After dozens of articles on CBD and anxiety involving 100's of NIH studies, one thing kept popping up.
CBD is VITAL if you use cannabis or THC products in any way.
Writing from California where cannabis is legal (at the State level anyway), you can go into a dispensary and find a range of products.
Some shouldn't be on the market, frankly.
They're all THC and at jacked-up levels.
If that industry wants to continue, they may look at mandated levels of CBD in any product.
You'll understand why when we get into it below. We're going to focus at how CBD can offset the damage and excess of THC in research.
Let's also be honest.
As a father of two high schoolers, cannabis is EVERYWHERE with teens. And sure it's cliche... but it's not the same pot from the 70's!
Forget the music, media, snap chat, Instagram, Soundcloud, and just about everything that tells them that pot is healthy and natural.
It's a cyclical thing very similar to the '60s.
You're naive if you think this isn't the case at your school.
Straight THC products are available through vaping, pods, and dab pens to middle and high schoolers NOW.
I preached and educated but as my older son said…"Dad, I can count on one hand the number of kids who haven't smoke pot and that number's dropping by the week".
That was sophomore year.
My new mantra now is this…"Make sure to get your CBD if you smoke out" after preaching about downsides of THC.
We're going to dive into research on why this is important for everyone but especially for teenagers (really up to age 25).
The main topics we'll cover:
- The differences between THC and CBD
- Putting to rest the whole "entourage effect" of THC and CBD
- Do you need THC to activate CBD
- CBD versus THC for brain development
- CBD versus THC for neuroinflammation
- CBD versus THC for oxidative stress
- CBD versus THC for mitochondria response
- CBD versus THC for anxiety
- CBD versus THC for memory and mental function
- CBD versus THC for hormones
- CBD versus THC for addiction
- CBD versus THC for CB1 function
- CBD versus THC for anandamide
- Pregnenolone and THC for overdose
See our article on why companies that sell only high THC should get a lawyer.
If the sellers of high THC products don't adjust, they better lawyer up (cue Tobacco, Opioids, Glyphosate, Juul, etc).
Let's get started!
The differences between THC and CBD
First, both THC and CBD are cannabinoids, a family of chemicals found in nature, primarily in the cannabis plant.
They are the two most prominent cannabinoids in cannabis by a landslide.
See our article on do you need THC to activate CBD.
They naturally occur in different ratios to each other and that ratio is critical to effects within the body.
In general, THC interacts with CB1 receptors in the brain and nervous system.
It mimics anandamide, our naturally occuring "bliss" molecule named after the Hindu goddess of bliss, Anand. Think "just high enough" to feel good.
Here's the issue longer term.
Anandamide is readily created as needed and almost immediately broken down.
THC hits much harder and stays much longer at that CB1 receptor.
Hence the "high", side effects, and with longer term use...tolerance!
CBD's effect is more subtle.
It works like a feedback mechanism in the endocannabinoid system.
You can learn exactly what this all means below.
You can also get more information on CBD versus THC here.
The big difference is how the two chemicals work.
THC directly plugs into the CB1 receptor as if it is the intended key (Anandamide in this example).
Anandamide is our 2nd most prominent endocannabinoid in the brain and nervous system.
"Endo" just means "within" since our body makes it naturally.
CBD works in a completely different way.
First, it doesn't directly boost CB1 or CB2 activity.
A quick intro to neuron communication!
Most neurotransmitters (such as serotonin, GABA, dopamine, etc) are carriers of a message from one neuron to another.
CBD goes the other way!
It's a reply from the receiving neuron to the sender.
Think of it as a promoter of the checks and balances system in our nervous system.
The reply!
This is a subtle difference but powerful in effect.
That's why there hasn't been an overdose on CBD by itself.
It supports the endocannabinoid system's primary role...to find balance or homeostasis in other key systems.
THC, on the other hand, punches one aspect of it. CB1 activity!
Let's look at some common questions and misconceptions based on our new understanding.
Putting to rest the whole "entourage effect" of THC and CBD
Oh...the beloved "entourage effect".
You see this everywhere and it's repeated by everyone like gospel.
We took a deep dive into the question of THC versus CBD here but a quick synopsis.
Many (many) people state that you need THC to activate CBD.
See our article on do you need THC to activate CBD.
