What Research Says About Weed or THC versus CBD for Anxiety

THC or weed versus CBD for anxiety
 

We can finally speak to this.

 

Research is actually there which looks at the difference between weed or THC and CBD's effect on anxiety.

 

There are numerous studies that dive all the way down to what genes are turned on and off with either.

 

The results are pretty clear when comparing the two.

 

Maybe more importantly, new research is pointing to how THC might structurally change the brain to make it more prone to future anxiety and depression.

 

We're not anti-weed but people need to make informed decisions.

 

If anything, CBD might help to protect from these changes and even repair them!

 

Let's look at new research on exact effects on the anxiety circuit in the brain.

 

 

Interestingly, many people describe a calming sensation from cannabis or weed.

 

How does that fit with the research?

 

We'll cover these topics:

  • Research on weed and THC versus CBD for anxiety
  • The relationship between THC and CBD for anxiety
  • Long term changes from THC to anxiety circuit
  • Dosage effects of THC and CBD for anxiety
  • Best type of CBD for anxiety (i.e. histamine or allergic response to cannabis)

 

Let's get started. 

Research on weed and THC versus CBD for anxiety

We're going to use weed and THC interchangeably.

 

Why?

 

The two most prominent cannabinoids in cannabis or weed are:

  • THC
  • CBD

 

By far!

 

The other cannabinoids (CBC, CBG, CBN, etc) are generally found in very small, almost negligible levels.

 

If you look at any purported "full spectrum" CBD 3rd party testing, you'll see parts per million usually for these chemicals.

 

That's just the way the plant is.

 

Yes, that is becoming more skewed with each passing year.

 

Meaning...there are new strains with much higher levels of THC for more recreational effects.

 

This is generally at the expense of CBD in the plant...an unfortunate result in terms of anxiety as we'll see below.

 

We'll get into why this matters below as their relationship is pretty interesting.

 

The psychoactive effects of weed or cannabis is primarily due to its THC level.

 

What does research show in terms of THC and anxiety?

 

There are three aspects to look at:

  • THC's and CBD's direct effects on the anxiety circuit
  • Allergic reactions to THC for 24-36% of the population
  • Other contaminants, pesticides, heavy metals, etc in weed or cannabis

 

Let's start with THC's direct effect on anxiety.

 

It's really tough to find THC by itself since effects of weed or cannabis will also include CBD which has a known anti-anxiety effect by itself (see CBD and anxiety here).

 

Most of the studies are on cannabis.

 

The effects of THC via weed on the anxiety circuit appear to be biphasic depending on dose.

 

The majority of users report that consumption of modest amounts of cannabis and CB1 receptor agonists results in euphoria, relaxation, heightened perception, sociability and creativity, moderate to high doses have been reported to elicit phobia, agitation, panic, dysphoria, psychotic manifestations and cognitive impairments

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691841/

 

Lower doses of cannabis (THC by proxy) may have a calming effect while higher levels can have the opposite effect.

 

7.5mg THC significantly reduced self-reported subjective distress after the TSST and attenuated post-task appraisals of the TSST as threatening and challenging. By contrast, 12.5mg THC increased negative mood overall i.e., both before and throughout the tasks,

https://www.ncbi.nlm.nih.gov/pubmed/28599212,

 

Again, CBD is blended into this effect.

 

There are many studies that show a relationship with cannabis or weed use and anxiety but cause/effect is difficult there.

 

Are people with anxiety self-medicating or is the weed use causing anxiety?

 

Cannabis use at baseline was significantly associated with anxiety at follow-up in N = 5 studies adjusted for confounders (OR = 1.28, 95% CI: 1.06-1.54, p = .01).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032500/

 

To get to the heart of THC's effects on anxiety, let's look at some well-known components:

  • THC versus CBD and the Amygdala - seat of emotional and fear response
  • THC versus CBD and the Prefrontal Cortex - rational part of brain that offsets fear response
  • THC versus CBD and the Hippocampus - a modulator of fear signals
  • THC versus CBD and the Uncinate Fasciculus - communication link between the two tied to anxiety
  • THC versus CBD and GABA levels - the "brake" in the brain tied to calming sensation

 

One at a time!

