In today’s post, I examine a boatload of research on CBD, THC and Hashimoto’s and autoimmunity. While there are lots of claims about it’s effectiveness, I was really surprised by how little critical analysis there is of the research that is out there.
So, naturally, I took it upon myself to dig in and see what I could find. And I’m posting this on 420 day for all you fans.
With the movement of many states here in the US legalizing marijuana for both recreational and medical uses, there has been a lot of attention over the last few decades on why this plant may be so effective in treating certain types of health issues.
One of the main reasons for the therapeutic value of marijuana is cannabinoids.
Scientists have identified close to 500 phytochemicals in hemp plants. Hundreds of them are compounds called terpenoids.
Terpenoids give fruits, flowers and herbs many of their pleasant aromas, flavors and other special properties. Cannabinoids are a sub-class of these terpenoids.
There are over 60 cannabinoids found in hemp and cannabis — it’s the only place they are found. This is one of the many reasons hemp stands alone in the plant kingdom as a potent repository of nutrition.
What’s interesting to note about cannabinoids is that, for some reason, our bodies evolved with receptors for them. We have our own endogenous cannabinoid system.
These endocannabinoids and their receptors are found throughout the body: in the brain, organs, connective tissues, glands, and immune cells.
In each tissue it seems that cannabinoids perform different tasks, but one thing that seems to be consistent is that they help promote homeostasis or balance within the body.
And this ability to promote balance exists on various levels of biological life, from the macrocosm to the microcosm.
For example, autophagy, the process where cells isolate parts of themselves to be self-digested and recycled is mediated by the cannabinoid system.
This is an area of extreme interest for those of us with autoimmunity because this is the very system that has gone haywire. In fact researchers are currently looking into find drugs that affect this system to improve outcomes for patients with autoimmunity.
Another interesting notion is that endocannabinoids and cannabinoids are important players in the communication and coordination between different systems of the body. And this occurs on both the macro and micro levels.
For example, at the site of an injury, cannabinoids can be found decreasing the release of compounds from injured tissue, stabilizing the nerve cell to prevent excessive firing, and calming nearby immune cells to prevent release of pro-inflammatory substances.
Three very different mechanisms of action on three different cell types all working together for a single purpose: to minimize the pain and damage caused by the injury.
Cannabinoids are really effective in reducing pain and are a viable alternative to opiate based painkillers and have far fewer downsides. They are also clearly effective in helping to reduce inflammation systemically.
Again, this has important implications for autoimmune disease and Hashimoto’s. As I have said repeatedly in my writing and in my presentations.; Autoimmunity is a systemic problem, many systems of the body are impacted and begin losing balances.
This is why Hashimoto’s is literally a mind, body and spirit condition. And the endocannabinoid system, with its complex actions in our immune system, nervous system, and all of the body’s organs, is also a kind of bridge between body and mind.
By understanding this system we can see a mechanism that explains how things that affects the mind and spirit can promote health or disease.
Virtually every species, from all vertebrae on down to tiny nematodes (worms), share the endocannabinoid system.
Cannabinoid receptors are present throughout the body, embedded in cell membranes, and are believed to be more numerous than any other receptor system.
When cannabinoid receptors are stimulated, a whole bunch of physiologic processes follow.
Researchers have identified two cannabinoid receptors: CB1, predominantly present in the nervous system, connective tissues, gonads, glands, and organs; and CB2, predominantly found in the immune system and its associated structures.
Many tissues contain both CB1 and CB2 receptors, each linked to a different action. And emerging research has found that immune cells may express both CB1 and CB2 receptors.
These receptors can be acted upon by our own natural cannabinoids (ends cannabinoids) or by plant based (phytocannabinoids)
Delta-9-tetrahydrocannabinol, or THC, is the most psychoactive and certainly the most famous of these substances, but other cannabinoids such as cannabidiol (CBD) and cannabinol (CBN) are have become more popular with researchers due to a variety of healing properties. Here’s a good breakdown of a number of different cannabinoids.
Most phytocannabinoids have been isolated from cannabis sativa, but other medical herbs, such as echinacea purpura, have been found to contain non-psychoactive cannabinoids as well.
Some studies show that treatment with endocannabinoids leads to increases in certain types of immune proteins (like IL-10) and that they help to diminish others (like IL-17), this can result in suppressing delayed type hypersensitivity response.
Both of these immune proteins have been found to play important roles in Hashimoto’s. IL-10 can block other destructive immune proteins and IL-17 is a kind of immune instigator that can make tissue destruction more intense.
If you aren’t familiar with these proteins, check out this post for detailed discussion of them in a Hashimoto’s context.
These studies also suggest that endogenous cannabinoid system is one of the homeostatic mechanisms that the body uses to down-regulate immune response to foreign antigens as well as combat autoimmunity.
Targeting of this system could yield valuable therapeutics in the future.
Let’s take a look at a few of these in the context or Hashimoto’s and autoimmunity.
