CBD versus Xanax or Ativan - Research on Replacement, Withdrawals, and Comparison of Pathways
With rolling anxiety and panic attacks, my general doctor went straight to benzos.
One in particular...Xanax. Alprazolam is generic.
This was after a 10-minute discussion (and no real look at my hormones which had dropped off (see CBD and perimenopause anxiety here).
This same thing is playing out 1000's of times a day across the US.
The new generations of benzos are fierce.
Xanax and Ativan take the potential dangers of Valium and magnifies them.
It's like comparing a Monster caffeine drink to green tea.
If you look at the research, it's hard to justify.
We'll get into that below as well as a host of other key questions and pieces of research.
Most importantly, we'll look at the share pathways between CBD and Xanax and see that they have very different means of action.
These are the areas we'll cover:
- How does Xanax (Alprazolam) or Ativan (Lorazepam) work?
- Xanax or Ativan and the GABA receptor
- Why does the brain build a tolerance to Xanax or Ativan and cause withdrawals
- How is CBD different from Xanax or Ativan
- CBD and GABA function versus Xanax or Ativan
- CBD effects on anxiety versus Xanax or Ativan
- CBD safety profile versus Xanax or Ativan
- Does CBD help with Xanax withdrawals
- Can you take CBD and Xanax together
- How I used CBD to taper off Xanax
- What's the best CBD to get off Xanax
Lots to cover. Weaning off of Xanax was one of the hardest things I ever had to do.
Let's look at how we might make that transition easier.
How does Xanax (Alprazolam) or Ativan (Lorazepam) work?
We won't get too deep into the weeds but it's really important to understand how Xanax and Ativan work.
Xanax and Ativan are newer members of the benzodiazepine class of medications.
It's currently one of the most popular out there (behind SSRIs) and provides the grist for the next epidemic after opioids.
This class of medications has a very simple action in the nervous system..
It boosts the function of GABA.
GABA acts as our main "brake pedal" in the nervous system.
It's key to feeling calm and/or sleepy. Too little of it is also implicated in seizures (important for withdrawals below).
Its main opposing force in the brain is glutamate (and histamine to a lesser extent).
The balance between GABA (brake pedal) and glutamate (gas pedal) is key to feeling grounded.
Too much of either for prolonged periods is tied to a range of issues from autism and schizophrenia to anxiety and insomnia.
It's the latter two that are typically the basis for a Xanax (or any benzodiazepine for that matter).
Valium was the first benzo and many have followed.
Xanax (alprazolam) and Ativan (lorazepam) are newer additions to this family.
Not to geek out but the way benzos work is interesting.
We'll look at it quickly so we can move on to more pressing questions.
Xanax or Ativan and the GABA receptor - how it works
We have GABA receptors all over the brain. They sit on neurons and make up the most prominent neurotransmitter messaging system that we have.
It's estimated that 40% of neurons are under the sway of GABA.
These receptors basically act as a gateway to change the electric charge difference between the inside and outside of the cell.
By doing this, GABA can calm down activity both within the neuron and between neurons...even between entire brain areas.
Benzos like Xanax can attach to spot on the GABA receptor that contorts it just a bit so that GABA can enter the cell much more easily.
It's like a puzzle piece where Xanax helps to line up the pieces to fit better.
Alcohol uses this same spot while barbiturates have a different spot (which keeps the GABA gate open and leads to easier overdoses).
It's all about manipulating the flow of GABA.
GABA is so important that we did a full look at CBD and GABA function here.
It makes Xanax and Ativan very effective to reduce anxiety and cause sleep. Temporarily.
Turns out the brain isn't about to sit idly by.
Why does the brain build a tolerance to Xanax or Ativan and cause withdrawals and addiction
The brain is heavily focused on balance.
Yes, there can be ebbs and flows for specific reasons (GABA during sleep or Glutamate during mental focus) but always back to balance.
That's actually the role of the endocannabinoid system which CBD works within.
When an outside influence (like Xanax or Ativan) spikes GABA activity, the brain pushes back the other way.
