Tag Archives: cannabinoids

Looking up an itch found a synthetic cannabinoid in clinical trial for four diagnoses; Resunab

Cannabinoids are the active phytochemicals found in marijuana which include the euphoric THC and many, many non-euphoric types. A synthetic version of one of them has reached trial stages for autoimmune and skin related diagnoses and for the life shortening genetic condition Cystic fibrosis.

I stumbled across the information while looking up whether marijuana has been found helpful for preventing or treating eczema or the autoimmune skin condition psoriasis, [link] – yes was potential answer and a specific synthetic cannabinoid was mentioned: Ajulemic acid.

A 2007 study published in the Journal of Dermatological Science found that Cannabinoids, having anti-inflammatory properties, work to inhibit the proliferation of skin cells called keratinocytes, which play a role in causing psoriasis. [link]

Its Wikipedia page led me to the company and the clinical trials. The synthetic molecule is being purified and called Resunab by the company Corbus Pharmaceuticals. They have already been approved for Phase Two trials for the drug for four different serious diagnoses: Cystic Fibrosis, Systemic Sclerosis, Dermatomyositis, Systemic Lupus Erythmatosus. The synthetic cannabinoid activates the CB2 receptors and does not cause symptoms of euphoria as does THC, the euphoria promoting chemical found in marijuana. [Read more regarding Resunab and the clinical trials by Corbus Pharmaceuticals]

And why was I looking up eczema and psoriasis and cannabinoids? – the incredible itchiness I’ve been experiencing since only a few days off of my medical marijuana. Some autoimmune symptoms are worse and a previously tiny itchy spot is now raised scabby patches over a large area of my back – arrgh. (It’s talk like a pirate day.) My genetic study and personal life experience has proven to my satisfaction that my body needs an external source of cannabinoids — and a non-euphoric source would be nice but a euphoric source in the meantime is less itchy than having no source – for me at least and maybe for the other psoriasis patients who participated in previous research studies.

Take home point for patients with one of the four diagnoses in Stage 2 trials – contact the company for more information regarding whether they are still looking for patients to participate.

Take home point for me – I’m not 100% sure but my back is itchy, and I think the take home point is that my body needs an external source of cannabinoids and I should just accept that and adapt my life to the current realities of limited legality, limited access, difficulty traveling legally, etc. Marijuana has been found to help promote brain cell growth, prevent cancer, and help reduce inflammatory symptoms associated with autoimmune disease. And previous reading had suggested that I have a genetic problem in my keratinocytes that may be associated with, drum roll,  migraines, TMJ, IBS, and eczema. I have had all of those problems for many years of my life, decades of discomfort, hours of lost time with my children, hours of reduced productivity at work.

But marijuana is a powerful drug and the strains and quality of what is available to medical patients varies greatly. It is safest when the strain has a good balance of euphoric and non-euphoric cannabinoids — both types have medical properties and affect the neurotransmitters in the brain and throughout the nervous system.

Previous (very messy collections of notes) posts on keratinocytes:

  1. Substance P, neuropathic pain, migraines, and the cannabinoid system
  2. An article on Morgellons; a link, and a comment I added re keratinocytes

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

 

And what do osmomechanical stress, changes of temperature, chili powder, curry powder, ginger, Benicar, hormone D, steroids, and cannabinoids have in common?

// 7/1/16 addition: This post is for people suffering from Irritable Bowel Syndrome (IBS) which is not well understood, easy to diagnose or treat, and can be life threatening when more severe symptoms continue long term. The condition can continue for years or be a life long issue that flairs up at times and is less severe at other times.

Dietary tips can be helpful but why some foods seem to trigger symptoms while others don’s has not been well understood either. The common factor underlying why some foods seem to be triggers for many people may be the TRP channels that are found in cells throughout the intestines and actually in most cells of most life forms. //

So what do osmo-mechanical stress, changes of temperature, chili powder, curry powder, ginger, Benicar, hormone D, steroids, and cannabinoids all have in common?

They all may be able to overstimulate Transient Receptor Potential channels (TRP channels) within the gastrointestinal system and cause severe diarrhea in susceptible individuals.