In general, there seems to be a big connection between the brain and immune system and cannabinoids. As I have written about on many occasions, Hashimoto’s has a profound impact on the brain and much of autoimmunity’s impact on the body can be found in both the brain and the gut.
And the cannabinoid system seems to be firmly in the middle of this axis. For the purposes of this post, I have focused mostly on the THC and CBD research.
CBD and THC can have opposite effects on regional brain function, which may be why they cause different symptomatic and behavioral effects.
CBD is also known to be able to block the psychoactive effects of Δ-9-THC.
While THC promotes sleep, CBD may actually have the opposite effect and promote wakefulness or make it more difficult to sleep.
In gerneral, there seems to be a kind of yin and yang effect with THC and CBD, they appear to balance and counteract one another.
They also behave a little differently in the way that they influence the immune system.
Studies have shown that THC increases TH-2 and suppresses TH-1 by inhibiting IFN and IL-12 and it affects IL-12 receptors. IL-12 can turn on genes that cause destruction of certain tissues, like the thyroid. So, inhibiting it can be a good thing for people with Hashimoto’s.
In addition it promotes IL-4. This is not always a good thing. IL-4 can activate IgE which is involved with allergic reactions and some sensitivities.
Also, the fact that both CB1 and CB2 receptors have been found on immune cells suggests that cannabinoids play an important role in the regulation of the immune system.
Recent studies demonstrated that administration of THC into mice triggered apoptosis (cell death) in T cells and dendritic cells, resulting in immunosuppression.
In addition, several studies showed that cannabinoids downregulate cytokine and chemokine production and, in some models, upregulate T-regulatory cells (Tregs) as a mechanism to suppress inflammatory responses.
This is a very good thing for Hashimoto’s. Boosting T-regs is an important goal for calming the immune system and in maintaining health and balance in the gut ecosystem.
Later studies using activated peripheral blood T-cell cultures showed that treatment with THC inhibited cell growth and the generation of Th1 cytokines, including IL-12, by CB2-mediated mechanisms. Again demonstarting that THC can be a TH-1 suppressant.
So how does this relate to Hashimoto’s?
Hashimoto’s was originally thought to be a TH-1 dominant autoimmune disorder, but has since been shown to be an over simplification and some people have overactive TH-2 systems.
So while THC can definitely be anti-inflammatory, it may not be if you are TH-2 dominant or already have an over active TH-2 response. Context always matters when you make decisions on what is right for you.
That being said, there is ample evidence that it can help calm TH-1.
The most common side effects seem to be anxiety, potential for addiction, short term memory loss, loss of motivation.
Like any herb, or drug you can overdo it and this can result in adverse reactions.
Some people get really anxious and paranoid after consuming THC. CBD can help counter act this.
THC also has a profound effect on the brain and the hippocampus and cerebellum are both rich with cannabinoid receptors. These are both important parts of the brain for memory, learning and integration.
This can suffer with excessive THC consumption.
I also think the potential for addiction and abuse is also a real concern. Much of the hype around THC is that it is not physically addictive like opiates and this is true.
However, as anyone who lives in the 21st century knows, some people get hooked and smoke weed pretty religiously. It may be easier to quit, but it can still be habit forming if you are predisposed to addiction.
Next, let’s take a look at CBD and the immune system.
CBD acts not only through the endocannabinoid system, but also has an impact on serotonin receptors.
Cannabidiol has also been found to calm glial cells in the brain. These are the immune cells in the brain and they are very easily excited and the body has no natural way to calm them down. So this is a very valuable outcome.
CBD has also been found to treat Type I diabetes by decreasing TH-1 and increasing TH-2.
However, In another study of the medical literature, the action of CBD was summed up this way:
“On the whole, our results and data from the literature indicate that cannabidiol can exert different effects on the macrophages. It seems to inhibit the precocious steps of the inflammatory process throughout reduction of chemotaxis and NO (nitric oxide) production, whereas it can activate the following phases of macrophage activation, by increasing IL-12 and decreasing IL-10 production therefore favoring the development of a Th1 response.”
Hold on what? This suggests that CBD increases TH-1 response. IL-12 is also involved in turning on genes that result in attacks on specific organs and has been implicated as an important player in Hashimoto’s. And this is clearly the opposite of what we just learned about THC.
They go on to say: “However, the inhibition of chemotaxis can also be interpreted as a signal of arrest, a fundamental step for the macrophage cell to fully express its antimicrobial and pro-inflammatory potential once it has reached the appropriate tissue. Indeed, it is possible that cannabidiol, by enhancing the efficacy of the macrophagic response, could lead to a faster resolution of an inflammatory/infective process.”
Or that this may mean that CBD speeds up the resolution of the immune response. This may be beneficial, but it could also be a problem if you have an overzealous TH-1 response in your body.
Certainly, this should give you pause if you are considering taking CBD supplements alone as these will not have the TH-1 reducing powers of THC.
However, CBD has been shown to be quite effective as a pain reliever, especially topically and it’s ability to clear out these circulating immune cells and proteins may be one of the reasons why.
