Wednesday, 21 November 2018

The super-popular cannabis compound, explained.

The coffee shop in my Brooklyn neighborhood has a chalkboard outside. It usually reads something like, “Our soup of the day is coffee.” Recently, though, it’s had a marijuana leaf on it, drawn in green chalk.

Recreational marijuana is not legal in New York state. What the coffee shop is selling is CBD-infused lattes; CBD, which stands for cannabidiol, is a non-psychoactive compound found in the cannabis plant. Out of curiosity, I bought one. It cost $9 and tasted like a latte with that hint of marijuana herbiness you get from a weed cookie. Google research informed me I would not get high but would be calmer, less anxious, maybe a little sleepy. I have no idea if I felt anything at all. Mostly, I felt like I just spent $9 on coffee.

My coffee shop is not unusual in selling CBD products. In New York, and all over the country, you can find CBD oil in convenience stores, CBD vapes in smoke shops, and CBD tinctures and topical creams in beauty stores. You can buy CBD dog treats in Chicago, a $700 CBD couples massage in Philadelphia, and CBD chocolate chip cookies in Miami. CBD is also being combined with ice cream, savory snacks, and cocktails. Even Coca-Cola is reportedly working on a CBD-infused beverage.

CBD exists at the confluence of three huge consumer trends. The first is the herbal supplement boom, a $49 billion-a-year industry that has seen rapid expansion since about 2010. The second is the rise of the anxiety economy, in which all sorts of products, from fidget spinners to weighted blankets, are pitched as reducers of the mild panic of everyday life. And the third is the near-overnight creation of a legitimate cannabis industry, thanks to the spread of marijuana legalization.

The exact legality of CBD is tricky. The Drug Enforcement Administration maintains that CBD is federally illegal but will not bother going after anyone for possessing or using it. Many argue that a provision in the 2014 farm bill allowing industrial hemp pilot programs, mostly aimed at the textile industry, actually makes non-THC use of cannabis legal; the much-delayed 2018 farm bill would make CBD and industrial hemp legal nationwide if passed as it stands.

It doesn’t really matter: The result is that anybody, in any state, can seemingly buy CBD online or in a local brick-and-mortar shop without fear of arrest. That availability made CBD at least a $350 million industry last year; some estimates suggest that by 2020, annual sales of CBD products could top $1 billion — and some say it already has.

The fast-casual chain By Chloe recently introduced a line of CBD baked goods called Feelz by Chloe.
Leslie Kirchhoff/By Chloe

Dez, a Middle Eastern restaurant in New York City, offers soft-serve ice cream topped with CBD-infused olive oil.
Dez

Despite this, CBD is something nobody knows much about, and certainly nobody is monitoring it properly. CBD is widely marketed as a supplement, despite the Food and Drug Administration saying it does not qualify as such (this is because it is an active ingredient in drugs which are either approved or under investigation to be approved). CBD goes largely unregulated by the agency; on the FDA’s FAQ page, a vague answer maintains there are “many factors in deciding whether or not to initiate an enforcement action.” The Department of Agriculture handles research grants and pilot programs for hemp, but that’s where its involvement ends.

Research and regulation of cannabis in general is decades behind other crops and drugs because of its long prohibition. We’re in the early stages of a chaos period that will last a decade at minimum — a substance has to be legal in order for scientists to figure out how it works and for the government to figure out how to ensure it’s safe. Clinical trials take years to complete and will have to build on each other to create a competent understanding. Coupled with modern technology’s ability to disseminate truths, half-truths, and complete lies, this means we’re in a phase ripe for scams, intentional and not.

Both researchers who work with CBD and professionals who actually grow the raw material — those who best understand this compound and how it interacts with the human body, the people with the most investment in and knowledge about it — are skeptical to the point of scornful about consumer CBD products.

Esther Blessing is a professor and researcher at NYU who performs and reviews clinical trials on CBD’s effectiveness in treating post-traumatic stress, anxiety, substance addiction, and other conditions. Speaking about widely available and unregulated CBD oils, she says, “This is the main scam, snake oil thing going on out there now.”

CBD is about as poorly regulated and understood as a product this popular can possibly be. It’s not accurate to say that CBD, as a whole, is bullshit. From a medical perspective, it’s promising; recreationally, it’s interesting. But that doesn’t mean the stuff you’re buying works.

Anyone who tells you anything definitive about what CBD — or THC, for that matter — does to your body is lying. Nobody knows. The legitimate research out there is extremely limited, and the slow drip of legalization — medical use, then personal use, federally illegal but permitted by certain states and cities — has made it incredibly hard for researchers to do their jobs.