In many cases, the activation mechanism of TRP channels is unclear (Figure 1), but known activators include specific agonists such as mustard oil (TRPA1) and capsaicin (TRPV1), an increase in intracellular Ca2+ (TRPM4, 5), temperature (heat: TRPV1, 2, 3, 4, TRPM4, 5; cold: TRPM8, TRPA1), mechanical or osmotic stress (TRPV4, TRPCs?) and phospholipase C (PLC) activation. TRP channel activity can be further modulated by intracellular phosphatidylinositol phosphates, such as PI(4,5)P2 and membrane potential, but also by inflammatory mediators, cannabinoids and steroids (Nilius, 2007; Rohacs, 2007; Nilius and Voets, 2008).” [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012403/]

The TRP channels are a large group found in many species of life from yeast, to worms, fish and mammels. The agonists/activating chemicals for many of the types of TRP channels have not all been identified as of yet.

One type of TRP channels were formerly called Vanilloid Receptors, and are now called TRPV channels. Vanilloid Receptors were known to be activated by capsaicin found in hot peppers and chili powder. And more recent or less well known research has also found that they can be activated by cannabinoids and steroids, (see the link from the excerpt above), and osmomechanical stress.

Osmo-mechanical stress might be a precursor to edema, excess fluid in the extracellular space; if an organ or cell over fills with fluid it would mechanically be adding physical pressure to the organ or cell — and instead of popping like an overfull water balloon the TRP channels open in response to the physical pressure and let the excess fluid leak out into the extracellular space or into the area surrounding the heart for example. [http://www.ncbi.nlm.nih.gov/books/NBK92821/] Fibrotic heart disease would be adding mechanical stretching stress within the heart. TRP channels are being studied for possible use in preventing fibrotic heart disease. From that research article, we are told that changes in temperature may also activate them:

The activation mechanisms of TRP channel are highly diversified. Some TRP channels appear to be constitutively active, whereas others are activated by Gq-linked receptor activation, oxidative stress, changes of temperature, or an elevation of intracellular Ca2+ [126128]. All the TRP channels appear to be regulated by PIP2 [134137] .” [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874073/]

  • PIP2 = phosphoinositides = phosphatidylinositol phosphates (PIPs) = phosphorylated deriviatives of phosphatidylinositol (PI) [http://www.annualreviews.org/doi/abs/10.1146/annurev.cellbio.21.021704.102317]
  • PIP2 = phosphatidylinositol-4,5-bisphosphate and PI, and phospholipase C (PLC) from the first excerptare involved in cannabinoid metabolism within plasma membranes: [page 9 Kendall et. al., Behavioral Neurobiology of the Endocannabinoid System (Springer, 2009, New York)]

Steroids and hormone D function similarly. And Benicar and curcumin can function similarly to hormone D. And curcumin is a medically active extract from turmeric, a powdered spice that is a main ingredient in curry powder. Turmeric is made from the root of a plant that is biologically very similar to ginger,  which is also a root that is used as a dried spice or  may be used as a chopped vegetable in stir-fry dishes and other foods. Ginger has over 400 active phytochemicals, and one of them might be acting similarly to the curcumin — but that is speculation based on the similarity of symptoms of Irritable Bowel Syndrome that both ginger and curry powder stimulate.

Because — what else do osmomechanical stress, changes of temperature, chili powder, curry powder, ginger, Benicar, hormone D, steroids, and cannabinoids all have in common? — They all may irritate Irritable Bowel Syndrome, (IBS), for some people, along with emotional stress and other things like eating fructose in much quantity (example: from a piece of fruit or fruit juice) or gassy vegetables like cabbage and cruciferous vegetables and beans (gas would be adding mechanical pressure to those TRP channels which might be an over-active culprit in IBS patients).

  • The book, “Tell Me What to Eat If I Have Irritable Bowel Syndrome; Nutrition You Can Live With; Including Dozens of Healthful Mouth-Watering Recipes,” by Elaine Mager, M.P.H., R.D., includes dietary advice and other information about Irritable Bowel Syndrome (IBS). (Warning – most of the recipes contain gluten
  • Re corticosteroids and hormone D:  http://www.oapublishinglondon.com/article/1471

Other diseases that are not well understood but which involve edema and excess fluid entering the area between cells include Chronic Obstructive Pulmonary Disease (COPD) and Congestive Heart Failure (CHF).

So a lack of adequate potassium or magnesium might be involved in allowing too much calcium to enter the interior of cells where it can act as a trigger to increase the flow across the TRP channels even more.

A summary:

/Disclaimer: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes./