Last week, South Dakota became the first state to place medical and adult-use cannabis legalization measures on the same ballot, a situation that has its challenges, as well as unique opportunities, according to Marijuana Policy Project (MPP) Deputy Director Matthew Schweich.

“It’s exciting that we’re able to make progress more quickly, and we did our research and we found that a majority of South Dakota voters support both medical marijuana and adult-use legalization,” Schweich told Cannabis Business Times. “We’ve done our homework and we’re confident that both can pass if we run an efficient campaign.”

South Dakota is currently one of three U.S. states that has no legal cannabis program on the books whatsoever.

The Secretary of State officially certified the adult-use legalization initiative, led by South Dakotans for Better Marijuana Laws, on Jan. 6, after the campaign submitted over 50,000 signatures.

The initiative, a constitutional amendment called Constitutional Amendment A, would legalize cannabis for adults 21 and older, establish a system for regulated sales and require the state legislature to enact a hemp cultivation law by 2022. The measure would also establish a 15% tax on cannabis sales and use a portion of the revenue to fund the state’s public school system.

Last month, New Approach South Dakota submitted over 30,000 signatures for a statutory initiative, called Initiated Measure 26, to enact a medical cannabis law for patients with debilitating medical conditions.

“It’s a pretty standard medical marijuana law that resembles a lot of what’s been passed in other states,” Schweich said. “It establishes a framework for allowing patients to get recommendations from their doctors and includes provisions that would address how dispensaries are regulated by the Department of Health.”

MPP has worked closely with both campaigns in the state and will continue to do so through the election. The organization helped oversee the signature drive and will contribute to the creation of a public education campaign specific to South Dakota in the months leading up to the election.

“Every state is different—different media markets, different levels of population density,” Schweich said. “We’ve got to take an approach that works for South Dakota.”

This approach will likely include connecting with voters through social media, local newspapers and radio, TV, print and digital advertising.

“We’ll be looking to pick up endorsements and do press conferences to point out the different benefits of legalization and medical marijuana,” Schweich said. “We’re just in the planning phase now, but we’ve worked on these campaigns before and we’ve been successful in getting our message out there to the public, and I expect we’ll be just as effective doing so in South Dakota.”

MPP has generally avoided allocating resources toward legislative lobbying in South Dakota, however, as it has proved challenging to get any meaningful bills passed through the legislature.

“Last year, the legislature passed a hemp law and the governor vetoed it,” Schweich said. “If they can’t get a hemp law passed, it’s very unlikely that they can get a medical marijuana or adult-use legalization law passed through that legislature, which is conservative and overwhelmingly controlled by the Republican party. So, really, to make progress in South Dakota, a ballot initiative is our only recourse.”

MPP’s message to voters is to pass both initiatives this fall, but the measures do not conflict with one another, so if one passes and the other does not, the successful initiative can still be implemented and take effect.

In addition, continued momentum toward legalization at the state level will continue to put pressure on the federal government’s prohibitionist policies, he added. “If we look ahead to federal reform, it’s important that we continue momentum as a movement, passing legalization in as many states as possible in 2020 through both ballot initiatives and legislation. It’s going to set us up for success in 2021 at the federal level. We’re hopeful that something can get passed this year at the federal level, but if that doesn’t happen, then the best way to ensure success in the next Congress is to pass as many state legalization laws as we can.”

Placing both issues in front of South Dakota voters on the same ballot does pose some challenges, however.

“We’re going to need to be thoughtful about how we communicate with voters,” Schweich said. “There’s going to be a segment of the electorate that’s 100% ready to approve medical that might have questions about adult-use legalization, and there are going to be voters who are confused about having both options on the ballot at the same time. We’re going to have to do a lot of public education to explain that the initiatives work together, but they’re not dependent on one another, explain the differences, and then make the case for both of these policies.”

Then, should one or both of the initiatives pass, the torch will be passed to the South Dakota Legislature to implement the will of the people.

“Hopefully, we will pass both initiatives with strong margins and those strong winning margins can serve as a mandate from the people, a message to the legislature that these policies should be implemented in a timely manner,” Schweich said. “It’s hard to say at this early juncture how much resistance there’s going to be.”

A constitutional initiative, like the adult-use measure, cannot be changed by the legislature unless it puts a question back on the ballot, he added, although lawmakers could ostensibly block implementation.

“We’re still evaluating how we would push back on that,” Schweich said, adding, “We’re in a very good position, establishing a constitutional amendment beyond the reach of any legislative bills.”

As a statutory measure, the medical cannabis initiative would become a state law like any other, and the legislature would have the ability to amend or even repeal the law, although Schweich does not expect much pushback since medical cannabis has overwhelming support among South Dakota voters.

“We’ll need to be engaged in 2021, assuming both initiatives pass,” he said. “We’re going to need to have a presence at the state capital in Pierre. We’re going to have to make sure that the medical law is not damaged through any bills, and we’ll have to make sure that they don’t block the implementation of adult-use legalization. It’s a question that remains to be answered."