This falls under a general idea called the entourage effect that the various cannabinoids (there are others but in much smaller amounts) work together synergistically.
The origin of the term should shed some light on it and also stands as a great intro for our entire article.
The term came from the Godfather of cannabis research, Raphael Mechoulam, to basically reflect that CBD could offset some of the negatives of THC!
Ummm...that's very different from how marketers are using it for cannabis and even full-spectrum CBD.
A slight mutation of this thought then gets expressed this way.
Do you need THC to activate CBD
The number of times I've heard this from people.
And it's said with so much conviction as if you were saying the sky is blue.
See our article on is CBD effective without THC.
Not only do you not need THC to activate CBD, but the two are also diametrically opposed to each other in many pathways (which we'll see below).
Literally opposite effects.
Even countering effects where CBD will block THC's metabolism and function.
More like de-activate!
It happens in the liver as well as across the CB receptors themselves.
Now, let's get into some of the differences that are so important and the reason we wrote this to begin with.
CBD versus THC for brain development
There were rumblings of THC's impact on the developing brain for years now but one study really brought it all home.
A group of researchers looked at brain changes in scans after just one use of cannabis at age 14.
Consuming just one or two joints seems to change gray matter volumes in these young adolescents,
https://www.sciencedaily.com/releases/2019/01/190114130855.htm
Where this was occurring in the brain is interesting in terms of anxiety which is the #1 mental health issue for young people now.
The biggest differences in gray matter were in the amygdala, which is involved in fear and other emotion-related processes, and in the hippocampus, involved in memory development and spatial abilities.
We've covered the amygdala and hippocampus in-depth at our CBD and general anxiety disorder or CBD and hippocampus neurogenesis.
This is occurring at a critical period of remodeling in the brain.
It's not just those areas though.
The prefrontal cortex and white matter communication links are also affected by THC.
Our evidence suggests that exposure to cannabinoids during adolescence alters brain maturation in the prefrontal cortex,
https://www.sciencedaily.com/releases/2018/11/181106150439.htm
So...what's the potential result of this brain change (increase amygdala, decrease prefrontal cortex, and hippocampus function)?
Those are the primary pieces of the anxiety circuit by the way.
Check out CBD and the mechanisms of anxiety.
Just this for more significant use:
Weekly or more frequent cannabis use in teenagers predicted an approximately twofold increase in risk for later depression and anxiety (1.9, 1.1 to 3.3) after adjustment for potential baseline confounders. In contrast, depression and anxiety in teenagers predicted neither later weekly nor daily cannabis use.
https://www.ncbi.nlm.nih.gov/pubmed/12446533/
We'll look more closely at why this may be in the anandamide and neuroinflammation sections below.
Very fascinating new research!
We actually looked at whether people use cannabis to calm glutamate hyperactivivity.
Very interesting for the roughly 9% of people who become addicted to cannabis.
So that's the bad news unless you have a time machine.
The good news is that CBD can directly counter these effects.
First, the amygdala:
CBD decreased the activity of the left amygdala-hippocampal complex, hypothalamus, and posterior cingulated cortex while increasing the activity of the left parahippocampal gyrus compared with placebo.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412699/
The Amygdala is the emotional, fear center
That's the opposite of what THC did (so much for entourage effect) and speaks to CBD's benefits for anxiety.
As for the prefrontal cortex:
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
This is your rational brain area that keeps the fear center in check.
Synaptogenesis is a fancy way to say making new brain connections.
BDNF is a key "fertilizer" in the brain and CBD directly drives its activity.
Check out CBD and long term anxiety or CBD and neurogenesis to understand why this repair component is so important.
That's another example of opposite effects in the brain for maybe the most important part of the brain.
It's the piece that makes you...YOU! You know...human.
The prefrontal cortex.
We'll cover some other areas below but the key is this.
Adolescent use or chronic adult use of cannabis or THC without CBD is essentially brain damage.
We're trying for hyperbole because that works about as well as the Just Say No campaign these days.
The takeaway is this, CBD is a powerful offset to THC's negative effects in the brain.
This brings up a good question...why is THC causing this damage?
Cue the inflammation!
CBD versus THC for neuroinflammation
We went deep into this subject at our CBD, microglia, neuroinflammation and anxiety article.
It's really the cutting edge of brain research right now.