It actually will reduce the natural GABA pathway to offset this increase.
In fact, researchers have found that the body will downregulate DNA which makes the proteins needed to form the GABA receptors after a few weeks of use.
We see this with SSRIs and serotonin (see CBD versus SSRIs since your doctor will probably try to put you on those right after Xanax like mine did).
Opioids are another classic example where the body downregulates the entire opioid complex in response to an artificial spike.
Tolerance is the effect that you need more and more of a given medication to have the same effect.
This is because the brain has downregulated the entire pathway.
Law of diminishing returns.
This is all with the aim of coming back to balance.
Withdrawal is a more immediate effect.
Imagine that you have a certain GABA level (albeit, maybe lower if you suffered from anxiety or insomnia barring another pathway).
Xanax will spike your GABA level. The brain will respond by boosting glutamate, reducing GABA function, etc.
When that Xanax wears off, you're now worse off than when you started.
Don't take our word for it...check out the FDA warnings and research at our CBD versus benzos for anxiety page.
A broader review is at our CBD versus anti-anxiety medications.
What about the addiction piece?
Obviously, having your GABA calming levels plummet when Xanax wears off will make you want (need more like it) to take another Xanax but it goes deeper than that.
Hello nucleus accumbens and dopamine!
Remember how we said that GABA is one of the most prominent chemicals in the brain?
It's involved in almost every pathway.
It can dampen other neurotransmitters in different areas of the brain...such as dopamine:
Such disinhibition, which relies on α1-containing GABAARs expressed in these cells, triggers drug-evoked synaptic plasticity in excitatory afferents onto dopamine neurons and underlies drug reinforcement.
Goodness, let's decipher that (Xanax can slow cognition by ripping acetylcholine which is tied to dementia. Just an FYI).
Dopamine is the "do that again" neurotransmitter. Not pleasure as most people think, but rinse repeat.
Benzos like Xanax will hit GABA levels is a specific way that primes dopamine release.
In fact, studies found that benzos will actually prime the dopamine receptors to respond more greatly to future interactions.
This is the whole basis of addiction. (do that again - do that again - do that again).
So we have two things working against us.
- Our GABA level plummets which makes us feel even more of why we were originally prescribed the benzo
- Our dopamine system (reward center tied to addiction) is primed to respond more and more strongly to benzo inputs
Benzos can actually "lock-in" this pathway by affecting our brain's plasticity.
Essentially, it's harder to "unlearn" benzo addiction.
You see this with many drugs such as cocaine (see CBD and addiction here).
Neurogenesis (or the ability to build new pathways) is key to unlocking this "marbleized" effect.
We'll touch on that below.
So, we have a rough look at the basis for Xanax and Ativan function, addiction, tolerance, and withdrawals.
Let's now focus on why new benzos like Xanax and Ativan are a perfect killing machine for this pathway.
As well as a source of billions in revenue each year.
Why Xanax and Ativan are so prone to addiction and withdrawal
There are some important considerations in how the benzos differ from each other:
- Metabolites (breakdown products that linger and mirror the effect of the primary benzo)
The original benzo, Valium, which took the nation by storm in the '60s (estimated that 1/3rd of women over a given age were prescribed).
Potency is obvious as the bigger the hammer to your GABA level, the bigger the opposing force from the brain.
Half-life though is more subtle and arguably, important.
The new generations of benzos like Xanax and Ativan are complicit on both accounts.
Xanax and Ativan rate highest for:
- Speed of action
- Shortness of duration
- Half-life of effect
They come on hard, last a shorter period of time, and drop off fast.
The older benzos like valium last much longer and even produce metabolites (breakdown products) with similar effects.
The trailing off is much more gradual.
Let's compare Valium, Xanax, and Ativan to clearly see the difference.