Here’s what we do know: The cannabis plant contains a wide variety of chemical compounds, many of which fall under the broad category of cannabinoids. There are more than 100 — exactly how many, we’re not sure. The best-known and certainly most profitable are tetrahydrocannabinol (THC) and cannabidiol (CBD). Both of these compounds stimulate the same receptor in the brain, called CB1, but have differing effects on the brain. Researchers aren’t totally sure why.

It may have something to do with the fact that THC stimulates that CB1 receptor a lot, in turn triggering the psychoactive effects of marijuana like disturbed sensory perception, impaired motor skills, and anxiety. Conversely, CBD stimulates CB1 very lightly, causing some effects that seem downright opposed to those of THC including relief from anxiety, stress, and hyper-excitability.

Unlike with THC, CBD’s effects aren’t limited to that single receptor. These effects are not precisely known, though CBD certainly has some impact on CB1’s sister receptor (CB2) as well as a receptor called 5-HT1A. When the 5-HT1A receptor comes into contact with a material that agonizes it, the effects can include reduced anxiety and increased calmness.

The limited studies out there indicate that CBD has, in its various interactions with the brain and immune system, some anti-inflammatory and anti-anxiety effects. It can balance out the effects of THC by reducing the anxiety THC sometimes brings, and many in the industry are big on “broad spectrum” or “full spectrum” configurations, which use many cannabinoids at once.

There are a few ways to get CBD into your body. The most common, used in both clinical trials and consumer products, is via an oil in which CBD, which is naturally soluble in fat, has been dissolved. CBD oil can be taken orally, inhaled as a vape, or applied topically. Topical application is supposed to work sort of the way Icy Hot does, affecting a local muscle area specifically to reduce aches and pains, but the other methods produce full-brain and -body effects.

Ingesting — think CBD lattes, edibles, or just a drop of oil on the tongue — is likely much less effective than inhaling, says Blessing. When CBD-containing oil is ingested, it wants to join the other fat in your body; most of the CBD taken this way will just stay in that fat, inert and never getting to the brain. When inhaled, CBD bypasses the digestive system, which wants to store fat.

For ingested CBD, that fat solubility is a problem. “[Ingested] CBD has a very low bioavailability, something between 6 and 15 percent, which varies between people,” says Blessing. Because ingested CBD is so inefficient at actually getting to the brain to stimulate CB1 and other receptors, the doses shown to be effective have to be very high. “There’s no evidence that doses below 300 mg of CBD have any effect in any psychiatric measure,” says Blessing. “And in fact, dose-finding studies show that the lowest clinically effective dose of CBD for reducing anxiety is 300 mg.”

The only study that has tested the bioavailability of inhaled CBD is from 2014; it found a bioavailability of about 25 percent for 100 mg and 200 mg doses of CBD using a Volcano vaporizer. (The topical lotions are even less studied; there have been no clinical trials on them at all.) This is more efficient than ingesting CBD, in the same way that vaporizing THC is more efficient than eating it. To get an effect, you should ingest a different amount of CBD than you’d inhale … but how much is that? How much is too much?

CBD is most commonly consumed via an oil in which the compound has been dissolved.
AFP/Getty Images

The few CBD studies out there give us limited information, and hardly any about recreational CBD use. One study gave people different amounts of ingested CBD (100, 300, and 900 mg), as well as, for comparison, a placebo and Klonopin; those people then had to give a public speech, an action associated with high levels of anxiety in the broad populace. Neither 100 mg nor 900 mg, nor the placebo, had any effect. The 300 mg dose, though, did have a measurable calming effect on heart rate, blood pressure, and anxiety. (The Klonopin also worked.)

This indicates that CBD has what’s called an inverted bell curve of effectiveness; it works within a window, like Goldilocks’ porridge. Another study showed success in treating social anxiety with doses of 400 mg, though the study was small — just 10 patients.

Other studies have been done in lab animals, or in vitro (meaning in a test tube, using animal brain tissue). Those studies have found anxiety-reducing effects but only at midlevel dosages, in the range of 10 to 20 mg per kg. As an example, one study found that CBD can, in rats, be an effective anti-inflammatory painkiller — at 20 mg per kg. It’s not a direct translation, but that dosage would be somewhere in the range of several hundred milligrams for an adult human.

“There is a huge void of research in terms of confirming most effective dosing for various symptoms,” says Eric Baron of the Cleveland Clinic Neurological Institute, who has written several papers about the effects of THC and CBD on headaches, “so most of this is done by trial and error and self-titration.” Yes, most of the research on CBD is being done by consumers who are just … trying stuff.

“The standard dosage, I would say, is around 20 mg per serving,” says Joshua Tavares, the general manager of Clover Grocery, which sells a wide variety of CBD products including gummies, tinctures, and topical lotions. (Tavares describes the shop, which also sells artisanal potato chips, as a “bougie bodega.”) “The main benefits that we touch upon when selling the products are that CBD is helpful for anxiety and providing you with a sense of calm. I would say it’s our top seller since we brought it in. The CBD category in general is really booming right now for us.”

