WSLCB - Work Group - Cannabinoid Science - Public Meeting
(February 1, 2023) - Summary

[ Event Details ]

Without guidance in defining ‘cannabinoid,’ consensus on its meaning or the scope of work for the group proved difficult, but agreement to prioritize regulatory issues emerged.

Here are some observations from the Wednesday February 1st Washington State Liquor and Cannabis Board Cannabinoid Science Work Group (WSLCB - Work Group - Cannabinoid Science) Public Meeting.

My top 4 takeaways:

  • Several members weighed in on the best way to define a cannabinoid, trying to typify an “abstract” concept inclusive of some cannabis compounds and metabolites, in addition to receptors in the human endocannabinoid system.
    • Hoffman offered some example definitions of ‘cannabinoid’ along with citations (audio - 4m, video):
      • General:
        • …any of various naturally-occurring, biologically active, chemical constituents (such as cannabidiol or cannabinol) of hemp or cannabis including some (such as THC [tetrahydrocannabinol]) that possess psychoactive properties (Cannabinoid Definition & Meaning - Merriam-Webster).
        • …several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds (Gupta, et al., 2021; Medline Plus, 2017). 
      • Botanical:
      • Chemical: …inactive close analogs of THC but exclude a growing number of substances structurally remote from THC that share its actions (Weissman, 1981). 
      • Pharmaceutical: …a chemical compound in cannabis or marijuana (Medical Definition of Cannabinoid (rxlist.com))
    • Chris Beecher, ​​IROA Technologies Founder and Chief Scientific Officer, thought, “as a chemist…I understand the chemical definition. But as a biologist, you need the fact that it…binds to a receptor…that is going to have that effect, or people are going to be able to” circumvent a definition (audio - 1m, video).
    • David Gang, Washington State University Center for Cannabis Policy, Research, and Outreach (WSU CCPRO) Director and WSU Institute of Biological Chemistry Professor, felt they needed to understand “what the purpose for the definition is going to be.” He urged them to deal with “what specific purposes we need the definitions for, and then have a definition that fits each one of those” (audio - 1m, video).
    • Infinity Laboratories Senior Scientist Holly Moody was familiar with the laws in Arizona, stating officials there “defined the metabolite…delta-9-THC as only 11 hydroxy and that was for the purposes of [impaired driving] for people who had  medical card[s].” He asked “do we count metabolites as cannabinoids? Because they're not necessarily made by the plant. They're made by the human body. So that's a whole other issue” (audio - 1m, video).
    • Schauer said, “I appreciate…the reasons to make it a broad definition, but I think it can get so broad that suddenly there's not going to be clarity about are we are we talking about,” be it the cannabis plant, synthetic compounds, or anything “that may incidentally bind to the endocannabinoid…receptors.” She observed that the topic “still feels very abstract to me” (audio - 1m, video).
    • Jessica Tonani, Verda Bio CEO, advised that having seen previous efforts to define cannabinoids in relation to what affected cannabinoid receptor type 1 be “a little bit loose…there's a number of compounds that we probably don't need to regulate or think of like terpenes that bind those receptors.” On the other hand, there were also “these compounds people are producing and calling cannabinoids that are probably outside of the scope of what we as a group want to look at,” she said. She included that “I'm not sure it's great” to have “structure and function being required within a definition.” Unsure how others felt, she wondered whether “the word ‘cannabinoid’ in general [was] something, maybe the space has outgrown,” though she recognized “that we need to, probably, live within that bounds still” (audio - 1m, video).
  • Turning to the scope of work, staff began with an interest scoring table that was used to frame a discussion around the group’s purpose and duration, along with how members wanted to prioritize their endeavors.
    • Hoffman provided three potential categories identified by staff based on the research interests specified by work group members during their previous meeting (audio - 1m, video):
      • Effect of Cannabinoids on the Body
      • Cannabinoids and DUI
      • Cannabinoids and Regulation
      • Hoffman mentioned that it was an open question “which of these concerns are long-term, which are short-term.” She then made clear that although “there's crossover between all of these…when we started analyzing all of the different research interests these three buckets became very obvious.”