- Valium: 20-80 hours
- Xanax 6-27 hours
- Ativan 10-20 hours
What about metabolites (to smooth the backend transition away from benzo activity):
- Valium: Multiple with half-lives up to 100 hours
- Xanax None
- Ativan None
Time to peak levels in the blood:
- Valium: greater than 2 hours
- Xanax 1-2 hours
- Ativan 1 hours
Just a head's up….sublingual (under the tongue) will boost the time to peak and total potency since it bypasses the liver.
Based on everything we looked at for addiction, tolerance, and withdrawal, you can see how Xanax and Ativan are like throwing lighter fluid on a fire.
If I wanted to create a product that rivaled opioid's ability to cause addiction, I would craft a benzo with all three factors just like Ativan and Xanax.
- Very potent
- Starts very fast
- Lasts a short duration
- Drops off very fast
There's a great read here on how getting off of benzos was worse than opioids.
And it's given out like candy despite the black box FDA warning and reams of NIH research.
If you're reading this now, you or a loved one is likely in the well of Xanax or Ativan use which brings up a few questions.
Let's compare CBD and Xanax or Ativan now.
How is CBD different from Xanax and Ativan
We've covered a great deal of research at our CBD versus Benzos or CBD and GABA function here but the important pieces.
We'll cover the following to contrast CBD and Xanax or Ativan:
- CBD and GABA function versus Xanax or Ativan
- CBD effects on anxiety versus Xanax or Ativan
- CBD safety profile versus Xanax or Ativan
Let's start with the root mechanism of benzos...GABA.
Xanax and Ativan pump up the throughput of GABA into the neuron.
What about CBD?
CBD does not bind directly to the GABA receptor-like benzos.
Let's drill down to the receptors before taking a broader look.
Researchers compared CBD and 2AG (our most prominent endocannabinoid) in the brain on GABA receptors:
The maximal level of enhancement seen with either CBD or 2-AG were on α2-containing GABAA receptor subtypes, with approximately a 4-fold enhancement of the GABA EC5 evoked current, more than twice the potentiation seen with other α-subunit receptor combinations.
Remember that GABA receptors are essentially electric gates. Yes, they move chlorine particles in but that's only to let in the charge they carry.
As that charge increases, the activity of the neuron slows down.
CBD was able to boost this charge difference and cause an increase in GABA potential.
An important difference versus Xanax and Ativan:
The potency of CBD increased and efficacy preserved in binary α1/α2β2 receptors indicating that their effects do not involve the classic benzodiazepine site.
This is good news since we don't want the same side effects (we'll touch on that below).
Let's scan out a bit as the net effect of this activity on receptors starts to affect brain-level balance.
This next study is very informative.
Researchers were looking at differences in brain excitation (GABA/Glutamate balance) between people with autism and those without.
They wanted to study the effects of CBD on this pathway:
Across groups, CBD increased subcortical but decreased cortical, Glx. Across regions, CBD increased GABA+ in controls, but decreased GABA+ in ASD; the group difference in change in GABA + in the DMPFC was significant.
This is very telling.
Essentially, CBD boosted GABA function except for the area where it was already diminished...in the prefrontal cortex of people with Autism!
That's the DMPFC part.
Read that back again because it's the key difference between CBD and Xanax or Ativan.
Benzos like Xanax and Ativan will boost GABA levels with higher dose with the following staircase of effects:
- Dead! (function stops altogether)
One direction with increasing doses.
CBD does not follow this trajectory and we'll get into why below.
GABA is not the only pathway affected by CBD in terms of anxiety and sleep.
The bigger one may be serotonin (see CBD and serotonin).
This is the target of SSRIs like Effexor, Lexapro, Zoloft, and Paxil.
There are other targets as well such as GPR55 (See CBD and GPR55) which may be the key to anxiety and CBD.
What does GPR55 do?:
recent studies suggest that GPR55 could be modulating procedural memory , motor coordination , anxiety and hippocampal release of glutamate .
So anxiety and release of glutamate, the opposing force to GABA!
Check out CBD and GPR...it's an interesting read.
GABA and Serotonin are two key pathways we can look at with CBD.
So...is CBD even effective for anxiety (the most common basis for Xanax and Ativan prescribing)?
