We've written extensively on many aspects of anxiety in general.
A few 100 thousand words now and 100's of NIH studies.
Regardless of the particular pathway (social anxiety, anxiety, and cortisol, child anxiety, etc), one trend becomes apparent.
A great deal of uncontrollable anxiety is the result of past insults on the working of the brain:
- Chronic stress
- Infection and/or antibiotiFcs during critical brain development
- Epigenetic signatures from past generations
- Gut bacteria imbalances
- Trauma
It's the last one we're going to focus on for PTSD obviously.
This one is personal for us.
After three nights of no sleep from Lexapro landed me in the hospital, an ER doctor administered an anti-nausea drug known to have severe side effects with Lexapro.
It basically sent me into a psychotic break and was by far, the most traumatic event of my life.
I can honestly say that of all the benefits I've personally seen from CBD, its effect on "separating" from that experience has been the most powerful.
For that reason, we're going to do a deep dive into PTSD.
Wait till you see the effects of BDNF (our brain's fertilizer) on the ability to forget bad memories.
NPY is a fascinating actor which acts roughly as our "resilience" chemical.
Studies on its effect for people in war who later do or don't get PTSD are very interesting.
Of course, we're going to look at research on CBD and how it affects the pathways both in terms of the stress response and for brain repair (the holy grail).
Finally, we're going to look at forgetting bad memories.
Yes, there's an actual system for this process.
We'll cover these areas:
- What causes PTSD in the brain
- PTSD and the anxiety circuit
- Neurotransmitters and PTSD (BDNF!!!)
- Brain inflammation and PTSD
- NPY and PTSD risk
- The genetics of PTSD
- The endocannabinoid system and PTSD
- Can CBD help with PTSD
- CBD versus PTSD medications
- How much CBD to take for PTSD
- The best kind of CBD for PTSD
Let's get started.
What causes PTSD in the brain
First, an introduction to your brain.
We like to think it's hardwired and will remain roughly the same but that's not the case.
It's incredibly "plastic".
Most people think of plastic as being hard but the actual meaning is something that can be molded (which makes sense with actual plastic!).
Your brain is actually changing a bit just by reading this sentence.
Mastering Chinese or ping pong will result in bigger changes.
There are systems for creating this change and even erasing changes within the brain.
Otherwise, we would never learn anything new or forget anything of no use.
This ability to change is both a blessing and a curse.
You can learn trauma as well as you can learn ABC's from the neuroanatomical point of view.
This maladaptive learning is especially possible:
- During critical points of brain development
- With overwhelmingly intense experiences
- With genetic predispositions either to blunt the effect or repair the brain afterwards
Before we all get depressed about a lack of time machines, just know that we'll cover ways to "unwind" this effect in the brain below.
For now, know that intense experiences, both positive and traumatic, can "marbleize" into the actual structure of the brain.
Let's quickly look at the three concerns above before diving into the brain areas affected.
Trauma during critical points of brain development
There are many examples of early life stress and resulting in anxiety or PTSD risk.
For example, one study looked at rats that are handled often (touch) and those that are not.
The ones with more handlings showed changes in their stress response system throughout their life:
Rats handled during infancy had a permanent increase in concentrations of receptors for glucocorticoids in the hippocampus, a critical region in the negative-feedback inhibition of adrenocortical activity.
https://www.ncbi.nlm.nih.gov/pubmed/3340858
Glucocorticoids are our stress response hormones. Important!
Put a checkmark next to that hippocampus area. It figures strongly into the anxiety circuit with PTSD and more importantly, how we can actually help later on.
Basically, rats that had more attention early on showed reduced levels of stress activation (glucocorticoids).
The net effect of early life attention was obvious:
Increased exposure to adrenal glucocorticoids can accelerate hippocampal neuron loss and cognitive impairments in aging. Hippocampal cell loss and pronounced spatial memory deficits emerged with age in the unhandled rats but were almost absent in the handled rats.
Why is this important for PTSD directly?
They have found that people who have severe, chronic cases of PTSD have smaller hippocampi. This indicates that experiencing ongoing stress as a result of severe and chronic PTSD may ultimately damage the hippocampus, making it smaller.
https://www.verywellmind.com/the-effect-of-ptsd-on-the-brain-2797643
We've looked at this in detail at our CBD and hippocampus neurogenesis article and CBD and brain repair.
Not only is the hippocampus the seat of memory (including traumatic ones), it functions as a "switch" for anxiety states.
This partially makes sense since the brain must use past experiences (memories) to guide what to be afraid of going forward.
For now, just know that studies are showing reduced hippocampus volume and activity in people with PTSD.
Chronic or acute stress (aka trauma) can actually damage the hippocampus.
Early exposure to this trauma can manifest itself as PTSD later or make a person more susceptible to PTSD.
The age matters as well.
Trauma experienced before age 13 had a higher risk for PTSD later in life:
In the childhood group, conditional risks for PTSD and major depressive disorder were 17.0% and 23.3%, respectively, compared with risks of 13.3% and 6.5%, respectively, in the adolescent group.
https://www.ncbi.nlm.nih.gov/pubmed/15172941/
The brain is in a period of massive plasticity during childhood.
Check out CBD and teen anxiety or CBD and child anxiety to understand this process better.
