norepinephrine in that they are both excitatory.
In fact, glutamate is the primary excitatory neurotransmitter in the brain.
One final study is probably the most important.
Their results (we'll decipher afterward):
Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex
The study is basically saying that CBD's primary effect on depression is via neurogenesis (brain repair) in the area that's most implicated in depression...the prefrontal cortex.
Again, really read the review of CBD and depression to get a lay of the land.
Remember that neurogenesis was at the heart of how SSRI and SNRI's like Effexor works for depression (and off-label prescriptions for that matter).
Serotonin drives BDNF which drives brain connections.
Think of depression as a disengaging brain...where connections are atrophying or shriveling.
So...CBD appears to "rescue" serotonin function. How are they different?
This is where it gets interesting.
How is CBD different from Effexor
CBD doesn't have a pronounced effect on norepinephrine although there is interaction with dopamine, it's the upstream driver.
See CBD and dopamine.
Both CBD and effector appear to boost serotonin which leads to increased neurogenesis.
The big difference is on the back end.
How does the brain respond to this outside influence?
We know that Effexor will build tolerance as the brain seeks to get balance by reducing serotonin pathways over time.
This is why you have withdrawal systems regardless of the Orwellian name (Serotonin discontinuation syndrome).
What about CBD?
Here's where it's fascinating.
CBD technically is called an allosteric negative modulator for serotonin function.
Where Effexor and SSRI's push serotonin in one way - technically called an agonist (which is why you can get serotonin syndrome), CBD works more like a feedback system.
- If the affected pathway is running low, it can increase or "rescue" as noted in the above study.
- If the pathway is too high, it can send a message backward (neuron to neuron) to reduce.
This is why we don't see serotonin syndrome with higher CBD doses.
You would expect as doses increase, we start to see some of the very nasty side effects of serotonin syndrome.
Researchers don't. In fact, they've tested up to 1500 mg with no real change side effect profile.
No better example of this varied effect can be seen than with cancerous cells.
- Healthy cell with low oxidative stress- no effect
- Healthy cell or neuron with high oxidative stress - reduces inflammation
- Cancerous or virally infected cell or neuron - CBD INCREASES inflammation
Three different effects depending on the internal state of the cell or neuron.
How is this possible? CBD's not magic but it has an interesting role in the very system that's tasked with balancing other key systems.
The endocannabinoid system.
It's tasked with balancing these systems:
- Immune system - inflammatory agents
- Endocrine system - hormones such as estrogen which drive serotonin, Ladies!
- Nervous system - neurotransmitters like...serotonin and dopamine (which turns into norepinephrine).
CBD's role as a feedback mechanism within this system along the serotonin pathway is it's secret.
By the way, THC works very differently...almost opposite to CBD.
It's an agonist for the endocannabinoid system and resembles anandamide.
That's why you can have too much of it!
More importantly, as a result of this subtle effect, CBD doesn't build tolerance or have withdrawal effects.
Some practical questions.
Can you wean off of Effexor with CBD
We've looked at how I used CBD to wean off SSRIs here.
A quick caution.
It's well documented that a person should not stop SSRIs or SNRIs like Effexor cold turkey.
Again, serotonin is an important regulator of all human behavior plus lots of housekeeping roles (sleep, heart rate, etc).
Pulling the plug on this especially if our natural pathway has been suppressed due to tolerance is ill-advised.
You should work with your doctor or naturopath with this endeavor.
We see above how CBD works with the same pathways but in a different way.
Both are processed by the liver so it's important not to take them at the same time.
The general rule is at least 4 hours away from each other.
SNRI's are generally taken in the morning since norepinephrine is stimulating by default (it is adrenaline after all).
The new Effexor XR is extended-release and the only available option in the US now.
When we weaned off Lexapro (a common SSRI), we used a pill splitter and slowly reduced the amount over a month's time.
We took 300mg of CBD at opposite ends of the day in conjunction.
Many customers have responded back with similar approaches for both SNRI's and benzos.
Research is pointing to receptors normalizing at about 30 days and potentially up to 2 months.
SSRIs and SNRIs like Effexor may take longer for the serotonin pathway to normalize depending on how long you were on for.
Again, the genes that make the receptors have to be turned back on the following tolerance so this is not a quick recovery.
That being said, CBD boosts neurogenesis which is the key to not only depression or how SNRI's work but also the main driver of this recovery process.
The key is how we'll feel during this process.
Let's look at that.
