Category Archives for "Endocannabinoid System"

Cannabinoid Synergy With Hyperbaric Oxygen

Dr. Bogner’s presentation at AutismOne 2018 on Cannabinoid Synergy

The literature supports various pathophysiologies in individuals affected with autism spectrum disorder (ASD), including cerebral hypoperfusion, inflammation, mitochondrial dysfunction and oxidative stress. It has been hypothesized that children affected with ASD might benefit from Hyperbaric oxygen treatment (HBOT) owing to the increase in cerebral perfusion occurring during treatment. Here I present my theories on potential cannabinoid synergy with hyperbarics.

Watch the presentation below or YouTube | View or Download my Deck

The cell-danger response and endocannabinoid signaling pathways have been described as possible key elements in the pathophysiology of microglia driven neuroinflammation, with resulting behavioral problems associated with ASD.

Cannabinoid Synergy = Phytocannabinoid + Hyperbaric Oxygen Synergy

With the growing body of evidence in the literature that describes beneficial phytocannabinoid effects in patients affected with ASD, we highlight the principle mechanisms of a novel concept, e.g. phytocannabinoid-hyperbaric-oxygen synergy and its role in paving the way for faster and lasting clinical benefits. HBOT is approved for several clinical disorders including decompression sickness, gas gangrene, cyanide poisoning and diabetic wounds. Inhalation of above-atmospheric oxygen might result in an elevation of arterial partial pressure of oxygen, leading to increased oxygen delivery to the brain.

Cannabinoid Synergy with HBOTHBOT might also have anti-inflammatory properties due to the reduction of pro-inflammatory cytokines (tumor necrosis factor–α, interferon-γ, and interleukins 1 and 6). Furthermore, HBOT might improve mitochondrial dysfunction, as well as up-regulate the production of antioxidant enzymes. While some studies suggest improved cerebral perfusion, others showed decreased markers of inflammation and did not worsen oxidative stress markers in children with ASD. In the reviewed studies, HBOT had minimal adverse effects and was well tolerated.

Most of the reviewed studies relied on changes in behavioral measurements, which may lag behind physiological changes. In our protocol, we utilize different ATAs in monoplace chambers for all ASD children. The molecular collusion of hyperbaric oxygen and phytocannabinoids suggests synergistic properties, aiding in anti-inflammation, detoxification, improved synaptic plasticity and central nervous system homeostasis.

The Highwire interview: Del Bigtree on Cannabis Science for Autism

In autism, major protective brain mechanisms become interrupted and neuroinflammation emerges. A variety of toxins are responsible for the consequential great demand for neuronal protection. This is where cannabis science comes in to play. And guess what? It’s backed by a lot of solid research. I can vouch for this: I’ve personally gathered cannabis papers for autism in the original Michigan petition 3 years ago and helped support 4 states’ petition as well. It’s a banker’s box full of the finest research papers.

Cannabis programs are implemented in 58% of all states in the United States, yet the federal government says it has no medicinal value and classifies it as dangerous as heroin (or natural peyote). What evidence is being defended to keep it that way? Congressional members are sticking their necks out to make sure individual states are not targeted by Jeff Sessions and the Feds.
Why is the FDA approving cannabis-like pharmaceuticals? When we dive into the more than 35,000 scientific articles that are available in regards to cannabis, we can clearly see that the current main stream narrative on its implementation in autism and other medical conditions is flawed. In a big way too.
Del wanted to get to the bottom of cannabis science for autism. He invited me to discuss the current status quo. Autism is just one of many conditions that respond to cannabis, with a safety profile that justifies de-scheduling on a federal level completely. The autism cannabis science we will present is just the tip of the iceberg. Cannabis is already heavily studied in other countries such as Israel. We will discuss some results of human trials and take a deeper look on the federal fraud of prohibition.

Where is the Cannabis Science for Autism?

John’s Hopkins University found a 25% reduction of overall annual mortality from opioids due to state cannabis program implementations. The science speaks volumes. It is time to de-schedule cannabis, not primarily to have states cash in billions of dollars, but to benefit the ones who really need need it: the patients who suffer and are dying of mostly ineffective and dangerous pharmaceutical intervention.