Try learning a language after age 18!
We're going to learn all about BDNF below but for now:
Brain-derived neurotrophic factor (BDNF) is a growth factor that is dynamically expressed in the brain across postnatal development, regulating neuronal differentiation and synaptic plasticity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5089164/
So, early childhood trauma can mold our brain's response to future stress and trauma:
Considered together, these findings suggest that early in the postnatal period there is a naturally occurring brain plasticity in key neural systems that may “program” an organism's biological response to stressful stimuli.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181836/#ref79
That article has dozens of examples from animal studies to the poor children in the Romanian orphanages.
This effect appears to be more pronounced in women in terms of cortisol (stress hormone) and CRF (stress initiator) levels in response to trauma.
We'll cover both of those below.
The net net...
Early childhood adversity such as physical and sexual abuse, emotional neglect, parental loss, etc., are major risk factors for the development of a range of psychiatric disorders in adulthood, including posttraumatic stress disorder (PTSD)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3582641/
Another study looked at mothers who gave birth after 9/11. There were increased stress hormone markers in the uterus:
This suggests that stress-induced elevations of glucocorticosteroids during pregnancy may affect fetal brain development and thereby induce permanent changes in the glucocorticoid (GR) programming of the offspring.
https://pure.uva.nl/ws/files/1341029/96814_06.pdf
One effect of early trauma is on how the serotonin system works later in life:
A history of severe trauma exposure in the PTSD and TC groups was associated with marked reductions in the caudate, the amygdala, and the anterior cingulate cortex.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244836/
In fact, the earlier the age, the more significant the effect on serotonin activity.
We'll cover serotonin in depth below.
It's just interesting that with more sophisticated tools, they can actually pinpoint the molecular pathways on how early trauma leaves its mark.
Again, we'll look at good news on this front below.
Then, there's just pure intensity of experienced trauma.
With overwhelmingly intense experiences
Our brains are designed to learn from experience and adjust accordingly.
If an event is too traumatic, it can overwhelm this system.
An experience with enough intensity is designed to be remembered for a reason.
In fact, there's a whole process of the brain to unwind fears that are no longer needed.
It's called "fear extinction" by scientists.
It's critical to PTSD risk:
Recent prospective studies in emergency services have identified impaired fear extinction learning and memory to be a significant predictor of Posttraumatic Stress Disorder (PTSD),
https://www.sciencedirect.com/science/article/pii/S0149763416301701
It's one thing to "write" fear into the brain circuit, but what about erasing (albeit with time).
That's the piece that's interesting based on new research.
Again, we see the "builders" of the brain such as Serotonin and BDNF at work here:
Since BDNF appears to enhance the extinction of fear, targeting impaired extinction in anxiety disorders such as PTSD via BDNF signaling may be an important and novel way to enhance treatment efficacy.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3389160/
You'll never guess what system in our body governs the growth and removal of brain circuitry in the nervous system.
The endocannabinoid system!
Yes, the very system that CBD interacts with.
As this study goes on to say:
In addition, there are different systems that seem to alter fear extinction through BDNF modulation like the endocannabinoid system and the hypothalamic-pituitary-adrenal axis (HPA).
We'll circle back around to this later in our section on neurotransmitters and the endocannabinoid system.
Speaking of endocannabinoid, the ability to unwind fear memories in the brain is intimately tied to anandamide, our naturally occurring endocannabinoid in the brain.
It's called the "bliss" molecule and named after Anand, the Hindu goddess of bliss.
Follow this 1-2 punch for PTSD:
People with PTSD have a lower level of anandamide.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3752332/
Another endocannabinoid in the system called FAAH is tasked with breaking down anandamide.
We covered it in detail for the woman who can't feel pain or anxiety (due to no FAAH).
How does this pertain to PTSD?
The more FAAH you have, the less anandamide and consequently, the less CB1 processing of adverse fear memories.
Obviously, having no fear of memories is a dangerous thing.
After all, anxiety and pain are warning signals in the brain to stop doing something that's potentially dangerous to survival.
We'll circle back around to all of this but forgetting traumatic experiences is a key ability.
Put a checkmark next to BDNF and Anandamide.
See article on the research on CBD and neurotrophins like BDNF.
Finally, why do some people have traumatic responses to a given situation while others don't (besides early life trauma as we looked at above)?
Let's look at genetics and trait anxiety.
With genetic predispositions either to blunt the effect or repair the brain afterwards
Our response to trauma is partially dictated by genes and even epigenetics (passed down markers from prior generations).
Check out the CBD and long term anxiety to see that effect from studies on holocaust survivor descendants.
We're getting closer to understanding more of the genetic side of things (more on that below).
Let's look at the anxiety circuit now.
PTSD and the anxiety circuit
We've covered this in detail at our CBD and anxiety or CBD and general anxiety disorder but a quick refresher.
There are a few key brain players at play in the anxiety circuit which also pertains to PTSD:
- Amygdala - our fear and emotional processing center
- Prefrontal cortex - our rational brain in charge of offsetting the amygdala's initial fear response
- Hippocampus - memory center and key "switch" in the anxiety circuit
These are the big players.