Let's look at one key player (maybe THE key player) of our brain's immune response to inflammation.
Microglia.
They are the sentries of our brain on the lookout for bacteria, viruses, and even stress!
An infection of your skin such as acne is mildly irritating and embarrassing on a date.
Infection in the brain is a death sentence.
The brain can't swell in its confinement.
For this reason, the microglia are vigilant, everywhere, and occasionally trigger happy.
So many of the "modern" diseases are a result of our immune system going haywire from stray bacteria getting out into the body and brain.
Just check out CBD and autoimmune.
If microglia go into hyperdrive, surrounding brain tissue can become collateral damage.
Just a note...early trauma, infection, or stress can hyperactivate this whole process alter in life which might be why THC feels so good to some people.
Why does this matter for THC and CBD?
How does this tie into the damage to our prefrontal cortex which is so important being human (literally).
Just this:
In pilot experiments, we have replicated the finding that adolescents, low-dose THC activates microglia in the prefrontal cortex via CB1 cannabinoid receptors and increases IL-6 mRNA. The increase in IL- 6 was prevented by concurrent cannabidiol.
http://grantome.com/grant/NIH/R21-DA039463-02
Did you catch that last part?
"Prevented by concurrent cannabidiol".
CBD!
CBD literally blocked the overactive reaction of our immune system.
In the prefrontal cortex!! One note...inflammation in this area is key to anxiety, depression, and just about every mental health issue.
Check out CBD, microglia, and neuroinflammation for anxiety. Very neat stuff (the research...not our writing!).
We could literally end this article right now and be done.
But we're not!
CBD versus THC for oxidative stress
Look...oxidative stress may be the linchpin for aging and age-related diseases.
It's the nasty waste material from energy production and nowhere is it more prevalent and more destructive than the brain.
After all, the brain uses more energy per cell than any other part of the body.
It's energy-hungry and creates a lot of oxidation as a result.
Oxidation left uncheck is literally a wrecking ball (sharp chemical scissors actually) to our brain and more importantly, our DNA!
What about THC and CBD for oxidative stress?
First THC.
Tetrahydrocannabinol Induces Brain Mitochondrial Respiratory Chain Dysfunction and Increases Oxidative Stress: A Potential Mechanism Involved in Cannabis-Related Stroke
https://pubmed.ncbi.nlm.nih.gov/25654095/
We'll look at mitochondria below.
What about CBD?
Everyone's heard about Vitamin C and Vitamin A as powerful antioxidants.
Move over losers!
Although all of the antioxidants attenuated glutamate toxicity, cannabidiol was significantly more protective than either α-tocopherol or ascorbate.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC20965/
Check out CBD and Oxidative stress to get the full lowdown.
Then there's our most powerful naturally occurring antioxidant, glutathione.
If you haven't heard of glutathione, get to know it...QUICKLY.
It may be the single biggest thing you can do to slow down aging.
Check out CBD and glutathione here.
So...what about THC and CBD?
Are they "synergistic" (gag) here as well?
We know that smoking cannabis is known to draw down glutathione:
Alveolar macrophages obtained from habitual MJ smokers displayed low levels of glutathione compared with macrophages from nonsmokers.
https://www.ncbi.nlm.nih.gov/pubmed/10340948
Which reflect its effect on oxidative stress:
MJ smoke containing Delta9-THC is a potent source of cellular oxidative stress that could contribute significantly to cell injury and dysfunction in the lungs of smokers.
That may be more a function of the smoking delivery.
By the way, new studies show that smoking nicotine (via cigarettes or vaping) kill neural stem cells.
Ummm...those are the nurseries of new brain cells!
https://www.sciencedaily.com/releases/2019/07/190701144416.htm
We digress…
What about THC directly on glutathione levels?
GSH levels in the liver and kidney were decreased by 14% and 7% respectively.
https://www.ncbi.nlm.nih.gov/pubmed/1666916
The liver is glutathione's primary place of work to clean out toxins.
And CBD and glutathione?
Cannabidiol (CBD) has been shown to exhibit anti-inflammatory, antioxidant and neuroprotective properties.
https://www.ncbi.nlm.nih.gov/pubmed/22178458
How does it do this?:
Moreover, CBD treatment of BV-2 cells was found to induce a robust change in the expression of genes related to oxidative stress, glutathione deprivation, and inflammation.