CBD effects on anxiety versus Xanax or Ativan
Both Xanax and Ativan have powerful initial effects on anxiety which drop off quickly and diminish over time (tolerance).
At first, they're powerful releasers of GABA which takes a sledgehammer to anxiety.
What about CBD and anxiety?
We have an entire review of CBD and anxiety studies here.
Some key takeaways.
A large study on CBD's effect on anxiety and sleep found the following:
Anxiety scores decreased within the first month in 57 patients (79.2%) and remained decreased during the study duration.
A large review of many studies had the following summary:
We found that existing preclinical evidence strongly supports CBD as a treatment for generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder when administered acutely;
Interestingly, another study pinpointed serotonin function as the critical level with CBD and anxiety.
Most of the studies demonstrated a good interaction between CBD and the 5-HT1A neuro-receptor.
5HT is our primary serotonin receptor.
Serotonin is a curious neurotransmitter with hands in many pies.
Check out tryptophan and CBD for social anxiety resilience as an example of how it's tied into EVERY kind of behavior we display.
Our favorite study is on CBD for public speaking anxiety.
For the cherry on top, they did this test to people with a diagnosed social anxiety (Thanks, researchers. Mighty kind).
Here is the key takeaway:
The SSPS-N scores evidenced significant increases during the testing of the placebo group that was almost abolished in the CBD group.
Let's break that down because it's really cool.
There were standard elements of episodic anxiety (tied to a given situation) improved by CBD prior to the test but the SSPS-N is special.
It's short for Negative Self Statement Scale.
Essentially, it's a measure of how positively or negatively you view yourself.
This obviously goes hand in hand with social anxiety (check out the tryptophan study….really fascinating).
The negative thoughts symptoms were "abolished" by CBD during the public speaking test.
Keep in mind that these people had a diagnosed social anxiety disorder!
We've covered CBD's effect for general anxiety disorder (a general state) as well.
So...what about safety versus Xanax and Ativan?
CBD safety profile versus Xanax or Ativan
NIght and day.
The common side effects for CBD:
- Lower blood pressure
- Dry mouth
This is for CBD isolate (CBD by itself).
Full-spectrum CBD may have a host of other issues depending on your histamine response (allergies).
That's why we only focus on CBD Isolate at IndigoNaturals.
Plus all the research is on Isolate.
More importantly, what about the following issues with Xanax and Ativan:
Let's look at each because this is too important...we don't want to trade one nightmare for another.
The keyword there is hedonic...which means to cause pleasure.
That's the thing where a mouse will continuously click on the lever for cocaine over food.
Is CBD hedonic?:
CBD, which is nonhedonic, can reduce heroin-seeking behavior after, for example, cue-induced reinstatement.
Did you catch that?
CBD is showing powerful effects on unwinding addiction!
Opioid, alcohol, and even….wait for it….THC.
See CBD and addiction here.
What about CBD and tolerance?
This one is crucial.
The mechanism behind Xanax and Ativan's nightmare is this process where the brain downregulates GABA because it's being juiced from outside.
Does CBD build tolerance?
Bergamaschi et al. list an impressive number of acute and chronic studies in humans, showing CBD safety for a wide array of side effects.1 They also conclude from their survey, that none of the studies reported tolerance to CBD.
This is sooo important.
THC does build tolerance which means we're stealing from tomorrow's function to have it today.
It's emotional and well-being DEBT!
Check out the book, Never Enough for a great run-through of how this works by drug class.
If the brain isn't suppressing natural function, we would expect no withdrawals (when the drug effect drops and there's no safety net).
What about CBD and withdrawal symptoms?
A study on Epeliodex (synthetic CBD which has its own issues):
In healthy volunteers, no evidence of withdrawal syndrome was found with abrupt discontinuation of short-term treatment with CBD.
More importantly, CBD is being looked at to help with withdrawals from other addictive drugs like opioids, alcohol, THC (Cannabis) and…..benzos.
Let's go there.