Flower Power, which sells CBD-infused coffee to cafes like Caffeine Underground in New York City, puts 5 mg of CBD in each serving of coffee. The company, like many involved in the sale of CBD, is extremely careful about what it says regarding CBD’s effects for fear of FDA intervention. The standard language for CBD packaging and website documentation is similar to that of many supplements (think: milk thistle, echinacea, elderberry, turmeric) and is some variation on: “These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease or ailment.”

Flower Power coffee packs contain 5 mg of CBD per serving.
Flower Power

“I’ve got to be really careful what I say when it comes to preaching about benefits that CBD can bring,” says Richard Roocroft, the vice president of global sales and marketing for Flower Power. “We just say, have a cup of coffee once a day to keep the doctor away.” I ask about his dosage and whether he has information indicating it has any effect. “To answer your question, ‘Do we have the studies?’ No. We have nothing that would support that,” he tells me.

“We’ve found that an effective dose for psychological issues, like stress anxiety, generally tends to start out at 6 mg and can go up to 20 mg,” says Zachary Clancy, a horticulturist and clinical herbalist at the Alchemist’s Kitchen, which sells a wide range of CBD goods at its retail store in lower Manhattan and also sells wholesale to restaurants. (Clinical herbalists can complete any of a variety of educational programs and apprenticeships to gain that title.)

Clancy says his dose estimates are based on a book called CBD: A Patient’s Guide to Medicinal Cannabis: Healing Without the High. The co-author of that book is Leonard Leinow, the founder of Synergy Wellness, which calls itself a “hand crafted artisanal CBD cannabis collective.” He is not a doctor or a scientist, but he is a sculptor of erotic bronze pieces, like a yin-yang symbol made up of two interlocking penises.

These dosages are pretty standard in the consumer CBD industry and, per the research available, nowhere near the doses proven to be effective in clinical trials. NuLeaf Naturals, a prominent online CBD seller, sells 240 mg of oil for $38.50. It does not specify dosage but measures its CBD concentration in single drops; there are 100 drops per bottle, each containing 2.4 mg. You would have to take the entire bottle, according to Blessing, to get close to the absolute minimum dose that studies show might be effective for reducing anxiety. A $3 squirt of CBD oil on your ice cream or coffee? Probably right around 10 mg. You’d need 30 times that amount to get to the levels at which researchers have found stress-relieving results.

Roocroft explained his company’s low dose by saying, “Everyone’s different, so when it comes to microdosing, they can control their cup of coffee, which is a 6-ounce serving per brew.” He’s not the only person I talked to who used the term “microdosing.” Blessing says he’s misusing the term. Microdosing means using very small amounts of very powerful drugs; sometimes, this can have extremely mild or even totally different effects from what is considered a full dose. But the key is microdosing still has a provable effect.

“If you use a tiny amount of psilocybin, it still does something,” says Blessing. “Microdosing with psilocybin still has effects biologically, but there isn’t any evidence that low doses of CBD, like 5 mg, do anything at all.” The only study I could find indicating that low doses of CBD have an effect concluded that a rare form of childhood epilepsy called Lennox-Gastaut syndrome is treatable using 10 mg of CBD. For anxiety in adults? Nothing.

Research on low levels of CBD is, you guessed it, incredibly limited; just a single paper on the medical research database PubMed specifically looked at CBD in these low doses, as a treatment for Crohn’s disease. (It was not found to have an effect.) As such, it wouldn’t be fair to say that 5 or even 20 mg of CBD oil in your coffee is proven to do nothing; that hasn’t been proven. It’s more accurate to say that 20 mg of CBD oil in your coffee has never been proven to do much of anything, and related research indicates that’s probably way too low of a dose to have any measurable effect.

I tell several sellers of CBD food and drink what I learned from Blessing and ask what they think. “Return customers who come back, and swear by it and love it, buy two at a time to stock up for the week because they do find it to be very helpful,” says Tavares. Clancy echoes this: “We rely a lot on consumer feedback and testimonial, and generally it’s positive when taking that minimal amount. Now, that very well could be a placebo effect, but either way, people have come back and reported significant benefits when it comes to easing social anxiety.”

Is it possible that all of this is just … the placebo effect? It feels condescending to suggest that, given there are hoards of people who love their CBD tinctures and gummies and claim effects from it. It’s a tremendously rude thing to say, hey, you’re all being hoodwinked. But the placebo effect is much stronger than you might think.