Tracks of white matter and specific brain areas can also add inputs but anxiety and PTSD is generally a function of:
- An overactive amygdala initiation of fear
- An underactive prefrontal cortex response to the amygdala
- Poor function in the hippocampus (which tends to be smaller with PTSD both before and after trauma)
The hippocampus is very susceptible to stress both chronic and acute (traumatic).
It's one of the most plastic or malleable areas of the brain which makes sense due to its ability to make new memories is dynamic.
Otherwise, we would never learn from our mistakes (pain and anxiety).
You can learn all about exactly how stress, infection, and inflammation attacks our brain areas here:
Maybe, more importantly, there are ways to offset the effects of these insults.
Some pretty good reviews of this brain circuit and PTSD can be found here:
- https://www.brainline.org/article/how-ptsd-affects-brain
- https://howcbdworks.net/how-does-cbd-work-for-PTSD.html
Let's start to drill down lower into actors we can actually influence.
We'll start with neurotransmitters.
Neurotransmitters and PTSD
First, focus on some of the heavy hitters with direct ties to PTSD:
- Serotonin
- BDNF
- GABA
See our article on can CBD boost GABA.
The first two are major players and both directly affect the ability of the brain to repair and respond to damage (and fear imprints).
First, serotonin.
As we saw above, a set of genes tied to PTSD dealt with our serotonin pathway.
We go through the power of serotonin for anxiety at our CBD versus SSRI's for serotonin and anxiety here.
Let's narrow the focus to PTSD specifically.
First, there's the interesting mechanism between early life trauma and a key receptor for serotonin function called type 1B
The Effect of Early Trauma Exposure on Serotonin Type 1B Receptor Expression Revealed by Reduced Selective Radioligand Binding
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244836/
Basically, early trauma reduces the functioning of serotonin for a key pathway in the brain.
One note...serotonin does a lot in the nervous system.
Researchers originally didn't know if the serotonin receptor itself was tied to PTSD symptoms or if it was something further downstream.
They actually tested it on the 5H1a receptors known to have anti-anxiety effects and boost GABA activity (key to anxiety and how benzos work).
Unexpectedly, we found no difference in 5-HT1A receptor expression between the groups (Figure 2). This result suggests no direct role for the 5-HT1A receptor in the pathophysiology
of PTSD;
Interestingly, this same study showed that by blocking serotonin activity, the effects of SSRI's would also be thwarted.
This points to what other studies show...the real power of serotonin is to repair neuronal tissue.
In fact, SSRI's primary lever was found to operate through endocannabinoid pathways!
It's not just about serotonin levels for anxiety or PTSD...otherwise SSRI's would have a much better response than they do.
It's about serotonin "function". Receptors tie directly into this process.
You can flood neurons with serotonin but if they're lacking sensitivity and the pathway isn't working, you just end up with Serotonin Syndrome (see CBD for serotonin syndrome) for nasty side effects.
In fact, studies are showing that the serotonin genes for PTSD may have more to do with the pathways:
Patients with PTSD who carried the short allele of the serotonin transporter gene promoter responded more poorly to treatment than other PTSD patients. This study highlights that the serotonin system is implicated in responding to cognitive behavior therapy
https://www.sciencedaily.com/releases/2010/06/100617102712.htm
The CBT (cognitive behavior therapy) connection is not surprising if our main premise is that serotonin is for rebuilding.
CBT involves using behavior to resculpt the brain (neurogenesis).
Next up...a major builder in the brain...BDNF.
BDNF and PTSD
We've seen this actor many times up above.
Think of it as fertilizer for neurons and the connections between them.
Its full name should be indicative of this:
Brain-Derived Neurotrophic Factor
Check out a full review of CBD and BDNF for brain repair.
Nowhere is it more important than our most vulnerable area tied to the anxiety circuit:
The BDNF gene codes for the BDNF protein which is then expressed to promote the growth and survival of neurons, particularly those in the hippocampus
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742797/
There's an interesting genetic connection for BDNF.
Researchers have found two main variants or "flavors" of this gene in the population.
One of these variants results in less BDNF especially in the hippocampus and the effects of this:
This means that in met carriers (rather than val homozygotes) sufficient BDNF protein may not be released into the hippocampus for it to respond appropriately to the demands that the environment may place on it, such as the demand for consolidating traumatic experiences into long term memory
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742797/
This speaks to the flashbacks and recurring thoughts or hypervigilance.
The traumatic experience memory is stuck between short term (feels present) versus long term memory (in the past).
Of course, the body responds accordingly as if we're in the traumatic experience all over again.
Remember how smaller hippocampus volume and activity was tied to PTSD symptoms and risk?
BDNF could be the key there.
Specifically, the study revealed that the allelic frequency of BDNF met was twofold higher in those with probable PTSD.
About 30% of the population has this version of the BDNF gene.
Studies show a 30% risk of heritability (genes) from twin experiments and others for PTSD.
Hmmmm.
This brings us back around to fear extinction.
BDNF is a major player here.
Simply put:
Using a local pharmacological infusion of BDNF protein, or an antibody against BDNF, we found that BDNF in the IL, but not prelimbic (PL) prefrontal cortex, is both necessary and sufficient for fear extinction. Infusing brain-derived neurotrophic factor (BDNF) into the infralimbic (IL) prefrontal cortex is capable of inducing extinction.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104333/
They further found that the hippocampus was key to this process of fear extinction.
