If you google "benzodiazepines", it goes directly to abuse and addiction within the headings of many listings on the 1st page.
Google's incredibly powerful as providing information based on past searches.
Apparently, that's a billion-dollar model.
Another billion-dollar model surrounds benzodiazepines.
Our apologies for being jaded but we've personally experienced their prescription and subsequent withdrawal.
The issue is that they are very fast and effective for anxiety.
This speaks to the target of their action which is GABA in the brain.
We have an entire article on GABA, CBD, and anxiety here.
Since benzos can only really be used short term, can CBD be an alternative?
Is it effective and safe for anxiety versus benzos?
Those are the questions we're going to tackle based on research.
Some quick stats which we'll touch base on later:
- Senior's percentage for benzo prescriptions more than double younger age bands
- Women's prescriptions are almost double men's here
- 3 of the top 10 psychotropic drugs are benzos (Xanax is #2) here
- Between 1996 and 2013, prescriptions increased by 67%
- OD deaths went up 8 fold from 99-2016
- About 1 in 5 people who take benzos are misusing them here
We'll look at the whole class of benzos but with a focus on Xanax (alprazolam) since it's so popular.
You can even google the Xanax street value. Not a good sign.
We'll cover these areas:
- How benzos work in the brain for anxiety
- Pro's and con's of benzos for anxiety
- The endocannabinoid system and anxiety
- CBD versus benzos for anxiety according to research
- Comparing the different benzos for anxiety
- CBD versus Xanax
- CBD versus Ativan
- CBD versus Valium
- How much CBD to take for anxiety
- Best CBD for anxiety
Let's get started.
How benzos work in the brain for anxiety
We have an entire article on the root causes of anxiety here.
We also compare the anti-anxiety medications versus CBD here.
Let's focus down on benzos now.
We have a separate article for SSRIs versus CBD which are quickly replacing benzos in terms of standard practice.
Before we jump into benzo's effect, a quick review of the roots of anxiety especially in light of how benzo's work.
Anxiety can be driven by the following:
- Imbalance in brain area signaling (i.e. too much Amygdala)
- Imbalance in neurotransmitters (i.e. too little GABA - key to Benzo target)
- Brain inflammation and loss
- Histamine response
- Chronic stress
- Gut bacteria imbalance
Those are generally the core drivers of anxiety.
Typically, there are either genetic or environmental factors that lead to one (or more) of these drivers.
Early trauma or infection (even in utero) can trigger long term changes in all these areas and we covered it here.
Benzos focus on one key aspect...the final "lever" of anxiety that can result from other sources.
This is the level of GABA in the brain.
GABA is our main inhibitory chemical in the brain.
It acts like a "brake" for activity.
This not only slows down transmission in the brain but causes the net effect of feeling sleepy and relaxed.
You need GABA to fall asleep and feel calm.
As with all things in the brain, there's always a countering force.
In this case, it's generally glutamate or histamine which are both "excitatory" - the gas pedal.
Ideally, we have a balance between the two as both states are needed (alert versus sleep).
When there's an imbalance with too little GABA, the net effect is a feeling of anxiety.
Sure, it gets more complicated than that (different areas of the brain, the HPT axis, hormones, etc) but we've covered most of that at our CBD and anxiety article for further reading.
How do benzos play into all of this?
GABA.
They are a hammer (in one direction) to boost GABA levels and signaling in the brain.
That's not the only effect that benzos can have in the brain.
They can also directly impact our dopamine reward circuit which is generally the key to addiction:
We observed a statistically significant increase in striatal dopamine concentrations only with alprazolam, during the period corresponding to the behavioral stimulatory effects.
https://www.ncbi.nlm.nih.gov/pubmed/11226811
Let's look at the pros and cons of benzos.
Pro's and con's of benzos for anxiety
The pros are simple.
The benzos have fast-acting effects on anxiety via the GABA levels (and some may affect serotonin but at very low levels).
Again, GABA is the key immediate lever of anxiety and panic attacks.
