The challenging cannabis climate

Cannabis research has experienced a challenging climate over the years. Scientific progress, intwined with political and legal factors, has suffered significant limitations for the advancement of cannabis-based applications and therapeutics.

To use the plant cell growth analogy, a formative phase of research included exploration of cannabis phytocannabinoids, identification of endogenous cannabinoids, and discovery of the endocannabinoid system. An expansion phase followed in which individual cannabinoids were characterized, purification methods were developed, and therapeutic research continued to grow.

Cannabis research has now entered a differentiation and maturation phase – where public and private research efforts have led to formidable growth for the medicinal cannabis field. A case in point, FDA-approval of the first cannabis-derived CBD prescription drug was followed closely by rescheduling of Epidiolex from a DEA Class 1 to Class 5 drug – allowing the CBD medication to be legally prescribed and further research to potentially ensue.

As cannabis research enters this new phase of growth, much interest and anticipation await -- in what areas will new therapeutics emerge? mood disorders and depression, neuroinflammatory diseases, cancer? There is no question that significant political and legal barriers remain. However, the cannabis world stands to reach a new high as the field of cannabis research continues to mature.

Research progress in the face of limitations

Cannabis has both a venerable and controversial history. The plant has been cultivated for thousands of years and used in everything from textiles, to oils, to herbal remedies. Despite its widespread utility, research into the medicinal attributes of cannabis have been hampered, largely by the enactment of laws around the perceived health effects and the psychoactive traits of THC.

Identification and isolation of most of the major cannabinoids including THC was achieved by 1980. Identification of two major cannabinoid receptors followed in the 1980s followed by initial characterization of endocannabinoids shortly thereafter. This pioneering work, despite a federal ban on cannabis and limited federal funding, set the stage for more targeted research towards medicinal cannabis applications.

Cannabis research grows and expands

Beyond THC, potential analgesic effects of alternative plant-based cannabinoids and chemically related compounds began to come to light. Cannabidiol and β-caryphylene, and combinations of thereof, for example, showed early promise for chronic pain treatment – without adverse psychoactive effects seen previously with THC.

With the turn of the century came substantial progress into methods for cannabinoid compound purification. Chemical synthesis approaches began to yield productive results as well.

Research led to FDA licensing of three drugs based on cannabinoids. Dronabinol (Marinol) is a synthetic delta-9 THC drug clinically indicated to counteract nausea associated with cancer chemotherapy and to stimulate appetite in chronic AIDS patients. A synthetic analog of delta-9 THC, nabilone (Cesamet) is approved for similar indications. In July 2016 the FDA approved Syndros, a liquid formulation of dronabinol. Two others have been reviewed and are approved for use internationally.

Cannabis research approaches maturation

Several key developments mark the changing public, political, and legal atmosphere.

• Public perception and acceptance is at an all-time high.
• Private development and FDA-approval of cannabis-derived CBD has potentially opened the door for further formulations and applications of natural cannabis compounds.
• Legalization of CBD - with FDA jurisdiction - has created the climate to allow CBD clinical research to grow and other potential FDA-approved drugs to follow. 

Research trends on the rise may include:

• Ongoing studies into the chemical profile of cannabis varieties and the relative abundance of cannabinoids, terpenoids, and phenolic compounds. It is now understood that the “identity” of cannabis varieties goes beyond simple genetic characterization. Chemical profiles or chemotypes involve factors such as cultivation conditions, gene expression and regulation, metabolic production, and persistence of cannabis compounds. As such, the classical concept of strain has been replaced with the concept of chemovar or chemical variety. Further chemical profiling of chemovars will help clarify cannabis authenticity, improve production quality and standards, as well as stratify the therapeutic potential of cannabis compound formulations.

• Better understanding and analysis of pesticide compounds in cannabis products. It’s known that traditional routes of inhalation such as smoking, while effective, are fraught with concerns. Toxic residues can remain in smoke and heating can exacerbate the presence of carcinogenic compounds. Accelerants and propellants used for vaping often contain propylene, glycerol, and other chemicals. Pesticide testing panels will continue to change with evolving regulations. Research into analytical and clinical pesticides testing and toxicology will help in determining safe production guidelines as well as optimal routes of entry.

• Advancements in contaminants testing and heavy metal remediation. Cannabis is a bioaccumulator, and heavy metals in the soil are readily taken up through the root system of cultivated plants. This obviously has significant implications for public health. Further research and development into contaminants testing will help establish safety standards and testing guidelines. The potential exists for using hemp as a bioremediation resource, and further research may explore applications in this area as well.

• Creation of cannabis information resources to facilitate further understanding and transparency in the industry. The continued development of resources such as PhytoFacts will aid in creating reliable and robust platforms for cannabis chemovar analysis. Information sharing resources will improve the transparency of cannabis processing and may help drive the development of universal standards for testing, reporting, product labeling, and other quality measures. 

The outlook for cannabis research

Other research areas that stand to benefit from the current climate may include: optimized methods for terpenes analysis and purification, enhanced growth and breeding techniques, improved genetic and chemotype classification systems, and the list goes on. Not to be overshadowed is the advancement of preclinical research and blinded clinical trials in order to further identify and validate therapeutic applications.The benefits of increased knowledge may extend far beyond cannabis, to the world of opioid addiction and drug treatment in general.

Of course, challenges remain in terms of access to funding, resources, and in some cases, cannabis itself.

Despite these challenges, the cannabis industry stands to reach new heights with the promise of this new climate for research.