I want to thank Del Bigtree for creating the platform for the conversation and inviting me to help spread awareness on the cannabis science for autism spectrum disorders.

Cannabis Science for Autism with Dr. Christian Bogner

Cannabis Science for Autism with Dr. Christian Bogner on The HighWire Show with Del Bigtree


Cannabis is plant GcMAF – Central Immune Energy

Even some of the best car engines out there require a specific ingredient in order to run smoothly: Oil.  It reduces friction, heat and wear in the numerous components. Without oil, parts will overheat and break. Even a Tesla motor requires grease to run smooth. Although the human body is a million times more complex in it’s self-sustaining metabolic existence than a luxury 21st century car engine, science reveals parallel concepts. Just as engine oil provides the optimal “viscosity” for prevention of steel friction, in our bodies cannabinoids appear to be directly responsible for a constant anti-inflammatory drive towards systemic balance, or homeostasis. These cannabinoids are either self ( = endo-cannabinoid) produced or plant ( = phyto-cannabinoid) derived. The Cannabis plant has been used for millennia to treat a wide range of human illnesses as evidenced by medicinal reports issued in China and India. The main active compound of Cannabis sativa, delta-9-tetrahydrocannabinol (delta-9-THC), was identified and characterized in 1964 [1].
Cannabis is Plant GcMAF

How Cannabis Interacts with your Immune System

The last decade has provided us with a deep understanding of our endocannabinoid system’s involvement in immune regulatory functions. Hundreds of research papers have demonstrated the beneficial immune properties of this 10,000+ year old plant. One of many revelations are that cannabinoids derived from the plant (e.g. phytocannabinoids) interact with our defense receptors. The evidence is overwhelming. So much in fact, there is cannabis like drugs approved in different countries for immune disorders. Marinol is approved in Denmark for multiple sclerosis since 2003. Sativex is approved to treat spasticity caused by multiple sclerosis in Spain (July 28, 2010), Canada (Aug. 31, 2010), Czech Republic (Apr. 15, 2011), Denmark (June 8, 2011), Germany (July 4, 2011), Sweden (Dec. 22, 2011), Austria (Feb. 7, 2012), Italy (May 7, 2013), and Switzerland (Nov. 27, 2013). The drug is also approved in Finland, Israel, Norway, and Poland [2].

A common misconception about cannabis is that it calms the immune system. In fact, the opposite is true. Cannabis activates your immune system! The calming is a secondary effect and is the result of coordinated chemical reactions which neutralize the threat. This means the immune system must be receiving a message, e.g. a signal to start cleaning up the foreign substance that lead to the inflammation in the first place (e.g. an antigen like gluten, aluminum, bacterial toxins, yeast etc). This signal literally carries with it the secrets to self regenerative processes. It appears that exactly these processes are the target of industrial and agricultural chemicals that end up in your food and elsewhere. According to the CDC, every other American suffers from a chronic disease [3]. This is a serious problem. Exactly how these chemicals paralyze some of your defenses is described below.

The Immune System’s Executive Branch: Macrophages

Macrophages + CannabisMacrophages are little Pacmans. They are big, smart white blood cells that chase, capture, engulf, and digest intruders and foreign substances once they receive the appropriate”signal“. They also present antigens to the adaptive immune system, which means they help create a lasting memory. Macrophages are fighting micro-wars on a cellular level so you can enjoy being healthy. When toxins cause inflammation, macrophages need to be activated by a molecule called GcMAF to get to clean up the foreign, potentially harmful substance [4]. Vitamin D helps to activate macrophages to get to work and clean up. In essence, our bodies produce GcMAF whenever there is inflammation.

GcMAF and Vitamin D3

A vaccine is injected into your muscle. Macrophages are crucial in orchestrating an immune response with the task to remember the antigen for future exposure (creating immunity) and cleaning up the toxins that were contained in the vaccine (e.g aluminum, thimerosal, nanoparticles, human DNA, viral epitopes etc).

