In this video Jahan Marcu, lead auditor for ASA’s Patient-Focused Certification program, discusses lab testing, safety protocols, adverse events reporting, and regulatory standards for the cannabis industry. Thank you to Care By Design for helping to sponsor this video series.
Transcript:
Project CBD: We’re speaking with Jahan Marcu. Jahan is the scientific advisor to Project CBD. He’s received his PhD from Temple University where he did his dissertation on the structure and activity of cannabinoid receptors. He’s also been involved in some very important scientific papers documenting the anti-cancer activity of compounds in cannabis. He is currently the chief scientist for Americans for Safe Access and the chief auditor for the Patient Focused Certification program of Americans for Safe Access. We’ll be talking about that in a little bit. He’s also served on various committees of trade associations and science organizations, including the American Chemical Society, the International Association for Cannabis as Medicine, and the American Herbal Products Association. Thank you for being with us, Jahan.
I wanted to ask you initially about cannabis and safety protocols. I mean, for those who aren’t wearing “reefer madness” blinders, I think there’s a wide recognition that cannabis is a safe substance. Frances Young, a former DEA administrative chief law officer actually referred to it in a legal document as cannabis being safer than many foods, many common foods that we eat. If it’s so safe, why is it important that in the industry today here should be regulations and standards for safety?
Jahan Marcu: It’s a good question. I think the most basic answer is that those are the rules. In this country, if you sell products that people are going to consume they need to be tested for safety. Those are the simple rules of what it boils down to.
Project CBD: So what does that mean in terms of setting standards of safety protocols? What is a “standard” in this case?
Marcu: Standards usually begin as a best practice. A group such as the American Herbal Products Association (or AHPA) several years ago started these working committees where members of industry, various stakeholders, laboratory operators, patient advocates got together and discussed standards. What makes a good manufacturer? What makes a good cultivator? What makes a good dispensary? What makes a good laboratory (probably the most important aspect of medical cannabis standards)?
And so these best practices get adopted. And as we’ve seen with the AHPA standards, they have been adopted by 11 states, along with the American Herbal Pharmacopoeia standards. And so, would you call the same legislation being adopted over and over again, those are standards. And, they set standards such as how much metal and lead you’re allowed to have in your products. Or, how much fungus or pesticide you’re allowed. Similar standards that what you’d expect when you buy a salad at a grocery store or you buy a pack of vitamin C or some sort of plant extract from anywhere – you’d expect a certain level of safety – and that it was intended for human consumption. It wasn’t intended to feed animals. It wasn’t intended to make a shirt out of it or put some sort of oil in your car. It was intended for human consumption.
I think, also there’s a confusion, too, in what “quality” means to some people. Quality – it refers to purity. And we have to remember that quality is also a term that’s used to describe things like motor oil and poison. And there are high quality of everything. But we have to understand what we mean when we say purity consistency. And, as medical cannabis products are rolling out and people are using them, a lot of medical cannabis users are looking for something that’s going to repeat, it’s going to be consistent. And that’s where we will see the new studies coming through.
You know, there are 6,000-plus rare diseases that exist, where there’s no treatment for them. And if we ever hope to develop treatments for them, we better have standardized medicine that can be used for long-term investigations. And those only come from having standards. That’s just one avenue of what standards can do for an industry, is to help create long-term clinical trials such as the ones that aren’t currently available.
Project CBD: So with cannabis though we’re dealing with a substance, an herb, that is federally illegal. So how do you establish standards that are going to be applicable nationally when it’s only in certain states that cannabis is legal as a medicine and just a few states where it’s legal for adult use. What are the challenges in terms of developing standards and implementing them in this context?