People...this is exciting news!
We're unraveling the complicated mechanics of PTSD like the layers of an onion (the one we want to forget!).
Here, using a step-down inhibitory avoidance learning paradigm in rats, we show that intrahippocampus infusion of function-blocking anti-BDNF antibody immediately or 6 h after extinction memory reactivation impairs the reconsolidation of extinction.
https://www.jneurosci.org/content/35/16/6570
Okay...we're geeking out a bit here.
GABA and PTSD
See our artilce on can CBD boost GABA.
GABA is the brake in the brain and it's being overworked.
Every time a reliving of the traumatic event occurs, it sets off a roller coaster of excitatory and inflammatory pathways.
Cortisol spikes. CRF spikes.
See our article on how CBD affects CRF corticotropin releasing factor and does CBD reduce cortisol.
It's the increased heart rate, pulse, and sweaty palms.
GABA has to dampen that fire and a pathway in the brain can become exhausted when overburdened.
It's more of a general player in the anxiety circuit but still very important.
So...follow the steps:
- Early trauma or genetic susceptibility.
- Damage or reduction in key brain pathways
- Reduced ability to repair and replenish
We looked at #1 and #3.
What about #2...brain inflammation.
Brain inflammation and PTSD
We looked at early life trauma and its effect on PTSD risk later on.
Infection and inflammation can also take a toll.
We have an entire article on CBD, neuroinflammation, and anxiety or CBD and inflammation and anxiety here.
It's fascinating!
Basically, our brain's immune system can do just as much damage as any invading bacteria.
A key player in that system is the microglia cell.
What's the role there for PTSD:
PTSD differs from prenatal stress by exacerbating activated microglial cells along with dysfunctional cell proliferation in the hippocampus
http://iba.fmrp.usp.br/sites/default/files/inflamacao_esquizofrenia.pdf
There's the hippocampus again. One more insult to our fear extinction manager.
You see the full range of inflammatory markers that correspond with PTSD:
This is supported by increased levels of pro-inflammatory cytokines such as IFN-γ, IL-6, TNF-α, and IL-17 in the plasma, and increased levels of immune-stimulatory Th1 and inflammatory Th17 cells in the blood
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681483/
A study that looked at Marines on deployment found that an inflammatory state before leaving could predict PTSD risk upon return:
For example, high levels of CRP in Marines before their deployment were predictive of PTSD following deployment; this study suggested inflammation to be a contributor to PTSD
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681483/
We're not surprised.
If you look at CBD and inflammation or CBD and stress for anxiety, this is just one "insult" our brain takes and if we have susceptibility genetically or due to early life "training", PTSD can result.
Then there's our ultimate stress defender molecule - the so-called "resilience" chemical.
NPY.
NPY and PTSD risk
Think of NPY as a responder to stress.
Stress is not always bad.
Stress is any push or pulls on the system from balance.
The technical term is homeostasis (cue that for our discussion later on the endocannabinoid system).
Homeostasis just means balance and NPY is a powerful responder to pushes on the system!
Trauma is more of a shove if not right uppercut to our system.
Here's where it gets interesting for PTSD.
Think of NPY as the "Right Stuff" molecule.
Cool under pressure.
First, we had studies reflecting levels in military special forces:
Plasma NPY levels were significantly increased compared to baseline following interrogations and were significantly higher in Special Forces soldiers, compared to non-Special Forces soldiers.
https://www.ncbi.nlm.nih.gov/pubmed/10807963
These are people who go into one traumatic situation after another and remain cool under pressure.
Then there was a study on returning soldiers.
The relative levels of cortisol and NPY were a strong indicator of PTSD after deployment:
Blood samples taken from soldiers in the training programs showed those who fared best under extreme stress had lower levels of the stress hormone cortisol and higher levels of neuropeptide y, a chemical that dampens the body’s stress response.
It's also involved in neurogenesis (brain repair) in the hippocampus.
Check out CBD and performance anxiety for more information.
The tie between NPY and PTSD is not only in cause/effect but in the intensity of symptoms:
NPY is inversely related to PTSD symptoms, with low CSF NPY correlating specifically with the presence of intrusive traumatic memory (Sah et al., 2014) and lower haplotype-driven NPY expression in humans with a heightened amygdala response to a threat
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795352/
They've even looked at supplementing NPY for people with PTSD and there was an immediate effect.
Also, check out two associated actors for PTSD:
Next, let's look at genetics.
The genetics of PTSD
It's estimated that roughly 30% of the risk for PTSD is genetic:
Using genome-wide genomic data, the researchers found that, among European American females, 29% of the risk for developing PTSD is influenced by genetic factors, which is comparable to that of other psychiatric disorders. In contrast, men’s genetic risk for PTSD was substantially lower.
https://www.hsph.harvard.edu/news/press-releases/molecular-genetic-evidence-ptsd-heritability/
They tend to cluster around certain pathway suspect, some of which we discussed already above:
Association studies have investigated 8 major genotypes in connection with PTSD. They have tested hypotheses involving key candidate genes in the serotonin (5-HTT), dopamine (DRD2, DAT), glucocorticoid (GR), gamma-aminobutyric (GABRB), apolipoprotein (APOE2), brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY) systems.
https://pure.uva.nl/ws/files/1341029/96814_06.pdf
Serotonin is a workhorse neurotransmitter we'll discuss below.
