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Pour one out for Millennials—their tipsy may soon be reaching a tipping point.

Earning less and often working more, maybe multitasking younger generations simply can’t afford it. Or perhaps it’s the ubiquity of walking, talking media brands—their peers—and their eagerness for salacious new content keeping those spontaneous (often compromising) wild nights at bay.

Whatever the reason, the numbers are sobering: Drinking among teens and early twenty-somethings has declined each generation since the Boomer era. Meanwhile, nonalcoholic beer sales have grown by 3.9% on average for the past five years, making it the fastest-growing segment in the beer industry. Young people, it seems, just aren’t getting stupid like they used to.

Thirsting for new revenue streams in a market fixated on wellness, some of the nation’s biggest beverage brands have begun to make inroads in the wild world of cannabis. Cannabis drinks pulled in $86 million in 2018, and are expected to be a $1.4 billion industry by 2023, according to beverage industry analyst Zenith Global. Last year, Anheuser-Busch InBev, Molson Coors, and Corona-maker Constellation Brands each announced partnerships with Canadian cannabis companies. And Diageo, parent of spirits such as Tanqueray and Johnnie Walker and recent majority holder of nonalcoholic spirit label Seedlip, is poised to make a similar move in the U.S.

Whether this is a prescient pivot or flimsy bandwagon betting is yet to be seen, but it does provide a unique opportunity for the cannabis market: a new way to consume for a broader, more mainstream customer base. Unlike smoking—obtrusive and stinky!—sipping has the potential to feel less like an illicit drug and more like the socially acceptable ones, like coffee and alcohol.

But there are some potential hiccups on the road to mainstream use, starting with the price. A four-pack of THC-infused bottled (nonalcoholic) margaritas runs around $25; so too could one 12 oz. bottle of gnarly lemonade. Just a glimpse could scare away consumers before they get to the details, like potency, which informs the price but is a wildcard all its own.

The potential pitfall with potency is that it’s all over the map. Early on, when the medicinal cannabis market was more niche, infused drinks reliably skewed strong. Now, a beer-sized infused drink might contain a modest 2.5 mg of THC…or a walloping 100 mg and beyond. While products with mind-erasing potencies are often divvied up into reasonable servings in fine print on the back label, one can easily see how they could induce a real nightmare for uneducated consumers (i.e., first-time buyers). If the goal of many of these brands is to replace social alcohol drinking, an uninvited psychosis isn’t the way there.

Perhaps the most basic issue regarding premades so far has been, does it actually taste good? With terms ranging from soapy and barnyard to dirty socks and urine, the Wall Street Journal surveyed many startups’ struggles to tamp down on the trifling taste of cannabis drinks, whether by soaking and straining, nanoemulsion, or selectively enhancing more palatable flavor profiles in the plant while attempting to minimize others, all to varied success.

As is often the case, some of the complications come from the oily, hydrophobic properties of cannabis compounds. This makes THC and CBD drinks prone to unsightly separation, with all of the greasy, grassy cannabis taste floating to the top, ready to kiss your lips. (Then again, lots of people routinely find a way to look past the less-than-exquisite taste of alcohol, so maybe there is hope?)

A newer wave of infused beverages, however, comes in the form of powder and liquid mixes, many of which use technology to extract the active ingredients while filtering out the unsavory elements, rather than fussing with flavors to disguise them.

“The problem with most mixes is that there’s usually some clumping or sediment, or like premades, the mix doesn’t stay suspended,” says Michael Frid, chief scientific officer at Manna Molecular Science. Another common problem, he says, is all the sugar.

“We always keep in mind that some of our customers may be diabetic or have diets that don’t involve carbohydrates or just people who watch what they eat,” Frid says. “So we’re very cognizant of not adding anything that will meaningfully impact anybody’s dietary intake.”

By extracting only the desired plant compounds and tweaking their chemistry, he and his team are in the lab developing drink mixes to get around these pitfalls, starting with the flavor: flavorless.

“If someone is drinking coffee, then presumably that person likes the taste of coffee,” he says. “We don’t want to interfere with what people already like.”
Employing the same nanoencapsulated liposomal technology used in Manna’s other products, the mixes are expected to similarly boost absorption rates and disperse evenly throughout the drink with a modest shake, Frid says.

Further testing, including pharmacokinetic studies, which are commonly done on new pharmaceuticals to examine what the body does to a drug, is planned sometime near the products’ launch, which is expected in early 2020.

