Cannabinoids are NOT User Friendly
Within the cannabis plant there are at least 480 distinct compounds. Among those at least 111 have been identified as phytocannabinoids and another 111 have been identified as terpenes. The principal cannabinoids appear to be delta-9-tetrahydrocannabinol (Δ9-THC) cannabinol (CBN), and cannabidiol (CBD). Working together they produce “Entourage Effects.” Their relative concentrations depends on a number of factors such as the cannabis strain plant genetics, the soil climate conditions, the cultivation techniques and most important the extraction technology for producing cannabis extracts.
Cannabinoids are nearly insoluble in water. Their poor solubility and low dissolution rate in the aqueous gastrointestinal fluids and significant first-pass liver metabolism result in low and unpredictable oral cannabinoid bioavailability Consequentially, cannabinoids require high doses to reach therapeutic plasma concentrations, especially when ingested.
Owing to their lipophilicity, cannabinoids accumulate in the lipid part of cell membranes and occupy binding sites localized on hydrophobic portions of integral membrane proteins. It is thought that various adverse effects associated with chronic use of cannabis, including increased tolerance over time, result from the interaction of cannabinoids with cell membranes. Furthermore, cannabinoids exhibit a slow clearance from the body.
Limitations of Current Methods of Use
The current methods of taking cannabis and cannabinoid products include:
- Inhalation delivery methods of smoking, vaporization and aerosols.
- Oral ingestion methods into the GI tract of infused products, edibles, extract oils, tinctures, soft gel caps, drinks, tablets, lozenges and gum.
- Intra-oral delivery methods via sprays tinctures, extracts, and emulsion compositions, and cannabis-containing chewing gums.
Each of these delivery methods has numerous problems and limitations.
Inhalation Delivery Methods of smoking and vaporization have no reliable dosage as medicine. Bioavailability following the smoking route was reported as 2−56%, due in part to intra- and inter-subject variability in smoking dynamics, which contributes to uncertainty in dose delivery. Bioavailability varies according to depth of inhalation, duration and breathhold. About 30% of the Δ9-THC present in a cigarette is destroyed by pyrolysis. Additional, THC is lost in the cigarette buttside-stream smoke, and incomplete lung absorption in the lungs. Inhaling the smoke of burning cannabis can irritate the lungs.
Oral Delivery Methods of ingesting extracts, infusions, edibles cannabinoid capsules have a delay in the onset of their actions making it extremely difficult to ingest the correct dosage of cannabinoids. Oral absorption of Δ9-THC is slow and unpredictable, with peak blood concentrations occurring 1–5 hours post dose. Psychotropic effects after oral use have been shown to set in after 30–90 minutes, peak between 2 to 4 hours, and decline to low levels after 6 hours.
Initial degradation of Δ9-THC is caused by digestive acids in the stomach and intestine. Extensive first-pass liver metabolism further reduces oral bioavailability of THC before it reaches the sites of action. The oral absorption of THC and CBD are typically reported as 6% bioavailability (4-12%) to the systemic circulation.
The hydroxylation of ingested Δ9-THC in the liver to 11-hydroxy-THC creates significantly higher levels of this metabolite compared with inhalation that produces stronger psychotropic effects and greater tendency for adverse effects without warning.
Intra-oral delivery methods of cannabinoids to the sublingual or buccal oral mucosa delivery in the forms of oral mucosal sprays (like Sativex), tinctures, aerosols, drops, lollipops and chewable are an ineffective delivery system for transporting cannabinoids through the oral mucosa. The physiology of epithelium lining and oral mucosa poses a formidable barrier that prevents cannabinoids from penetrating the mucosa and entering systemic circulation to produce any noticeable effects.
These products fail at intra-oral delivery for a number of reasons:
- The native cannabinoid molecular structure has poor permeability across the oral mucosa
- Their cannabinoid molecules are too large in size and weight to pass through mucosal layers into the systemic circulation.
- They deliver too high a fluid volume to diffuse across the approximately 100cm2 of surface area of oral mucosa into the systemic circulation. Effective dosages are measured in microliters not millimeters.
- They have unfavorable oil-to-water partition coefficients and lipophilcity (fat-solubility) of uniozable compounds for sublingual absorption.
- Salivary washout causes the cannabis to be swallowed.
A continual flow of saliva causes premature swallowing of the cannabinoids to pass from the mouth down your throat and are metabolized the same as ingesting an edible. They do not produce significant pharmacokinetic differences from orally ingested cannabis products.
Proof of this is found in the product monograph of the oral mucosal spray cannabis product Sativex by GW Pharma. Maximum plasma concentrations of both CBD and THC are quoted as typically occurring within 2 to 4 hours, like eating edibles. Sativex’s Δ9-THC forms the same blood profile of 11-hydroxy-THC from first pass liver metabolism as expected from being swallowed.
Viscoelastic NanoGels …The Delivery Solution
NanoSphere encapsulated cannabinoids are manufactured as stable viscoelastic nanoparticle gels that we refer as NanoGels. Patent-pending NanoGel Cannabinoids are a major advancement in delivery technology.
- NanoGel Cannabinoids, are proven effective as carriers for sublingual, buccal, intranasal, oral and transdermal delivery. Their fluidity, adhesive and viscoelastic properties effectively transport cannabinoids across cell mucosal membranes into the blood stream, past the blood brain barrier, binding to receptors and signal transduction.
- As a delivery platform, NanoGel Cannabinoids effective cannabinoid loading and allows administering NanoCanoids™ in precision-metered dosages through intra-nasal, intra-oral, perusal and transdermal routes of administration.
- NanoGel Cannabinoids can enter the bloodstream within 15 minutes and achieve peak blood concentrations within 60 minutes.
- NanoGel Cannabinoids can increase the bioavailability bioactivity of cannabinoids 2-fold to 8-fold compared to bioavailability without NanoSphere encapsulation.
- NanoGel Cannabinoids can decrease the dose of cannabinoids 2-fold to 8-fold less than an amount of cannabinoids needed to produce the same effect compared to non-encapsulated cannabinoids.
- Lipid based NanoGel Cannabinoids are highly-stable, biocompatible, biodegradable and easily produced by versatile and scalable and replicable patent-pending unified sequential assembly process.
Dr.med. Napoleon DeLeon holds a degree in medicine from the United Arab Emirates College, Al Ain, UAE.
With over 15 years of experience, he is an expert in evaluating and curating healthcare web content based on clinical evidence.