Accurate Education: Cannabidiol (CBD)- Dosing, Products and Formulations

Over-the-Counter CBD Products

Product Purity

Types of CBD Products

There are three basic types of over-the-counter (OTC) CBD products: Isolate, Broad Spectrum and Full Spectrum. They differ in  the presence of other cannabis-based constituents than CBD. In addition to different types of CBD products, there are also different formulations of CBD products. Because CBD oil is very poorly soluble in water and is not absorbed well with oral ingestion, special formulations are being introduced to the commercial marked designed to enhance absorption and improve effectiveness (See “Commercial Products” below, at the bottom of this page).

Whole plant CBD-rich hemp has been historically grown for fiber or seed and is typically low in cannabinoid and terpenes content. However, CBD-rich hemp plants and flower buds are now available OTC with CBD content of 20% or more.

These are the different CBD types:

CBD Isolates

A CBD oil “Isolate” is 99+% pure CBD, with no THC or other cannabinoids and no terpenes.  Compared to whole plant CBD-rich cannabis, industrial hemp grown for fiber or seed is typically low in cannabinoid content. A huge amount of fiber hemp is required to extract a small amount of CBD, which raises the risk of contaminants because hemp, a bioaccumulator, draws toxins from the soil. This is one important reason why it is stressed to obtain a “Certificate of Analysis” of any CBD product before purchase. CBD oill from hemp may be labeled “isolate” as opposed to “whole -plant derived” or derived from “aerial parts” (all plant parts above the ground, excluding roots). CBD products listed as being derived from “whole plant” or “aerial parts” are likely to be broad or full spectrum.

Without any other cannabinoids or terpenes, CBD isolates do not allow for the “Entourage Effect” (see below) in which the therapeutic benefit of CBD is believed to be enhanced by the presence of other plant-based cannabinoids and terpenes. Based on this argument, “Broad Spectrum” and “Full Spectrum” CBD products may provide greater therapeutic benefits.

Broad Spectrum CBD

“Broad Spectrum” products are processed to maintain the presence of CBD and other cannabinoids and terpenes but remove THC so they have zero THC. The concentration and ratios of these compounds in the “Broad Spectrum” product will vary based on the specific strain of the plant(s) from which the CBD was extracted as well as the growing conditions and extraction techniques. Sometimes individual cannabinoids and terpenes are also added back into CBD oil products to raise the potency of the product. Third party lab reports or “Certificates of Analysis” should be readily available from reputable manufacturers that identify which cannabinoids and terpenes are present in the product and at what concentrations.

Full Spectrum CBD

Like “Broad Spectrum” CBD, “Full Spectrum” refers to CBD oil products that are extracted from the cannabis plant and contain not only CBD, but also terpenes, other cannabinoids and even some THC. The concentration and ratios of these compounds in the product will vary based on the specific strain of the plant(s) from which the CBD was extracted as well as the growing conditions and extraction techniques. Sometimes individual cannabinoids and terpenes are also added back into CBD oil products to raise the potency of the product.

Full Spectrum CBD products may also contain small amounts of THC and although minimal (less than 0.3%) and unlikely to contribute significant effects, they can still trigger positive urine drug tests. As with Broad Spectrum products, third party lab “Certificates of Analysis” should be readily available from reputable manufacturers that identify which cannabinoids and terpenes are present in the product and at what concentrations.

Advantages of Broad Spectrum and Full Spectrum CBD Compared to Isolates

The possible advantages of Broad Spectrum and Full Spectrum CBD oil products are due to the “Entourage Effect,” in which cannabinoids and terpenes work together in synergy, providing supplemental therapeutic benefits in addition to those of CBD alone (See below).

CBD Formulations

Improving Bioavailability

Thirty percent of top marketed drugs in the USA and 70% of all new drug candidates are lipophilic and exhibit poor water solubility. With these physiochemical properties, the oral bioavailability of these compounds is very limited and extremely erratic. Different lipid-based formulations have been explored in the past few decades to improve the oral delivery of such compounds. In recent years, the most popular approach is their incorporation into self-emulsifying drug delivery systems (SEDDS), with particular emphasis on self-nano-emulsifying drug delivery systems (SNEDDS).