The sequence of events are: toxin > inflammation > vitamin D activation in liver and kidneys > production of GcMAF > macrophage activation > neutralization of offending antigen > inflammation controlled


The herbicide glyphosate inhibits this vitamin utilization process (it inhibits the p450 enzyme process) [5], rendering vitamin D supplementation less useful. Because of less GcMAF, immune defenses are weakened. The toxins may slip past macrophages undetected until they enter your blood, because the macrophages did not get an “order” to “arrest and neutralize” the offending toxin.

Cannabis corrects P450 Enzyme in Liver

Glyphosate is found in common genetically modified foods (GMOs) [6], baby formula [7], prenatal vitamins and literally every vaccine that was tested [8]. High glyphosate exposure renders individuals vulnerable to vaccine injury, as many vaccines contain toxins and foreign molecules such as aluminum, polysorbate 80, fetal bovine serum, aborted fetal cells and thimerosal [9]. These toxins are neutralized by macrophages in a final showdown, which plays out in your lymph nodes and spleen. It is exactly these areas where glyphosate is providing the final hit: the lymphatic system. But has this been really proven to be accurate?

Evidence of glyphosate toxicity

The World Health Organization (WHO) is governed by the United Nations. They have established the International Agency for Research on Cancer (IARC) in 1965.  In a special report by the IARC on glyphosate (92 pages with extensive research), it was concluded that

“Two large case–control studies of Non-Hodkin’s Lymphoma (NHL) from Canada and the USA, and two case–control studies from Sweden reported statistically significant increased risks of NHL in association with exposure to glyphosate.” [10]

Prenatal Vitamins contain Glyphosate

Prenatal Vitamins – We tested this brand positive for glyphosate

Furthermore, analyzing 44 individual research projects published since 1980, the scientists, writing in the International Journal of Environmental Research and Public Health, said that people exposed to the weed killer glyphosate, marked by Monsanto under the brand name Roundup, had double the risk of developing non-Hodgkin’s lymphoma [11]. This information is crucial, because if the toxins are not neutralized here, in your lymphatic system,  the next target is the blood, where glyphosate and other toxins have fast track access to all organs, including the brain. Protein leaks result in auto-immune problems. Other toxins “leak” as well and can lead to organ inflammation and ultimately damage.

Cannabis can do what GcMAF was supposed to do

When we cannot utilize vitamin D correctly to activate macrophages, because glyphosate inhibited its necessary conversion to GcMAF, plant cannabinoids may be able to jump in and directly activate macrophages in a similar fashion. Activating the cannabinoid receptor CB1 leads to macrophage phagocytosis [12], which means Cannabis literally tells your body to clean up by activating macrophages.

Gastrointestinal Homeostasis. Yours truly: Cannabis

Gastrointestinal Homeostasis - Cannabis

Since there are so much cannabinoid receptor up-regulation in the inflamed GI system, could raw cannabis juice be the answer?

The human body is home to trillions of bacteria, which outnumber our own cells 10 to 1. The length of the adult gastrointestinal system spans from mouth to anus and is roughly 25 feet (7.5 meters). The intestine represents the largest compartment of the immune system. It is continually exposed to antigens and immunomodulatory agents from the diet and the commensal microbiota, and it is the port of entry for many clinically important pathogens. Convincing evidence suggests that the endocannabinoid system is expressed in the gut and maintains intestinal homeostasis by modulating many important functions including the immune system, motility, sensation, and secretion [13]. The intestinal immune system is continuously exposed to a variety of antigens. An effective immune response must be launched against pathogenic antigens.  There is a macrophage that is called CX3CR1hi, which neutralizes these antigens and limits inflammation [14]. These macrophages can be activated by endocannabinoids such as anandamide (AEA) [14] , an intestinal cannabinoid you produce while you read this sentence. Plant cannabinoids can do the same, as they act on the same receptors.

Brain macrophage activation. Yours truly: Cannabis.