This week, the Utah Department of Health announced the 10 companies that will ultimately be licensed to sell medical cannabis at 14 locations across the state beginning in March. Elsewhere, Illinois dispensaries grappled with supply issues in the state’s nascent adult-use market, with some retailers halting adult-use sales.

Here, we’ve rounded up the 10 headlines you need to know before this week is over.

• Federal: The House Small Business Committee advanced the Marijuana Opportunity, Reinvestment, and Expungement (MORE) Act (H.R. 3884), making it the second House committee to advance the legislation, which would end federal cannabis prohibition. The House Judiciary Committee passed the bill Nov. 20 in a vote of 24 to 10. Read more
• Utah: The Utah Department of Health announced the 10 companies that will ultimately be licensed to sell medical cannabis at 14 locations across the state beginning in March. The medical cannabis pharmacy licenses were divided among four geographic regions and will open in two phases, with eight retailers opening in March and the remaining six launching sales in July. Read more
• Illinois: At least six Chicago cannabis dispensaries halted sales to adult-use customers Jan. 6 due to supply issues, while others placed limits on adult-use sales. Illinois saw nearly $3.2 million in adult-use cannabis sales Jan. 1, the first day of sales. Read more
• Meanwhile, the Illinois Department of Agriculture has released the applications for Cannabis Infuser, Transporter and Craft Grower licenses. The department will begin accepting completed applications Feb. 14 and will award licenses by July 1. Read more
• Massachusetts: The state drew $420 million in total cannabis sales in 2019, with adult-use sales only just beginning in November 2018. As of January, Massachusetts has more than 30 licensed adult-use cannabis retailers. Read more
• South Dakota: South Dakota’s Secretary of State officially certified an adult-use legalization initiative for the 2020 ballot Jan. 6, and, in December, a separate medical cannabis ballot initiative was also certified. South Dakota will now be the first state in American history to vote on medical and adult-use cannabis legalization initiatives on the same ballot. Read more
• Florida: Rep. Shevrin Jones is backing a cannabis decriminalization bill that would reduce criminal penalties for the possession of 20 grams or less of cannabis and make first-time juvenile offenders eligible for civil citations or diversion programs. Under current law, the possession of 20 grams or less of cannabis is a first-degree misdemeanor, but many Florida cities and counties have granted law enforcement the option to issue a civil citation in these cases. Read more
• New Hampshire: The New Hampshire House passed legislation Jan. 8 that would add insomnia and opioid use disorder to the state’s list of qualifying conditions. The same day, the Senate voted against a more expansive bill that would have legalized medical cannabis for any condition that a medical provider determined could be helped by the substance. Read more
• Tennessee: Sen. Janice Bowling has reintroduced a bill this legislative session that would legalize medical cannabis in the state. Bowling introduced similar legislation last year, but the bill ultimately stalled in the legislature. Read more
• Mississippi: A medical cannabis initiative will appear on Mississippi’s 2020 ballot after Mississippians for Compassionate Care submitted more than the required number of signatures in September. The secretary of state’s office certified the signatures as Ballot Initiative 65, and the initiative was formally filed with the state legislature Jan. 7. Read more

As 2019 came to a close—a year defined, in many ways, by a sharp rise in cannabis research interest—a report from a team of Italian researchers in the journal Nature on the first-ever isolation of two newly named natural cannabinoids: Δ9-tetrahydrocannabiphorol (THCP) and cannabidiphorol (CBDP). 

The structural identification and potential potency of THCP at CB₁ and CB₂ receptors is of particular interest to pharmaceutical development and may help elucidate why some cannabis chemovars are seemingly more potent to consumers, both in their therapeutic and intoxicating effects.

Understanding THCP in Relation to THC

Since its isolation and synthesis in 1964 by a team of Israeli researchers led by Dr. Raphael Mechoulam, THC has held the spotlight. More is known about this common cannabinoid and the way it engages with the mammalian endocannabinoid system than any other cannabis compound because of the molecule’s potent concentration in the plant and its powerfully intoxicating effects via engagement with the CB₁ receptors in the brain. 

The Cannabis sativa L. plant is capable of producing nearly 150 individual cannabinoids, most of which are unique to the plant. The way in which these compounds play out together in a given phytochemical profile and the endless combinations of these cannabinoids between varietals, or “strains,” makes cannabis a “pharmacological treasure trove” unlike any other, according to Mechoulam. 

Most of these rarer cannabinoids, however, have yet to be isolated or characterized. Advances in cutting-edge chemical analysis have only recently made it possible to begin siphoning out trace quantities of these minor molecules. With the isolation of THCP, scientists have uncovered another piece of the complex pharmacological puzzle that is cannabis. One that is seemingly more powerful than THC itself.  