We'll look at CRF and cortisol for the glucocorticoid piece.
GABA is our main "brake" pedal and figures strongly into the anxiety circuit (it's the main lever for benzos with anxiety - see CBD versus benzos for anxiety)
BDNF is our brain builder which we looked at above.
NPY is our resilience hormone which we'll break out specifically for PTSD.
We're going to walk through CBD's effect on all these pathways below!
Yes, there's a very real effect there (exciting news).
We can loosely center these genes around pathways:
- Stress response (glucocorticosteroids, Apoe, NPY)
- Brain repair and maintenance (serotonin, BDNF, dopamine)
- Brain activity (GABA)
All of these should be familiar if you've read any of our articles on CBD and anxiety.
You can start with the CBD and anxiety mechanisms here.
Finally, let's look at the system that CBD works in before jumping to CBD.
The endocannabinoid system and PTSD
We all have this system and by all, we mean every living animal.
It dates back about 600 million years.
Research is finally teasing out its role in the body.
It's tasked with balancing other key systems:
- Nervous system - including neurotransmitters such as serotonin, BDNF, and GABA
- Endocrine system - including cortisol, crf, histamine and others
- Immune system - inflammatory and immune agents such as microglia and cytokines
Did we just list off some of the biggest players in PTSD?
Here's an amazing fact.
Remember how we talked about the body trying to return to homeostasis or balance after a "stress" exerts a force on it?
That's the JOB of the endocannabinoid system.
It's checks and balance system.
Trauma can be so powerful or underlying systems already weakened to a point that the endocannabinoid system can't right the ship.
PTSD may very well be an illness of this system.
The clues started earlier.
A study looked at CB1 receptors in people with PTSD.
They found that they had lower levels of anandamide in their fear processing centers (amygdala).
Consequently, they had more CB1 receptors as the brain attempted to make up for it.
Results showed that participants with PTSD, especially women, had more CB1 receptors in brain regions associated with fear and anxiety than volunteers without PTSD.
https://www.sciencedaily.com/releases/2013/05/130514085016.htm
We discussed anandamide a few times up above.
Another study looked at a synthetic cannabinoid for symptoms of PTSD.
The results were impressive especially since most medications are pretty ineffective for PTSD.
Nightmares are a common symptom of PTSD. The results:
The majority of patients (72%) receiving nabilone experienced either cessation of nightmares or a significant reduction in nightmare intensity.
Researchers looked at blocking the break down of anandamide (such as blocking FAAH) to see what effect that would have fear extinction and PTSD symptoms.
The results are encouraging:
Noteworthy, all drugs exerted beneficial effects, but URB597 (0.1 mg/kg) induced the best improvements by enhancing extinction consolidation and restoring normal social behavior in traumatized rats through indirect activation of CB1 receptors.
https://www.ncbi.nlm.nih.gov/pubmed/29265107
URB597 works similarly to reducing FAAH. Just remember: lower FAAH raise Anandamide - Good!
There are those CB1 receptors again!
Then there's our favorite...allopregnanolone.
This is a powerful neuroprotective chemical.
It's the basis for that $25,000 postpartum medication.
By the way, you can get pregnenolone, it's a precursor for $10 online here.
Go figure.
Check out our full review on pregnenolone here.
Anyway, for PTSD, allopregnanolone is showing interesting ties.
First...
PTSD in women is associated with a block in the conversion of progesterone to the GABAergic neurosteroids allopregnanolone and pregnenolone measured in plasma.
https://www.ncbi.nlm.nih.gov/pubmed/29727810
You remember GABA, our brain's brake system and the key lever for how benzos work (till the addiction kicks in).
Another study tracked the actual pathway of allopregnanolone for PTSD:
These results demonstrate that AC-5216 has a clear anti-PTSD-like effect, which might be partially mediated by binding to TSPO and the subsequent synthesis of allopregnanolone.
https://journals.sagepub.com/doi/abs/10.1177/0269881115625115
Why do we bring this up (besides that the fact that if can help lots of people) with CBD?
The novel discovery that the endocannabinoid system regulates the biosynthesis of neurosteroids, including allopregnanolone has recently opened the field for assessing valuable PTSD biomarkers at the interface of these neuronal systems.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091574/
In fact, endocannabinoids are the main driver now in treatment development:
In recent years, cannabinoid-based agents have become an integral part of drug discovery for PTSD treatment
By the way, BDNF, serotonin, GABA, and are all "moderated" by the endocannabinoid system.
The hormonal effect was even more powerful in women:
PTSD in women is associated with a block in the conversion of progesterone to the GABAergic neurosteroids allopregnanolone and pregnenolone measured in plasma.
https://www.ncbi.nlm.nih.gov/pubmed/29727810
We've seen GABA as our brain's main brake.
Again, check out the review for pregnenolone and anxiety here
Let's move to the real purpose of EVERYTHING above.
Can CBD help with PSTD (plus a few other favorites to consider)?
Can CBD help with PTSD
CBD is one of the most promising agents for PTSD.
It started with animal studies on fear extinction.