There's one place where CBD will increase oxidation and reduce glutathione.
Cancer cells!
That speaks to the endocannabinoids system's role in balance and homeostasis.
Check out the CBD, glutathione article or the CBD and oxidative stress article.
The cancer piece is wild! Big review on CBD and Turkey tail for cancer.
So far, the entourage effect: 0 . CBD to protect from THC effects: 4.
It sure is a nifty marketing slogan though!
Next up, the little guys making all that oxidation in the first place.
CBD versus THC for mitochondria response
Every cell in your body is teeming with mitochondria.
Little ancient bacteria our ancestors hijacked into their cells.
They even have their own DNA (bacterial DNA).
If you spend a few 1000 hours buried in NIH studies, you start to realize that this is a hole in the aging dam that eventually brings the whole thing down.
You can learn all it about at our CBD and mitochondria here but let's look specifically at THC versus CBD for our energy producers.
First, THC.
Δ9-Tetrahydrocannabinol disrupts mitochondrial function and cell energetics
https://www.physiology.org/doi/full/10.1152/ajplung.00157.2002
Interestingly, the effect continued:
Mitochondrial function remained diminished for at least 30 h after THC exposure.
What was the effect similar to?
Comparison with a variety of mitochondrial inhibitors demonstrates that THC produced effects similar to that of carbonyl cyanide-p-trifluoromethoxyphenylhydrazone, suggesting an uncoupling of electron transport
Another study looked at THC's impact or cause of a stroke as a result of this effect on mitochondria:
THC increases oxidative stress and induces cerebral mitochondrial dysfunction. This mechanism may be involved in young cannabis users who develop ischemic stroke since THC might increase a patient's vulnerability to stroke.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310259/
It basically reduced energy production at all 4 stages of mitochondrial "respiration" (energy production essentially) and increased oxidation.
People...don't think of energy as the ability to get off the couch (although, it's there as well).
This is cellular energy:
- Fixing DNA.
- Building proteins.
- Making neurotransmitters.
Really nuts and bolts stuff.
You run this down and aging plus illness is the result.
This is THC by itself.
What about CBD?
There's a lot of interest in CBD following extreme levels of oxidation and damage such as following stroke or sepsis.
How does CBD figure into this?
This study is the first to document the neuroprotective effects of CBD against OGD/R insult, which depend in part on attenuating oxidative stress, enhancing mitochondrial bioenergetics, and modulating glucose metabolism via the pentose-phosphate pathway, thus preserving both energy and the redox balance.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5247568/
This is in the hippocampus which is key to a player we looked at above! The entire energy and energy waste complex improve under catastrophic conditions!
One more example of CBD having an opposing and protective effect on THC.
CBD versus THC for anxiety
Many of the component pieces we looked at above eventually find their way downstream into various issues.
See our article on best CBD to THC ratio for anxiety
Anxiety is front and center, especially for brain activity.
We've covered dozens of topics on CBD and anxiety which you can find at our mechanisms of anxiety review.
We even look specifically at THC versus CBD for anxiety here.
Interestingly, THC at low levels is anti-anxiety but becomes pro-anxiety as the level increases.
Check out our article on CBD for greening out with THC here.
Those are reviews of the chemical and brain area changes that occur from the two chemicals.
Again, opposite in effect.
Let's look at another aspect which we'll flesh out more below.
First, the brain changes described above (increase amygdala activity, reduced hippocampus, and prefrontal cortex) from THC use are basically a recipe for future anxiety and depression.
OCD, phobias, and a range of other issues share this "circuit".
Furthermore, THC has other attributes since it directly affects CB1 activity.
The brain doesn't like this.
It sees it as an artificial imbalance and attempts to correct it by…
Dropping CB1 activity!
This means that your natural threshold for anxiety and depression is a tiny bit worse. Over time.
It's part of the nature of addiction (plus dopamine) really. Check out CBD and addiction.
It's also why THC normalizes with time.
This means you need more and more in order to get the same effect.
Again, we're assuming more chronic use.
Eventually, you're not using THC to feel high but to just not feel terrible.
We did a full review on CBD and cannabis addiction.
Look...CB1 is where anandamide (our bliss chemical) does it work.
Reduce CB1 activity means less "bliss". Period.
