An Updated View of CBD and The Pathways of Sleep with a Focus on Mental Health
August 01, 2020
It's on everybody's mind these days.
In fact, there's an epidemic of poor sleep across the US.
Interestingly, science is teasing out the mechanics of both good and bad sleep.
Not a moment too soon.
Brain scans that looked at the effects of poor sleep looked identical to severe anxiety.
We'll get into why this is the case and how roughly 1/3rd of our lives spend in slumber (hopefully) is so critical to the other 2/3rds.
No stone left unturned.
Here are the main topics we'll look at:
- The purpose of sleep
- The cycles of sleep
- Brain areas and sleep
- Neurotransmitters and sleep/wake cycles
- Hormones and sleep
- Stress and sleep
- Sleep apnea
- What drives Insomnia
- Endocannabinoid system and sleep
- Research on CBD and sleep
- How much CBD to help with sleep
- What's the best CBD for sleep
Let's get started!
The purpose of sleep
It's not just about rest.
A complex process of housekeeping occurs during sleep (especially deeper sleep) for the body and most importantly, the brain.
In fact, a rather newly discovered system was shown as a conveyor belt to remove waste products from the brain during sleep.
The brain uses more energy and therefore creates more toxic waste (oxidative stress, inflammation, etc) than any other part of the body.
Now, researchers at Boston University in Massachusetts have found that during sleep, the fluid present in the brain and spinal cord — called the cerebrospinal fluid — washes in and out, like waves, helping the brain get rid of accumulated metabolic “trash.”
The immune system is also more active and this isn't about fighting infection.
The immune system has a side hustle of managing the birth and death of neurons.
It's literally pruning and growing new connections during sleep.
The "birth" side of this equation is key to anxiety, depression, dementia, and just about every mental health issue out there.
It's called neurogenesis and we'll look at that below.
In fact, some mental health issues like bipolar and schizophrenia have sleep/wake cycle components directly baked in (with implicated genes as well).
Just look at this stat:
Chronic sleep problems affect 50% to 80% of patients in a typical psychiatric practice, compared with 10% to 18% of adults in the general U.S. population.
https://www.health.harvard.edu/newsletter_article/sleep-and-mental-health
This will make sense when we look at neurotransmitters and hormones involved in sleep.
There's a tremendous carryover to mental health issues and insomnia is a very common side effect for many medications.
We're focusing on the brain and nervous system but every bodily system requires sleep for the same repair, remodel, and growth process.
- Wound healing
- Skin replacement
- Bone formation
Everything!
One note, Human Growth Hormone is released during sleep and it's critical for the rebuilding process.
There's a lot of damage (wear and tear) during the day.
HGH drops from about 2000micrograms to about 200 by age 50.
The implications of this is profound!
Check out SeroVital as an option to supplement for this.
Let's start to dig deeper into sleep so we can understand where it goes wrong.
The cycles of sleep
First, we have to understand that sleep is an animal of cycles.
There are 5 main stages of sleep that occur over roughly a 1-2 hour time frame:
- Stage 1: Initial transition from wakefulness to sleep - generally a few minutes
- Stage 2: Still light sleep with further slowing of activity, no eye movement yet; occasional spikes of electric activity (called K spikes) This is the longest part of the cycle
- Stage 3: Deep sleep - the key to feeling good the next morning; longest period of sleep during the cycle (this is the Holy Grail people - where housekeeping gets carried out)
- Stage 4: REM sleep - Eyes move about (REM - rapid eye movement) and dreams occur
Rinse repeat! This cycle repeats during the night.
You may wake up between these cycles (although not fully) such as to use the bathroom.
There are electrical patterns associated with each of these stages which is interesting.
In general, the waves slow down and voltage increases.
Except for during REM where activity closely resembles wakefulness.
This is the period of dreaming!
There's also the circadian rhythm which cycles daily.
This is driven by adenosine (driven by light to the eyes) which slowly builds up while we're awake (think of an hourglass that triggers sleep when full).
Melatonin then gets released when dark and that's a key substance for sleep.
Research is also showing it's tied to longevity as well...many hats.
Let's turn our attention to the brain. It's really important (and hopefully interesting) to understand how sleep works in order to dissect when it is not!
Brain areas and sleep
Since everything sleeps, you would expect this to managed in the more ancient parts of the brain.
Indeed it is.
Parts of the "reptilian" brain - the oldest areas evolutionarily speaking, govern a great deal of sleep initiation and process.
Original studies on cats pointed to brain stem areas but new research has narrowed the search quite a bit.