In my previous article [15], we learned that in autism there is evidence of focal brain inflammation. Countless anecdotal reports from parents who treat their kids with cannabis exist, glorifying its benefits. The reason is the signal cannabis is sending to brain macrophages in that particular patient population(in the brain macrophages are called microglia). In the brain, the CB2 receptor is up-regulated once microglia (e.g. brain macrophages) undergo transformation into the pro-inflammatory state [16]. This means that the moment your brain has any sort of inflammatory process going on, CB2 receptors are produced in high quantities (healthy brains have barely any CB2 receptor expression!). Remember, glyphosate, contained in our diets (and every vaccine) inhibits our own body’s production process to produce a compound (5,6EET-EAs) that is strong enough to activate brain macrophages [17].
Cannabis is Plant GcMAF

Evidence of beneficial cannabinoid effect on brain microglia

  • CB2 activation via anandamide suppresses pro-inflammatory cytokines, TNF-alpha and nitrous oxide [18]
  • Cannabinoids potentiate the production of anti-inflammatory cytokine IL-6 [19]
  • Cannabinoids prevents pro-inflammatory cytokine production which was induced by LPS [20]
  • Endo-and phytocannabinoids activate CB2 to induce cell migration (to tell other microglia to help with the clean-up and restructuring) [21][22],[23]
  • Cannabinoid activates CB2 on microglia to increase beneficiary M2 state proliferation [24]
  • THC-mediated CB2 activation resulting in fewer number of microglial cells and fewer number of degenerating neurons [25]

Dr. Jeff Bradstreet’s GcMAF Study

In 2012, Dr. Jeff Bradstreet published a paper entitled “Initial Observations of Elevated Alpha-N-Acetylgalactosaminidase” [26].

Dr. Jeff BradstreetHe reported that a specific enzyme called nagalase destroys GcMAF. This enzyme is elevated possibly due to inflammation. He concluded that nagalase levels are higher in patients affected with autism. While he treated them with GcMAF, 67.5% of individuals had significant improvements. Their nagalase levels dropped. Dr. Bradstreet died June 19th, 2015. The circumstances surrounding his death are extremely troublesome. After a recent Discovery Channel ID special, one could clearly see the continued need to investigate this as a homicide rather than a suicide. Watch this quick interview with his brother Thom Bradstreet (including wife Candace) regarding the latest updates [27].

The bottom line? Exposure of cannabis to the intestinal tract, especially the liver could theoretically produce beneficial effects on macrophage activation, similar to GcMAF. GcMAF production is possibly limited due to genetic predispositions of activating alternative and synergistic detox mechanisms. One of those includes a mutation in the MTHFR gene, leading to less glutathione production and hence more vulnerability to glyphosate.

Studying cannabis is not really permitted (but not impossible. It took Sue Sisley 8 years to get it through the regulatory processes to study PTSD). Just as GcMAF labs are getting raided [28],[29], federally, cannabis remains one of the most dangerous substances you could ingest. It is considered as dangerous as meth [30].  What proof does the government provide to defend the current schedule? The science that the National Institute of Drug Abuse, under the guidance of Dr. Nora Volkow, puts out is nothing short of deceiving. I will address that particularly in my next article. Meanwhile, countless patients that could benefit, are suffering instead. And so are their families. There is a whole generation out there that is injured. Mental disease numbers have never been higher. For the millions of us who have children affected with autism for example, it would be more beneficial to have options like cannabis available. At the same time it is probably equally important to eradicate chemicals like glyphosate (there is many other chemicals like it) from this earth. It is not only a threat to humanity, but to the planet itself. Shame on us.

Christian Bogner, MD

Key Molecules Involved

Alternative name: Calcidiol / 25-hydroxycholecalciferol / 25-hydroxyvitamin D
Producer: liver, via enzyme cholecalciferol 25-hydroxylase
Origin: Vitamin D3 (cholecalciferol)
Time from consumption to production of calcifediol: 7 days

Vitamin D binding protein (VDBP)
Alternative name: Gc protein
Producer: liver
Size: 53-kDa
Binds Calcifediol and Caclcitrol
Delivers Vitamin D to target tissues

Alternative name: Activated vitamin D, 1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin D3
Producer: kidneys, via enzyme 25(OH)D-1a-hydroxylase
Function: increase absorption of calcium from kidneys and gut inflammation results in the hydrolysis of terminal galactose and sialic acid of the Gc protein and this is mediated by membrane-bound β-galactosidase present on activated B-cells and sialidase on T-cells to produce Gc protein-derived macrophage-activating factor (GcMAF)

