Dr. Mechoulam’s Latest Cannabinoid Discovery

Dr. Raphael Mechoulam has collaborated with EPM, a US based global biotechnology company, to produce the latest innovation in cannabinoid research. It is called EPM301 and it is a synthesized cannabidiolic acid methyl ester molecule. The researchers believe it is much more potent and effective than CBD and THC with the potential to replace steroids and opioids. In this article I will give a brief biography of 88-year-old Dr. Mechoulam and an overview of EPM. I will also explain why the synthesis of EPM301 is such an important development for the cannabis industry regarding the production of pharmaceutical medicine on a commercial large-scale.

Dr. Raphael Mechoulam 

If you are unfamiliar with Dr. Mechoulam, here is a short biography of his origins and of his achievements. He is an Israeli organic chemist and a professor of Medicinal Chemistry at Hebrew University of Jerusalem. Born in Bulgaria in 1930, he and his family emigrated to Israel in 1949 in order to avoid religious persecution. Known as the “Father of Cannabis Research,” in the 1960s he and his research team discovered delta-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG) and several other cannabinoids. In addition, his team also discovered two naturally occurring endocannabinoids; anandamide and 2-AG.

Cannabinoid Acids

All the cannabinoids in the cannabis plant start out as cannabinoid acids. For example, THCa becomes THC when heat is applied. Very little research has been done on cannabinoid acids when compared to that of cannabinoids. Not much is known about the therapeutic effects of cannabinoid acids. EPM has focused its research specifically on cannabinoid acids. The results indicate that they are much more potent than cannabinoids, particularly when it comes to anti-inflammatory and anxiolytic activity.

Cannabinoids acids are the first substances to appear in the development of the cannabis plant. Cannabinoids are secondary substances and appear later in the maturation process.

The problem with working with the acids is that they are extremely unstable and have been unsuitable for use in any pharmaceutical applications. That has all changed with Dr. Mechoulam’s discovery. The team was able to stabilize the cannabidiol acid for a long enough period using a process called *esterification. This process makes it viable for large-scale production and for pharmaceutical experimentation. The instability of the acids had previously made it impossible to produce accurate results.

*Esterification is a chemical reaction in which two reactants (usually an alcohol and an acid) form an ester as an end product.


EPM301 is a synthesized cannabinoid methyl-ester molecule which is very stable, potent and consistent in its effects. EPM, under the guidance of Dr. Mechoulam’s research team, has been testing this molecule on animal models along with 11 others. The results are extremely promising in the therapeutic potential that they hold in their ability to relieve symptoms of many different conditions without side effects. These include the following:

  1. Irritable Bowel Disorder (IBD)
  2. Obesity
  3. Metabolic related syndromes
  4. Inflammatory skin conditions such as psoriasis
  5. Anxiety and depression
  6. Nausea after chemotherapy

CannMed 2019 Conference

The CannaMed Conference is the world’s leading cannabis-focused research conference with patient care as its priority. In September, 2019 the EPM team presented preclinical data for EPM301 at the CannMed Conference held in Pasadena, CA.

EPM and Their Upcoming Projects

The goal of EPM is to be the intermediary between the cannabis and pharmaceutical industries. The company was co-founded in 2017 by Dr. Mechoulam, who heads the cannabis research team, along with Reshef Swisa and Asaf Ohana. Swisa is the CEO of EPM and he was the co-founder and General Manager of NPG, China’s first antibiotic free poultry producer. Ohana is a cannabinoids entrepreneur and was one of the first Israelis to be treated with CBD. The EPM team believes that their success with EPM301 is founded in their ability to produce a product which is potent, consistent and patented.


EPM301’s activity is equal to that of steroids in effectiveness for inflammatory diseases.


EPM301 is produced with large-scale industrial capabilities in pharmaceutical facilities that are approved for Good Manufacturing Practices.


All of EPM’s products are patented and IP protected. They are currently working on many more pharmaceutical drug formulas that they see as having the potential to treat several other medical conditions.

Replacement for Steroids and Opioids

For several years, CBD and THC have been considered to be a reasonable alternative treatment option for addictive prescription medications without their adverse side effects. For some patients, they do not provide the symptom-relieving properties of steroids and opioids. The EPM team now believes that their synthesized cannabidiolic acid, EPM301, is a comparable substitute.

IBD Animal Model Trials

EPM301 was evaluated, both orally and topically, for potency on both acute and chronic animal models when compared to the steroid, prednisone, and the anti-inflammatory drugs, TNF inhibitors. They both have serious side effects. The results suggest that EPM301 has a similar efficacy to both types of prescription medications.

Inflammatory Skin Disease

EPM301 was evaluated with a topical application in an ex vivo model for inflammatory skin disease. The results indicated a similar efficacy to hydrocortisone.

Upcoming Human Trials with EPM301

  1. Oral application in clinical trials with healthy volunteers are scheduled to start at the beginning of 2022.
  2. Topical application in clinical trials with healthy volunteers are scheduled to start at the beginning of 2022.
  3. Investigational New Drug (IND) approval expected for EPM301 to treat those with life-threatening COVID-19 symptoms at the end of 2021.

Projects in the Works at EPM

EPM has 10 more cannabinoid-like molecules, EPM 302-311, currently in pre-clinical development.

Final Word from Dr. Mechoulam

Dr. Mechoulam cautioned pharmaceutical companies of the importance of correctly classifying and regulating medications for medical use to avoid unwanted side effects. Furthermore, he urged them to be attentive to consistent language for specific indications and dosing to avoid confusion between recreational and medicinal use.

forbes.com, More Potent than CBD, THC: Dr. Mechoulam Explains His Latest Discovery, July 12, 2020, Javier Hasse
leaderpost.com, Newly Discovered Cannabis Compound Is Stronger Than THC and CBD, July 14, 2020, Emma Spears
prnewswire.com, EPM Introduces Groundbreaking Cannabinoid Acid Technology and New Commercial Licensing Platform at CannMed 2019 Conference, Sept. 23, 2019