We described above how fear extinction or the ability to "forget" trauma was a critical component for PTSD.
One study compared CBD, a synthetic cannabinoid, and a benzo:
AM404 (1.0 microg/microl, i.c.v.) and CBD (2.0 microg/microl, i.c.v.) facilitated extinction of contextual fear memory, with persistent effects.
https://www.ncbi.nlm.nih.gov/pubmed/18706790
The persistent effects are critical there as benzos are short-lived band-aids that do not address the underlying mechanisms of PTSD.
They simply pump up GABA (see CBD versus benzos for GABA and anxiety).
This line of study was then expanded to humans:
Cannabidiol enhances the consolidation of explicit fear extinction in humans.
https://www.ncbi.nlm.nih.gov/pubmed/23307069
There's a slew of studies showing CBD directly bolsters the fear extinction process which is managed by CB1 receptors.
In fact, when they genetically or chemically blocked CB1 activity:
The authors showed that blocking the action of CB1 receptors, either by pharmacological antagonism or genetic deletion, in previously conditioned mice resulted in strongly impaired short- and long-term extinction in fear-conditioning tests
CBD is also shown to positively affect key symptoms of PTSD such as sleep quality and of course, our favorite (or least favorite)...anxiety.
Human studies are underway now.
This was prompted by the results of a young girl who had PTSD as a result of early abuse (hits a few of our requirements above).
She was plagued by nightmares, night terrors, and anxiety.
Other medications were not successful so they used CBD with significant results:
However, CBD oil (given at a dose of 12–25 mg once a day) appeared to relieve key symptoms, such as anxiety and sleep disturbance, while inducing minimal side effects.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101100/
The net result…
After 5 months, the patient was sleeping in her own room most nights and handling the new school year with no difficulties. No side effects were observed from taking the CBD oil.
It's anecdotal (just one person) but read the review.
What about more expanded studies?
We're finally getting those in.
From the total sample of 11 patients, 91% (n = 10) experienced a decrease in PTSD symptom severity, as evidenced by a lower PCL-5 score at 8 weeks than at their initial baseline.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482919/
The mean total PCL-5 score decreased 28%, from a mean baseline score of 51.82 down to 37.14, after eight consecutive weeks of treatment with CBD. CBD was generally well-tolerated, and no patients discontinued treatment due to side effects.
The PCL-5 is a standard PTSD test used by Veteran Affairs. 33 (from 0-80) is usually the cutoff for further treatment.
You can see how CBD brought levels almost down to that level.
We're disregarding studies on cannabis and PTSD because of the potential downsides of THC.
Check out CBD versus THC for anxiety here.
Aside from addiction, there are inflammatory responses from THC in the brain which are counterproductive.
THC directly affects the CB1 receptors as opposed to CBD which has a more nuanced and supported effect.
This has not proven productive with PTSD as it's psychoactive and can cause anxiety.
Let's drill down into the mechanisms of PTSD we looked at above.
First, brain repair!
Serotonin and BDNF were both important players with BDNF being the star for PTSD.
Let's look at serotonin (called the 5ht pathway chemically).
In a study, when mice were subject to predator stress, they found that the 5ht1A pathway was upregulated in the hippocampus and frontal cortex.
Repeated CBD administration prevents the long-lasting anxiogenic effects observed after predator exposure probably by facilitating 5HT1A receptors neurotransmission.
Their conclusion…
CBD has beneficial potential for PTSD treatment and that 5HT1A receptors could be a therapeutic target in this disorder.
https://www.ncbi.nlm.nih.gov/pubmed/22979992
The lingering of fear. It's the opposite of fear extinction and it depends on serotonin function.
Check CBD and serotonin for anxiety to learn all about how CBD affects this pathway.
Serotonin is a workhorse in the brain...across many different pathways.
One of them deals with the reward center and effects on PTSD can be found here:
Cannabidiol Modulates Fear Memory Formation Through Interactions with Seroonergic Transmission in the Mesolimbic System
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061893/
They went on to say...
CBD dose-dependently blocks the formation of conditioned fear memories measured with conditioned freezing behaviors
That same article describes how THC as an opposite effect on this pathway!
Again, CBD isolate...not cannabis or THC according to research.
What about BDNF...which really showed genetic association with PTSD risk (that 30% of population variant in the BDNF gene).
Maybe one of our favorite studies:
Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex.
https://www.ncbi.nlm.nih.gov/pubmed/29869197
Remember, BDNF is the fertilizer for our brain's garden (not the worse analogy with its branches and roots, right??).
The prefrontal cortex is our rational brain in the "anxiety circuit" which is responsible for containing our fear processing (amygdala).
Boosting new brain growth there is critical.
Check out CBD and brain inflammation for anxiety here. It's fascinating what goes on with the microglia there.
Speaking of the amygdala (fear processor):
CBD attenuated the level of blood oxygenation in the amygdalae of healthy subjects exposed to different levels of anxiety
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604171/
Less activity in the amygdala.
Back to serotonin and BDNF...remember how the hippocampus was especially vulnerable to stress and trauma...and how people with PTSD showed smaller hippocampus volume both before trauma and following….
chronic CBD treatment may facilitate neurogenesis in the hippocampus
https://www.ncbi.nlm.nih.gov/pubmed/23298518
More studies have since come out that it definitely does.