The con's are equally obvious.
- High risk of addiction
- Normalization (need a higher and higher dose for the same effect)
- Severe withdrawal effects
- Cognitive impairment
There are subtle differences between the most popular benzos that can affect both the pros and cons.
The mechanism of the effect on our dopamine system is common across most of the class:
Their findings strongly suggest that this juncture occurs when dopamine surges in response to drug-taking initiate a change in synaptic plasticity in dopamine-producing cells
Remember that GABA is an inhibitory signaler. It turns things down.
The benzos affect GABA restraint on dopamine neurons which results in a surge of dopamine being released.
This is at the heart of most addiction since dopamine is the workhorse of our reward system.
It's even showing in a key part of the brain tied to addiction:
We observed a statistically significant increase in striatal dopamine concentrations only with alprazolam, during the period corresponding to the behavioral stimulatory effects.
https://www.ncbi.nlm.nih.gov/pubmed/11226811
With imaging, researchers were able to see the specific effect in the brain at a specific area:
first direct evidence in humans that alprazolam (Xanax) acutely increases perfusion in the nucleus accumbens, a key reward-processing region linked to addiction.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957329/
Why does that area matter?
Just this
As a whole, the nucleus accumbens has a significant role in the cognitive processing of motivation, aversion, reward (i.e., incentive salience, pleasure, and positive reinforcement), and reinforcement learning
https://en.wikipedia.org/wiki/Nucleus_accumbens
This goes beyond anxiety effects and GABA levels.
Pleasure. Incentive. Reward. Reinforcement learning.
This speaks to this fact:
Benzodiazepines’ newly discovered mechanism for producing reward is comparable to those of opiates, cannabinoids, and GHB.
This explains why benzos are the follow-up addiction behind opioids.
The road to addiction deals with structural changes in the brain as the continued use of benzos starts to change the structure of the brain to respond more strongly to future use:
These receptors render the cell more susceptible to stimulation by the excitatory neurotransmitter glutamate, and as a result, the cells respond to future drug exposures with larger dopamine surges that produce even more intense pleasure.
Furthermore...their assessment after watching structural changes in the dopamine neurons:
Even if you clear the drug from the body, there are long-lasting changes in brain architecture.”
Learn more about the sad state of this net effect on addiction at our CBD versus anxiety meds article.
Short term cognitive impairment is a known issue but what about longer-term use on the brain?
There's a great history and look at damage caused to the brain from longer-term benzo use here:
Benzos were never intended to be long term medications and the medical literature speaks to this.
Let's look at CBD but first, we need to look at where it operates.
The endocannabinoid system, benzos, and anxiety
We've detailed the endocannabinoid system significantly in our CBD and anxiety article or our CBD and antianxiety medications here.
Just a quick recap as it applies to benzos.
The endocannabinoid system is critical to balancing other key systems such as:
- Nervous system - including neurotransmitters like GABA, Serotonin, and others tied to anxiety
- Endocrine system - hormones including progesterone, estrogen, histamine, and others
- Immune system - including inflammatory response and cell growth/death cycles
We have naturally occurring cannabinoids that interact with this system.
The most prominent in the nervous system (critical to anxiety) are:
- 2-AG
- Anandamide
Since benzo's focus on the GABA levels for anxiety, we'll stay there.
It's definitely not the only lever at play with anxiety but we'll leave that to our comprehensive summary of CBD and anxiety above.
First, is there any connection between this system and the action of benzos?
Yes!
studies in our laboratory showed that cannabinoid CB1 receptor knockout mice (CB1-/-) presented increased anxiety-like behaviors that did not respond to the anxiolytic actions of benzodiazepines
https://www.ncbi.nlm.nih.gov/pubmed/19825899
Let's decipher this a bit because it's really important to our discussion.
CB1 is a cannabinoid receptor that's primarily expressed in the brain.
This is where cannabinoids like CBD do most of their work.