“The research represents a starting point towards a wider investigation to understand how much THCP and CBDP are present in the different cannabis chemovars,” study author Giuseppe Cannazza wrote in an email to Cannabis Business Times. “Indeed, we have reported the presence of these phytocannabinoids in one particular chemovar of medicinal cannabis supplied by the Italian state. We do not know whether other chemovars can produce THCP and CBDP and to what extent. Being unknown, they have never been searched, remaining among the numerous unnamed peaks in the chromatographic analyses of cannabis chemovars.”

Although scientists have not found THCP at the same profound percentages as THC within the plant, both in vitro (outside of a living organism) and in vivo (within a living organism) preliminary studies by the research team have demonstrated cannabimimetic properties—meaning the compounds are able to engage with the endocannabinoid system, specifically via CB₁ activation—that far exceed the potency of THC agonism (activation) at CB₁ and CB₂ receptors in the neutral, or decarboxylated form. Activation of cannabinoid receptors by raw, unheated THCPA was not examined in this study.

As a point of reference, investigators used the known dosing response curve and cannabinoid receptor binding affinity of the synthetic cannabinoids CP55940 and WIN 55212-2 on purified human CB₁ and CB₂ receptors in an in vitro model (cell culture). What they found was a naturally-sourced cannabinoid with a binding potential that rivaled these synthetic compounds—both known for having potent receptor engagement. Of course, the trick with CB₁ activation in the brain is that the stronger the engagement, the easier it is to end up with unwanted, potently intoxicating effects. In the case of THCP, less may be more.

The CB₁ binding potential of THCP was further evidenced via an in vivo mouse model that demonstrated behavioral and physiological effects similar to THC in a classic tetrad test but at half the dose typically needed to produce the known effects of CB₁ agonism—specifically, hypomotility (movement deficiency), analgesia, and catalepsy (a trancelike state marked by loss of voluntary motion in which the limbs remain in whatever position they are placed, according to Merriam-Webster). The strong binding potential could help explain why certain chemovars are better at giving strong therapeutic relief unexplained by THC alone. Now that the compound can be identified through phytochemical testing, it may prove particularly important for medical patients searching for potent chemovars. This discovery further highlights the need for full-spectrum testing, not just THC and CBD, for flower products within a dispensary setting. 

RELATED: 5 Ways Cannabis Businesses Can Move Toward Phytochemical Data for Better Consumer Outcomes

The potential potency of THCP is associated with how many carbon atoms it carries on its molecular tail—its chemical structure. As the authors of the Nature study point out, for molecules that readily engage with CB₁ receptors, like THC and THCP, scientific literature suggests that CB₁ affinity increases as the alkyl side chain extends. For instance, THC has a 5-carbon, or pentyl chain whereas both the synthetic reference molecule CP55940 used in this study and THCP have 7-carbon, or heptyl chain structures. 

Strengthening the previous findings on the relationship between carbon length and CB₁ activation, the investigators discovered that THCP engagement was 33-times more active at CB₁ receptors and as much as 10-times more active at CB₂ than THC. According to the authors of the study, this suggests cannabis chemovars with THCP presence may be more pharmacologically potent and likely to intensify intoxicating effects in consumers than the presence of THC alone would explain.

The researchers believe these molecules to be the first natural cannabinoids to present with more than five carbons on their molecular tails. Until now, only synthetic cannabinoids have demonstrated such long-chain potency. That is not to say, however, that there won’t be others that demonstrate equal or greater receptor affinity as scientists begin to isolated and characterize the many other natural cannabinoids the plant is capable of producing.

The isolation and characterization of THCP is only the beginning. The authors noted in the study that they will continue exploring the pharmacological activity of THCP and its relevancy to both the legal consumer market and pharmaceutical development. 

Additionally, now that the cannabinoid has been identified, analytical testing labs working within the consumer market and chemovarietal research may want to review historical data and look for the now recognizable THCP peaks. The Italian study used one source, an Italian government-provided chemovar known as FM2, generally classified as a Type II chemovar. It remains unknown just how prevalent THCP is across chemovarietals or how a cultivator might breed for THCP-rich content. By looking at historical records across an industry teeming with phytochemical data, an understanding of just how common this new cannabinoid is will happen faster.

RELATED: Type I, Type II, Type III: How Science Is Changing the Way the Industry Describes Cannabis Varieties 

The study pointed out that evaluation of cannabimimetic activity for CBDP is also ongoing but was determined to not hold the same priority as THCP because the molecule, like cannabidiol (CBD), does not show a strong affinity for CB₁ and CB₂ receptors, likely preferring peripheral pathways similarly to CBD. Rather, ongoing investigations will be comparing the effects of this compound to the known anti-inflammatory, antioxidant and anti-epileptic benefits of CBD to determine if it is more or less effective at similarly studied doses.

“Our ongoing studies aim to address the biochemical pathways responsible for the biosynthesis of these new phytocannabinoids,” Cannazza wrote. “This could allow in the future for the selection of chemovars with high content of heptyl phytocannabinoids like CBDP and THCP.”