    • Schauer wanted to know what area would be most impactful to agency leaders for work group members to look into. “From a policy and rules perspective the regulatory pieces are the most important to us at the agency,” Hoffman replied, “and they may be for others within the state of Washington, as well.” She expected overlap, particularly when regulatory questions had “connections to the effect of cannabinoids on the body.” Task force members responded in general agreement to start with regulatory concerns (audio - 2m, video):
    • Hoffman read from the scoring table topics for cannabinoids and regulation, which included (audio - 1m, video):
      • Regulatory effects of cannabinoids
      • Regulating components of the plant in rapidly changing environment to protect public health/safe while supporting industry
      • Regulation of diverse compounds with different risks/rewards
      • Creating a simple way or scale to express psychologically active/non-psychologically active cannabinoids in end product labeling. 
    • Returning to how they should be defining cannabinoids, Moody hoped to clarify “what regulations do we need to work within.” He brought up regulations based on paying “by the unit of…cannabinoid in the substance for tax collection, or it can be like a dosage of metabolites in someone's bodily fluids.” Given that WSLCB was “working in a regulatory frame, that probably sounds to me like the best way to look at it” (audio - 3m, video).
      • Tonani called for establishing “what we want to regulate, and what we think is maybe outside of the scope of regulation,” mentioning “there's a lot of chemistry that's going on that at some point…is no longer cannabinoids, and we may have to say ‘these are what we're interested in and these other things people are calling cannabinoids are maybe outside of the scope of what we're looking at.’”
      • Amber Wise, Medicine Creek Analytics Science Director, suggested they review applicable statutes and rules, along with “some potential legislation that are active, that are trying to redefine some of this.”
      • WSLCB Chemist Nicholas Poolman reported having reviewed the definition for cannabinoids in some other states with “legal markets…most of them essentially defined phytocannabinoid; they essentially said ‘cannabinoid is something that comes from the cannabis plant.’ I think we've talked about” how “that's not the only cannabinoid that there can be,” and that centering a definition around phytocannabinoids might not be “where we want to be.”
    • Considering phytocannabinoids, Hoffman was aware it had been used to define cannabinoids in New York, and asked about its applicability. Moody argued, “you can't define a term with…its own definition (audio - 4m, video).
      • Tonani believed one of the biggest challenges with reducing youth access was from compounds which “are produced outside of the plant,” naming delta-8-THC as a substance “people are synthesizing.”
      • Taylor Carter, University of South Carolina School of Medicine Columbia Postdoctoral Fellow and researcher, said he looked at THC from an “immunological standpoint” and hand worked with endocannabinoids and compounds could behave “differently in the immune system compared to psychoactive…THC, the way that it enters into the active side can either be an agonist or antagonist in the periphery, so sometimes CB1 antagonist mirror what I'm seeing with THC.” He wanted the group to “keep in mind with natural, non-natural…the way that it behaves in the immune system, sometimes is slightly different than how it behaves, and the impact that can have, developmentally.” Carter encouraged regulators to follow cannabinoids from the “up-and-coming immunological standpoint” because the “impact that it can have can be rather large.”
      • WSU Department of Integrated Physiology and Neuroscience Assistant Professor and WSU CCPRO researcher Ryan McLaughlin commented “when we're studying novel compounds” from a behavioral standpoint, they did a tetrad test where “we test for four things” in a substance: “Its ability to reduce locomotor activity, to produce hypothermia, to produce catalepsy,” and also “analgesia.” When cannabinoids had that impact on people “​​usually that's through binding to CB1 or CB2 receptors,” he told the group. McLaughlin said this approach had limits, noting cannabidiol (CBD) “really doesn't act through CB1 or CB2 receptors, but…I don't think anyone would take the side that cannabidiol is not a cannabinoid.” He admitted he found it “really tough to answer, actually. “
    • Board Member Jim Vollendroff voiced an interest in "long-term things,” like the possibility of “starting within the LCB our own research group. And so, if we do some long-term research, I would love for this group to help us be thinking about what are things we should be focusing on.” Schauer appreciated that perspective, but still wanted a better understanding of “the charge of the group,” speculating (audio - 3m, video):
      • “Is this gonna be the place where the discussion about how to regulate hemp derived products happens?”