In fact, there are relatively small clusters of neurons that trigger different aspects of sleep and wakefulness as well as the neurotransmitters that carry out their orders.
A master controller lies in the hypothalamus, a very old part of the brain which acts as a regulator of many automatic processes.
Sleep being one of them!
Interestingly, it's light to the eyes that triggers part of this response and we'll look at the ebb and flow of melatonin and adenosine below.
It definitely speaks to reducing light exposure before bed as this is a critical piece.
That's why blind people can have significant issues with wake/sleep cycling.
Once the trigger is set, messages go out to other areas such as the brain stem to set off a cascade of different processes for sleep.
One of these message receivers is the pineal gland where melatonin is released.
The message keeps propagating outwards to the forebrain where adenosine is released.
Caffeine blocks adenosine by the way!
We'll get into those below.
Speaking of which, let's look at the moving pieces that carry out the orders from these brain areas.
Neurotransmitters and sleep/wake cycles
This is the fascinating piece.
We see the effects with medications that affect these substances and in fact, sleep aids directly impact them.
Benzos directly boost GABA levels, our brain's "brake pedal", in the brain.
So does Alcohol and a slew of other medications.
Check out CBD and GABA or CBD versus Benzos for GABA.
It can quickly get very complicated with sleep since so many pathways work together.
To make it easier, let's break it down into neurotransmitters that are excitatory (wakefulness) and inhibitory (sleepiness).
We'll start with sleepiness since that's our goal generally:
- GABA - this is really the key driver of sleep in the brain
- Glycine - works alongside GABA as a secondary brake
- Serotonin - dual purpose but needed for the initiation of sleep in the ancient parts of our brain
- Acetylcholine - the key driver of the rest and digest system; opposite of adrenaline
And excitatory:
- Norepinephrine - adrenalin but in low doses, wakefulness
- Acetylcholine - needed for focus, attention, etc - the target of nicotine
- Glutamate - the brain's "gas pedal"
- Serotonin - switches to wakefulness in the thinking parts of our brain now
There are also hormones involved (histamine, cortisol, etc) which are excitatory.
Of these, GABA and serotonin are probably the driving forces of sleep. Having too much of the excitatory drivers can obviously overwhelm the sleep elements.
Balance and a carefully choreographed rhythmic dance.
We only need to look at the effect of benzos based on increasing doses on GABA:
- Calm
- Drowsy
- Sedated
- Hypnotic
- Amnesiac (can't remember)
- Anesthetic (can't move)
- Dead! Functions slow to a point where even breathing stops
Of course, benzos bring along addiction, tolerance, and withdrawal symptoms so they're not ideal as the brain tries to push back against this unnaturally strong effect on such a key system.
Just make a note that GABA is a key player in sleep.
Serotonin is more nuanced. The key here is that it's involved in the "switch" to fall asleep.
This is key to insomnia. In fact, insomnia is a listed side effect for SSRI antidepressants which boost serotonin.
See CBD versus SSRIs or CBD and serotonin for more detail.
Again, it's about balance.
Let's touch on hormones since they're integral to this process.
Hormones and sleep
Why on earth do antihistamines make us drowsy?
It turns out that histamine, in addition to getting back things out of us fast (allergic response) is also a powerful player in the sleep/wake cycle.
At this stage, it has an antagonistic role versus GABA, our brain's main brake pedal.
Many people (especially women) are essentially using antihistamines to help with sleep.
This is Benadryl, Tylenol PM, and a slew of similar meds.
The issue is that these antihistamines reduce acetylcholine which is quickly becoming the key to dementia and Alzheimer's.
Many drugs reduce acetylcholine so it's not surprising that we have such an epidemic for dementia.
Check out our acetylcholine review.
There's a good review by Harvard on the types of medications that reduce acetylcholine:
https://www.health.harvard.edu/blog/could-medications-contribute-to-dementia-2018052313872
The net takeaway is that histamine is a key wakefulness agent in the brain.
Then there's cortisol...our stress hormone.
It also figures into driving wakefulness within a certain range (before anxiety kicks in).
Check out CBD and cortisol to learn more about this.
Don't think we skipped out on the steroidal hormones. They're next.
Estrogen and progesterone for sleep
We saved the most powerful for last and for our ladies.
There are known bouts of insomnia around early pregnancy, perimenopause, menopause, and even during the monthly cycles.
We gave dozens of reviews on perimenopause since this is what led us to CBD, to begin with.
Check out CBD and perimenopause sleep issues.