When those receptors were "knocked out" with gene editing in mice, benzos no longer had their anti-anxiety effects!
This means that the endocannabinoid system is key not only to the function of benzos in the body but perhaps to the underlying issue with anxiety itself.
As they put it…
Taken together, these findings revealed that the cannabinoid CB1 receptor plays a pivotal role in the pharmacological actions of benzodiazepines.
Since benzos are just a workaround to increase GABA levels (in terms of anxiety), do endocannabinoids affect GABA directly?
Researchers found that cannabinoids do indeed affect not only GABA levels (our nervous system's brake) but also glutamate (our nervous system's gas pedal):
Endocannabinoid 2-AG Potentiates GABAA Receptors.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3207709/
This just means that 2-AG boosts the signaling of GABA receptors in the body.
Interestingly, the researchers went on to study the effects of 2-AG and a common benzo, diazepam (Valium).
They found that 2-AG boosted the effect of diazepam on GABA production:
These results clearly suggest a superadditivity between the modulation by diazepam and 2-AG.
So, clearly the endocannabinoid system is intimately involved in GABA levels, the means by which benzos have their effects, and anxiety in general).
Check out our article, Can CBD boost GABA levels here.
We'll stop there so we can look at CBD directly to see what effect it might have on this pathway.
Again, this is not the only pathway we want to explore with anxiety.
Serotonin is a longer-term pathway:
Check out here:
- CBD, inflammation, and anxiety
- CBD and serotonin for anxiety
- CBD benefits for anxiety (summary level across different pathways)
CBD versus benzos for anxiety according to research
We compared CBD and the various classes of anti-anxiety meds including benzos in our comparison page.
Let's look specifically at the CBD versus benzos for anxiety.
First, does CBD affect the GABA pathway that benzos affect?
There's quite a bit of research now on how CBD boosts GABA signaling and the exact methods of how it does this.
Much of this was found researching its initial effects on epilepsy which is partially an issue of hyper-excitability in parts of the brain (GABA is a brake after all).
Let's look at some of the studies on CBD and the benzo pathway for GABA.
One study looked at 2-AG (endocannabinoid mentioned above) and CBD:
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
https://www.ncbi.nlm.nih.gov/pubmed/28249817
4x the GABA signaling potential for CBD.
Interestingly, CBD's effect did not operate on the same site of the GABA neurons that benzos use (they have their own site by the way).
The potency of CBD increased and efficacy preserved in binary α1/α2β2 receptors indicating that their effects do not involve the classic benzodiazepine site.
A very fascinating result came out of this experiment.
When GABA levels were low, CBD and 2-AG had the most effect.
As levels of GABA increased, the boosting effect tapered off.
This is the beauty of the endocannabinoid system...it's a system of checks and balance!
You can definitely overdose on benzos with increasing doses and it's a new epidemic.
That's not the case with CBD.
There is not a reported case of overdose which we can find.
In fact, for anxiety, the response of CBD appears to be on a bell curve which we'll discuss below in the amount of CBD section below.
Right now, inflammation is all the rage in research on anxiety.
One study looked at how inflammation reduced the levels of GABA in the brain and how CBD offset these changes.
https://www.ncbi.nlm.nih.gov/pubmed/17672854
We're going to wrap this section with our favorite study to date.
Let's introduce a new player, CFR ( corticotropin-released-hormone )
CFR is basically the chemical messenger of stress from the rest of the body and nervous system.
It basically signals the hippocampus to ramp up glutamate (gas pedal) and turn down GABA.
This then affects a range of endocannabinoids including 2-AG, Anandamide, and FAAH.
Stick with us here...there's a payoff.
Researchers found:
In brain areas related to neuropsychiatric disorders, exposure to acute stress leads to a rapid decrease of AEA while inducing a delayed increased in 2-AG levels
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742214/
Basically, the great balancer of our nervous system is over-worked by stress.
Why does this matter for CBD?
CBD supports both Anandamide and 2-AG levels in the body and brain!
Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316151/
It affects 2-AG by inhibiting the endocannabinoid (MAGL) that breaks 2-AG down.
The net effect of this is that GABA reduction at the hands of stress is countered.
We have an entire article on CBD's effects on GABA for anxiety here.
Let's look at the benzos in more detail.
Comparing the different benzos for anxiety
There are subtle differences between the most popular benzos that can affect both the pros and cons.
Here's the main list of the most popular medications in this class:
- alprazolam (Xanax)
- clonazepam (Klonopin)
- chlordiazepoxide (Librium)
- diazepam (Valium)
- lorazepam (Ativan)
- temazepam (Restoril)
- triazolam (Halcion)
Here's a good description of the major ones:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684331/
There are some distinct differences between the various benzos that really matter here:
- How quickly the drug takes effect and goes away
- Do they produce metabolites
- Chance of addiction
All the benzos work more or less on the benzodiazepine area of the GABA neuron.
That's their primary lever for anxiety.
All the variants above conspire to make some benzos more addictive than others.
Ironically, the most popular (Xanax and Ativan) are affected by this calculation.
If we were jaded people, we might draw a conclusion there but for now, let's just explain.
Benzo's came out in waves...generations if you will.
The first wave started with Valium.
It's estimated that at one time, 1/3rd of women over a certain age were on benzos during the '70s.
Hence the song, Mother's Little Helper by the Rolling Stones (that's Valium by the way).
The history of benzos is fascinating and not very flattering of how our society views women's health and wellbeing.
That's another article (or two).
Back to why the distinctions matter.
Here's the net net.
The newest generation of benzos work very quickly, drop off very quickly, and carry a big stick.
They have a shorter "half-life" which means that their effects drop off faster.
Some of the older ones (like Valium) produce metabolites which have similar anti-anxiety effects and produce more of a slow, trailing off anti-anxiety effect.
It's like the fumes when you're running out of gas. It still gets you somewhere.
Xanax and Ativan don't produce these metabolites and they are shorter-lived.
We did a deep dive on Xanax and Ativan here since they are even more difficult.
This means the re-introduction to the underlying anxiety is faster, harder, and more severe.
Keep in mind that the core reason for GABA signaling deficiency isn't solved a bit by benzos.
They're just there to mask the symptoms.
Stress. Inflammation. Hormonal imbalance. Gut bacteria imbalance. Brain area signaling.
Core issues.
Anyway, on top of the underlying rebound anxiety, there are the new additional withdrawal symptoms.
https://www.ncbi.nlm.nih.gov/pubmed/7841856
For the short term benzos like Xanax and Ativan, this can occur within a day if not immediately.
Remember from above how the Dopamine neurons were literally primed to react to future benzo exposure with more ferocity.
It's a vicious cycle which is why the medical literature recommends not to stop benzos all at one.
Serious health effects can occur.
Even if you follow the protocol for weaning, this process has been called one of the hardest in the addiction field.
Check out how I used CBD to wean off of benzos here.
We'll discuss that below in terms of CBD.
Let's look quickly at the biggest benzos.
CBD versus Xanax
Xanax is the top seller of benzos.
As we mentioned above, it's one of the fastest acting and fastest leaving of the class.
This makes it especially difficult to manage from an addiction perspective.
Xanax is at the heart of the prescription addiction crisis.
Benzos are right up there with opiates, alcohol, nicotine, and meth in terms of difficulty in stopping.
Xanax causes addiction in much the same way that other drugs, including opiates like oxycodone, cause addiction
https://drugabuse.com/xanax/is-addictive/
Its half-life is roughly 6-29 hours. Peak levels are usually in 1-2 hours and it's cleared primarily by the kidney.
Xanax has one of the shortest duration of any of the benzos and has no metabolites to lessen the drop-off.
This might be why it has a street value and a slew of nicknames on the streets.
There's even a rapper called Lil Xan and it punctuates a great deal of the SoundCloud rap scene despite being involved in the death of many prominent entertainers.