That's all the brain repair side.
What about the stress response side?
We've touched based on key players there:
- Cortisol - our primary stress responder
- Corticotropin-releasing factor - starts the physical cascade of fear and anxiety
- NPY - our resilience chemical (the soldiers who came back from war with no PTSD)
Remember, the goal is to STOP the damage to the brain as well as repair what's already there.
First cortisol from a sleep study which makes sense since cortisol is the "wake" agent to GABA's "sleep agent".
Another crossover study showed that plasma cortisol levels decreased more significantly when given oral CBD, 300 to 600 mg, but these patients experienced a sedative effect.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326553/
Next, the corticotropin-releasing factor (CRF) and PTSD
YOu probably haven't heard of CFR but you should definitely read up at our CBD, and CRF for anxiety article.
It's fascinating!
CRF is the reason that SSRI's initially cause a spike in anxiety and depression for the first few weeks.
Yes, an increase which shows just how flawed trying to jack up serotonin levels is (as opposed to improving function as CBD does).
Remember how anandamide levels being low were tied to PTSD?
What's driving that?
Corticotropin-releasing hormone drives anandamide hydrolysis in the amygdala to promote anxiety.
https://www.ncbi.nlm.nih.gov/pubmed/25740517
Anandamide hydrolysis just means that it's being broken down by FAAH.
Why is your brain turning against you?
It isn't. The brain uses CRF to signal to the body (and you) that everything is not alright...get ready for fight or flight.
Remember that the hippocampus isn't correctly converting trauma over to long term memory.
It's stuck in the short term...NOW!
Okay then, respond accordingly...flood a bunch of CRF to get ready for a fight (anger, irritability) or flight (fear, panic).
Sound familiar?
So what does CBD do with anandamide and FAAH?
Read this sentence slowly:
In terms of the cannabinoid receptor-dependent effects of CBD on learned fear regulation described above, CBD increases anandamide levels by inhibiting its transporter-mediated reuptake and degradation by FAAH
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486906/
- Learned fear regulation. Check
- Anandamide levels increase. Check
- FAAH levels blocked. Check
Goodness, if that isn't tied up neatly in a bow.
Really fascinating dives into both.
Finally...what about NPY?
It's the weird resilience molecule.
We'll look at that just to show how far and wide the endocannabinoid system reaches into every facet of our body.
Here's the connection between NPY and anandamide:
The cannabinoid agonists anandamide (AEA) and CP55,940 both significantly augmented resting and KCl-evoked NPY release.
We can think of NPY as the anti-CRF (before we get too crazy with alphabet soup).
And we know what CBD does with Anandamide.
Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316151/
We'll stop there for CBD.
A few other notes.
In our research, we come across other things that have positive effects on PTSD.
- Meditation and exercise. Both boost brain repair agents like BDNF and serotonin. See CBD, meditation, and exercise for neurogenesis and long term brain repair
- Allopregnanolone - you can get pregnenolone (it's a precursor) here
I've used all of these plus CBD.
Also, there's brand new research on resetting the sympathetic and parasympathetic (fight/flight versus rest/digest) systems with electric stimulation of the vagus nerve via the ears.
My ear clips have been ordered and I'll keep you posted.
There's one lingering issue from PTSD which is that I'll wake up with a shot of adrenaline or cortisol about half the time when I come out of sleep.
The study on the vagus nerve stimulation is here and I'll let you know how I respond to it:
https://www.inverse.com/article/58227-tickle-therapy-nerve-stimulation-aging-effects
Of course, CBT (cognitive behavior therapy) is a standard approach.
It can be effective but requires effort and time (obviously worth it if you're suffering).
Since it's geared towards rebuilding new brain pathways, why not use CBD to speed the process!!!
Just our 2 cents since they both spur neurogenesis.
Let's look at the current medication front for PTSD.
CBD versus PTSD medications
The medications for PTSD fall in line with the course for anxiety in general.
With less effective results.
As researchers summarized:
At present, approved treatments for PTSD involve anxiolytics and antidepressants, which are inefficient and have considerable side effects
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066583/
The usual suspects are there:
- Benzo such as Xanax, Ativan, and Valium (see CBD versus Benzos for GABA and anxiety)
- SSRI's such as Lexapro, Zoloft, and Effexor (see CBD versus SSRI's for serotonin and anxiety)
The primary levers of these two classes of drugs are pretty clear.
- GABA for Benzos
- Serotonin for SSRI's.
We've already covered the effects of CBD on both of these pathways (and others) above.
Here's the rub as you can learn about from CBD versus anti-anxiety medications.
- Benzos can only be short term since they're highly addictive.
- SSRI's have pretty significant side effects, are not effective for everyone, and eventually "normalize".
This means the brain starts to adjust to the boosted levels by reducing its natural production.
When you eventually wean off of the SSRI (See CBD to wean off SSRI), it's doubly brutal.
They don't officially call it an addiction because dopamine is not in play but I can personally tell you, it's one of the hardest things I've ever had to do!
Serotonin functions so intricately across many systems in your gut and nervous system, that messing with its levels can be brutal (up or down).
The effect on CRF above which actually causes more anxiety/depression in the first few weeks is just one example.
More importantly, the core pathways of SSRI's:
These mechanisms include the stimulation of neurosteroid and endocannabinoid biosynthesis and neurotrophic factors, such as BDNF, which are found deficient in PTSD. Increasing allopregnanolone levels is also associated with increased BDNF expression
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091574/
We covered BDNF and CBD. Allopregnanolone can best be achieved with a $10/bottle of pregnenolone which we review in detail at our pregnenolone (happens to be an endocannabinoid) article.
Educate yourselves. That's all we're saying. Benzos and SSRI's are the typical response for PTSD.
Of course, investigate the following:
- CBT (cognitive behavioral training) - just a slower form of neurogenesis
- EMDR (eye movement desensitization and reprocessing) - I got some relief from this in the thick of everything
- Mindful meditation (see Mindful meditation and anxiety) - again….neurogenesis
- Exercise - aerobic exercise is a huge boost for BDNF and antioxidants...just not too long or intense
- Yoga - similar response as mindful meditation
- vTNS - electric stimulation of the vagus nerve through the ear (this could be huge for PTSD)
You can youtube all of these.
As for the medications, work with your doctor but...
These medications are associated with limited response rates and residual symptoms, particularly in PTSD, and adverse effects may also limit tolerability and adherence
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604171/
And when you do come off of SSRI's...what's the prognosis:
Unfortunately, independent of the duration of the trial, the discontinuation of SSRIs is associated with the relapse of PTSD symptoms
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126802/
Remember, fear of extinction is our goal. That's governed by the endocannabinoid system as we saw above.
That's why researchers are so excited about this pathway although Pharma's more interested in synthetics they can patent.
One final note...many people with PTSD self-medicate with cannabis.
They are probably getting the results of the CBD (and other cannabinoids) but that also comes with THC.
There are issues there. Check out THC's effect on neuroinflammation and anxiety.
We want THC free.
Check out CBD versus THC for anxiety or CBD versus anti-anxiety medications.
We have spent 100's of hours researching the many facets of anxiety because it almost did me in.
The self-medicating with THC makes sense since cannabis addiction is usually tied with trying to replenish anandamide which is naturally lower in people with PTSD or at risk for PTSD.
The problem is that chronic use will actually reduce CB1 activity and reduce baseline anandamide...the opposite direction we want to go.
Remember that CB1 activity is a key driver of PTSD.
Yes, THC feels good now but at the expense of tomorrow.
So...practical questions...how much CBD for PTSD.
How much CBD to take for PTSD
Let's focus on the neurogenesis piece.
Anxiety effects are dose-dependent which means that they will increase to a point as our dose goes up.
The neurogenesis piece (which is critical for actually improving long term) has a different response.
It was shown to peak at 300 mg of CBD.
So even if the immediate effect on anxiety or sleep keeps going up to 600 mg, the neurogenesis effect actually goes down from 300 to 600 mg.
Check out how many mg of CBD for anxiety.
For that reason, we probably want to peak there.
Most people start around 25-30 mg as a test amount to see how they feel.
One note...CBD can use the same liver pathways as other medications so always work with your doctor and take at least 2 hours away.
A general response for anxiety can usually be felt from 50-160 mg depending on your state.
PTSD tends to be more severe.
When I had my strongest PTSD reactions, I was taking 160 mg in the morning and 160 at night.
As for safety, many of the studies on more serious issues have tested around 600 mg to 800 mg daily with strong safety profiles.
The best kind of CBD for PTSD
The usual requirements are first and foremost:
- Organically grown in the USA
- CO2 processed (cleanest option)
- THC free (we looked at the effect of THC on CB1 activity, brain inflammation, and anxiety above)
- 3rd party tested free of:
- No pesticides
- No heavy metals
- No bacteria
- No mold
So..those are the basics but unfortunately, it will rule out 90% of the product out there.
There's a lot of crap.
Then there's insufficient CBD.
Many companies rushed to the market with bottles that total 250 mg of CBD.
That's a ripoff and actually makes us very angry.
There's real research behind CBD (see above and throughout the site) but at sufficient levels.
Finally, there's full-spectrum versus CBD isolate.
Everyone's pushing full-spectrum (see full spectrum versus CBD isolate for anxiety).
Problem is that 40-60% of the population has histamine issues and all that plant material is going to feel terrible.
Just check out CBD, histamine, and anxiety.
All the research is on CBD by itself….not full spectrum.
As for PTSD specifically, we want to reduce histamine response:
Mast cells play a crucial role in the peripheral inflammation as well as in neuroinflammation due to brain injuries, stress, depression, and PTSD.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733004/
This is the whole inflammatory response in the brain pathway.
In fact, antihistamines have been used for nightmares from PTSD!
Pharmacologic treatment of patients with post-traumatic stress disorder often involves antidepressant drugs. Combat nightmares often persist. The addition of cyproheptadine, in a median dose of 16–24 mg orally at night, controls the nightmares.
https://academic.oup.com/milmed/article-abstract/156/2/100/4848683
Check out CBD's effect on histamine or mast cells.
Again, everyone out there is slinging full-spectrum when the research points to CBD Isolate.
Like we said...we do our research.
IndigoNaturals was crafted based on it!
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.