      • “Is this a place where we're just sort of making a bucket list of these regulatory areas with science underpinning that need to be discussed, and maybe we…chunk those into discussions?
      • “Is this the place where we're talking about what long-term research could LCB support that would be valuable to influence policy, consumer safety, markets, et cetera?”
      • According to Hoffman, the idea of a scientific advisory body came about after Senator Karen Keiser put it in a bill in 2022, but it was "a little bit ambiguous" and what such an advisory body would do needed to be pared down. This was why there had been an initial call for research interests so during the second group meeting they could narrow “those interests down even further and it sounds like we are going to go on the cannabinoids and regulation side.”
    • Beecher realized that members were willing to help, but believed “the question…is what does the board need?” He felt they’d convened a group possessing “quite formidable” expertise, “but the board really has to say…we need help understanding how to deal with” specific topics or policies (audio - 4m, video).
      • Stressing the “pretty general” nature of the work group, Hoffman referred to the charter as defining the group’s purpose to “collaboratively and transparently explore and build foundational understanding of the plant” as defined in state statute. Moreover, she said their “responsibilities may include reviewing and discussing available research data and regulations related to cannabinoids, and providing recommendations on potential guidelines for safe methods of manufacturing, extracting, and synthesizing cannabinoids.”
      • Upon hearing her explanation, Beecher felt “that's actually very clear. I'm sorry…I missed it the first time around.”
    • Next, members delved into how to prioritize the different timeframes and questions posed in the cannabinoid and regulatory subject areas. Hoffman started off asking what issues should be looked at in the short-term versus in the long-term (audio - 18m, video).
      • Cannabinoid products derived from hemp was the most pressing short-term topic in Schauer’s mind. Acknowledging there had been input from the Washington State Hemp in Food Task Force and legislation on the matter, she nonetheless perceived that “discussions are gonna be valuable for our state…and also frankly nationally…this is the year when the Farm Bill reauthorization is gonna happen and…to some degree that could override whatever states have done anyway.” Her sense was that “we won't all agree on definitions, and…that's [not] necessarily productive to continue to highlight where there are differences.”
      • Tonani agreed an overview or summary on the existing laws as well as any changes which may have been proposed by the task force or lawmakers could help in “maybe trying to understand…what we believe should be included, and not included, in a definition to start with.”
      • Poolman felt the “quotations you have in the charter is almost the definition that we can use for cannabinoids…if we're saying…the cannabinoids created by cannabis and their synthetic equivalents, then we kind of know which ones we want to talk about, the quote-unquote cannabinoids, or this group.”
      • McLaughlin considered the conversation the agency wanted to have to be “about regulation of diverse compounds” to be complicated by a lack of “any research to base” those regulatory changes on. While officials had been confident “delta-9-THC [was] the primary psychoactive constituent. It's the one with the abuse liability. It's the one that is the problem,” he noted that only CBD had “been shown to be relatively innocuous…but it feels difficult from my perspective to offer regulatory advice on compounds that don't have any evidence to support them being regulated.” Concurring, Schauer commented "we're in a reality where policy is already happening" and that they would have to rely on “extrapolations” based on “research on a lot of the minor cannabinoids” which had been studied “with the levels at which they exist in the plant.” She continued, finding that “we need to do our best to bring science to policy…we need to get around the table and use the science. We have to have some thoughtful discussion even if it's woefully inadequate science at best.”