Compared to HCs, [11C]OMAR VT was 15% lower in CDs (effect size Cohen’s d=−1.11) at baseline in almost all brain regions.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742341/
HC is health control... non-cannabis users. OMAR is a way to measure CB1 activity.
That's cannabis. What about the ratio of THC to CBD which can vary wildly?
Higher THC and lower CBD were associated with this hippocampal volume reduction, suggesting neurotoxic effects of THC and neuroprotective effects of CBD.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797438/
The hippocampus is our mood switch hub in addition to memory center.
Check out our ratios of THC to CBD for anxiety for more detail there.
This really figures into our discussion of addiction below since a big part of breaking THC addiction is to rebalance CB1 activity.
Check out Judith Grisel's book, Never Enough. It's an amazing explanation of how THC interacts with the brain in this capacity.
There's a good indication that people drawn to chronically use THC may be trying to self-medicate for lower anandamide levels of CB1 activity OR increase glutamate.
Many people that use THC daily speak of their brain's running "hot". Repetitive thoughts. OCD. Anxiety.
Really look at the immune system (inflammation and resulting gluatamate) may be the driver here. There are better ways to calm this response!
Again, CBD doesn't directly plug into CB1 receptors so research shows it doesn't normalize. Or build addiction.
Let's jump to mental function.
CBD versus THC for memory and mental function
Remember the prefrontal cortex up above?
It's called the seat of executive functioning.
That's a fancy way to say thinking!
Seriously...planning, calculation, organization.
It's all right there plus much more.
We saw how THC impedes function there both through brain activity and immune response to inflammation (the microglia).
Does this have an impact on mental function?
Anyone who's been high would say "Well, YEA!!" but we want to look longer term.
First, there are some misleading studies on cannabis.
Cannabis has both THC and CBD which act very differently (as we've hopefully established).
We want to see just THC and just CBD.
For THC, the age of use and amount of THC are very important.
We saw above how brain development is affected up above by even small amounts of THC.
In contrast, occasional users and regular users seem to show memory impairments after both high doses and low doses of Δ9-THC, with Δ9-THC impacting on memory function in a dose-dependent manner
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931635/
We can actually pinpoint this to THC itself from the following:
For instance, increases in Δ9-THC concentration were associated with a linear decrease in performance in short-term memory tasks.
A single dose (aside from when the brain is developing) is unlikely to have a long term effect on memory.
And CBD's effect there?
However, considering that CBD may be protective for some aspects of memory function by inhibiting the Δ9-THC-induced impairments in episodic memory in humans and spatial memory in animals,20,61,62 but not in working memory,60,61 CBD may have therapeutic potential in reversing certain cognitive impairments induced by cannabis.
"reversing certain cognitive impairments"! Can we drop mic now?
The good news for SOME people...even a heavy long term user of cannabis (5000+ uses) can see the effect go away after abstinence:
However, by day 28, the two groups did not differ any longer, and initial Δ9-THC concentrations were not related to task performance, suggesting that memory impairments in long-term cannabis users may not persist beyond the impact of Δ9-THC-induced “residual effects.”
This is not true across the board...others see a persistent effect on cognition and researchers don't exactly know where the difference is.
There's lots of research with varied setups and results but one thing is consistent when THC and CBD levels are explicitly measured:
cannabis users who smoked cannabis high in CBD and low in Δ9-THC were protected from the memory-impairing effects associated with cannabis strains high in Δ9-THC
This requires a deeper study than we can do here.
CBD versus THC for hormones
Once you pull the cork on studying hormones, it's a tidal wave.
That system is so complicated but there are a few critical pieces we've come across between THC and CBD.
First, the mother of all hormones, pregnenolone.
This substance was so fascinating to us as researched it that we did a comprehensive review of pregnenolone for health here.
There's a curious tie between THC and pregnenolone.
In fact, pregnenolone is the primary reason it's so difficult to overdose on THC.
Not impossible, but difficult.
The brain immediately spikes levels of pregnenolone in the brain to offset THC's effects via the CB1 receptors:
We found that pregnenolone blocks a wide spectrum of THC-induced endophenotypes typically associated with psychotic-like states, including impairments in cognitive functions, somatosensory gating, and social interaction.
https://www.ncbi.nlm.nih.gov/pubmed/28220044
This makes pregnenolone a potential ally to CBD for offsetting THC negatives as well as a powerful tool for greening out or having an adverse reaction to THC.