This is one area that gets almost no attention and it took some digging for me to find it and I think it’s important to look at the whole picture.
In this paper, they looked at a number of studies and deduced:
“Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters (heart rate, blood pressure and body temperature), does not affect gastrointestinal transit and does not alter psychomotor or psychological functions.”
All good things, obviously.
“Also, chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans. Conversely, some studies reported that this cannabinoid can induce some side effects, including inhibition of hepatic drug metabolism, alterations of in vitro cell viability, decreased fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters.”
So let’s unpack that:
Inhibition of hepatic drug synthesis means CBD may impact how some drugs are metabolized. This is probably caused by CBD’s effect on the enzyme P450. Over 60% of medication that is prescribed is metabolized by this pathway including thyroid hormone.
In vitro cell viability: it seems that CBD helps promote apoptosis or the destruction of cells. This can good if they are cancer cells and not so good if they cells that you need. This property induced by CBD in normal lymphocytes (immune cells) could contribute to the immunosuppressive effects induced by this cannabinoid.
Decreased fertilization capacity: Suppression of follicular steroidogenesis (production of testosterone, progesterone and estradiol-17) has been demonstrated in vitro at a wide range of CBD concentrations (100-200μM).
Luteinizing hormone (LH)-stimulated accumulation of progesterone and testosterone decreased, while estradiol accumulation was only slightly affected. Low progesterone is a common problem for women with hypothyroidism, so this is a real concern is you are struggling with infertility issues or low progesterone.
A probable mechanism is that cannabinoids modulate the release of cholesterol from its ester storage in lipid droplets and, thus, limit the availability of the substrate for steroidogenesis.
Many people with Hashimoto’s have altered cholesterol metabolism because of the effects of thyroid hormone on this process. Some have high cholesterol and others have low cholesterol. If your is low, CBD might make that problem worse.
It has also been found to decrease Testosterone and lower sperm count. Of course dosage matters and this is less significant in lower doses.
All in all, I think there are some significant potential benefits for to using THC and CBD, but like anything there are risks of over doing it.
As in all decisions regrading your body, context really matters. You need to look at your underlying issues and weaknesses and then look at how THC and CBD behave.
The do a risk/benefit analysis. Are you TH-1 or Th-2 dominant? If you’re TH-1, then strains with more THC might better for you.
If you are TH-2 dominant, then strains with more CBD might be better for you.
If you are low in cholesterol or low progesterone, then CBD might cause more problems. If you are high in cholesterol, it could be beneficial.
Finally, I think, in moderation, and applied in the appropriate context both THC and CBD could be beneficial for some of the underlying issues of Hashimoto’s.
Particularly for important issues like pain, anxiety and some types of immune system imbalances.
Here’s a cool infographic that summarizes some of the pain relieving effects of both. This is courtesy Greencamp.com.
https://www.ncbi.nlm.nih.gov/pubmed/26054920 Autophagy and autoimmunity
http://journal.frontiersin.org/article/10.3389/fimmu.2013.00088/full Autophagy and autoimmunity crosstalk
http://www.medicalnewstoday.com/articles/269432.php THC alters gene expression and can help calm autoimmunity.
https://www.sciencedaily.com/releases/2014/06/140602150914.htm THC suppresses immune function
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448900/ CBD calms glial cells and makes opiates more potent!
http://www.medicalnewstoday.com/articles/269432.php Marijuana for autoimmune disease
http://www.sciencedaily.com/releases/2014/06/140602150914.htm THC and immune functions
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2270485/ CBD arrests Type I Diabetes
http://files.iowamedicalmarijuana.org/science/cancer/Klein%202003.pdf The cannabinaoid system and immune regulation FASCNATING!
http://www.nature.com/nature/journal/v394/n6690/full/394277a0.html Control of pain by endogenous cannabanoids
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828614/ Cannabanoids as novel anti-inflammatory drugs
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1576166/ CB2 receptors, cannababoids IL12 and IL10
http://www.jneurosci.org/content/23/16/6470.full.pdf IL-1 and Cannabanoids
http://www.febsletters.org/article/S0014-5793%2898%2900851-5/abstract Cannabanoids potentiate IL6
http://www.ukcia.org/research/CannabidiolModulatesChemotaxis.pdf Cannabanoids other than THC and IL10 and IL12
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974854/ Cannabanoids reduce IL 17 and Increase IL10
https://www.zamnesia.com/content/260-cbd-thc-cbg-exploring-cannabinoids different types of cannabinoids
http://www.ncbi.nlm.nih.gov/pubmed/22625422 Mechanism of action of CBD
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023456/ CBD as a sleep deterrrent
http://www.medicinalgenomics.com/wp-content/uploads/2013/01/Bergamaschi_2011.pdf safety and side effects of CBD
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055598/ Opposite effects of CBD and THC
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697699/ Cannabanoids as treatment for motor dysfunction
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579248/#b98 Cannabanoids for neurdegenerative disorders