Last we checked, there was no rapper called Lil Oxy.
CBD's peak level is from 4-6 hours and generally lasts about 24 hours in the body.
More importantly, CBD doesn't cause the rush of dopamine associated with Xanax.
Studies have shown that it not habit-forming or hedonic.
Hedonic is the key there.
It's a scientific word that means pleasure causing. Remember the dopamine rush centers were tied to pleasure and behavior reinforcement for Xanax and other benzos.
CBD studies have shown it to be:
- Non-hedonic
- Non-habit-forming
- Not subject to normalization (need more and more for the same effect)
- Not psychoactive
These are the key differences between CBD and Xanax.
In 2013…
national ED visit data and national prescription data show that alprazolam is related to more ED visits related to drug misuse per prescription (1 in 311) than the next 3 most commonly prescribed benzodiazepines—lorazepam (1 in 540), diazepam (1 in 517), and clonazepam (1 in 321)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846112/
We did a specific review of CBD versus Xanax or Ativan since this new class is so problematic.
Speaking of other benzos...
Let's look at the next popular benzo, Ativan.
CBD versus Ativan
Ativan generally comes in the top 10 for psychoactive drugs (after Xanax).
Like with all benzos, it carries the general risk of addiction.
Ativan is different from Xanax in that it lasts longer and has a greater effect at a smaller dose.
The snap-back of Ativan wearing off is not as strong as with Xanax but the risk or normalization (needing more and more of Ativan for the same effect) is higher due to the stronger effect.
The time to peak levels is 1-6 hours (versus Xanax at 1-2 hours).
Ativan's effects last much longer in the body.
It also doesn't produce metabolites that can soften the blow when its effects wear off.
Ativan and Xanax are generally thought of as the two fast acting and short duration benzos.
They're also the most prescribed and merit the most attention for addiction risk.
Go figure.
The same calculus with CBD and Xanax applies to Ativan.
Check out CBD and Anxiety for information on its effectiveness with anxiety.
Make sure to check out what research says on levels of CBD for anxiety below.
CBD versus Valium
We end at the beginning.
Valium was the first big benzo to hit the scene and it was a blockbuster!
It's estimated that 1/3rd of women over a certain age were using valium in the '70s.
Valium is part of the first generation of benzos.
It's generally slower acting and lasts longer.
Its peak plasma level is at 1-2 hours (short) but its duration in the bloodstream is 20-80 hours.
Compare that to Xanax at 6-26 or Ativan at 6-20.
Maybe, more importantly, the body's breakdown of Valium results in metabolites that have similar anti-anxiety qualities (little mini-benzos).
This causes the effect of Valium to "trail off" rather than drop off a ledge.
The half-life for one of these metabolites (desmethyldiazepam) can last from 40-120 hours!
This doesn't prevent valium from having a potential for addiction.
It may just take longer to take effect.
It has all the tell-tale symptoms including normalization, hedonic effects, and withdrawal symptoms.
Speaking of benzo withdrawal.
CBD to help get off of benzos
Millions of people have been prescribed benzos (many from a General Practitioner...perhaps with little warning of the downside).
We get the question often...can CBD help when coming off benzos?
First, a warning.
There's an entire process of weaning off benzos.
It can be dangerous to drop them cold turkey, especially the fast-acting variety like Xanax and Ativan.
Even if you follow the manufacturer's instructions, the process can still be very difficult.
Otherwise, we wouldn't need to write this article!
A quick review of that here:
https://www.ncbi.nlm.nih.gov/pubmed/7841856
When my spouse had to come off of the benzos (that crazy story here), we had a pill cutter we would use to slice slivers off every few days.
And even that was brutal!
Xanax is especially difficult.
The rebound anxiety can be very intense.
Check out CBD to get off Xanax, Ativan, and Valium.
Benzos don't address the core drivers of anxiety
We now have layered withdrawal symptoms on top of the unresolved anxiety
For this reason, many people look at CBD to smooth out this process.
