There's a great deal of misinformation surrounding all aspects of CBD these days.
That's why we have 1 million+ words on research alone.
In the lore of CBD, confusion surrounds the question of THC.
It's time to unpack this whole question based on research and really dive in deep.
We're going to look at every aspect of the two chemical cousins including the following:
- A quick introduction to CBD and THC
- How do CBD and THC work in the body
- What pathways do CBD and THC work on in the body?
- How does CBD and THC interact
- Comparison of CBD with THC versus CBD without THC
- The histamine issue with THC (that NO ONE talks about)
- Does CBD without THC work
- THC tolerance difference between THC and CBD
- What about the entourage effect with CBD and THC
Let's get started. Lots to clear up!
A quick introduction to CBD and THC
CBD and THC are both cannabinoids which are chemicals naturally found in the cannabis plant.
They are the two most prominent (by a long shot) cannabinoids in the plant amount dozens.
Most of the effects, beit good or bad, result from these two players.
We naturally have an endocannabinoid system in our bodies with which they interact.
This system dates back about 600 million years and we share it with all living animals.
Nature appears to like this system and there's a good reason why!
It's tasked with balancing other key systems in response to "stress":
- Nervous system - neurotransmitters and more
- Immune system - inflammation and the cellular birth/death balance (key to cancer and aging)
- Endocrine system - hormones - both steroidal and metabolic
In fact, you see endocannabinoid receptors across almost every cell in the body and brain.
There are two main ones:
- CB1 - mainly in the nervous system - very important for how THC works
- CB2 - mainly in the rest of the body with strong ties to the immune system
Other receptors have been shown to interact with endocannabinoids but the above serve as the main stage.
We have naturally occurring cannabinoids that work the machinery of this system by interacting with these receptors.
There are two prominent ones as well:
- Anandamide - the so-called "bliss" molecule calms activity across the body generally as needed
- 2-AG - sets the general "tone" for this response
So 2AG is the ocean water (tone) and anandamide is the wave (phasic).
It's kind of like a gas pedal steady speed and a turbo boost when needed (acceleration).
One note...we put "stress" in quotes because scientists use it to mean anything that pushes on a pathway one way or another. Out of balance.
Okay...that's the lay of the land….let's now introduce our two players to the field.
How do CBD and THC work in the body
This is very important and drives the difference between the two.
In general, THC mimics anandamide and increases CB1 activity
Now, if the endocannabinoid system is under duress (trauma, inflection, stress, social rejection, pain, etc), THC may feel good up a point.
Hence, the response of calm, sleepy, etc plus other positives.
The key there is "up to a point".
The issue with THC is that anandamide is constantly made and broken down almost instantly by the body (by an enzyme called FAAH specifically).
The body can't break down THC the same way so it lingers too long and at much higher levels.
That's why you can have side effects depending on amounts including anxiety, paranoia, and even psychosis (very high levels).
The number of ER visits are increasing with legalization and the potent THC product on the market.
THC boosts CB1 activity in one direction. This also tolerance if we use it chronically which we'll get into below.
What about CBD?
CBD works completely differently.
It functions as a feedback mechanism in the endocannabinoid system.
Technically, it's called an allosteric negative modulator.
This is really the beauty of CBD.
- If a pathway is running low, it will boost it.
- If it's running high, it might even reduce it.
Oxidative stress is a perfect example (of dozens):
- Healthy cell with low oxidative stress- CBD has no effect
- Healthy cell with high oxidative stress - CBD reduces oxidative stress
- Cancerous or virally infected cell - CBD INCREASES oxidative stress
Read that back over because it's really fascinating.
Especially once you realize that the immune system boosts inflammation (oxidative stress) to naturally kill wayward cells.
Chemo and radiation are essentially massive doses of oxidative stress!
We see countless examples where CBD will support a pathway when running low and curtail it when running high.
Even with different effects depending on the area.
For example, with schizophrenia, there's a situation where we have too much dopamine to one area of the brain (striatum) and not enough to another (prefrontal cortex).
Most antipsychotics squash dopamine which helps with half of the equation but not the others.
Check out CBD and schizophrenia to looks at the results.
As for anandamide, CBD can boost its levels by blocking FAAH (which eats up anandamide) but it doesn't directly boost CB1 activity.
Let's now zero down in the pathways affected by both.
What pathways do CBD and THC work on in the body?
We'll work our way up...starting with actual pathways in the body and looking at the effects we perceive from affecting these pathways.
There's a great chart here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345356/table/T1/
For THC, we see the following:
- CB1 - agonist (means a boost in one direction as we described above)
- GPR55 - agonist
- Serotonin (5HT3a) - antagonist - blocks activity
- Glycine - a general inhibitor of nervous system activity - similar to GABA
- PPAR - inflammation - agonist
- TPRV - agonist or antagonist
There's also some work in the opioid system.