Marcu: That’s a great question. So the reason the American Herbal Products Association and other standards groups have gotten involved, is because they are not controlled by the DEA. You’re allowed to create – it’s not the first time ever that a substance from a plant has been discovered and made into a legal medicine. It’s happened, for instance you might remember there’s a plant called the Poppy plant, and opium and morphine and these things and we discovered another endogenous system by investigating that plant. And there have been rules and standards for that. But there’s really, what’s interesting is that some organizations are prevented from issuing standards. So the USP (United States Pharmacopeia) is not a government organization, but when it issues monographs it gives pharmacists certain abilities. For instance, it allows them to compound with a substance. Well, the USP may not be able to release a formal monograph until cannabis is rescheduled because they would be out of compliance with their DEA standards. However, a group like the American Herbal Pharmacopeia doesn’t have to worry about DEA compliance. A group like AOAC (Official Methods of Analysis) or other groups that are developing analytical standards do not have to work directly with the DEA. They might come to them for help with forensic testing and other issues, but we’re going to see standards – we would hope that the USP would come up with a standard to be adopted by all states and everything would be great and solved over night. But the reality is, it’s going to be a slow process. The monograph and AHPA standards provide a foundation for the industry for consistency.
Project CBD: By AHPA, you’re referring to American Herbal Products Association. Maybe tell us a little bit about the monograph that you were actually involved, with others, in composing.
Marcu: The American Herbal Pharmacopeia has put out about 28 monographs, I believe, on various plants. This is standards for identifying it, and cultivating it, and producing it to meet botanical medicine standards, as well as guides on dosing and administration. And the reason, you know most people can readily identify cannabis, but there are a lot of plants that look like it, like the Japanese Maple for instance and several other members of the Cannabaceae family, all have a very similar leaf structure. So, just a conceptual example: you need a standard method for how you identify it, both by looking at it and by doing chemical analysis. And that’s in the monograph. The monograph has testing standards, testing limits such as residual solvents, identified methods for identifying pesticides, fungal, bacteria limits, and these – while some people criticize any regulatory document – I think you have to remember that there was probably close to 100 people involved in writing this, and there’s an old saying that if 100 people say that this is the way to do it, they might be on to something. Especially since the people that worked on it came from all different disciplines and they were all experts. For instance, this monograph was undertaken by Ethan Russo, Mahmoud ElSohly, Raphael Mechoulam, Appendino, and the list gets a little more esoteric, but we’re talking about people who have worked with the FDA, people who have worked with the USDA, reviewing, editing, all contributing to the creation of this document.
Project CBD: You’re talking about some of the leading lights in the scientific community.
Marcu: Yeah, including one of the final reviewers of the monograph which contains information about individual cannabinoids and their effects, is currently the most published pharmacologist in the world – Vincenzo Di Marzo. He has over 500 publications on endocannabinoids and cannabinoids alone.
Project CBD: Let’s talk a little about “testing.” It’s going to come down to the reliability of the lab that’s doing the testing. And you, through your work with the Patient Focused Certification program of Americans for Safe Access, you’ve been involved in auditing these labs and so forth. What do you see out there in terms of the labs that are servicing the cannabis community in terms of consistency? Is there a long way to go? Are we doing a good job in that respect? What do you find in your work when you are auditing these labs?
Marcu: Some of the labs are absolutely ready to be regulated. Some of the labs also have inspections from state agencies. Like Washington state, they already have some inspectors coming in, the Fire Department, and such. However, I think the biggest challenge for some operators in general is just getting their staff ready for a regulatory inspection. It’s different than interacting with law enforcement. It’s different than interacting perhaps with other municipalities. So I think being ready for an auditor to show up at your place and go through your books, I think it’s a new concept for some people.
Project CBD: Well it implies a certain level of professionalism that may not have been there at the beginning of the whole experience with labs servicing the cannabis industry.
Marcu: I think what first has to happen is the labs need to get on board with “best practices.” Some labs have done a great job in observing this. Other labs, for instance, want to create their own standards and they don’t realize that – you know the monograph was a 19-year project, it involved several phases. Standards aren’t going to be created overnight. I mean, it’s going to take a long time, five to10 years for any organization to even release method 1 right now. And so, I think in order for things to be scientifically valid, things to be consistent, laboratories have to get on board with agreeing on some set of standards. You know, it’s a historical moment. Once – you know this is a scientific problem right now that is in the process of being solved by medical cannabis laboratories, but it represents policy, regulation, breakthroughs in analytical chemistry, and it’s even anthropological. And this is a historic moment right now. We’re going to look back on this later and be really surprised with how far our labs have gone with testing cannabis and what they can do.
Project CBD: There’s an ISO-certified lab. What does ISO stand for? And is that a kind of a certification that should – it’s kind of top of the line? Or is that sort of your base level that has to be there for a lab to be operating well? How does that criteria fit in, because that’s an international thing?
Marcu: Yeah, ISO is an international standards. The ATOA is an organization that trains a lot of those assessors who go in and look at ISO to see if a place is ISO compliant. And they have different regulations. There’s ISO17025, is for analytical laboratories. But they have also general management systems. Like ISO9000, which a hotel can be or a police station, you know, for managing their paperwork a certain way. And it’s important. It includes, for instance, ISO requires there to be for a lab, to be validated methods being used, that staff – but, however, it doesn’t necessarily cover training or tell you whether or not your operation is legally operating within its jurisdiction for cannabis. So, there are a lot of standards out there. Some are better than others. Some address more than others. And some have a different scope. For instance, for Patient Focused Certification we also look at method validation. Having an ISO compliance or being accredited will definitely help you pass a PFC audit, because it will make the review of the data methodology much easier. You’ll have updated Standard Operating Procedures. But I also look at training records, look at licensing, look at zoning, look at how you dispose of your waste. We look at methods that aren’t validated but you’re also using on site. We kind of look at everything. We also look at batch tracking and adverse events reporting, making sure that you know who extracted what and what did it go into and where did it go, so that if there’s an issue, the product can be tracked or recalled.
Project CBD: You mention issues. Let’s talk about some of the issues, because one of the jobs of a lab, you would think, would be to report adverse findings, adverse events, when they come upon them. Project CBD has caught a lot of flack when we reported that in certain CBD-rich products there were solvent residues that shouldn’t have been there. How do you relate to this adverse event reporting? Is that something the industry should be embracing? Should we be shunning that? I mean, it doesn’t necessarily cast an industry in the best light, and yet…
Marcu: I would gently disagree. I think that any operation that engages in a recall plan is engaging in product safety. Any company that is following up on adverse events claim and making a determination about whether or not that product should be recalled or an advisory should be issued, or perhaps labeling should be changed. These are public health issues. And I think it’s important that we not chastise companies for engaging in this recall. Let me give you – and also labs are not the gatekeepers of adverse events. It is the producers of these products, the distributors of these products, are the ones who should be having an adverse events program. And we have to keep – we should praise those companies that engage in this. Because they’re not always wrong. Their products are not always tainted. While there are recalls happening, it seems like every week we hear about them in Colorado.
What’s not publicized very heavily or discussed are the products that are released after they’re deemed clear, because the lab wasn’t using a validated method and condemned these products when they were safe. But it’s best to see this program working. It brings a lot more legitimacy, a lot more of a scientific foundation to what we’re doing when – you know, adverse events should not be shied away from. There should be an open discussion about them. There should be a national repository where operators in this industry can review them and look into them. The community needs to be its own FDA, in this regard, and for many other things. For the most part, states right now do not have the capacity to act like an FDA for the industry. OSHA (Occupational Safety and Health Administration) has enough issues, work safety inspections – but they will get around to the cannabis industry sooner or later. And I think we have to be prepared. We have to be our own FDA. We have to be vigilant. And we’ve seen a lot of other products come off the market due to a lack of pharmaco-vigilance, keeping track of adverse events and addressing them. And a lot of times people will say, well you know it’s adverse events. We can’t really prove that cannabis caused it, just that the products were there at the scene. And I think that that’s even something that needs to be reviewed and tracked as well.
Project CBD: You mention the FDA. I remember Dr. Tod Mikuriya referred to the FDA as the “Fully Discredited Administration.” What role, if any, should the FDA be playing in this situation? Because they’ve recently issued letters, pretty much a slap-down of CBD hemp oil companies for mislabeling or making false claims and so forth. Does the Food and Drug Administration, the federal Food and Drug Administration, have a role to play that’s valid in this context?
Marcu: They are playing a role. Right now. As you said, with these FDA letters. They’re looking at labeling of products. They are not the DEA, though. They don’t have officers that come and arrest you, per se, but they do have officers or representatives who will show up to your laboratory and manufacturing site and fine you for every little thing: lack of approved standard operating procedures, a lack of secure hardware and software, uncalibrated equipment. There are 483 Violations. So right now we’re just hearing about labeling violations, and I think that soon they might actually show up to facilities – in our lifetime definitely – and issue citations. And I think this is what they do if sometimes they’re laboratories they’ll show up with a van and fine you per day until you fix the corrective actions or go out of business.
Project CBD: There’s another kind of adverse event at play here, and that, irrespective of the quality of the product that a person might consume, there are a certain percentage of people that may have a bad experience and that perhaps shouldn’t be exposing themselves to cannabis. I think the number that’s typically bandied about by federal agencies is like 9 percent will develop cannabis abuse. I think that’s way high in terms of the number. But what about that very small percentage of people who are being exposed to something that might prove difficult to them? How does that play out in terms of the concerns that you address?
Marcu: So the research that that is based upon is very difficult, because it contains no standardized products. These are interviews with people where they derive this information. And that 9 percent figure of the number of people who develop cannabis use disorder or dependence, more than half of those, more than 50 percent of that number is generated from court-ordered drug treatment due to possession or something like that. So the number may be around 5 percent or less. We may eventually find out. But studies with cannabis medicine, such as FDA-approved Marinol, which is an oral THC dissolved in sesame oil, and Sativex, the hash oil extract that’s dissolved in ethanol – those have been studied very intensively and they both have extremely low abuse potential. They have virtually no black market value. And these are standardized preparations. If you were to measure, let’s say let’s talk about pain, and you were to measure say every patient in a study and say, if you had a 12-week study involving five patients, that would be 60 weeks, if you added up all the patient years you’d have about 6,000 patient years of data from patients using Sativex and Marinol, and other standardized preparations of cannabis to look at pain. And they have looked at adverse event profiling. They’ve looked at withdrawal. They’ve looked at abuse potential. And it’s very low with standardized preparations. When you don’t know what you’re getting, when the dose can be high, low, medium, the active constituents can vary from day-to-day, I think that that is the biggest issue right now when it comes to adverse events, is that the predictability and guidance on how to use these products.
Project CBD: Well Marinol and Sativex you mention. Marinol is actually an approved pharmaceutical one can access – it’s a pure THC product – with a doctor’s prescription. Sativex is actually in Phase 3 clinical trials now for cancer pain in the United States. It’s an approved medication in many different countries. Essentially it’s a 1:1 CBD:THC tincture. Well, the obvious benefits for standardizing these medicines are significant, that one can take something that they know what it is, and be assured that they can repeat that if it’s helping them. But I think there’s another edge to these kinds of medications that are approved on a federal level, it raises the question what will happen to the medical experiment that’s been unfolding at the grassroots in California and other states that have medical marijuana laws. What will the fate of the medical marijuana – the great laboratory experiment in democracy that’s been unfolding in medical marijuana states? In light of the move toward legalizing for adult use recreationally, if you can gaze into the crystal ball and see what do you think is going to happen in the future with respect to medical marijuana, as opposed to big pharma utilizing individual cannabinoids as medicine?
Marcu: I think the first thing that has to happen is rescheduling. And rescheduling of cannabis, even to Schedule 2, will not give the pharmaceutical companies a big incentive to get involved. I think we’re really far away from the total pharmaceuticalization of cannabis. But what perhaps rescheduling would do to cannabis is allow laboratories to access the standards they need. Allow groups like the AOAC, and other analytical standards groups, to develop certified reference standards for inter-laboratory tests across state lines. Schedule 2 DEA licenses are much easier to get then Schedule 1 licenses. I think we would only strengthen the industry. We’d only strengthen the safety of cannabis patients if cannabis was Schedule 2, and laboratories, manufacturers, were actually able to engage in more thorough quality control without being unfairly handicapped by Schedule 1 status.
Project CBD: Do you think Schedule 2 goes far enough in the end?
Marcu: It’s a good step. I think it’s far enough to make waves internationally. And I think what we will experience is not that a single country will change the law, but that it will happen at the international level. I think we’re on the precipice of having some really interesting discussions around the UNODC table or around the various United Nations groups that discuss drugs and psychoactive substances.
Project CBD I think this has been an interesting discussion. I thank you for your participation, Jahan Marcu. Good luck.
Marcu: Thank you.
© Copyright, Project CBD. May not be reprinted without permission.