Estrogen and progesterone directly power key and opposing pathways for sleep.
Estrogen is a major driver of serotonin which is the only source for melatonin (some lights should go off).
When it drops at menopause or during early pregnancy, insomnia can result.
Many women turn to alcohol to try to separately boost serotonin but the body builds tolerance to this.
Check out CBD versus alcohol during perimenopause.
Then there's progesterone. The founder takes it at night and it's literally like a benzo (without the nasty addiction effects).
Keep in mind that progesterone drops by about 50% at age 40!
Why does it have this effect? A key metabolite of progesterone called allopregnanolone drives GABA!
If you remember, GABA is our brain's main brake pedal and the key to sleep.
Side note...allopregnanolone happens to be the basis for the new blockbuster postpartum depression medication (a synthetic version of it which costs $25,000).
You can get pregnenolone for $10 here. Check out a full review of pregnenolone.
Anyway, the estrogen and progesterone are both essential to proper sleep (and everything else in the body).
Read our review of estradiol supplementation here to look at research on supplementation.
And what about testosterone?
You would think that's the opposite of calming and sleep-promoting.
Low testosterone may affect overall sleep quality which is improved by replacement doses.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955336/
Of course, the opposite is also true. Bad sleep leads to low testosterone which has a range of different health effects.
It's important to get your levels tested. The Dutch Test is the best approach if affordable.
There's one more hormone which deserves to be broken out separately.
Human growth hormone.
Human growth hormone and sleep
Mark our words, this will be a big health push over the next few years.
HGH drops from around 2000 ml to 200 mg from age 20 to 50. It continues on a decline from there.
You need to think of this as something different from adding inches to height.
Remember how sleep is key to repair and rebuilding from the stresses and strains of the day?
HGH is part of this equation.
Not only is HGH released only at night (body and brain is too busy during day with activity), but it even shapes sleep itself!
For example:
Four months of rhGH replacement therapy partly reversed sleep disturbances previously observed in untreated patients.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832204/
The current thinking is that HGH provides a feedback mechanism to the hypothalamus, the control hub of sleep process.
You can probably extend this effect across almost every system in the body.
The most tantalizing to us is the thymus, the seat of our immune system.
New studies on longevity are pointing to this system as the linchpin for aging.
HGH's effect?:
Evidence from animal and some human studies shows that growth hormone stimulates regeneration of the thymus.
There are ways to supplement this as we get older of course.
Let's turn our attention to a fascinating new piece to the puzzle...a hormone in vitamin's clothing.
Vitamin D and sleep
Vitamin D isn't really a vitamin after all.
It's a steroidal hormone that directly impacts 1000's of pathways.
Most people are deficient in D and it's finally getting some props after the pandemic since immune response is also driven by D.
It's very important to test D levels periodically as we don't want to go too high.
The net net of D deficiency:
By comparing the lowest verse highest levels of serum vitamin D, we found that participants with vitamin D deficiency (VDD) had a significantly increased risk of sleep disorders (OR: 1.50, 95% CI: 1.31, 1.72).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213953/
You have D receptors in key points of the sleep control system including the hypothalamus.
More importantly, D drives the pathway of acetylcholine in our ancient brain areas which manage sleep.
That's just the start!
Vitamin D helps regulate a key enzyme that makes sure we have enough serotonin in the brain.
Keep in mind that the key sleep hormone, melatonin, is made from...serotonin. Exclusively!
We're so excited about D that we'll do a full review on it shortly.
Again, you have to test your levels but a large percentage of people are low. Especially with darker skin since melanin blocks production.
If you read our review on acetylcholine and think of D deficiency does, this is a critical piece of the mental health puzzle.
We're getting there...let's turn to the building process. Building brain and connections that is.
Neurogenesis and sleep
It takes so much energy just to be conscious that repair work really needs to happen at night.
During sleep
Research is pointing to this:
There is strong evidence that disruptions of sleep exceeding 24 h, by total deprivation, selective REM sleep deprivation, and chronic restriction or fragmentation, significantly inhibit cell proliferation and in some cases neurogenesis.
https://pubmed.ncbi.nlm.nih.gov/24218292/
This is a real issue.
A study looked at rats and neurogenesis in the hippocampus (seat of memory and mood control) after sleep was interrupted.
The results:
However, this increase in cell survival was abolished in the sleep-restricted animals, and, importantly, sleep restriction also impaired hippocampus-dependent spatial learning.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771197/
As we mentioned above, neurogenesis is quickly becoming a hot topic for all things mental health and even addiction.