Pregnenolone is the main precursor to our sex hormones.
There are many effects further downstream.
Of course, there are gender differences with THC and CBD for hormones.
In general, THC reduces testosterone and is estrogenic (when smoked) in the body.
The THC-induced block of GnRH release results in lowered LH and FSH which is responsible for reduced testosterone production by the Leydig cells of the testis.
https://www.ncbi.nlm.nih.gov/pubmed/6090909
A lot of the focus is on reproduction as THC affects upstream hormones that govern other effects:
These changes in pituitary hormone levels produce decreases in sex steroid hormones and cause disruption of ovulation and spermatogenesis
https://www.ncbi.nlm.nih.gov/pubmed/6090911
Then there's growth hormone.
It's not just for teenage years!
Just like pregnenolone, growth hormone drops as we age.
This speaks to increased frailty and extra fat around the belly as we get older.
This isn't surprising since DHEA (a downstream hormone from pregnenolone) boosts growth hormone and preg directly drives choline function in the brain!
DHEA treatment increased serum GH 1.8-fold
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868401/
PREG significantly improved the synaptic plasticity of memory-related brain areas of aged rats, significantly increased brain cholinergic activity and thus helps to improve learning and memory in aged rats.
https://www.ncbi.nlm.nih.gov/pubmed/23848990
People...read up on the effect of choline on dementia and Alzheimer's (plus microglia - see CBD and neuroinflammation).
We digress (after geeking out)..soo...back to growth hormone.
First, THC:
A diminished maximal serum human growth hormone (GH) increase followed the prolonged THC ingestion.
https://www.ncbi.nlm.nih.gov/pubmed/1270583
And CBD:
Basal prolactin (11.5 +/- 4.3 ng/ml) and growth hormone (1.5 +/- 0.7 ng/ml) levels were unchanged after placebo and CBD.
https://www.ncbi.nlm.nih.gov/pubmed/8257923
Cortisol, however, did drop with both THC and CBD which speaks to the anti-stress mechanism.
Check out CBD and cortisol for anxiety for more information.
As we said, hormones are a full review by EACH hormone!
We did a deep dive on estradiol for perimenopause (our most potent estrogen) and took us days to research and complete.
Let's move on.
To one of the most fascinating differences.
CBD versus THC for psychosis
So much for the entourage.
You almost can't find a better example of how different THC and CBD can be than this.
THC, at a high enough dose, mimics psychosis.
Not only in symptoms but in actual brain activity.
In fact, this shows across ER hospitals visits for CIP (Cannabis Induced Psychosis):
In 2011, the Substance Abuse and Mental Health Services Administration (SAMHSA) and Drug Abuse Warning Network (DAWN) estimated a total of 1.25 million illicit-drug–related ED visits across the US, of which 455,668 were marijuana-related.
https://www.psychiatrictimes.com/substance-use-disorder/cannabis-induced-psychosis-review
The tie between THC itself and this result is well-documented:
CIP is commonly precipitated by a sudden increase in potency (eg, percent of THC content or quantity of cannabis consumption; typically, heavy users of cannabis consume more than 2 g/d).
https://www.psychiatrictimes.com/view/cannabis-induced-psychosis-review
Again, remember that pregnenolone is our brain's powerful way to respond to the THC's psychotic symptoms.
It's important to have this around and you can get it here. It's cheap!
We won't get into the research on cause and effect between THC and schizophrenia as that's a more complicated question.
Some interesting studies show that they share similar immune reactions in the prefrontal cortex with hyperactive microglia (see CBD and microglia here).
That's the past trauma, infection, and stress piece (learn more how to address it).
The net net for all that franken-cannabis on the market now (high THC, no CBD)??:
Cannabis is associated with psychotic outcomes in numerous studies, an effect that is commonly attributed to (9)-tetrahydrocannabinol ( 9-THC)
https://www.ncbi.nlm.nih.gov/pubmed/21592732
This brings us to CBD.
Let's look at one angle of psychosis which is incredibly complex in terms of brain function.
Paranoia.
What does CBD do there?
Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment
We actually did a deep reviewon CBD and paranoia here. Also, a big review on CBD and psychosis.
And yet...CBD calms these pathways.