Macrophages are big and smart white blood cells that chase, capture, engulf, and digest intruders. They trap and phagocyte (literally, “eat”) their enemies. They can multiply rapidly when necessary. 
Receptor: vitamin D receptor (VDR)
Ligand: Calcitriol > Calcifediol
Activator: GcMAF [inhibits M1 activation, enhances M2 macrophage activation]

Receptors: CB1, CB2, GPR18, GPR55 (“CB3”), ?GPR119
Target: Central nervous system, liver, gastrointestinal system, cardiovascular system, bone, skin


[1] Mechoulam R, Gaoni Y. Hashish. IV. The isolation and structure of cannabinolic cannabidiolic and cannabigerolic acids. Tetrahedron 21:1223–1229, 1965.
[13] [14]
[16] Onaivi ES, Ishiguro H, Gu S, Liu QR. CNS effects of CB2 cannabinoid receptors: beyond neuro-immuno-cannabinoid activity. J Psychopharmacol (Oxford). 2012;26(1):92-103.
[17] Snider NT, Sikora MJ, Sridar C, Feuerstein TJ, Rae JM, Hollenberg PF. The endocannabinoid anandamide is a substrate for the human polymorphic cytochrome P450 2D6. J Pharmacol Exp Ther. 2008;327(2):538-45.
[18] Molina-Holgado F, Lledo A, Guaza C. Anandamide suppresses nitric oxide and TNF-alpha responses to Theiler’s virus or endotoxin in astrocytes. Neuroreport. 1997;8:1929–1933.
[19] Molina-Holgado F, Molina-Holgado E, Guaza C. The endogenous cannabinoid anandamide potentiates interleukin-6 production by astrocytes infected with Theiler’s murine encephalomyelitis virus by a receptor-mediated pathway. FEBS Lett.
[20] Puffenbarger RA, Boothe AC, Cabral GA. Cannabinoids inhibit LPS-inducible cytokine mRNA expression in rat microglial cells. Glia. 2000;29:58–69.
[21] Walter L, Franklin A,Witting A,Wade C, Xie Y, Kunos G et al. (2003). Nonpsychotropic cannabinoid receptors regulate microglial cell migration. J Neurosci 23: 1398–1405.
[22] Klein TW, Lane B, Newton CA, Friedman H. The cannabinoid system and cytokine network. Proc Soc Exp Biol Med. 2000;225:1–8.
[23] Franklin A, Stella N (2003). Arachidonylcyclopropylamide increases microglial cell migration through cannabinoid CB2 and abnormal cannabidiol-sensitive receptors. Eur J Pharmacol 474: 195–198.
[24] Carrier EJ, Kearn CS, Barkmeier AJ, Breese NM, YangW, Nithipatikom,K et al. (2004). Cultured rat microglial cells synthesize the endocannabinoid 2-arachidonylglycerol, which increases proliferation via a CB2 receptor-dependent mechanism. Mol Pharmacol 65: 999–1007.
[25] Kreutz S, Koch M, Ghadban C, Korf HW, Dehghani F (2007). Cannabinoids and neuronal damage: differential effects of THC,AEA and 2-AG on activated microglial cells and degenerating neurons in excitotoxically lesioned rat organotypic hippocampal slice cultures. Exp Neurol 203: 246–257.



Endocannabinoid Signaling & Cannabis Treatments in Autism – AutismOne

The endocannabinoid system plays part in the pathophysiology of autism. Protective brain mechanisms are interrupted and neuroinflammation occurs. Organophosphates are potent inhibitors of crucial brain enzymes. The systemic consequences of defective microglial signaling, nagalase surges, and GcMAF metabolism are interconnected into the basic idea that autism is an environmentally triggered neuroinflammatory condition.

When we dive deep into brain mechanisms in autism, you realize that localized brain tissue is inflamed from foreign substances. There is a plethora of evidence in the scientific literature that is inflammation, mostly in the cerebellum of the brain, is triggered by pesticides and herbicides, aluminum and other adjuvants in vaccines, human DNA and viruses. The dynamics of this injury, as well as potential anti-inflammatory therapies, are discussed in my speech (video above) at AutismOne, 5/27/2017.

View my entire presentation slides as well.