More than 40 deaths and 2,000 sickened—each time you check, the numbers keep ticking up.

While much is still unknown about the vaping crisis, the saga has increasingly underscored the perils—and proliferation—of the cannabis black market. Some 78% of reported cases are tied to illicit THC products, according to the CDC, though there have been nicotine-only cases as well.

Known variously as VAPI (vaping-associated pulmonary injury) and, more recently, Evali (e-cigarette, or vaping, product use associated lung injury), the condition, which officials began noticing in the spring, includes symptoms such as coughing, chest pain, shortness of breath, abdominal pain, nausea, vomiting, and diarrhea.

The response by some states has been swift. Michigan, New York, Washington and Rhode Island quickly announced stopgap bans on flavored vaping products, while Massachusetts has gone whole hog prohibiting any vaping anything. New Mexico now requires warning labels on all vaping cartridge packaging.

Before a battery of TV cameras, Donald Trump, announcing plans to ban flavored e-cigarettes to curb use among minors, declared his assessment of the crisis in trademark style: “It’s really not wonderful—I think that’s one thing we can say definitely.”

So how is the legal cannabis industry, which is already on shaky regulatory ground, responding to this not-wonderful turn of events? The answer, it turns out, is not by going on the defensive, but by amplifying the message its had all along: legalize and regulate us.

“People on the street are not trying to make their own Tylenol, you know?” says Michael Kahn, president of MCR Labs, a Massachusetts firm that tests thousands of cannabis products each month for potency and safety. “And if they did, somebody might die, but they don’t because it’s a really well regulated product.”

In mid-September, a high point in the epidemic’s media attention, the National Cannabis Industry Association similarly issued a call to Congress:

“These unfortunate illnesses and deaths are yet another terrible, and largely avoidable, consequences of failed prohibition policies. Current federal laws interfere with research, prevent federal regulatory agencies from establishing safety guidelines, discourage states from regulating cannabis, and make it more difficult for state-legal cannabis businesses to displace the illicit market. These policies are directly bolstering the markets for untested and potentially dangerous illicit products,” NCIA Executive Director Aaron Smith said in a statement. “It is now the responsibility of Congress to end prohibition and regulate cannabis without delay.”

Publishing their findings in the New England Journal of Medicine, researchers at the Mayo Clinic have since found the injuries to resemble chemical burns akin to mustard gas rather than an infection, as was initially suspected. Still, much of the inquiry is focused on vitamin E acetate, a popular thickening diluent used to cheaply cut illicit THC cartridges for more profit. In early October, a federal investigation concluded that nearly half of the vaping injuries studied contained it.

When heated by a vaporizer, vitamin E acetate transforms from a liquid oil to a vapor, which is then inhaled by the user. Once in the lungs, it reverts to a liquid state, wherein could lie the harmful effects.

As a result, many cannabis labs are adding vitamin E acetate to their list of things they screen for.

“If it’s not Vitamin E acetate, somebody’s going to cut something with something to make more money,” Kahn says. “Generally the regulated market doesn’t do that; it’s too risky.”

About a week after reports named vitamin E acetate as a possible culprit, he and his team began offering two free tests for it to anybody who was concerned about the products they had.
Since then, the extra scrutiny on bootleg cartridges (aka carts) has both added to the case for federal legalization and raised questions about legitimate-seeming manufacturers.

A recent Leafly investigation tracing a common route of illicit carts—from raw materials in Shenzhen, China, to dirty-cash suppliers in LA’s Toy District to crackpot “labs” in Midwestern rental homes—shines a light on how frighteningly easy it is for anyone with an internet connection to make illicit THC carts, fake Juul pods, and CBD whatever.

That includes Dank Vapes and Chronic Carts—two black market “brands” cited in the epidemic that aren’t tied to companies but are merely packaging that can be bought by the boxload and stuffed with anything by anyone willing to part with a few pennies.

On the other hand, the incident involving Kushy Punch, a very real, licensed California cannabis manufacturer, has been an untimely black eye for the industry. In October, state officials raided a warehouse near Los Angeles and seized millions of dollars’ worth of illegal, untested Kushy Punch–branded vapes and edibles allegedly made by the company, raising the specter of legal, above-table brands’ capacity for double-dealing. Elsewhere in the state, legal brands are spending millions on packaging redesigns to stay one step ahead of counterfeit copycats.