So, THC generally pushes certain pathways in one direction (agonist, antagonist, etc).
By far, the CB1 activity is the crux of its effect since anandamide is definitely an upstream player to many systems.
What about CBD?
- GPR55 and GPR18 - antagonist - both are tied to inflammation
- Serotonin (the 5HT ones) - big deal regarding all human behavior - negative allosteric modulator (feedback mechanism)
- Opioid system - allosteric modulator
- PPAR - agonist -anti-inflammatory effect
- Glycine and GABA - modulator
- TRP - agonist
Of all these, serotonin and GABA are the two big ones in terms of mental health (see CBD and mental health).
You can't boost these in one direction (up or down) as there are very nasty side effects either way.
It's all about balance.
Check out CBD and serotonin or CBD and GABA to learn why.
Feeling "right" is really about balancing these two players.
So...that's all technical mambo jumbo...what's the effect that we can feel?
What effects does CBD and THC have on the body and brain?
Based on these pathways, let's look at big effects from THC and CBD:
THC positive primary effects:
- Calms brain activity (acts like a wet blanket on glutamate activity - our primary "gas" pedal)
- Calms immune response
- Reduces pain pathways
- Calms inflammation
- Initiates sleep but may interfere with deeper sleep
- Increases appetite
- Elicits a "high" feeling (remember, anandamide is called the "bliss" molecule
Those are the primary positives with short-term use.
Since THC isn't able to say when (agonist), it can push pathways too far in one direction.
The potential negative effects of that are:
- Sedation
- Anxiety
- Psychosis (with high amounts)
- Cognitive impairment (memory, etc)
- THC also boosts dopamine in the brain which is key to addiction.
Research is pointing to the percentage of people that become addicted as being low (around 9%) but our theory is that those people are self-medicating to reduce an over-active mind (repetitive thoughts, hyperactivity, anxiety, etc) by squashing glutamate.
Learn more about that here.
There are other, safer ways to do that without the addiction and tolerance.
- PEA is essentially THC without the high and excess activity.
- NAC acts like a "sink" for excess glutamate
- CBD balances GABA and glutamate via its feedback mechanism
The problem of course is that the brain builds tolerance to THC and we'll discuss that below.
As for CBD, the potential positive effects:
- Calms anxiety -via GABA (target for benzos) and serotonin (Target for SSRIs)
- Boosts BDNF (neurogenesis) which is key to depression and just about every mental health issue - this is via the serotonin pathway
- Calms immune response and inflammation when too high (again, the result depends on the situation)
- Protects gut barrier and brain barrier
- Aids with sleep but not a sedative
- Reduces oxidative stress and supports mitochondria
- Aids with pain, especially due to inflammation
This is just a sampling since the endocannabinoid system has its fingers in many pies.
A list of CBD benefits are here.
CBD does not build tolerance since it works like a feedback mechanism.
Really this is the crux of the differences between CBD and THC in the body and the next section will shed more light on that.
How does CBD and THC interact
Quite opposite really.
There's so much hype around needing THC to activate CBD and a deep misuse of the term "entourage effect" with the two.
If you ask many people (even in the industry), they say with complete conviction that you need THC to activate it.
We did a deep dive of CBD versus THC and do you need CBD to activate THC.
Even though there's quite a bit of overlap in their pathways above you now know more than 99% of the people ...in the business!), CBD counters many of the "excesses" of THC.
In fact, CBD has been shown in research (which you can find at links above):
- Prevent or offset psychosis and anxiety from THC
- Offset negative effect on brain mass from THC use
- Offset additive qualities of longer-term THC use
- Offset oxidative stress increase
- Offset negative effects on mitochondria, our little cellular We plants
- Offset effects on motor skills, memory, cognition, and mood
Again, where THC pushes pathways too far (especially CB1), CBD reigns in this effect which makes perfect sense...it's a feedback mechanism whether too low or too high!
We've seen rare examples in research where they amplify effects but it's usually when the given pathway is very low.
That also makes sense since THC will boost many pathways while CBD will boost until it's balanced.
THC just keeps going while CBD dials it back.
Check out CBD and very high THC cannabis.
It's absolutely a must if you use cannabis.
Some practical questions.
Comparison or CBD with THC versus CBD without THC
We described how the two work above right down to the pathways (many shared but with differences).
A common question is to compare CBD with THC and CBD without THC.
For pain and sleep, CBD with THC might be more powerful but only in the short term since the body will push back against THC by going the other way.
CBD has lots of research for pain and sleep in its own right (see CBD and sleep or CBD versus Tylenol).
The bigger issue for many people is nothing that no one is talking about:
Histamine!
The key to allergic reactions.
The histamine issue with THC (that NO ONE talks about)
We learned this the hard way when we first started trying CBD with 3-4 of the biggest brands.
Total allergic reactions. GI issues. Clicking in the back of the throat. Skin irritation, etc.
Here's the deal…
Roughly 40-60% of the population has histamine issues.
This number goes up for women (thanks for leaving, Progesterone) and as we get older (system inflammation and immune over-response).
75% of these people are allergic to THC which puts the total population at around 30-45%!!
Goodness...most people are wondering why they have weird reactions to cannabis (besides all the plant material and assuming clean product).
Most people don't realize the connection between histamine anxiety (see CBD and anxiety) which is a powerful, excitatory neurotransmitter.
Do you know that allergic feeling where you feel like you're coming out of your skin?
Sound similar to anxiety?
If you don't have a good response to cannabis, this is likely the reason (or you have too much CB1 activity or serotonin to begin with).
Another question we get often.
Does CBD without THC work
We have 1 million+ words reviewing NIH research (dozens of studies) that look at pretty profound effects with CBD isolate - CBD by itself.
Some of the most profound (in our opinions):
- CBD and addiction
- CBD and schizophrenia
- CBD and public speaking anxiety (with social anxiety)
- CBD and autoimmune
- CBD and sleep
- CBD and pain
- CBD and gut inflammation
- CBD and longevity
100's of deep dives across the site but those are powerful, in-depth examples of CBD by itself.
In fact, almost all the research is on CBD by itself.
There negatives with THC and so researchers want to establish what CBD can do by itself without the issues.
We're not anti-cannabis as long as it's after the brain finishes developing (around age 25 through white matter continues scaffolding till our 40's) and it's not long-term.
The last part may be the most important difference between CBD and THC.
Let's go there now.
The tolerance difference between THC and CBD
This is by far, the most important difference between THC and CBD if we're looking at health.
Since THC pushes CB1 activity in one direction and the body can't readily break it down (via FAAH) the way it can with anandamide (THC is the substitute), there's a tolerance effect.
Let's break this down because it's too important.
If you use THC once, probably no big deal (unless age 14).
If you continue to use THC products longer term, the body panics.
It will actually start to reduce both the number and sensitivity of CB1 receptors down to the genetic level.
This is a scramble to offset so much CB1 activity at the hands of THC.
When the THC goes away, you're now left with an even lower "stress" response system.
Remember, anandamide is primarily a stress response player when needed.
This means that whatever the issue to begin with (anxiety, depression, sleep, etc) is now a bit worse with every passing day.
We've done deep dives on recovery from this effect (see CBD and tolerance or CBD and cannabis addiction).
It can take about 30 days of abstinence for the receptors to come back depending on how long and how potent the THC use was.
The good news is that with THC, most of the negatives will reverse after this process.
Since THC boosts dopamine, there can be a withdrawal process as well.
Our research shows the following for CBD to aid in this process:
- First 10 days - 600 mg of CBD daily (withdrawal period)
- Day 11- 60 - 300 mg of CBD daily (peak level for neurogenesis or brain repair)
See CBD and brain repair.
This same process is true opioid addiction, alcohol, nicotine, cocaine...you name it.
Really learn about BDNF which is the key player in "over-writing" the addiction pathway in the brain.
Tolerance is basically the effect of getting less impact with prolonged use.
What about the entourage effect with CBD and THC
The entourage effect will be offered as an explanation for CBD with THC.
Actually, the entourage effect is a term from the Israeli godfather of CBD research to explain how CBD would counter many of the negative effects of THC!
Read our "Why CBD is a must if you use cannabis" to learn more.
It's also used quite a bit for so-called full spectrum or broad-spectrum CBD.
This is usually CBD with other cannabinoids including up to .3% THC.
The problem is that the other cannabinoids are in such small amounts.
We've already covered THC and hemp oil can cause the very histamine issues we described above.
That's why so many people (see our reviews or comments) have bad reactions to CBD.
Increased anxiety. Sleep disruption. GI issues.
It's not the CBD at all but all the plant material and potentially THC.
In fact, CBD has been shown to calm histamines (see CBD and allergy or mast cell activation).
These side-effects almost always go away with a switch to CBD isolate.
It's not a sales pitch...we focus on CBD isolate after having responses to THC and full spectrum (see CBD full spectrum versus CBD isolate) and really getting benefits from CBD isolate.
If someone doesn't like their relationship with THC, check out our taper section:
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.