      • “These minor cannabinoids are now being either converted or being extracted and isolated and added at higher concentrations in legal products,” Wise remarked, but she didn’t see limited research as an adequate reason not to regulate consumables people were already buying. McLaughlin had no objection, although with “additives to e-cigarettes and all of these sorts of things that have been far more insidious and shown direct health effects that need clear legislation and regulatory action immediately,” he didn’t know how to push for regulations on a “compound like CBC [cannabichromene] for instance, when there's literally no research that's been done on it, just because it comes from a cannabis plant…several terpenes are also naturally produced by cannabis plant, but we're not talking about regulating terpenes right now, are we?” Wise didn’t consider them pushing for any regulatory scheme, “I think we're having a conversation about what we know about these in the plant and in products that are available.”
      • Tracy Klein, WSU Vancouver Associate Professor and WSU CCPRO Assistant Director, brought up that regulating "doesn't necessarily mean prohibiting something," and might as easily mean "providing for adequate testing and labeling that actually lets the public know what they're getting but they still can get it." Hoffman used this as an opportunity to “define what regulation means” in both the short, and long-term.
      • “Part of the charter is the manufacturing of these,” Tonani noted, saying even for “benign” cannabinoids such as delta-8-THC, if made synthetically there might be byproducts or residual materials, “so we have to look at the compound, and then also how people are making that compound.” Gang seconded this sentiment, indicating that “how the compound is generated is something that really is critical in this understanding…when you chemically transform something…there's lots of things that can happen, you get side reactions; none of that's being looked at” by FDA officials who had deferred on setting a standard for CBD products. “So if any state like ours [was] going to allow these products to be available to people, it's kind of incumbent upon the state to determine…what is safe and what types of processes that occur, or are allowable with the generation of these products,” argued Gang. He further felt “we really don't know the answers to a lot of these questions that people have. When you talk to legislators, they want a short…three sentence answer to things so they can quote ‘understand it’...but there is no such thing as that kind of an answer,” so it was “really difficult in being able to talk to people that are making these policy decisions based on no information.” Schauer also wanted manufacturing processes considered from a consumer safety point of view, but in the absence of research, “What does that mean? Is it taking a precautionary approach? Is it having some thresholds?”
      • Moody said when Washington State “used to test people for cannabis use when it was completely illegal everywhere, what they said was chronic use was two to three times a week.” However he knew “people who are medical cannabis users that use it two to three times an hour. So, how do we determine when people such as that are impaired beyond…whatever is legit to drive a car for instance or…operate machinery. We don't have anything defined that way nowadays.”
      • Klein wanted to gain a better sense of “who the audience is…typically regulations are there to protect the public, and so we can assume that our audience is perhaps the public that doesn't have much background or education at all, but we also have to at least provide some support for people who do.”
      • Richard Sams, KCA Laboratories Scientific Director, added a comment via chat: "Not only are minor cannabinoids being synthesized and sold to consumers, but the synthetic side products that are present in these synthetic substances are new chemical entities that have not been previously reported. We are testing consumer products that contain new chemical entities in higher abundance than the target substance that is named on the product label. We are also seeing mixtures of [THC] homologs and their acetates."
      • Hoffman moved the discussion to some “long-term issues that we want to think about.”
        • Tonani mentioned securing more research funding. Schauer was eager to “hear what the board's thoughts are on that and what, if any, areas the board…is interested” in lobbying for more study.
        • Wise wanted more consideration of “harmonizing regulations across states,” and Schauer agreed “harmonizing the lab testing the product safety standards, figuring out what that looks like, I think, is of critical importance.” Moody saw the “disparity between all the different products, even amongst the products in a single state” as “just confusing and there's no uniformity.” Schauer added this came up with CANNRA members, but with packaging and labeling frequently designed by state legislatures, “harmonizing” would be a large obstacle: “you'd effectively have to get every state legislature on board to make changes there.”
        • On January 11th, WSLCB staff talked about issues raised during a December 2022 CANNRA conference.

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