“You have a whole bunch of people who came into the industry who don’t have experience with chemistry and formulating drugs correctly, and they’re just making really bad assumptions that they can add ingredients that they really shouldn’t be adding,” Kahn says. “It’s incorrect, it’s unfortunate, and it’s happening because it’s just not a well regulated industry.”

Kim was freaking out. Her second surrogate child was on the way, and she craved some serious chill. Thus, the idea for a CBD-themed baby shower was born.

“Let’s zen out for a Saturday,” she said, clad in breezy taupe and surrounded by yoga mats, sound bowls, and a gong. Kris, Kourtney and Paris looked on. “So everyone have a puff and put on some oil.”

Suffice it to say, CBD—used by roughly 1 in 7 Americans—has found plenty of believers. Touted as a treatment for a wide range of ailments, from anxiety and insomnia to chronic pain and inflammation, it’s predicted to rake in some $5 billion in sales by year’s end—inspiring a slew of new products that grows weirder by the day.

“There’s always gonna be, like, Carls Jr. putting CBD in burgers, and people are gonna throw it in toothpaste and mouthwash,” says Manna Molecular CEO Nial DeMena. “It’s just gonna be, ‘put it in first, ask questions later,’ and I think that attitude is the exact wrong tact to take.”

CBD, or cannabidiol, is one of more than 100 compounds found in the cannabis plant. Unlike its cousin, tetrahydrocannabinol (THC), it’s nonpyschoactive, meaning there’s no “high” involved. Still, its piecemeal state-by-state legal status has made it a magnet for shady players, shoddy products and dubious claims.

“I just don’t wanna see CBD go the snake oil route when there’s so much research yet to be done,” says Adam Terry, a biochemical engineer and senior manager of product development at Integrative Health Products, which develops and distributes THC and CBD products nationally.

Next time you’re in the market for CBD anything, keep these tips in mind to ensure you’re getting a quality product that’s safe.

Things to know before buying CBD:

Verifying the product’s potency, isn’t just a good idea for your wallet, DeMena says. Because of CBD’s low bioavailability by default—edibles hover between 6% and 20%—users may be inclined to dose themselves many times over to get their desired effect, which is not only expensive, but floods the body with various outside agents could have long-term effects that are too early to know about.

“People think, ‘Oh, Vitamin D is good for you, so let me take 50,000mg of Vitamin D every day.’ Well, that can cause liver damage, kidney damage, and you’re pissing out 99% of that,” DeMena says, “so it is a big deal in terms of bioaccumulation and overall health.”

Consistent, extreme dosages over a period of time can also have a diminishing effect, as the body adapts by reducing the number of receptors for the drug in response. The solution, DeMena says, is to aim for products with high efficacy in the first place.

Quality aside, results will also depend on the delivery route, each of which varies in absorption rate and duration, and may act locally or throughout the body.

Connoisseurs might enjoy exploring the finer points, such as whether the CBD extract is pure (isolate) or contains other compounds found in the plant (full- or broad-spectrum), which some find to complement or enhance the CBD—what’s known as the “entourage effect.” Just how much these and other aspects play a role is, for now, largely a matter of perception.

“Placebo effect can have its own benefits,” Terry says. “As long as someone thinks it’s working and feels it’s working, then, for them, it’s working.” Believe it or not, it’s a powerful thing.

[Editor’s Note: Welcome to Lab Notes, Manna Molecular’s new blog exploring the ever-changing world of cannabis. Here, you’ll find exclusive insights from key thinkers and scientists in the space, industry news, and ruminations on the future in bloom, as well as the latest updates, innovations, and products from right here in the Manna-sphere—tools, we believe, to lead your best self-cared-for life.]

When the little blue pill hit the market in 1998, it changed the lives of millions of men struggling with erectile dysfunction. Dr. Harin Padma-Nathan remembers it well. As a longtime professor of urology at USC and lead principal investigator for ViagraⓇ, he oversaw the clinical trials and published it in the New England Journal of Medicine, all of which paved the way for the drug’s FDA approval, whose overnight eruption across news media and late-night routines began deflating the stigma of a condition that today hardly elicits a blush.

All the while, the void in Venus remained. “The unmet societal need was for women,” he says. “And women are far more complex than men, thus the drug therapies out there didn’t seem to be very effective.” In other words, challenge accepted. Seeing some strides—and roadblocks—in the chemistry of cannabis products in this area, he got to work developing his own.