 

We'll see that THC has a blanket effect across most areas of the brain since CB1 receptors (our natural endocannabinoid receptors) are found almost everywhere in the brain.
CBD affect CB2 receptors more so its effect is different from THC.


Let's start in the fear center.

THC or Cannabis versus CBD and the Amygdala

This is big and partially depends on age.

 

One study looked at health adult subjects and studied the effects of THC by itself on the Amygdala:

Relative to the placebo condition, delta-9-THC induced anxiety and modulated right amygdala activation while processing fear. 

https://www.nature.com/articles/s41598-017-14203-4

 

So adding THC to this area boost anxiety effects.

 

The real interesting research on this area deals with cannabis consumption during adolescents.

 

It was found that just 1-2 uses of cannabis at age 14-15 could thicken the amygdala and make a person more prone to anxiety later in life.

 

More Amygdala signaling...more potential anxiety.

 

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.

https://www.sciencedaily.com/releases/2019/01/190114130855.htm

 

This is frightening.  We'll look at ways to try and offset this effect later.

 

This now sheds light on past information:

 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/

 

Then, there's the connection between cannabis and panic attacks:

Acute cannabis use can be associated with the onset of panic attacks and panic disorder, and panic disorder which develops after cannabis use is responsive to pharmacotherapy.

https://www.ncbi.nlm.nih.gov/pubmed/14994319/

 

 

What about CBD and the amygdala?

 

We're only going to touch base on CBD since we have extensive articles on various aspects of anxiety.

 

A great deal of CBD's effects on the anxiety "circuit"...with the Amygdala being a key player as our "fear" center was found through studies on panic attacks:

 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/

 

CBD slowed down the activity in these areas tied to anxiety when overactive without affecting other mental processing which occurs primarily in the prefrontal cortex.

 

We'll go there now.

 

You can learn more about CBD and the anxiety circuit or CBD and and panic attacks here.

THC versus CBD and the Prefrontal Cortex - rational part of brain that offsets fear response

The prefrontal cortex is our newest addition to the brain area family...evolutionarily speaking.

 

It's basically what makes us human as opposed to animals with much of our executive functioning made here.

 

Big stuff like decision making and planning.

 

What does THC or cannabis do here:

Cannabis lowers activity in both ACC and DLPFC clusters, and for people with normal brain function this could lead to problems in executive function and decision-making

https://www.psychologytoday.com/us/blog/experimentations/201801/neuroimaging-cannabis-and-brain-performance-function

 

DLPFC is the part of the PreFrontal Cortex.  The ACC is an important connector (even translator) between the rational brain and our older emotional brain (the Amygdala above).

 

These three areas are the main players in the anxiety circuit if they're not working and communicating correctly.

 

Less prefrontal cortex means less oversight of our fear system.

 

This is very common during puberty when it shuts down for remodeling (see CBD and teenage anxiety here...it's fascinating!).

 

There's a great review of brain areas affected by THC (cannabis) here.

 

https://www.psychologytoday.com/us/blog/experimentations/201801/neuroimaging-cannabis-and-brain-performance-function

 

What about CBD and the rational "restraint" to the amygdala...our prefrontal cortex:

Confirming previous results systemic administration of CBD (10 mg/kg) decreased contextual fear and associated c-Fos expression in the prefrontal cortex (prelimbic and infralimbic regions).

https://www.sciencedirect.com/science/article/pii/S0166432809005890

 

Let's also bring up the middleman in this circuit...the anterior cingulate cortex (ACC).

 

The ACC is a relay messenger between the two big players in the anxiety circuit...the Amygdala (fear) and the Prefrontal Cortex (reason).

 

What does CBD do there?

 

functional neuroimaging (fMRI) study found evidence for attenuation of the blood-oxygen level dependent (BOLD) signal in the amygdala and the posterior and ACC in response to the presentation of fearful faces, combined with a reduction in subjective anxiety

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412699/

 

The "in response to fear" part is important.

 

It means that CBD's effects on this circuit is responsive and adjusts accordingly.

 

Remember that benzos will only dampen in one direction...to the point that your brain stops with enough dosage (hence, the explosion in overdoses).

 

Learn all about CBD versus anxiety medication or even CBD versus benzos for anxiety here.

