Non-Cannibinoids Bind Human Cannabinoid Receptors

CBD is big business but there's also possibly big potential for one ultra-rare disease:

The primary reason for my interest in cannabinoids and non-cannabinoid cannabinoid agonists is to reduce pain and visible inflammation (redness, shiny cutanous sclerosis, follicular damage) associated with linear scleroderma morphea en coupe de sabre.

Does Medical CBD Have Potential Use Case Besides as a Pain-Reliever?

Why do we care about cannabinoids anyway? Besides their push by popular culture as a cure-all, cannabinoids have been shown to slow fibrosis and block inflammation in scleroderma (Scleroderma News):


The chief chemical compound we concern ourselves with today when it comes to medical cannabis is CBD, or cannabidiol. Yet there are ove 60 identified cannabinoids, some of which are human cannabinoid receptor agonists and others of which act as antagonists (image credit Lily Den Farm):


Is CBD Perfectly Safe?

Cannot say. There are reports of an unmasking effect of schizoid disorders, especially in adolescent males. Possible hepatic and renal toxicity from longterm use. Medicinal cannabis farmers warn CBD inhibits cytochrome P450 enzymes. This is why non-cannabinoid cannabinoid agonists pose a promising therapeutic -- even if they are as an adjuvant (entourage effect). The more we understand, the better.

Possible Ubiquity of Phytocannabinoids in Nature

While we often associate cannabinoids with recreational marijuana, medical marijuana and medical hemp -- phytocannabinoids occur in several plant species besides cannabis (Wikipedia):


Blue-purple red colors found naturally in cannabis flowers (anthocyanins, delphinidins, malvidin), quercetin, curcumin, reservatrol show affinity for human cannabinoid receptors, though they are not cannabinoids themselves. Arachidonate (cacao) metabolites (prostaglandins and eukotrienes) show agonistic activity. Cannabinoids are lipophilic (they like fat, indicating best in oil, as skin-softening treatments for sclerodermoid diseases). 

Black carrots and black pepper have phytopharmacological compounds that are cannabinoid receptor agonists:

Moreover, cannabis (marijuana, hemp) belongs to a larger family called cannabaceae. This also includes humulus (hops) and celtis (hackberry). Recently, a phytopharmaceutical project in the Bay Area bred ancestral Far East Asian hops strains to express recessive CBD. It is plausible that cannabinoid-presence may be genetically expressed or carried in non-cannabis cannabaceae plants. From an ethnobotanical interest note, hops only became widely used as the flavoring of choice for beer around the 12th century; previously, various herbs such as mugwort and scotsbroom were used. Mugwort, wormwood (absinthe), mint, sage, oregano all containe ketone thujone -- which somewhat binds to cannabinoid receptors and shows some psychotropic properties (its chemical structure is coincidentally similar to psychotropic cannabinoid THC).

Disagreement/Need for More Research

There are conflicting reports regarding botanicals and their cannabinoid activity:


Despite the lack of agreement due to insufficient data there is preliminary evidence to suggest that triglycerides/fatty acids play some role in endogenous cannabinoid production, cannabinoid uptake, endocannabinoid system modulation. Coincidentally or not, ketones as indicated by the ketogenic diet also show lipophilia. It is worthwhile to explore these inititial observations/intuition regarding possible endocannabinoid system regulation beyond cannabis as they could pose significance to improving upon current methods for biomodulating human health.

Personal Interest/Morphea as a Worthy Orphan Disease

Just how destructive is ECDS? Here is are imagings/photos of fellow patients:



This rare and disfiguring disease overwhelmingly affects women and children. Specifically, if allowed to naturally progress, it causes de-construction along presumably the Blaschko lines of the skin/hair follicles to the deeper layers of the dermis, fat, muscle, bones, blood vessels, nerves, brain, and so on. Some of the more clinically interesting neurological abnormalities associated with it that I've personally experienced are multiple intercranial cysts, seizures, hemiparasthesia, hemiplegic migraines, dystonia. For these reasons, it is worthwhile to pursue further research into endocannabinoid system biomodulation as it possibly relates to disease outcome/alleviating pain/inflammation. Even if the outcome is fruitless, the process of scientific inquiry will be fruitful in and of itself.

Thoughts Regarding Anecdotal Evidence

As a scientist and rare disease patient, I am skeptical of MDs gone rogue, social media influencers, naturopaths who wear expensive watches, urban-dweller medical mediums (native healers don't brag about themselves as healers for fear of upsetting their ally spirits). As rare disease patient and scientist, I have to keep an open mind to potential promising treatments. Lupus affects more than 1 million people in the US but there's only 1 in a million of me. There is no blueprint for success. Basically, if I want to follow a path to healing I must largely pave it myself.

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