There are currently four cannabinoid-related, FDA-approved medicines. Because of regulatory oversight, such medicines must conform to GCP/GMP standards and be available in potencies and dosages that are consistent and reliable. However, in the basic research and pre-clinical phases of cannabis pipelines, and especially in the consumer marketplace of cannabinoid tinctures and panaceas, what you see is not necessarily what you get. In testing at a recent California Emerald Cup cannabis festival, only about 30 percent of cannabidiol (CBD) products actually contained the claimed percentage of CBD, and several tetrahydrocannabinol (THC) products contained no active THC. These discrepancies can also swing the other way, and several anecdotal and news reports since state-specific legalization took hold have described users ingesting what they thought were safe doses, then spending time in hospital with severe panic attacks. For cannabis research laboratories, it may therefore be difficult to secure approved suppliers who can guarantee accurate measurements of cannabinoid potency, although an assiduous focus on consistency as the industry matures can change that for the better. For now, the recent emergence of cannabis as a legal entity, and its persistence as a Schedule 1 substance, precludes a federal regulatory framework and state-to-state distribution networks. Moreover, a broad resistance to creating a Big Cannabis industry in the mold of Big Pharma has often prioritized the unique qualities of industry culture over uniformity of product.
The foundation of consistency is in the attention paid to the homogenization step before extraction. It is a necessary prelude to isolating and quantifying active extracts, and to testing for impurities and contamination. Downstream analyses rely on chemistry-intensive expertise and complicated instrumentation, such as GC-, LC-, and ICP-MS to quantify cannabinoids and terpenes, and to ensure safety from heavy metal and pesticide contamination. The associated time and expense alone provide strong disincentives against failing to respect these steps, and clear results can only be obtained with uniform emulsions of starting material.
Although cannabis emulsions can be created using hotplate stirrers or even basic rotor-stator homogenizers, resulting fluctuations in cannabinoid bioavailability can be as high as 50 percent, and the minimum particle size that can be obtained is on the scale of micrometers. In contrast, application of high pressure or ultrasonic homogenization can reduce particle size to less than 100 nanometers, and can generate consistent potencies within an error range of less than one percent. Emulsions with the smallest particle size maintain the longest stability, and improve quality by maximizing the bioavailability of active ingredients.
Ultrasonic homogenization is unrealistic at scale because of the smaller volumes sonicator horns can contact and efficiently disrupt. High-pressure homogenization (HPH) performs much better with higher volumes and greater viscosities. A powerful disruptive energy emanates from relaxation of pressure buildup across a valve, resulting in shear, turbulent, and cavitation forces. Valve geometry in addition to tightness and pore size can contribute to changes in exit pressures, resulting in proportionally small particles. Microfluidizers are modifications of HPH, and allow even higher pressures within an internal fixed chamber, eliminating some maintenance worries associated with moving parts. BEE International caters directly to the cannabis industry, and offers the DeBEE range of HPH instruments, varying from small benchtop models to production-scale automated homogenizers. Microfluidics International produces Microfluidizer processors that maximize shear forces to create nano-emulsions that conform to compliance standards and can therefore be relied upon in basic and preclinical research, as well as in the cannabis marketplace. A move toward optimization and standardization of homogenization steps will be crucial in the future growth of the cannabis industry and medical research field.