Check out CBD and addiction or CBD and brain repair.
Let's look at the other side of the coin...what's causing the damage potentially.
Stress and sleep
This may sound like a no-brainer but the research is clear:
Experimental stress resulted in fairly consistent changes: decreases in slow-wave sleep, REM sleep, and sleep efficiency (SE), as well as increases in awakenings.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266573/
Keep in mind that our primary stress hormone, cortisol, is also our primary wakefulness promoter!
In fact, cortisol cycles during the day with the lowest amounts around 4 am and starts to rise just before awakening.
If stress is driving cortisol, this will not treat the sleep cycles or circadian daily rhythm well.
We covered cortisol in detail at our CBD and cortisol review.
There's another important trigger for stress called CRH (corticotropin Releasing Hormone) which starts the cascade of the stress response.
This little gem is why SSRIs can actually make anxiety and depression worse for the first few weeks.
Like we said...serotonin is a master regulator! You can't just boost it in one direction without knock-on effects.
Check out CBD and CHR for more info (key to anxiety).
Interestingly, CBD works within the endocannabinoid system which just happens to be our primary stress response system.
In fact, anandamide, our key endocannabinoid is essentially a stress response buffer.
It's named after the Hindu goddess of bliss, Anand so you get the picture.
THC will imitate anandamide but the brain pushes back with longer use and actually suppresses our natural anandamide function.
Let's turn to a specific sleep issue.
Sleep apnea
Let's catch up to where research is now.
Yes, there's a tie with obesity and other risk factors but let's dig deeper.
Acetylcholine has an interesting role in sleep.
It's in charge of paralysis...essentially shutting down body movement (except for eyes and respiration).
It kicks in during REM sleep to lock the body while the brain is essentially in a wakeful state.
What's the connection with sleep apnea?
For example, acetylcholine-producing neurons are connected to the part of the brain that controls muscles of the upper airway and tongue -- and are involved in sleep apnea.
https://www.webmd.com/sleep-disorders/sleep-apnea/news/20030707/faulty-brain-may-cause-sleep-apnea
Why does sleep apnea affect us when we're older generally?
Acetylcholine levels drop with age.
There should be some connection with dementia then since acetylcholine is turning out to be the linchpin to dementia.
Is there one?
Researchers found that sleep-disordered breathing leads to a buildup of brain beta-amyloid, a key marker for Alzheimer's disease.
https://www.aarp.org/health/brain-health/info-2017/sleep-apnea-dementia-risk-fd.html
Hmmm. The plot thickens.
Vitamin D is an essential driver of acetylcholine function….is there a tie there?
Now, researchers have shown a correlation between vitamin D deficiency and a higher rate of obstructive sleep apnea (OSA).
One final piece to the puzzle.
There's interesting new research on metformin's effect on sleep apnea.
Personally, I take metformin for longevity effects (see metformin and aging review) but if I miss it, I'll "catch" while sleeping. This effect is within days.
If I go back on, that goes away completely.
What's metformin connection with acetylcholine?
Furthermore, there is also some evidence that metformin decreases the activity of acetylcholinesterase (AChE), which is responsible for the degradation of acetylcholine (Ach), a neurotransmitter involved in the process of learning and memory.
https://pubmed.ncbi.nlm.nih.gov/28589443/
So...it blocks the enzyme that breaks down acetylcholine.
We look forward to more research on this front.
Let's turn the real issue many people have with sleep.
Insomnia.
What drives insomnia
Insomnia is a complex issue with many different facets.
Let's zero in though on what research shows for the process of "falling" asleep.
That's an interesting term since it implies a sudden trigger.
Indeed it is and they know where the trigger is...the suprachiasmatic nucleus.
That's a mouthful!
There's a great review here:
https://thebrain.mcgill.ca/flash/a/a_11/a_11_cl/a_11_cl_cyc/a_11_cl_cyc.html
This is where serotonin really gets its dual role but only in the hypothalamus.
Serotonin is required to trigger the "fall" into sleep by acting in this particular brain area.
Completely opposite its role in the "thinking" areas of the brain where it promotes wakefulness.
You see this as a side effect of SSRIs with insomnia. Our founder was up for 3 days straight from Lexapro.
Her story is here.
Too little serotonin is also an issue since it needs to trigger falling asleep.
Then there's the staying asleep.
This is where GABA and Glutamate come into play. The brake and gas pedals of almost every brain pathways respectively.
This is where most of the sleep aid drugs work (we'll cover that below).
Too little GABA or too much glutamate is the enemy of sleep.
Check out CBD and GABA or CBD and glutamate to learn more.
One final stop before CBD. We promise!
Endocannabinoid system and sleep
This can get complicated fast so we'll skim the surface (so as not to put you to sleep :)
We looked at anandamide above with stress response.
By stress, we also mean anything that pushes a system up or down.
The systems that are "balanced" by the endocannabinoid system are:
- The immune system - inflammatory agents and cell/neuron birth-death cycles
- The endocrine system - hormones! Including all the sleep-dependent ones
- The nervous system - neurotransmitters and pathways such as GABA, serotonin, and acetylcholine
Goodness...it's the intersection of everything we've talked about.
Let's drill down a bit.
What about anandamide?
Systemic administrations of ANA (10mg/kg, ip) enhanced the extracellular levels of AD as well as the sleep time whereas the injection of SR141716A significantly blocked these effects.
Let's decipher that a bit.
Anandamide would increase adenosine during the day and sleep at night as a result.
Remember that adenosine is part of our 24-hour sleep/wake clock. It grows during the day in response to light (Vitamin A in the eyes) and triggers sleepiness when it reaches a certain level.
Anandamide directly supported this pathway.
This is just one example of their summary:
Taking together, the data suggest that the CB1 cannabinoid receptor could modulate sleep homeostasis
This system is intimately tied to every player in the sleep play.
Let's finally get to CBD's role and research. Thanks for your patience.
Research on CBD and sleep
We're going to tackle this from the ground up.
We'll break it down into these categories:
- CBD and Serotonin for sleep
- CBD and GABA/Glutamate for sleep
- CBD and adenosine for sleep
- CBD and cortisol for sleep
- CBD and histamine for sleep
- CBD and sleep-wake cycle
- CBD and insomnia and sleep studies
Let's get started!
CBD and Serotonin for sleep
We saw how too much or too little serotonin is ruinous for sleep.
It's all about balance and really balance can differ in various brain areas and by the time of the day.
This is why insomnia is such a side effect for many medications.
CBD's effect on serotonin maybe it's a single greatest trick since serotonin drives downstream processes across the brain and body.
Let's dive into some of the research.
A key study looked at CBD's effect on serotonin following injury (which essentially eats up serotonin since it governs pain sensitivity):
Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319597/
Allodynia is pain sensitivity. Anxiety is all too familiar these days.
"Normalized" 5-HT is what we're interested in. 5-HT is serotonin. Normalized means that it "rescued" serotonin function but did not keep boosting it higher!
Check out CBD and serotonin for more info but this is fascinating.
Remember...too much serotonin in one brain area and we get stress hormone release (CRH) and alertness (prefrontal cortex) leading to insomnia.
Too little in the hypothalamus and we get insomnia (the trigger for sleep isn't pulled).
Interesting, CBD was shown to reduce stress response WHEN stressed (but not in a normal situation):
Interestingly, cannabidiol at low (5 mg/kg) and intermediate doses (15 mg/kg) successfully blocked the effects induced by acute stress on corticotropin-releasing factor, pro-opiomelanocortin and glucocorticoid receptor gene expression
https://journals.sagepub.com/doi/abs/10.1177/0269881118805495?journalCode=jopa
Let's break that down, CBD did not affect the mice when they were in a normal setting but when subjected to intense stress (restraint), it calmed down the stress response system!
And the connection with serotonin?
Taken together, these data suggest the ability of cannabidiol to regulate acute stress hypothalamus-pituitary-adrenal axis activation might be explained, at least in part, by its action on 5-HTR1A receptors.
5-HT. Serotonin.
Goodness..that's the intersection of three complex and powerful systems in our nervous system.
Did you notice the hypothalamus angle there? The seat of sleep control?
There are many other studies at our CBD and serotonin pathway or CBD versus SSRIs for serotonin reviews.
Having varying effects depending on the state of the system is key though.
Next up, the heart of the sleep aids on the market.
CBD and GABA/Glutamate for sleep
We know GABA and glutamate all too well from our reviews of anxiety (see CBD and GABA for anxiety).
The main classes of sleep medications directly boost GABA in way or the other.
Of course, the brain pushes back on this and you're left worse off than when you started but we're sure the 10-minute doctor's consult went through that.
Sorry...coming off of Valium, Ativan, and Klonopin following a brutal perimenopause has left us jaded.
See CBD versus Benzos or How I used CBD to wean off Benzos.
GABA and glutamate balancing or cycles is really the key here.
