CBD and Klonopin - shared pathways with very different effects

cbd versus klonopin


In the early days of our founder, there was a series of benzos prescribed.


This was for anxiety, rolling panic attacks, and insomnia which hormones would eventually fix (full story here) from a brutal perimenopause.


It started with Valium but that was not working. Xanax was later prescribed but the new class of benzos like Xanax and Ativan have brutal drop-offs (see review on Xanax and Ativan).


Reactions to an SSRI (Lexapro) caused 3 nights of no sleep and it was getting very serious.


A doctor prescribed Klonopin as a final option since she couldn't sleep at all (had serotonin syndrome in the end).


I remember taking her to the local park just to get her out of the house and she was practically catatonic with the Klonopin.


It's a sledgehammer.


Eventually, she came off all of the meds and as part of that journey, we found CBD isolate.


In fact, there's interesting research on CBD with addiction (here) and withdrawals.


Let's look at the shared pathways of CBD and Klonopin and how they have such different means of action.


We'll cover these areas: 

  • How Klonopin works
  • The downside to Klonopin longer term
  • Why Klonopin is so hard to get off of
  • How CBD works versus Klonopin
  • Can you take CBD with Klonopin
  • How much CBD to take instead of Klonopin
  • What's the best CBD to replace Klonopin


Let's get started. 

How Klonopin works 

Klonopin (clonazepam) is pretty straightforward benzo.


It basically boosts the GABA pathway in one direction (technically called an agonist).


GABA is our brain's brake pedal.


It's critical for sleep, avoiding anxiety, lessening pain, and a range of different effects on the nervous system.




GABA opposes a host of different players which can exhaust GABA and lead to anxiety, insomnia, and more.


The main exhausting factors are: 

  • Stress (cortisol)
  • Histamine (excitatory in the brain)
  • Glutamate (brain's "gas" pedal)
  • Inflammation
  • Trauma (downregulates GABA; even if early in life)


You can learn all about the pathways of anxiety here or insomnia here since they're the two biggest reasons for prescribing Klonopin.


Klonopin is generally more on the sleep side of the equation because it lasts much longer in the body than the newer class of meds.


So…what's the downside to Klonopin acting on our GABA pathway? 

The downside to Klonopin longer term 

All the benzos have two things in common by how they work (the agonist push in one direction piece).


Benzos including Klonopin: 

  • Build tolerance
  • Cause addiction


Let's break these down as they are critical to the reason for this article.


Tolerance is the process by which the body pushes back against a medication or supplement's effect.


GABA is such a powerful player in the brain that the body doesn't like it to be boosted artificially (too strong and for too long).


With consistent use, the body will actually downregulate GABA receptor numbers and sensitivity.


This means you need more and more of the drug to have the same effect.


Unfortunately, this process continues to where your natural GABA level is much lower than when you started.


That's why you can't stop benzos cold turkey. Glutamate (the opposing force) actually gets ramped up as a countermeasure and it's possible to have seizures if you stop benzos cold turkey after a period of time.


This reflects an extreme GABA/Glutamate (excitability) mismatch due to the tolerance effect.


That's the rebound effect after the medication wears off and it builds with time.


Addiction is different.


That's dopamine (see CBD and addiction) and benzos are one of the most addictive classes of medications out there.


Dopamine is our reward pathway and it's basically a learning driver. It rewires the brain to reward a certain behavior and Klonopin spikes dopamine to drive addiction.


It can happen really quickly…estimated at 2 weeks+.


In fact, you see warning labels on benzos and doctors should warn newly prescribed patients (ours didn't).


Klonopin has another element to it in this regard. 

Why Klonopin is so hard to get off of 

Many people really struggle to come off of Klonopin. With good reason.


Klonopin is one of the longest-lasting benzos on the market.


The half-life is 20-50 hours! See our full review of all the benzos here.


So it doesn't have the sharp drop off of Ativan and Xanax but the long life causes another issue.


The period to GABA normalization (generally 30 days) takes much longer since the drug remains active and has metabolites that also mirror its effect.


This can make weaning off of Klonopin, especially the last bit of it…very difficult.


So…how does CBD work? 

How CBD works versus Klonopin 

CBD also affects the GABA pathways but in a very different way.


CBD works within the endocannabinoid system which is tasked with balancing other key systems: 

  • Nervous system - including GABA, serotonin, glutamate, and others
  • Endocrine system - hormones
  • Immune system - inflammation and cellular birth/death cycles


The cross-over with GABA is our first focus.


CBD doesn't just boost GABA in one direction (agonist).


