Issue link: https://www.e-digitaleditions.com/i/1466168
38 doctor focus cannabis patient care | vol. 3 no. 1 cannapatientcare.com Q: Since you said that you would be creating them synthetically, is it a complex process? A: Dr. Woody: When you're forming a new chemical entity, there are certain processes used to make sure that what you get at the end is uniform and it's exactly what you want. Our scientists have worked all of that out and determined how to make this medicine with three, four, or five chemical steps. They purify it, and we test it. Q: What makes this a novel use of CBD? A: Dr. Woody: Most of the cannabinoid compounds in cannabis are not orally absorbable. That means you can't take it orally, you must either smoke it, inject it, or place it under your tongue. We're developing a pill. We are trying to do that by making specialized salts of CBD com- pounds. So that when you take them orally as a pill, they get into your blood system at the level that we want. Getting to this point has been quite a difficult process. We still have several programs ongoing to pinpoint the best of these compounds. Q: Why use a synthetic analog, rather than a naturally occurring compound? A: Dr. Woody: In looking at the natural compounds, you have 100 different molecules. Trying to figure out which is the one or two that have the most beneficial effect is very challenging. And we've decided to approach it from the other direction using specific com- pounds that we think would be the right ones for the properties that we want. The synthetic compounds can be created in a lab and undergo testing, and can be reviewed by the FDA for approval. The FDA doesn't like compounds that are made up of hundreds of compounds as a mixture because it's difficult to determine which compound is the active one. It's a favorable way to do this and then have a real medi- cine that works and is dependable, reproducible, and able to help the patients. In due course, we'll talk with the FDA when we get all the data together. I think the non-addictive indica- tion will probably be in our favor. However, it's unclear as to where these trials will take place, as it's a couple of years off. Q: In 2021, 180 Life Sciences announced the selection of its lead synthetic CBD ana- logue (1). Could you walk us through the selection process? A: Dr. Woody: The way the process works is that many different compounds are identified that are slightly different. The chemistry of each one of them is examined. Then the compounds are tested in animals, usually mice or rats, for effect on inflammation and pain. We've taken a whole series of these compounds to look at effectiveness in both pain and inflammation. From that, we picked out one compound, HUM-217. It took our team about a year to do this kind of selection of our first lead candidate. There may be more that are better. But for the moment HUM-217 is the one we're working on. We were able to show in animal models that it reduces the inflammation that keeps the inflammatory blood cells from going into the joints and other tissues. It also is effective in pain, and it eliminates the damaging cytokines that are produced with inflammation. Those are all properties that we were looking for. Q: A publication from your company took a pre-clinical look at the effects of cannabig- erol (CBG) derivatives on pain, inflamma- tion and obesity (2). What where the findings of this study and what does it mean for the lead compound selected, HUM-217? A: Dr. Woody: I think the paper presented data that the compound had the benefit of stopping the inflamma- tory blood cells from going into the tissues and causing the inflammation. It was also effective in pain reduc- tion, and it reduced the cytokines IL-1 and IL-18 that also cause pain and inflammation. It had other properties that we liked. All those things go into trying to select the best lead candidate. Q: What are the next steps in the develop- ment of the synthetic CBD analog program? A: Dr. Woody: We're involved in the regular drug development process called preclinical testing. It leads to a pre-investigational new drug application (pre-IND) with the FDA. To test a drug in humans in the US, an investigational new drug permit with the FDA is filed. To reach that point, you must complete studies on the drug before you take the proposal to the FDA to say, 'okay, we think this is safe enough to be able to start administering to patients.' This involves making sure a compound is not toxic in a variety of doses, and how much of it you can give to a person or an animal. Does it have side effects or toxicities? Is it safe and is it effective? Does it really reduce the inflammation and pain that we're describing? Is it absorbable? How much of it is absorbed? How much do you have in the blood? How much do you need to get the effect of reducing pain and inflammation? The FDA wants all of those are questions answered. That's one part of this pre-IND application. The second is how to manufacture it. It has to be made under very specialized con- ditions called good manufacturing practice (GMP). Every step of the production of this must be described in detail. The FDA reviews all of this and makes a decision before studies be- gin with human patients. That regulatory oversight is present not just in the US, but in the European Union, the UK and Isra- el—everywhere really. All the regulatory agencies follow pret- ty much the same path.