CBD has a powerful effect on both in research.
Again, we can rely on anxiety and CBD studies for insight here.
We'll lead with a fascinating study that looked at GABA and glutamate levels in neurotypical brains versus people with autism.
This speaks to the size does not fit all effects.
CBD and adenosine for sleep
Okay...so adenosine is part of the pendulum that builds up during the day leaving us more and more tired as it increases.
Ideally.
Insomnia and sleep issues are now being tied to adenosine levels not reaching adequate levels.
So...what does CBD do there?
CBD increases brain adenosine levels by reducing adenosine reuptake. Increased adenosine is associated with neuroprotection and decreased inflammation after brain trauma
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938896/
Did you notice the other effects of adenosine?
This is also tied to CBD's anti-arrhythmic effects (countering heart skipping beats).
Interestingly, many mental health issues are showing not only effects on sleep but possibly causes from sleep issues.
For example, adenosine is now being research for schizophrenia and bi-polar:
A link between adenosine hypofunction and schizophrenia is also supported by clinical evidence: increased enzymatic degradation of adenosine by adenosine deaminase has been detected in patients with schizophrenia (11, 12), whereas allopurinol, a purine degradation inhibitor that increases adenosine tone, has shown clinical efficacy as add-on therapy for schizophrenia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386823/
Let's look at the other side...the wake-promoting agents.
CBD and cortisol for sleep
In large amounts, cortisol, our stress hormone, will make you anxious.
In smaller amounts, it follows a rhythmic 24-hour cycle peaking right before we need to wake up.
It's directly tied to being awake and if you have too much of it at say... 4 am, good luck getting to sleep.
When the founder was rocked by perimenopause, her cortisol was upside down.
High in the middle of the night and lower during the day.
Reverse. She also had terrible insomnia and sleep issues.
So..what is CBD's effect on cortisol?
We've covered CBD and cortisol here but there's a fascinating new study.
Researchers looked at CBD versus placebo versus health controls.
In the CBD and placebo group, these were people at high risk of psychosis as stress and cortisol are known issues for this group.
Essentially, during a social stress situation, the healthy controls had a spike followed by a drop in cortisol.
The placebo group just dropped across the board.
CBD's effect helped to bring the response half-way up to where the health control was.
The full study is here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113209/
The chart is here:
This is important because we know that stress is a key enemy for sleep and all things mental health.
What about the corticotropin-releasing factor, the instigator of our stress response system?
This newer study is so interesting and we'll explain why after:
Interestingly, cannabidiol at low (5 mg/kg) and intermediate doses (15 mg/kg) successfully blocked the effects induced by acute stress on corticotropin-releasing factor, pro-opiomelanocortin, and glucocorticoid receptor gene expression.
https://pubmed.ncbi.nlm.nih.gov/30324842/
What was fascinating about this study is that they were looking at CBD's effect after restraint stress.
Check out CBD and CHR here for more detail.
Let's turn to the allergic response hormone.
CBD and histamine for sleep
This is how we found CBD isolate, to begin with.
Histamine not only governs the allergic response but it also is part of our wake-promoting system.
A big part!
There's quite a bit of research on issues that result from histamine responses such as asthma.
The results are pretty clear there:
Cannabidiol reduces airway inflammation and fibrosis in experimental allergic asthma.
https://www.ncbi.nlm.nih.gov/pubmed/30481497
Check out CBD and histamines or CBD and mast cells (where histamine is released) to get further into the research.
Interestingly, this effect may be biphasic (different results depending on the state of the system).
In fact, CBD does not make you drowsy during the day. Check out Can I take CBD in the middle of the day.
We see this effect through many pathways which speaks to CBD's prime role as a feedback mechanism between cells and neurons.
The best example is with cancer (also governed by the immune system by the way):
- Healthy cell with no oxidative stress - CBD has no effect
- Healthy cell with high stress or inflammation - CBD reduces inflammation
- Cancerous or virally infected cell - CBD INCREASES inflammation
Read that back over again...what is going on?
You have to understand that the immune system uses oxidative stress to kill off cells that have gone awry.
We actually need histamine and cortisol to increase during wake periods so let's dig into the cycle now with CBD.
CBD and sleep-wake cycle
So, we know there are shift workers that come on the scene for light and dark periods.
Literally, light is guiding the process...the sleep "switch" we talked above sits right on top of the visual light center in the hypothalamus.
In fact, researchers have found that people that have lost most of their sight (the rods and cones in the eye) can still stabilize their circadian rhythm as long as that pathway is communicating to the brain.