Does CBD help with Xanax or Ativan withdrawals
First, let's look at new studies on CBD and opioid withdrawals (one epidemic at a time please).
A double-blind, placebo study did just that:
Acute CBD administration, in contrast to placebo, significantly reduced both craving and anxiety induced by the presentation of salient drug cues compared with neutral cues.
That's groundbreaking and why it's not front-page news….
More interesting though was this piece:
CBD also showed significant protracted effects on these measures 7 days after the final short-term (3-day) CBD exposure.
Read that again. The effects were long term!
We're not surprised as we've gone deep into CBD's effect on neurogenesis and BDNF (our brain's fertilizer and builder).
Remember how benzos like Ativan and Xanax will "re-wire" our brain's dopamine system and GABA pathway?
It rewires dopamine (do that again neurotransmitter) to respond more strongly to future benzos and downregulates GABA function (to the DNA level!).
The key to withdrawals is 2-fold:
- First, calm the initial effects of spiraling anxiety and discomfort
- Longer-term, bring GABA back online and normalize dopamine function
We have to survive the first to get to the latter.
Not easy as it can be agonizing (I've been there with Xanax).
We see above how CBD already helps with anxiety and now we see effects on withdrawals from opioids (the key symptom being...anxiety!).
Speeding up the rewiring of these systems is the next step and CBD shows powerful effects there.
In fact, if you dig deep enough into SSRIs, you'll find they basically boost BDNF and rebuilding!
In fact, when endocannabinoid receptors (where CBD works) are knocked offline, their effectiveness for depression/anxiety go away!
One final note...remember how Xanax and Ativan can rip acetylcholine?
Just our "cognition" neurotransmitters are responsible for focus, attention, and thinking.
Hence the tie in with dementia.
The pooled RR for developing dementia was 1.51 (95% CI=1.17–1.95, p=0.002) in patients taking BDZ.
That's a 51% greater risk with benzo use.
What about CBD and acetylcholine?
Altogether, these data demonstrate that CBD increases ACh levels in a brain region related to wake control.
As we would hope, this effect was during lights-on periods. You don't want attention or focus in the middle of the night.
We covered this "biphasic" or situational dependent result in our article, Can you take CBD in the middle of the day.
Just wanted to cover all our bases.
Let's get practical now.
For these next three questions, some caveats:
- We are not doctors and cannot address medical issues - work with your naturopath for this!
- We CAN provide feedback from many clients and ourselves who have used CBD to get off Xanax and Ativan (many in the reviews) as well info gleaned from a few 1000 hours of research.
We'll start with a basic question.
Can you take CBD and Xanax or Ativan together
In general, you should not take medications within 4 hours of CBD.
CBD and Xanax or Ativan use the same liver pathway for processing.
There are limited resources there (first come first serve).
If the liver is busy processing CBD, it can make the levels of benzos last longer or be more pronounced.
We listed the half-lives of both Ativan and Xanax above so that's a good guide.
CBD generally peaks about 4-6 hours after taking it.
When people are transitioning off of Xanax and Ativan, they generally said their best response is to time CBD for the benzo drop off.
This would put it at about 4-6 hours after taking benzo depending on your weight, liver function, etc.
Really, I would listen to my body and when I felt the withdrawal symptoms start to roar, that's when I would take CBD.
Again, it's important to work with a naturopath (many doctors won't know what you're talking about or prescribed the Xanax and Ativan, to begin with).
One note….for ladies in their mid 40's and later, you have to address the root cause of the anxiety and sleep issues, to begin with.
Taking benzos to make up for dropping progesterone (at 50% by age 40) and estradiol is never going to get there.
This is a huge chunk of Xanax and Ativan prescriptions!
Let's look at how I used CBD to taper off of Xanax.
How I used CBD to taper off Xanax or Ativan
I had been on various benzos for about 2 months before I decided that enough was enough.
I bought a handy pill cutter and planned to cut slivers off the Xanax each day with slightly smaller amounts each week.