One of our favorite studies of CBD is where they administer it to pre-psychotic people and then ran brain scans (which in itself, must be a task).
The effects:
The MRI results showed that the irregular brain activity in the three areas we mentioned above (striatum, medial temporal cortex, and midbrain - all tied to psychosis and schizophrenia) normalized to match those of the healthy control subjects.
https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2697762
Following the study, the majority were deemed by their doctors to longer meet requirements of psychosis!
There's a great walkthrough of both CBD and THC for this aspect of mental health here:
CBD versus THC for psychosis and schizophrenia.
You can't find a more black and white delineation between THC and CBD than this fundamental aspect of brain activity.
Next up...addiction.
CBD versus THC for addiction
There's a great walkthrough of CBD for addiction here. See our article on CBD for THC addiction tolerance and withdrawal and is glutemate the reason people chronically use THC.
Some key points.
We want to measure three things:
- Does CBD or THC have an effect on addiction pathway (dopamine and nucleus accumbens)
- Does CBD or THC normalize (need more and more to get the same result)
- Does CBD or THC blunt ability of the brain to "unlearn" habits
- Is CBD or THC hedonic (causes a feeling of pleasure)
The two are diametrically opposed on each count.
Prolonged use of marijuana or repeated administration of its primary psychoactive constituent, Δ9-tetrahydrocannabinol (THC), can lead to physical dependence in humans and laboratory animals.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606907/
Look..almost all addiction runs through the nucleus accumbens and dopamine pathway, our key "reward" center (more like the "do THAT again" circuit).
Studies in both animals and people show THC is no different:
These data suggest that marijuana exposure, even in young recreational users, is associated with exposure-dependent alterations of the neural matrix of core reward structures and is consistent with animal studies of changes in dendritic arborization.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988409/
Addiction is learned. Dopamine steers the ship and brain literally remodels towards this behavior.
THC definitely normalizes (need more and more to get the same effect).
The brain has a clear opposing effect to what THC does.
It responds by dampening CB1 receptor sensitivity and even actual numbers!
Below, we'll get into why this matters and maybe more importantly, why some people are self-medicating with cannabis.
There may be a better way!
Not everyone gets addicted to THC so clearly there are other drivers there (genetics, past history, etc).
As for hedonic (pleasureable), THC is basically Anandamide in disguise.
It can fit into the CB1 receptor in much the same way.
Anandamide is literally named after the Hindu goddess of bliss!
Anand.
Anandamide is behind the runner's high and even orgasm!
Yes, we can put a check by pleasurable (at the expense of future pleasure since the brain dampens down this system as a response!).
Let's look at CBD on these fronts.
It's very fascinating!
First, CBD does not directly pump the CB1 receptors (which is why it isn't psychoactive).
It boosts the anandamide system when it's low!
That's a critical difference and explains why CBD does not normalize.
Remember how THC is a one-way pump for anandamide-like function….up up up.
CBD is at the other end of the conversation (receiving neurons) and sends a modulation message.
"Too much, we're all good here. Too little, send it on over!".
That's partially how it had its effect on psychosis above:
Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316151/
When you take CBD, it doesn't elicit a pleasurable sensation like THC unless relief of anxiety is pleasurable (which we can argue).
There isn't a documented overdose on CBD, unlike other drugs that boost neurotransmitters in one direction (see CBD versus benzos or CBD versus SSRIs).
It's this one boosting that sends off alarms in the brain to go the other way as an offset.
Hence the CB1 and anandamide draw down after THC.
Let's look at those two aspects.
CBD versus THC for CB1 function
CB1 activity is key to feeling "grounded".
This system is in charge of homeostasis or balance.
When an outside stressor pushes on the system (stress, bad sleep, explosion, infection, you name it), our endocannabinoid system is tasked with righting the ship.
Too much outside "stress" for too long or too intensely can exhaust this system and you're going to feel it.
Out of whack. Janky. Frazzled. Whatever you want to call it.
Here's the interesting piece.
Some people naturally have an endocannabinoid system that's not functioning at full speed.
There are even genetic differences in CB1 activity and numbers.
Our theory is that this is why some women are getting hit so hard by perimenopause (that story here).
Some people immediately LOVE the feeling of THC.
It could just be that they're self-medicating for reduced CB1 activity or to reduce glutamate.
They're filling in a gap.