It's technically called an allosteric positive modulator. It's a feedback mechanism!


This means that it supports GABA when low and can even decrease it when too high.


For example, a study looked at CBD's effect on people with autism and found different effects matching their particular signatures: 

Across regions, CBD increased GABA+ in controls, but decreased GABA+ in ASD; the group difference in change in GABA + in the DMPFC was significant. 



Interestingly, it decreased the "brake" pedal in the thinking part of the brain…the prefrontal cortex for people with autism.


CBD's effect on anxiety and sleep are generally (partially) attributed to its support of GABA.


Here's the interesting piece.


With Klonopin (and other benzos), when you take a higher and higher dose, you follow a trajectory: 

  • Calm
  • Sedated
  • Hypnotic
  • Amnesiac
  • Catatonic!


Essentially, you're slowing the brain's functioning more and more with higher doses.


You don't see this with CBD. Again, feedback mechanism.


For this reason, CBD does not build tolerance, cause addiction, affect cognitive function, or have a rebound effect.


See CBD and tolerance for more. 


In addition to just GABA, CBD has the same feedback effect on serotonin (stress response buffer), histamine, brain inflammation, and glycine (the "switch" for sleep).


So some practical questions. 

Can you take CBD with Klonopin 

Both CBD and Klonopin use the same liver processing pathway so caution is advised.


Usually, we can take CBD far away from another med since the half-lives are much smaller Klonopin lingers for a long time in the system and has metabolites that continue on.


Taking CBD while Klonopin is still at a high level can magnify its side effect (and primary effect) profile since the liver is busy breaking down CBD.


It can also allow Klonopin to remain for a longer period of time.


Work with a doctor or better yet, a naturopath since it's probably the doctor that prescribed the Klonopin to begin with.


CBD should help support the dropoff in GABA and keep excess glutamate at bay.


After all, CBD's original claim to fame centered around seizures (the excitability mismatch).


Studies show that peak neurogenesis is around 300mg daily.


Neurogenesis is the process of re-writing brain pathways to undo the dopamine-driven "learning" of Klonopin addiction.


Otherwise, you're fighting the tide longer term.


It takes at least 30 days for the GABA receptors to come back online after no use of Klonopin.


The DNA literally has to be turned on to make the 5 proteins that make the GABA receptor.


Really check out the big reviews to look at other tools to help such as magnesium glycinate, glycine, NAC, and more.


We have to address the reason you were prescribed to begin with.


Otherwise, we're right back to square one. There's fascinating research on how early trauma or infection can downregulate GABA and serotonin while upregulating inflammation.


CBD helps here but there are other tools to get to the root of the issue. 

How much CBD to take instead of Klonopin 

This depends on where you are in the process.


Again, we don't mix high levels of both at the same time since they use the same pathway and it can amplify Klonopin's effect (and side effects).


Check out the review on peak neurogenesis dosage here.


One note..steroidal hormones are a huge driver since progesterone drives GABA and it drops by 50% at age 40.


Estrogen and testosterone drive serotonin, our key stress response buffer longer term.


We see many prescribed benzos and SSRIs the mid to late 40s which mirrors this deficit.


There's no band-aiding loss of steroidal hormones for mental health and sleep!


What about the type of CBD? 

Best Type of CBD to replace Klonopin 

There are a few mandatory requirements: 

  • From organically grown hemp in the US at an FDA registered farm
  • CO2 cold extracted
  • Third-party tested
  • No THC (THC builds tolerance)
  • No pesticides
  • No solvents
  • No heavy metals
  • No mold
  • No bacteria


Our third-party testing is available at the top of every page.


Then there's the question of full-spectrum versus CBD isolate.


All the research is on CBD isolate (see CBD versus benzos or CBD and GABA).


More importantly, 40-60% of the population has histamine issues.


This number goes up as we get older and for women (progesterone leaving).


Full/broad-spectrum can cause side effects from this histamine response that are not found with CBD isolate.


Remember that histamine is excitatory in the brain. It actually opposes GABA in the sleep/wake cycle. We did a deep dive on whether histamine is the key to insomnia.


You can see the reviews to pick up people's different responses between CBD isolate and full spectrum on the product pages.


Finally, there's cost.


To match the research, we're looking at 300mg for a period of time to drive neurogenesis.


The key is cost per mg of CBD in this case.


We've priced the 6000mg bottles at 2-3 cents per mg for this reason and it's before discounts up to 50%.


Klonopin was brutal to come off of and CBD can be a tool to soften that response. There's research on opioid withdrawals which establishes the process on both the withdrawal side and the addiction side.


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



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