You have sleep-promoting agents during the dark including GABA and serotonin and a slew of wake-promoting agents (cortisol, glutamate, acetylcholine, histamine, etc).
THC has been known to affect the sleep/wake cycle..what about CBD?
A study looked at just this question and their results:
The present findings support the proposal that CBD does not alter normal sleep architecture.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895650/
That was a double-blind placebo study.
Look at the note they made here:
Different from anxiolytic and antidepressant drugs such as benzodiazepines and selective serotonin reuptake inhibitors, acute administration of an anxiolytic dose of CBD does not seem to interfere with the sleep cycle of healthy volunteers
Benzos make up a large class of sleep medications (along with anxiety) but they have major addiction issues and build tolerance.
We'll look at the meds below.
Let's turn to everyone's dreaded enemy...insomnia.
CBD and insomnia and sleep studies
We can finally dive into the research specific to CBD and sleep...thank you for your patience!
There are many studies that look at CBD and THC's combined effect on sleep which is generally positive but we want to break out CBD by itself since THC has other issues (see CBD versus THC here).
We'll start with the animal studies.
There are well-documented effects of CBD on anxiety and anxiety is a known impediment to quality sleep.
One study looked at this effect specifically and found the following:
Conclusively, CBD may block anxiety-induced REM sleep alteration via its anxiolytic effect, rather than via sleep regulation per se.
https://pubmed.ncbi.nlm.nih.gov/21867717/
Check out CBD and anxiety or CBD and depression since both are tied to poor sleep.
A second study looked at CBD's effect on the sleep/wake cycle and quality of sleep:
The systemic acute administration of CBD appears to increase total sleep time, in addition to increasing sleep latency in the light period of the day of administration.
https://pubmed.ncbi.nlm.nih.gov/23343597/
So more sleep during that cycle and more alertness (latency or time to get to sleep) during the day.
Remember...we don't just want a sedative effect that pushes in one direction like benzos regardless of light/dark cycle.
Another study (in humans) compared CBD to benzo used for insomnia called nitrazepam:
Subjects receiving 160 mg cannabidiol reported having slept significantly more than those receiving placebo; the volunteers also reported significantly less dream recall; with the three doses of cannabidiol than with placebo
https://pubmed.ncbi.nlm.nih.gov/7028792/
Another study at higher doses found a significant drop in cortisol (stress and wake-promoting driver) and a sedative effect:
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/
Drowsiness is a noted side effect of CBD but it can also have a wake-promoting effect during light cycles.
A large case study looked at CBD's effect on anxiety and sleep.
There was a notable reduction which was sustained long term on both accounts:
Two months after the start of CBD treatment, 78.1% (32/41) and 56.1% (23/41) of patients reported improvement in anxiety and sleep, respectively, compared with the prior monthly visit;
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326553/
The main results in a graph are here:
You can see that the effect was most pronounced on anxiety and sleep issues driven by anxiety and stress (as opposed to hormones, etc) appear to drive the improvement on the sleep front.
In May of 2020, researchers announced a massive double-blind, placebo study for CBD and insomnia.
We look forward to its results and will note those here.
Also, check out the following which touches on sleep in many ways:
CBD and anxiety
CBD and depression
CBD and schizophrenia
CBD and ADHD
CBD and women's sleep
CBD and perimenopause sleep issues (hormones!)
CBD and glutamate
CBD and GABA
Let's look at the medications currently on the market.
CBD versus sleep medications
There are two main pathways that the majority of sleep medications affect:
- GABA - benzos and the new class of meds like Sonata, Ambien, or Lunesta
- Histamine - the over the counter workarounds like Benadryl and Tylenol PM
The main prescription meds for sleep all work to boost GABA availability
.
In fact, boosting levels of GABA has the following trajectory with increasing doses:
- Calm
- Drowsy
- Hypnotic
- Amnesiac
- Sedative
- Anesthetic
- Dead!
Yes, with increasing doses, even the respiration will slow down to a crawl.
Hence the risk for overdose but less than the old barbituates and usually in conjunction with another depressant (such as opioids).
Benzos like Xanax, Ativan, Valium, Klonopin, etc target a specific site on the GABA receptors while the newest classwork in a different way but also on GABA.
Here's the issue across the board with GABA boosting meds…
They build tolerance and can be highly addictive (as in the next addiction epidemic after opioids addictive).
There's a black box warning right on the packaging now from the FDA.
Check out CBD versus benzos or CBD and GABA.