Can CBD help with Effexor withdrawal symptoms
The withdrawal symptoms are driven by two factors.
- We're losing a boost to serotonin and norepinephrine
- Our natural system for both has been depressed
Really, it's a compounding of the reason they put a person on SNRIs for, to begin with!
This is the issue with tolerance.
You end up worse than where you started.
Hopefully, you have some neurogenesis built-in by then.
Low serotonin feels terrible. The side effect profile for serotonin discontinuation syndrome is well established now.
You can look at the symptoms to understand just how important and wide-spread serotonin is:
Flu-like symptoms (lethargy, fatigue, headache, achiness, sweating), Insomnia (with vivid dreams or nightmares), Nausea (sometimes vomiting), Imbalance (dizziness, vertigo, light-headedness), Sensory disturbances (“burning,” “tingling,” “electric-like” or “shock-like” sensations) and Hyperarousal (anxiety, irritability, agitation, aggression, mania, jerkiness).3
We've covered CBD and many of these here:
- CBD and sleep
- CBD and the gut
- CBD and pain
- CBD and anxiety
- CBD and perimenopause irritability (estrogen drives serotonin)
More importantly, CBD was shown in the studies above to "rescue" or "normalize" serotonin function after it's knocked askew.
That's the heart of withdrawal symptoms for Effexor.
As for the norepinephrine, check out CBD and dopamine since dopamine drives norepinephrine function.
It's the same story as with serotonin which is also not surprising since...serotonin regulates dopamine!
You see...serotonin really is the master regulator.
Check out CBD and opioid withdrawals for double-blind, placebo studies on how CBD reduced some of the most serious withdrawal symptoms out there!
What about interaction?
Does CBD interact with Effexor
We don't have good research on this front.
Both are processed by the liver so metabolism by one may interfere with the other if they overlap.
The half-life of Effexor is short (5 hours) but the new XR (extended-release) version throws a wrench in this calculation.
There is a metabolite from Effexor that continues to have a separate effect which can last up to 11 hours but at a lower effect.
When we used CBD to wean of Lexapro, we started low and ramped up to the peak level for neurogenesis.
Let's look at that process now.
The process we used to wean off Effexor
Again, work with your doctor or naturopath (the latter is who helped us through this process).
Effexor is known to have more issues with the heart due to its effect on the rhythm (call QT interval) of the heart than standard SSRIs (do not have the norepinephrine component).
We started slowly with low levels of 40-50 mg of CBD per day. We took this amount at night since sleep was a big issue coming off of Lexapro.
This is, even more, pressing with the norepinephrine component of Effexor.
We kept it there for about a week while taking slivers off the pill with a pill cutter.
During the month, we slowly ramped up to 300 mg of CBD per day in two doses (one before bed and one during the day).
Why 300 mg?
We thought you would never ask.
How much CBD to wean off Effexor
It's interesting after running through dozens of studies on CBD.
Higher levels are used for more acute situations (psychosis, social anxiety public speaking, etc).
These doses are generally from 600-800mg.
The long term effect that drives neurogenesis (our goal) peaks, however, at about 300 mg per day.
Neurogenesis is turning out to be THE linchpin across the mental health landscape!
You'll get to know the term BDNF pretty well within a few years.
In the meantime, peak neurogenesis starts to go down with doses higher than 300 mg as other pathways kick in.
For this reason, that was our target over a month period.
This brings us to the type of CBD.
What's the best CBD to wean or use with Effexor
First, we have basic requirements:
- Organically grown at an FDA registered farm in the USA
- 3rd party tested
- CO extracted
- No THC (see CBD versus THC to understand why)
- No Heavy Metals
- No Pesticides
- No Solvents
- No Bacteria
- No Mold
We test our CBD oils twice since our whole family uses it.
The next question is CBD isolate versus full spectrum.
All the research on this page and throughout the site is based on CBD isolate.
More importantly, roughly 40-60% of people have allergy or histamine issues.
This number goes up for women and as we get older.
All the plant material in full-spectrum CBD can lead to a slew of side effects.
Jus.t check our reviews to see the difference.
Finally, there's the cost.
With research pointing to 300 mg for peak neurogenesis, the cost per mg of CBD is the key there.
Many brands are ridiculously expensive.
We price our 6000mg bottle at around 2-3 cents per mg and that's before discounts up to 30%.
Be safe and work with a naturopath with any supplement including CBD.
Our story including weaning off of antidepressants like Effexor is here. CBD had a central part in that story.
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.