Ideally, they also address some of the key drivers (inflammation, balancing in neurotransmitters and brain area signaling, neurogenesis, immune response, etc).
Research is showing that CBD has positive effects on all these attributes which you can find in the link above.
A few important tips.
Always take CBD at least 2-4 hours away from medications including benzos.
They both use the same pathway in the liver for processing.
Check our CBD Quick Start guide for tips on how to get the most out of CBD for anxiety.
Finally...check out this article on CBD and addiction.
There's lots of research on how CBD may actually help to "unhook" the brain circuits that drive addiction.
It's fascinating and applies equally to benzos as it does to opiates, alcohol, and nicotine!
On to a very important piece…
How much CBD to take for anxiety
We actually have some hard research on CBD levels for anxiety.
First, always start slow to test how your body responds.
25-30 mg is generally a wellness dosage to test response.
Keep in mind that anxiety relief probably won't occur at this level especially if you're coming off of benzos.
What does the research show?
Help with sleep was around 160 mg.
The maximum relief for anxiety was around 300 mg!
That can be broken up (since peak level is about 4-6 hours).
Interestingly, the long term neurogenesis effects on anxiety decreased from 300 to 600 mg.
This speaks to CBD's role in the endocannabinoid system for balancing other key systems.
Benzo continues to build tolerance with further use which means your natural GABA pathways drops over time.
That's not the case with CBD.
Its effect will taper off past a certain point which why we don't see overdose, sedation, and cognitive issues.
Here's more information on how much CBD to take for anxiety.
The 300 mg of CBD is interesting though because it speaks to key factor...how do we afford this?
Best CBD for anxiety
The usual requirements apply here:
- Organically grown in the US
- CO2 extracted
- 3rd party tested
- Free of THC (THC can cause anxiety)
- Free of Pesticides
- Free of Solvents
- Free of Heavy Metals
- Free of Bacteria
- Free of Mold
That's just the start.
There are two considerations we have to look at for anxiety versus benzos.
Full-spectrum versus CBD Isolate for anxiety
Everyone out there is pushing full-spectrum (lots of plant material).
The big thing they're not realizing is that 40-60% of the population will have likely have a nasty histamine response to all that plant material.
That number is higher for women and higher yet over age 40.
Remember how we said benzos were prescribed for women at twice the rate and for older people at much higher levels!
Hmmm...just a bit of overlap there.
We're not surprised as histamine response may be a key driver of anxiety.
Check out our CBD, Histamine, and anxiety page.
There's a little known anti-anxiety med that's been shown to be equally effective and...wait for it…
It's an anti-histamine!
Check out the article above for more detail.
Full-spectrum is the wrong direction for anxiety for this reason.
That and the fact that all the research is on CBD by itself.
The "entourage effect" originally spoke to how CBD offset the negatives (such as anxiety) of THC.
The second consideration goes back to the 300 mg dosage shown in research.
That's a lot!
We have to be able to afford this.
For that, we need to look at the lowest cost per mg of CBD!
It should be around 4-5 cents per mg.
That puts a 2000 mg bottle at about $100. A $6000 bottle is about $300.
Since we've been in the throes of anxiety ourselves and desperately coming off of benzos, we priced our 2000 mg under $100 and our 6000 mg under $200 at IndigoNaturals.
For 300 mg, the 6000 is going to make more sense (that's about 20 doses in a bottle).
That's why we priced the bigger bottle that way. We wanted an option for people who really require larger amounts.
We've been there.
In fact, we take about 200 my daily (1 dropper of the 6000) to address anxiety from perimenopause.
Our entire family takes IndigoNaturals. It's been vetted personally for this reason
Other key reviews:
CBD and GABA versus alcohol, benzos, and gabapentin
Guide to CBD and Anxiety
Guide to CBD and sleep
CBD versus anti-anxiety meds
CBD to ween off benzos
Can you take CBD and Xanax at the same time
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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