Because CBD oil is highly lipophilic and therefore very poorly soluble in water, it is not absorbed well with oral ingestion (80% or more of ingested CBD is not absorbed. Additionally, THC and CBD are prone to extensive first pass mechanisms, meaning that the liver metabozizes a very significant proportion of these compounds immediately upon absortion from the gut before entering the blood. These absorption factors result in low and erratic, variable oral bioavailability, only a small fraction – less than 10% – of orally ingested CBD  actually enter a cells where they exert their medical properties (true also for other cannabinoids and terpenes in marijuana).  Instead, CBD remains in the blood until it passes through the liver and is metabolized.

New formulations of CBD are appearing on the market that offer enhanced water solubility and absorption that provide greater bioavaiability. These products include liposomal formulations,  nano-sized formulations and self emulsifying formulations. Furthermore, some formulations supplement with compounds such as piperine that enhance bioavailability with other mechanisms.

Liposomal CBD

Liposomal technology provides a method used to enable medications to be better absorbed from the gut and into cells. It is a technology commonly used in nutriceutical supplements, including products described elsewhere on this website (See: Meriva and Siliphos). Liposomes are small sacs with membranes made of phospholipids – the same type of membrane that encloses the cells in our bodies. Liposomal formulations involves enclosing individual drug molecules like CBD inside liposomes, which facilitates their entry into cells in the same way the body transports its own substances into and out of cells. Thus, liposomal CBD is more efficiently used by the body, estimated at possibly 4-5 times more efficiently.

Advantages of Liposomal CBDs:

• • Encapsulates the active ingredients and delivers them directly into the cell;
  • Reduces the breakdown of the CBD (avoids first pass metabolism by the liver); and
  • It improves the percentage of bioavailable CBD, as the full concentration can be absorbed

Nano Formulations

In general, cells can absorb particles only up to 50 nanometers (billionths of a meter) in diameter. Because CBD is hydrophobic and fatty, it binds with itself to a certain extent, creating chains of CBD that are too large to be absorbed by cells. Recent technology sometimes referred to as nano-amplification allows for the separation of CBD molecules  from each other.  Individually, CBD molecules are about 10-15 nanometers in diameter so that nano-forms of CBD are better absorbed by cells with less wastage.

Self Emulsifying Drug Delivery Systems (SEDDS)

Self emulsifying drug delivery systems (SEDDS) increase the oral bioavailability of poorly water-soluble drugs by multiple mechanisms in concert including:

• • Improvement in drug’s solubility
  • Reduced intra-enterocyte metabolism by CYP P450 enzymes
  • Reduced P-glycoprotein (P-gp) efflux activity
  • Reduced hepatic first-pass metabolism bypass via lymphatic absorption

Self-Nano Emulsifying Drug Delivery Systems (SNEDDS) of THC and CBD with Piperine

Advanced pro-nanolipospheres (PNL) formulation have also been devised to improve delivery systems. One such method is comprised of a medium chain triglyceride, surfactants, a co-solvent and the unique addition of a natural absorption enhancer, piperine, a substance derived from black pepper. Piperine inhibits both Phase I and Phase II metabolism of these cannabinoids in the liver. This combination of ingredients self emulsifies the cannabinoids into nano particles that entrap the cannabinoids and the piperine in their core which improve their solubility and inhibits their intestinal metabolism while being safe for human consumption.

In a trial of a THC-CBD-piperine-PNL formulation involving 9 healthy volunteers under fasted conditions, subjects received a THC-CBD (10.8mg, 10mg respectively) and piperine (20mg) in a PNL filled capsule. As a compartor, an equivalent dose of THC-CBD (the oromucosal spray Sativex®) was provided to the subjects.  Single oral administration of the piperine-PNL formulation resulted in a 3-fold increase in Cmax and a 1.5-fold increase in AUC for THC when compared to Sativex®. For CBD, a 4-fold increase in Cmax and a 2.2-fold increase in AUC was observed. To summariz, self-emulsifying formulations have increased bioavailability and increased Cmax within a shorter time compared to oromucosal spray, demonstrating the potential for self emulsifying formulation to improving oral bioavailability of lipophilic compounds.