 

Let's zoom in quickly to one other brain area in the prefrontal cortex tied to cannabis and anxiety.

 

The bilateral orbitofrontal gyri.

 

That's a mouthful.  It's important though!

 

It's key to decision making and emotional processing (the latter being important for anxiety).

 

Here's where cannabis comes into the equation:

Chronic Inactivation of the Orbitofrontal Cortex Increases Anxiety-Like Behavior and Impulsive Aggression

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5253363/

 

Long term (focus on chronic...the time frame, not the type of weed) use of cannabis' effect:

analysis demonstrates significant reduction of gray matter volume in bilateral orbitofrontal gyri (AAL atlas) in marijuana users compared with controls

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250161/

 

Interestingly, the brain tries to compensate by adding more connections in this area.

 

More detail here:

https://www.inverse.com/article/32158-what-weed-really-does-to-your-brain

 

One last big brain stop (we discuss others that are more specific in different articles on teen anxiety and CBD or social anxiety and CBD). 

THC and the Hippocampus - a modulator of fear signals

We don't cover the hippocampus as much in our main CBD and anxiety overview but as part of our old "reptilian" brain, it's definitely in play.

 

In fact, researchers have found an "anxiety cell" deep in the hippocampus that fires when the studied mice were in a state of fear:

The firing of the anxiety cells sends messages to other parts of the brain that turn on anxious behaviors; in mice, those include avoiding the dangerous area or fleeing to a safe zone.

https://www.cuimc.columbia.edu/news/anxiety-cells-identified-brains-hippocampus

 

Think of these cells as the instigator or "on switch" for anxiety response.

 

As the researchers put it:

Though many other cells in the brain have been identified as playing a role in anxiety, the cells found in this study are the first known to represent the state of anxiety, regardless of the type of environment that provokes the emotion.

 

Clearly, proper function of the hippocampus is part of the anxiety loop.

 

If you want a powerful example from this experiment:

By turning the anxiety cells off and on using a technique called optogenetics that allows scientists to control the activity of neurons using beams of light, the researchers found that the anxiety cells control anxiety behaviors

 

The could literally switch anxiety behavior on and off with these cells!

 

What does chronic cannabis (THC) do here:

Further pairwise analyses showed that cannabis users had smaller hippocampal volumes relative to controls. Users not exposed to CBD had 11% reduced volumes and 15% lower NAA concentrations. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5068875/

 

Did you catch that last part?

 

CBD actually helped to offset the damage and even reverse it.  

 

Neurogenesis or the ability to spur new brain growth after damage is very important here.

 

THC is shown to cause an increase of glutamate that can destroy brain mass in the hippocampus.  CBD is able to not only offset this damage but repair it:

CBD induced a substantial increase in net neurogenesis by a CB1 receptor-dependent mechanism

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4543605/

 

Yes, but does this even matter for anxiety?

These data are supported by evidence that repeated administration of CBD to wild-type mice increases hippocampal NPC proliferation via CB1 receptors, which may underlie the anxiolytic effect of CBD in chronically stressed animals

 

"Anxiolytic" just means anti-anxiety.

 

This is important because it goes towards a long term addressing of the anxiety circuit.

 

We address in more detail with our CBD and general anxiety disorder article.

 

If you really want to do some repair work for past weed use, check out how CBD, meditation, and exercise all help with brain repair.


Now let's look at some of the key communication links between brain areas tied to anxiety.

THC or cannabis versus CBD and the Uncinate Fasciculus - communication link between the two tied to anxiety 

There are lots of links between brain areas that are incredibly important to anxiety.

 

In our CBD and General Anxiety Disorder, we discussed the uncinate fasciculus for good reason.

 

Recent brain scans show that reduced activity in that one thoroughfare between the amygdala and the prefrontal cortex (our core anxiety loop) is not functioning correctly.

 

This is very important for cannabis and THC chronic users.

 

Regular cannabis users demonstrated reduced WM integrity in the bilateral uncinate fasciculus (UNC) (MD, right: p = .009 and left: p = .009; FA, right: p = .04 and left: p = .03) and forceps minor (fMinor) (MD, p = .03) compared to healthy controls.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4473294/

 

Check out the article on GAD and CBD for more detail but we want to strengthen that brain area...not weaken it for anxiety.