We're not talking about the one-off getting high on the weekend.
The chronic, daily users who use cannabis in the morning to get started.
To "right the ship".
Of course, the more you use THC, the more the brain goes the other way!
Reduced CB1 sensitivity and numbers.
This creates the dreaded self-reinforcing spiral till eventually, you're just seeking THC to NOT feel terrible.
Classic tolerance and maybe ddiction.
The good news is that abstinence can cause this system to come back but it's not going to feel great.
CBD has actually been looked at for THC withdrawals (as well as benzo, SSRI, and opiate withdrawals).
This case study illustrates the use of cannabidiol (CBD) oil to decrease the addictive use of marijuana and provide anxiolytic and sleep benefits.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718203/
Anxiolytic just means anti-anxiety for the withdrawal symptoms.
CBD bolsters the endocannabinoid system and relieves the withdrawal symptoms.
It's all about balance.
More importantly, it can help to address the keyhole people might be trying to fill with THC.
Anandamide.
CBD versus THC for anandamide
Who doesn't want bliss (literally built into the name of anandamide).
There's a reason everything tastes better, sounds richer, and feels more "luxurious" when a person uses THC (unless they have histamine reactions to it of course - 24-36% of the population).
You're directly stoking the "bliss" circuit of anandamide.
In fact, people who become chronically addicted to THC may have low levels of anandamide, to begin with.
Why do some people try cannabis and no big deal? Others try it and it's off to the races!
Self-medicating is basically trying to compensate for a reduced level of something naturally in the body.
- THC for anandamide
- Nicotine for choline
- Opioids for endorphins
- Alcohol for GABA (and backdoor, for Anandamide via estrogen)
- Fat for estrogen (age-related as well)
- Heck...cholesterol for pregnenolone (check out that crazy study at our review on pregnenolone)
Of course, the problem is that the brain will see this artificial spike in discount anandamide and respond by lowering the naturally occurring level.
When the THC wears off, you're now worse than when you started!
So back to the well.
- Spike THC,
- feels like anandamide - ahhh balance
- brains downregulates natural anandamide production
- Rinse, repeat
Here's where CBD is important.
As we saw above, CBD helps to normalize the anandamide pathway.
But wait, it doesn't boost anandamide so how does it do it?
Biochemical studies indicate that cannabidiol may enhance endogenous anandamide signaling indirectly, by inhibiting the intracellular degradation of anandamide catalyzed by the enzyme fatty acid amide hydrolase (FAAH).
CBD blocks FAAH (another endocannabinoid) which is responsible for breaking down anandamide.
In fact, FAAH may be the genetic underpinning between having too little, too much or just right amounts of anandamide.
Check out the woman who can't feel pain, anxiety, or depression as a result of a genetic deficiency in anandamide.
Having too much FAAH means very little anandamide and we can't wait to see the THC addiction studies on those people.
CBD slows down FAAH.
Eventually, we'll just CRSPR in our out gene variants so we can all naturally enjoy "balanced" levels of anandamide.
In the meantime, use CBD to counter THC's effects on this critical pathway to feeling alright.
Finally...one last protective piece we've looked at a bit up top.
Pregnenolone and THC for overdose
Check out Pregnenolone review for more detail but a quick synopsis.
Pregnenolone is the brain's natural protection against the psychoactive effects of THC.
One note...you're constantly "stealing" preg to offset THC, that's an issue.
Remember how we saw that THC reduced levels of key hormones?
Pregnenolone is the precursor for all those hormones (DHEA, cortisol, estradiol, testosterone, etc).
Preg is also showing powerful effects for schizophrenia and psychosis (go figure).
More importantly, preg gets turned into allopregnanolone which is the basis for new post-partum depression medication which is ridiculously powerful.
We don't want to steal preg to offset THC.
CBD and pregnenolone are critical if you use cannabis.
Also, all this research is based on CBD isolate!
If hyperactive immune response is why we're so drawn to THC, the last thing we want is a histamine response (part of immune) to full spectrum!
Finally...
If someone doesn't like their relationship with THC, check out our taper section:
If we can help people feel better and be healthier, this article is all worth it!
Related Research:
Is CBD effective without THC
The endocannabinoid system
CBD isolate versus full spectrum
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.
2 comments
this is the best explication on how cbd work ever
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