Are Cannabinoids More Effective in Nano Form?
[fa icon=”calendar”] May 28, 2016 5:27:08 PM / by Alexey Peshkovsky, Ph.D.
Medicinal uses of the cannabis plant (e.g., medical marijuana, hemp) have now been legalized in most US states. In addition to terpenoids and flavonoids, the plant may contain over 85 different types of therapeutically active compounds known as cannabinoids, the main two of which are tetrahydrocannabinol (THC) and cannabidiol (CBD). In recent years, medications based on concentrated cannabis extracts have become popular because they allow many routes of administration that are preferable to smoking the plant itself.
Oral administration using cannabis extract-infused food (edibles) or beverages is potentially one of the most convenient routes because it does not require special equipment and is appropriate for most patients. There are, however, several important challenges. Concentrates are sticky, viscous and hydrophobic substances, which are difficult to handle and incompatible with water. When consumed as edibles, they act through gastrointestinal absorption and exhibit delayed (up to several hours!) onset of action. Formulating “medicated” beverages has also been challenging due to cannabis extracts’ poor solubility in water, which severely limits the deliverable doses. In addition, poor water solubility results in low bioavalablility: only a small fraction of orally administered cannabinoids is absorbed, requiring patients to consume a lot more than would otherwise be necessary.
Luckily, the pharmaceutical and cosmetics industries have a well-established solution for overcoming these challenges: the delivery of a water-insoluble drug can be tremendously improved by formulating it as a nanoemulsion.
Benefits of Nano-Cannabinoids
Cannabis extract nanoemulsions (nano-cannabinoids) provide exceptionally high bioavailability and therapeutic effect, and are absorbed by the body, either orally or through the skin, very rapidly and completely. In fact, the uptake starts to occur in the mouth almost immediately upon oral administration. This means higher potency and faster onset of action for lower doses. In addition, nano-cannabinoids are water-compatible and can be easily mixed into beverages at essentially any desired concentration.
- Exceptionally high bioavailability
- Fast and complete absorption
- Water-compatible: easily mixed into beverages
- Long-term product stability
- Translucent formulations possible
- All-natural and non-toxic
Nano-cannabinoid formulations are simple to make with Industrial Sonomechanics (ISM)’ patented Barbell Horn Ultrasonic Technology. Our high-amplitude ultrasonic processors can continuously produce pharmaceutical-grade cannabis extract nanoemulsions on laboratory, bench and industrial scales, guaranteeing reproducible results and superior quality.
- Fast: several liters per minute (ISP-3000)
- Extremely small droplet sizes
- Low surfactant requirements
- Emulsifies all cannabinoids and terpenes
- No damage to any compounds
- Simple, economical and safe
- Easy setup and maintenance
- Direct lab-to-production scale-up
Making Nanoemulsions with Ultrasound: Basic Principles
During nano-emulsification with ultrasound, the necessary shear forces are created by cavitation, which produces violently and asymmetrically imploding vacuum bubbles and causes micro-jets that break up cannabis extract droplets down to the nanometer scale. High ultrasonic amplitudes on the order of 70 – 90 microns are necessary in order to take advantage of this effect. In addition to being able to produce high amplitudes, the utilized ultrasonic technology must be directly scalable. During the scale-up, it is essential to make sure that the ultrasonic amplitude and other conditions remain the same: this will ensure that the final product quality is unchanged while the productivity rate is increased.
Why ISM’s Ultrasonic Technology?
It all boils down to direct scale-up. Due to technological limitations, when a conventional ultrasonic processor is scaled up, the maximum ultrasonic amplitude it can provide (along with the resulting cavitation intensity) drops well below the level needed for nano-emulsification.
Although conventional ultrasonic systems with high power capacities are available, they still cannot provide high amplitudes. These systems achieve high power levels through a disproportionate increase in the horn surface area, not the intensity of cavitation.
ISM’s Barbell Horn Ultrasonic Technology (BHUT)-based bench and industrial-scale ultrasonic liquid processors are free from this limitation and can provide the same high ultrasonic amplitudes and cavitation intensities as are taken advantage of during laboratory optimization.
With our technology, one can expect reproducible post-scale-up results, where the production rates are increased by orders of magnitude without any loss in the final product quality. ISM’s commercial-scale processors are widely used in the pharmaceutical and cosmetics industries to continuously produce nanoemulsions with exceptional quality.
Further information about our technology is available in this video.
Written by Alexey Peshkovsky, Ph.D.
Dr. A. Peshkovsky is a co-founder and President of ISM. He is responsible for setting the overall strategic direction for the company as well as for overseeing equipment and applications development. Dr. Peshkovsky holds a B.A. in Chemistry from the University of Pennsylvania and a Ph.D. in Physical Chemistry from Columbia University. He is the author of over 40 scientific papers, patents and presentations as well as two books on ultrasonic liquid processing.
CBD Nano-Technology — Pseudoscience or Innovation?
If you’ve spent any time sifting through CBD products you may have heard the terms “nano CBD” or “water-soluble CBD”. What does this mean? Do they really work?