CBD has not been shown to build tolerance or create addiction. See CBD and tolerance or CBD and addiction.
This means there are no withdrawal symptoms with CBD.
As for the histamine side, this is the work-around group that many people (we're guessing women) have found for sleep.
Benadryl and Tylenol PM are at the top of the list.
Here's the issue. They also rip acetylcholine from the brain.
This has huge implications with long term use for dementia and a slew of other issues.
Acetylcholine is critical to every aspect of our working brain and its side role in the parasympathetic nervous system may just speak to how you feel.
This the "rest and digest" part of our background nervous system and acetylcholine is its primary messenger.
Check out CBD and acetylcholine to learn more.
SSRI's have also been shown to reduce acetylcholine along with a slew of different meds.
As for histamine itself, check out CBD and histamine response here since addressing an overactive immune response (which histamine is part of) strikes at the heart of the issue.
The big take away is that none of these meds are designed to address sleep long term since they actually cause a rebound effect by the brain in the given pathway (primarily GABA).
Let's get to some practical questions.
How much CBD to help with sleep
There are two take-aways from the research on CBD and sleep
First, 160 mg was noted as beneficial for sleep quality and duration.
That points to a starting level.
We also know that CBD appears to address sleep more prominently by affecting other detriments to sleep quality such as anxiety and depression.
This leads us to a different level all centered around neurogenesis or brain repair.
The research found that peak neurogenesis occurs at 300 mg daily.
Beyond that level, other pathways kick in and neurogenesis actually goes down.
Neurogenesis is going to the touchstone of the next decade for all things mental health and as we saw above, mental health is swirled around sleep.
The two go hand and hand!
In fact, all the exciting elements rest on this brain repair function:
- Psilocybin
- Mindful meditation
- Exercise
- Ketamine
And yes...CBD.
Check out CBD and brain repair to really understand this phenomenon.
The half-life of CBD is around 4-6 hours so taking it before bed is ideal.
It should be taken at least 4 hours aways from medications and work with your naturopath or doctor with any supplement.
Other tools that we come across are:
- Magnesium glycinate - (blocks glutamate, our brain's gas pedal)
- Glycine (works similarly to GABA pathway)
- Tryptophan (do not use with SSRIs, supports serotonin function)
- Melatonin - the "dark" molecule - made from serotonin - tied in with longevity as well
- Human growth hormone amino acids - such as SeroVital - very fascinating as we get older
- Siberian Rhubarb - marketed as menopause 731 - for women mid-40s and up Check out CBD and perimenopause sleep issues
Of course, progesterone (via pregnenolone) is a powerful driver of GABA activity and women lose about 50% of it by age 40.
Estrogen also shapes our sleep architecture and supports serotonin.
No wonder so many women in their 40's-50's drink alcohol.
Alcohol boosts GABA and serotonin (albeit with a rebound drop - tolerance).
See CBD and alcohol for more info.
Finally, what type of CBD?
What's the best CBD for sleep
First, we have the basic requirements:
- Organically grown in the US at an FDA registered farm
- 3rd party tested
- CO2 extracted (cleaner process)
- No THC! THC can affect sleep cycles and it builds tolerance
- No pesticides
- No solvents
- No heavy metals
- No bacteria
- No mold
Those are the basics and we test our oils twice since our whole family uses them.
Then there's the question of full-spectrum versus CBD isolate (CBD by itself).
All the research above and throughout the literature is based on CBD isolate.
The bigger issue is that roughly 40-60% of the population has histamine issues.
That number goes up as we get older and for women (as progesterone drops).
Full-spectrum is likely to send those people reeling with allergic responses and indeed, we see the side effects with customers who try full spectrum.
These generally go away with CBD isolate.
Remember that histamine also drives our wake cycle so an allergic attack at night is a killer for sleep!
Finally, there's the cost aspect.
If the research is pointing to between 160 mg - 300 mg (sleep to neurogenesis), the cost per mg of CBD is the key.
That's why we price our 6000 mg bottle at 2-3 cents per mg of CBD. The lowest on the market we can find for quality CBD.
This is before discounts up to 30% for referrals, subscriptions, and reviews.
If you read our story here, we've suffered insomnia as a result of Lexapro which almost broke us.
Three nights of no sleep landing us in the ER where they gave us a serotonin-based nausea drug which led to serotonin syndrome and a psychotic break!
A known no-no for the doctor but that's another review (CBD and serotonin syndrome).
We want to make CBD available to as many people as possible since we've been there.
Be well...look after one another.
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.