I started slowly on the CBD and tested what felt good on my system.
A starting level (don't expect too much) is generally 25-30 mg just to get a feel of how your system accepts it.
One note...we come across many people who have side effects only to find out it's because they're using full-spectrum CBD which is the majority of what's available on the market.
Learn all about CBD isolate versus full spectrum for anxiety here.
The last thing we want is more histamine (excitatory).
By the end, I would take CBD at 150 mg in the morning and 150 mg at night.
300 mg is the max level shown in research for neurogenesis (re-wiring GABA and dopamine reward pathways).
I've stayed on this 300 mg for a while now since I'm still in perimenopause which is what started my anxiety to begin with (that story is here).
As the benzo leaves, the brain will eventually start to "rescue" the GABA receptor protein production (all the way down to the DNA level).
This can take time and that's where people usually set stuck.
This is especially true if you've been on Xanax or Ativan for a while although the addiction can occur within weeks.
A higher dose of CBD may be important when you hit the waves of withdrawal and then can go down with time.
Keep in mind….you have to eventually address why you needed the Xanax or Ativan, to begin with.
If it was situational, the doctor probably shouldn't have put you on them, to begin with.
If it's general anxiety (longer-term), then definitely not since benzos are not recommended for the long term.
In my case, it was a drop estradiol and progesterone from perimenopause.
It can be a range of issues we covered at our mechanisms for CBD and anxiety including:
- Overactive immune response and neuroinflammation (see CBD and neuroinflammation for anxiety)
- Gut bacteria imbalance (see CBD and probiotics for anxiety)
- Genetic susceptibility (serotonin, GABA, or glutamate issues plus all the pathways that contribute such as B vitamins, MTHFR, etc)
- Past trauma or infection (see the neuroinflammation article)
- Stress response pathways such as Tryptophan and/or protein absorption issues (see Tryptophan and serotonin here)
Exercise, mindful meditation, forest bathing, and of course...CBD.
The next wave for anxiety and depression will be psilocybin (research here) which will be groundbreaking when legal.
We expect a similar trajectory to CBD.
Back to CBD...what's the best type to get off of Xanax and Ativan?
What's the best CBD to get off Xanax or Ativan
First, there's lots of junk product on the market.
Customers will send up pictures over of what their friend or chiropractor gave them.
No testing. No verified levels of CBD.
Just expensive junk.
A product needs to have the following as a baseline:
- Organically grown in the US at an FDA registered farm
- Cold C02 processed (cleanest method)
- 3rd party tested for:
- No THC (See CBD versus THC for anxiety...lots of misinformation on this note)
- No Heavy metals
- No solvents
- No pesticides
- No bacteria
- No mold
We actually test IndigoNaturals twice since our whole family uses it.
Our oldest son was given a prescription for Xanax. At the high school level, you don't really need a prescription since it's easily available and popular on the street (bars of it called a Xany bar).
Hopefully, it's obvious by our research that we don't mess around with testing.
The second big question is full-spectrum versus CBD isolate (learn more here for anxiety).
All the research is on CBD isolate. All of it.
Until we see differently, full-spectrum is just marketing and we're not going to trust our health to that.
We also want the cleanest product possible.
40-60% of the population has histamine or allergy issues.
This increases for women and as we get older (Thanks a lot progesterone!)
Adding all that plant material can increase histamine and histamine works against GABA...the very thing we're trying to support.
That's why an allergy attack can be served with an accompanying slice of anxiety.
Like you're "coming out of your skin".
We see lots of people who have side effects (GI, allergic, headaches, etc) with a full spectrum that goes away with CBD isolate.
It's exactly what happened when we first started on this journey.
We would have been perfectly happy to use one of the big full spectrum brands and IndigoNaturals would not exist.
This article would not exist. Hopefully, you get some benefit and insight since it does.
Check out more detail at how I used CBD to wean off benzos here or how I used CBD to taper off SSRIs here (since that's probably the next prescription you'll get).
Be very gradual...think weeks and months. Be safe and you can get there.
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.