Can nano CBD really absorb into the bloodstream faster than normal CBD?
The CBD industry is constantly pushing the boundaries, this time with CBD nano-technology. Considered the newest ‘buzzword,’ some swear by the benefits of nano CBD, while others think it is a myth. Apparently, nano CBD is the newest way to increase the absorption of CBD into the bloodstream.
But, what does the science say? Is it possible for nano CBD to end up in your bloodstream in a higher amount compared to regular CBD? Most importantly, is nano CBD safe?
Let’s take a closer look.
Table of Contents
What is Nano CBD?
Nanotechnology is the application “of extremely small things” conducted at the nanoscale — about 1 to 100 nanometers. Nanotechnology is pretty widespread in medicine, beauty products, biomaterials, robotics, and now organic compounds such as CBD.
Some companies refer to nano CBD as being “water-soluble CBD” — but this term isn’t scientifically correct. No CBD is water-soluble, it’s just that the smaller size of the molecules are able to appear water-soluble at the macro scale. We’ll get into how this works in more detail later.
(Source: Folium Biosciences)
The Bioavailability of CBD
If you’ve been a CBD aficionado for a while now, you already know that CBD has a low bioavailability rate.
What is bioavailability? The bioavailability of a substance is the rate and degree at which it enters the bloodstream to produce an active effect.
The bioavailability rate of a substance depends on several factors, including the method of consumption. For example, the oral method of CBD consumption has a high average bioavailability rate of 20% and a low average rate of 4%. So, if you consume 100 mg of CBD, only 20% of it (20 mg) will end up in your bloodstream to produce an active effect .
Vaporized consumption has one of the highest bioavailability rates, between 34-46% .
With oral consumption being so low, and vaporized consumption being heavy on the lungs, consumers are looking for the middle ground. To some, that’s nano CBD.
Why Would Nano CBD Work Better Than Regular CBD?
The reason CBD manufacturers and consumers became interested in nano CBD is the nature of the compound itself. CBD is a hydrophobic molecule —which means it won’t mix with water.
In addition to being hydrophobic, cannabinoids such as CBD are also lipophilic, aka they combine or dissolve in lipids or fats. Therefore, CBD molecules don’t naturally bind with water molecules. This is the reason why bioavailability is so low.
Think of it this way, your mouth and digestive tract are watery, while CBD is oily. Since water and oil don’t mix, most of the CBD particles stay hidden in droplets until fully digested.
Additionally, because of the ‘first-pass metabolism,’ a large percentage of CBD that gets swallowed is processed and broken down in the intestines. After all these processes are finished, only a small percentage of CBD remains to be absorbed into the bloodstream.
But, when the CBD particles become small enough (nano), they look and act like a dissolved substance. This is why they’re called “water-soluble CBD,” a term only used for marketing purposes. CBD doesn’t, in fact, lose its hydrophobic nature to become water-soluble. The compound still follows the fat absorption pathway but is delivered as tiny particles.
It’s easier for the body to digest and absorb nutrients from oil that’s broken down into tiny drops. This is because smaller oil drops have increased surface contact with the body’s enzymes and absorptive tissue, helping the body absorb the CBD molecules sooner.
CBD still needs further processing in the body to be fully distributed to the bloodstream, as opposed to true water-soluble molecules that can be used by the body immediately.
A 2016 study published in the European Journal of Pharmaceutics and Biopharmaceutics, looked into the efficiency of cannabinoid drugs when encapsulated. Researchers used a method to encapsulate cannabinoid drugs in nanostructured lipid carriers (NLCs).
Nanostructured lipid carriers (NLCs) is a smarter drug carrier system made up of physiological, biodegradable, and biocompatible lipid materials. NLCs is used for pharmaceutical applications for various routes of drug delivery, including oral, topical, ocular, etc. .
In short — encapsulating a drug with NLCs can help overcome complicated absorption issues, increase active bioavailability, decrease degradation, and target active tissue delivery.
This carrier system allows multiple routes of administration and offers advanced therapeutic efficacy and safety for more difficult-to-deliver drugs.
Researchers found that “NLC recovery, morphology, dimensional distribution and encapsulation efficiency are presented.” This means that smaller CBD particles are absorbed by the bloodstream more efficiently than regular-sized particles of CBD .
What The Research Says About Nano CBD
When manufactured correctly, nano CBD oil may increase the levels of CBD that enter the bloodstream. Although there is limited research, here’s what the science says about nano CBD.
A promising 2018 study published in the Journal of Pharmaceutical Sciences looked into the bioavailability of Sativex compared to a CBD/THC nanoemulsion in healthy male volunteers. The authors of the study noticed an increased overall absorption of the nanoemulsion .
A 2017 study published in the Journal of Controlled Release compared the bioavailability of a CBD/THC Piperine nanoemulsion with Sativex, an approved THC/CBD oromucosal spray in healthy volunteers.
The study showed a significant increase in absorption of THC and CBD compared to Sativex, but it should be noted that the nanoemulsion also included Piperine — a natural absorption enhancer .
Another 2016 study published in the Journal of Drug Development and Industrial Pharmacy looked at lipid nanoparticles as a platform for cannabinoid delivery.
The study focused on developing a valuable oral delivery carrier for a cannabinoid derivative CB13. According to the authors of the study, this derivative presents a therapeutic potential for certain chronic pain states that respond poorly to conventional analgesics. The lipid formulation used in this study proved to be a promising carrier for the oral delivery of the derivative .
This means that nanoparticles can be an effective asset for cannabinoid delivery to targeted tissues and help pain states that don’t react to conventional medicine.
What Are the Risks of Nano CBD?
Nano CBD holds promise, but there is a lot of room for research, especially when it comes to the safety of such products.
Dr. Pratap Singh, assistant professor at the University of British Columbia, said that nano-encapsulation “should require more clinical trials,” and “more rigorous testing if the size is below 50 or 20 nanometers.” This warning has been issued because nanoparticles can enter human cells and accumulate in various organs, potentially leading to inflammation and tissue damage.
A report on nanotechnology by The Organisation for Economic Co-operation and Development (OECD) discussed the risks and benefits of using nanotechnology regarding pregnancy.
The report points out that: “it is not clear, whether nanoparticles can pass from a pregnant woman’s body via the placenta into the unborn child.”
As the particles decrease in size, the small particles start behaving very similarly to the bigger particles. However, as the particles become even tinier, up to a few hundred nanometers, they show some properties different to normal particle sizes such as passing through gaps they couldn’t pass through before and reaching tissues that weren’t previously expected.
These small particles can enter into different types of tissues, aside from those that they are targeting.
However, Dr. Singh advised consumers to be more concerned about whether a product is being made safely and is not toxic than whether or not it has nanoparticles.
Summary: Is Nano CBD More Effective Than Regular CBD?
Research is scarce but promising — nano CBD is absorbed into the body more efficiently.
To consumers, this means they get more from less when using nano CBD.
However, there is still room for research, and CBD users should be careful when choosing their nano CBD brand. There is still some potential for risk when using nano CBD — but we can’t be sure until more research is conducted.
CBD brands that are selling nano CBD products tend to over-promise in order to sell their products. So, make sure to look for a company that offers rigorous third-party testing, and remains up to date with current research in the nano CBD space.
Nanoemulsion Technology for Infusing CBD in Consumer Products
Derived from the cannabis sativa plant, cannabidiol, better known as CBD, is the substance responsible for certain medicinal properties of cannabis. Unlike another component of cannabis, tetrahydrocannabinol — or THC — CBD is not psychoactive, meaning that it does not produce a “high.”
CBD can be extracted as part of a whole-plant extract. It is also commonly extracted in the form of CBD oil. Two common varieties of the cannabis sativa plant are hemp and marijuana, the former having a lower concentration of THC.
CBD oil is usually extracted from the flowers of cannabis sativa or, more particularly, from small hairs called trichomes that cover the flowers and leaves. Several different methods are used to extract CBD oil from the trichomes, including ethanol extraction, carbon dioxide (CO2) extraction, chemical solvent extraction with hexane or butane, and solvent-free extraction. Most procedures also include a heat decarboxylation step, in which the naturally occurring cannabidiolic acid is converted into CBD.
Challenges Associated With CBD Oil
Once the CBD oil is extracted, it is sometimes used as is. However, CBD oil by itself is not very palatable and may irritate the skin if applied topically. Thus, many companies are now adding CBD oil to products such as beverages, foods, tinctures and topical creams. Because many tinctures and creams are oil-based, infusing them with CBD involves mixing CBD oil with the tincture or cream. However, beverages such as water and tea require CBD extract or CBD oil to be water-soluble, which presents a bit of an issue.
Another challenge of administering CBD oil lies in the inconsistent amount of CBD delivered, which affects its efficacy and the ability to measure its therapeutic effect.
Using Nanoemulsion Technology to Make CBD-Infused Consumer Products
An increasingly popular solution for making CBD ‘water-soluble’ is to create a CBD nanoemulsion. To begin to form an understanding of how a nanoemulsion works, picture taking a bottle containing oil and water. When you shake that bottle of water, the single layer of oil will split to form many smaller droplets. When making a nanoemulsion, you’re doing this same thing but using specialized equipment that shears the particle size of the oil to under 100 nanometers. Other ingredients are also added to the mixture to make sure that the tiny oil droplets stay small.
When small enough (under 100 nanometers), the nanoemulsion can be used to infuse various liquid-based products with the now ‘water-soluble’ CBD. The term ‘water-soluble’ is a misnomer when referring to nanoemulsions, but more easily conveys the idea that the oil can now be put into water-based products and will disappear.
In addition to being ‘water-soluble’, nanoemulsions enhanced the amount of an active ingredient that is absorbed and also improve the speed at which it’s absorbed. CBD nanoemulsions have many benefits, and are becoming the preferred choice of many manufacturers when formulating and producing their infused consumer products.