Now, as Manna’s chief medical officer, Padma-Nathan is on the cusp of a breakthrough that could prove as girthy a discovery as the little blue pill was for men: Vella, a new line of CBD and THC sexual lubricants shown to amplify arousal and orgasms in women.

Here, he phones in from his office in LA to chat about what he’s working on, his life away from the microscope and the outer limits of scientific inquiry.

Your work on ViagraⓇ and CialisⓇ has been covered in The New York Times, LA Times, 20/20 and Nova. What has been your most memorable moment to date? I think one of the most interesting things was the first time I realized that ViagraⓇ was really a game changer. When these men took ViagraⓇ they were having normal erections again and that was mind-blowing. One of those eureka moments was when I had a patient who’d had a radical prostatectomy coming back and telling me this stuff is really working.

How did the idea for Vella come about? I noticed that there was some activity in the cannabis space looking at delivering THC and CBD by topical applications and the problem is that they’re typically in coconut oil, which ruptures condoms almost instantly. But I wondered what CBD did, and the problem was in the low absorption that one has with oil compounds, plus they don’t dissolve in aqueous solutions. But I knew, nanotechnologically, liposomes were a great way to make a fatty compound like CBD live in a stable, enclosed, or encapsulated, water-soluble environment, which would also make it condom-compatible. So I began working with a number of approaches to develop the kinds of liposomes to do this.

What do nanoencapsulated liposomes do exactly? Nanoencapsulation increases the bioavailability, and the liposomes are made with the same lining you find on cell walls, so what happens is these liposomes are attached to the cell wall, in this case at the labia, clitoris, and the distal vagina, and they’re actively absorbed, so the drug goes into the cell and is immediately passed to the cell next to it, which is the smooth muscle cell, and that’s where the drug works. The common problem with liposomes in a lot of treatments is they’re very tiny and usually unstable, so they don’t last a long time, and most importantly, they don’t carry a large payload. So, I developed large, multilamellar (multicompartmental, if you will) liposomes that were 1,000 times bigger to carry a large payload.

What does that mean for what women can expect to feel when using Vella? Women who have some degree of desire should see an increase in lubrication, clitoral engorgement and increased orgasm, increased time spent in orgasm and increased frequency of orgasm. But unlike other stuff out there, we’ve done studies to show this. We’ve studied isolated rodent vaginal tissue and demonstrated, for the first time, a dose-response to CBD with increasing smooth muscle relaxation to increasing doses of CBD. This is an unexpected, novel pharmacological response necessary for female sexual arousal. We’ve used vaginal plethysmography to show changes in blood flow to the vagina, in response to Vella, which causes arousal. We’ve also tested to make sure it is condom compatible. And lastly, we’ve used an at-home questionnaire to explore real-world experience with Vella, which is how the FDA does it too. At the end of the day, it’s all about their arousal, their orgasm, their satisfaction. While we can show a blood flow increase and smooth muscle relaxation, none of that means anything unless patients themselves experience a positive effect in those areas.

When you’re not knee-deep in work, what do you like to do? My great passion is skiing. You know that every Sri Lankan skis right?

I did not know that! (Laughs) Well, I might be the only one. Like the Jamaican bobsled team, I’m a Sri Lankan ski team member.

If you weren’t doing what you do now, what could you see yourself doing? Today we drive our kids to things that make money like finance and maybe entertainment or whatever, which is big in LA, but I couldn’t ever see myself doing that. I love numbers and math. And I like people and I like biology. The other thing I really like is astrophysics.

Oh really? What about it interests you? Yeah. I’ve become interested in quantum mechanics just because of the quirkiness of it, but what I really like is astrophysics—the science of black holes and neutron stars and that stuff. The bizarreness of quantum mechanics becomes the bizarreness of how science changes when you start to approach a black hole. And at the end of the day, that’s all really about the function of god to me. It is just the beginning, the end of the universe, multiverse, whatever, and to me that sort of borders on the meaning of life.

That’s fascinating. When we encounter these phenomena that threaten to break our understanding of science and physics, they could reorient what our beliefs are. Yeah. God is physics, physics isn’t god. It’s a concept that we understand so little of and it’s so confusing. Newtonian physics applies to some stuff on the earth, and relativity applies to a lot of stuff, but when you try to bridge quantum mechanics and relativity, quantum mechanics is like a bizarre trip. It’s so fascinating and unusual to try to blend the two with string theory…but at the end of the day, it’s all about trying to understand the bigger picture. We’re so consumed by our own little world, and it’s just a small part of everything out there.

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