 

There's a whole wrap up of how CBD affects another endocannabinoid called FAAH in connection with this critical brain area.

 


We've talked about brain areas and THC.  We've also brought up one powerful (for anxiety) communication link and THC and cannabis.

 

What about the chemicals that do all the communicating?  Let's focus on the big one for anxiety...GABA.

THC and GABA levels - the "brake" in the brain tied to calming sensation

GABA is our natural anti-anxiety chemical.

 

In fact, benzos directly increase GABA which is why they're so powerful for anxiety.

 

Unfortunately, they also increase dopamine which is key to addiction.

 

You can learn all about CBD and boosting GABA here.

 

What about THC and GABA?  We'll throw in THC and Dopamine and Glutamate (the gas pedal to GABA's brake) as well.

 

GABA's interesting in terms of THC and cannabis.

 

Some people can have a very negative reaction to THC and even experience psychotic-like effects similar to schizophrenia.

 

Recent research points to a reduced GABA level as a partial cause for this effect:

GABA Deficits Enhance the Psychotomimetic Effects of Δ9-THC

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839528/

 

SO….the big question since GABA is the key lever for anxiety…

 

What does THC (our proxy for cannabis) do for GABA levels?

These results suggest that Delta(9)-THC inhibits GABA release, but does not directly alter GABA(A) receptors or GABA uptake in the hippocampus.

https://www.ncbi.nlm.nih.gov/pubmed/20417220

 

It lowers GABA levels.  More importantly, what about Glutamate (the counter balance to GABA in the brain) levels?

 

In the prefrontal cortex: 

Delta(9)-THC (1 mg/kg, i.v.) significantly increased extracellular dopamine and glutamate levels and decreased GABA levels. 

https://www.ncbi.nlm.nih.gov/pubmed/12383968

 

This partially speaks to some of the disruption from cannabis in that area.

 

The more glutamate we have released, the more GABA gets used up to counter it!

 

The two are diametrically opposed in the brain (gas and brake pedal).

 

Dopamine is a whole other beast!

 

It's not directly implicated in the anxiety circuit but it's front and center in the addiction circuit.

 

It's our reward system chemical and where there's addiction, there's dopamine rush!

 

See our article on CBD versus benzos for anxiety if you want to see how that works!

 

So the net net for THC.

 

For long term brain signaling and structure, occasional use may be less impactful on the anxiety circuit.

 

Chronic use and early adolescent use can adversely affect brain areas and the connections between them directly tied anxiety (and depression).

 

In a given instance, low levels of THC can reduce anxiety (if you don't have the histamine issue below) while higher levels increase anxiety.

 

What about CBD and GABA?

 

GABA is so important to the anxiety circuit (millions of benzo prescriptions per year) that we did a thorough analysis of it in our CBD and GABA levels for anxiety article here.

 

The net effect is this:

Finally, the anxiolytic effects of systemic CBD partially depended on GABAA receptor activation 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604171/

 

Don't just stop there though...check out that article.  It's really fascinating since GABA activation has an immediate effect on anxiety.  

 

Also, check out CBD versus benzos for anxiety since they both hit this same pathway (but without the nasty addiction tied to benzos).

The relationship between THC and CBD for anxiety 

It's an interesting relationship that THC and CBD have when it comes to anxiety.

 

As we mentioned above, THC is shown to be anti-anxiety (for people without histamine issue) at lower doses but can cause anxiety at higher doses.

 

CBD has a pretty consistent anti-anxiety effect till very high levels where a separate channel (TRPV) gets triggered.

 

It's been known in research for a while now that CBD can offset the negatives of THC.

 

In fact, this was the original driver of the "entourage effect" which is now used to push full spectrum CBD.

 

For example, the example of the hippocampus damage from THC: 

Users not exposed to CBD had 11% reduced volumes and 15% lower NAA concentrations. Users exposed to CBD and former users did not differ from controls on any measure. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5068875/

 

Did you catch that last part?

 

"Did not differ from controls"

 

Basically, CBD blocked the negatives of THC in the hippocampus loss.

 

There's also a big misconception that you need THC to "activate" CBD.

 

Nothing could be further from the truth.

 

The two actually have competing and opposing effects throughout most of the pathways...especially the anxiety circuit on a long term basis.

 

We'll let the researchers sum it up:

Epidemiological studies of various neuropsychiatric disorders indicate that a higher CBD content in chronically consumed cannabis may protect against adverse effects of THC, including psychotic symptoms, drug cravings, memory loss, and hippocampal gray matter loss

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604171/

 

One of the "psychotic" symptoms was an intense anxiety effect.

 

Check out the new book, Never Enough from Judith Grisel for a good explanation of how THC affects multiple pathways across the brain.  Very interesting read.

 

Also, check out Full spectrum versus CBD Isolate for more research on THC versus CBD.

 

One final example out of dozens.

 

In a study, they gave CBD to one set of participants and a placebo to another set.

 

They then administered high levels of THC (enough to provoke a psychotic reaction):

pretreatment with CBD prevented the acute induction of psychotic symptoms by Δ-9-tetrahydrocannabinol. Δ-9-THC and CBD can have opposite effects on regional brain function, which may underlie their different symptomatic and behavioral effects, and CBD's ability to block the psychotogenic effects of Δ-9-THC.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055598/

 

Just look at the graph of anxiety scores for THC by itself, CBD prior to THC, and control group.

 

CBD and control are virtually identical while THC is significantly higher.

 

There's a big push these days towards higher and higher THC levels.  There's a corresponding increase in ER visits as well.

 

Another important stop regarding CBD versus weed for anxiety.

 

Histamines!

Allergic reactions to THC for 24-36% of the population

This is important consideration for people comparing cannabis or weed versus CBD for anxiety.

 

Here are the numbers.

 

Roughly 40-60% of people have histamine issues.

 

This gets worse for women and worse for all of us as we get older.

 

Research shows that an estimated 70% of those people have allergies to THC.

 

That speaks to why some people have bad reactions to cannabis.

 

All that plant material in the cannabis is going the wrong direction!

 

Histamine is a powerful excitatory chemical in the brain (eats up GABA).

 

Remember, we want to boost GABA for anxiety.

 

CBD actually has been shown to calm the histamine response by itself.

 

Check out CBD for histamine and anxiety here.

 

This only happens if we have the right kind of CBD (more below).

Other contaminants, pesticides, heavy metals, etc in weed or cannabis

At IndigoNaturals, we actually test our CBD isolate twice to be free of:

  • THC
  • Pesticides
  • Solvents
  • Bacteria
  • Mold
  • Heavy Metals

 

This is very important.

 

On the legal weed market, reports are showing lots of issues in terms of what is in the actual product.

 

Forget THC and CBD levels...actual issues with mold and bacteria.

 

Needless to say, this is tricky.

 

It can be even worse on the illegal market.

 

Long since banned pesticides are constantly turning up with illegal grows.

 

If you put it in your body for anxiety, it has to be 3rd party testing.

 

You can see our third party testing here.

 

Our families take IndigoNaturals so we're very serious about this.

 

What about dosage of CBD for anxiety.

Dosage effects of THC and CBD for anxiety

The ideal sweet spot for CBD appears to be around 300 mg for both short term and long term effects on the anxiety circuit.

 

Beyond 300 mg up to 600 mg, the anti-anxiety effect continues but the long term neurogenesis (in the hippocampus for example) goes down.

 

Of course, start low (25-30 mg) to test how it works with you.

 

More on best mg of CBD for anxiety here.

Best type of CBD for anxiety

 

There are prerequisites here: 

  • Organically grown in the US
  • 3rd party tested (see above)
  • Sufficient levels of CBD (1000 mg+) per bottle
  • THC free
  • No flavors, scents, etc
  • Clean base oil with low histamine response (we use MCT for this reason)
  • Affordable 4-5 cents per mg of CBD

 

We literally crafted IndigoNaturals CBD based on these guidelines and more importantly...based on research.

1000 mg cbd isolate for anxiety2000 mg of cbd isolate for anxiety

6000 mg of cbd isolate for anxiety

 

 

We've been there personally and went through many bad CBD options till we found the right mix.

 

The research is pretty clear on weed versus CBD for anxiety.  Especially on a longer term basis!

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