“Placebo response always needs to be taken into account for any treatment being studied,” says Baron. “Placebo response is actually quite high in many pharmaceutical trials, for example. In fact, there are many treatment trials for various medications and other treatments where benefit responses to placebo are actually higher than the treatment itself being studied.”

One study found that placebos sometimes work even when the subject knows it’s a placebo. Another, using that same public speaking setup that CBD studies have used, found that anxiety treatments are particularly susceptible to the placebo effect, with 40 percent of placebo-treated patients showing a decrease in anxiety symptoms while tasked with speaking to a crowd.

So is it possible that despite all this anecdotal evidence, low-dose CBD is a placebo? Sure, because, say it with me: We don’t know anything about CBD. “Unfortunately,” says Baron, “we are nowhere near close to having any definitive trials on effectiveness for most symptoms claimed to benefit from CBD with trials that are scientifically relevant, such as prospective randomized placebo-controlled trials.”

The Alchemist’s Kitchen and Clover Grocery are high-end stores that cheerfully tell customers where they source their products from and only stock brands with similarly transparent sourcing. This CBD usually comes from cannabis plants farmed in Colorado or Oregon, or, increasingly, states not normally associated with the cannabis trade. EarthE CBD, a prominent online seller of CBD products, for example, sources from local farms in New Jersey; it also publishes lab results on its website showing that its products have been tested to have no THC and the amount of CBD the company says they should have.

This is a weird Wild West time for CBD, and these companies are doing their best. They are not the norm. A potentially larger problem than dosage is the lack of accountability and dearth of information about the ingredients found in most CBD products sold across the country.

New York’s Hudson Hemp farm grows industrial hemp, which is used to produce CBD isolate.
Jeremy Sachs Michaels/Hudson Hemp

“Not all CBD on the market is created equal, and there is really a lack of understanding about even what cannabis is, let alone CBD,” says Melany Dobson, the chief administrative officer of Hudson Hemp.

Hudson Hemp began growing industrial hemp through a New York state pilot program that began in late 2017. Industrial hemp is extremely low in or entirely free of THC and is grown for fiber, hempseed oil, and, increasingly, CBD. Hudson Hemp grows Cherry Wine, one of several varieties, or strains, of the cannabis plant that have been bred to remove THC (which remains illegal in New York) and maximize CBD yield. Some strains are naturally high in CBD and very low in THC; others are high in THC and low in CBD; still others have similar levels of each.

CBD is derived by growing cannabis, drying it out, pulverizing it, and then, often, using a rotary evaporator filled with an ethanol solvent to extract the CBD. (There are some other methods, but the ethanol one is common.) It’s a pretty old and fairly low-tech technique, but it’s effective. What you end up with is, hopefully, about 99 percent pure CBD in the form of white powder, which is called CBD isolate. (Some CBD is billed as “full spectrum,” which means it contains other things from the cannabis plant, like a bunch of other cannabinoids, but there’s no formal definition for full spectrum.)

Hudson Hemp, like all cannabis farms in New York, has to get its CBD powder tested by one of only a few reputable labs approved by the state; if it contains more than 0.3 percent THC, it’s illegal.

Hudson Hemp caters to high-end CBD companies, and its accountability is unusual. Vast amounts of CBD products are sold online and in stores without any documentation or transparency. Online retailers say whatever they want. Big marketplaces, from eBay to Alibaba, sell mysterious vials of oil with odd labels, and people buy them.

These products are from places like Xi’an Lyphar Biotech Co. Ltd., which doesn’t mention that it’s one of the largest CBD sellers on Alibaba on its website, let alone reveal where it’s sourcing its CBD from. There are big companies and small companies, companies that provide elaborate chemical charts and companies that have no online presence at all. There are companies that run their goods — either as raw materials or as consumer-stage final products — through lab tests. There are those that say they do but provide no information on what the labs found or which labs tested their products.

Everyone wants a piece of CBD, and nobody is watching. Remember: There’s no regulation by the FDA or anyone else. An investigation by Natural Products Insider, a trade publication for the supplement industry, revealed that CBD producers are, at best, claiming to follow “good manufacturing practices” without any official oversight. It’s illegal to sell something that isn’t what its packaging claims it is — that falls under the purview of the Federal Trade Commission — but nobody is doing onsite testing.

To get caught, a consumer or partner would have to report a product to the FTC and/or FDA, and those organizations would have to work out among themselves whose job it was, and then they’d have to actually go investigate, all while the product remains on shelves.

So how can you be sure that your CBD oil actually contains what the package says it does?

Blessing told me that two clinical managers of pharmaceutical companies she knows have performed tests on various CBD oils they’ve found for sale, just out of curiosity. (They declined to talk to me on the record.) Some of these products had no CBD in them at all, they told Blessing. Some had levels of THC that exceeded the federal limit.

That lines up with one of the rare instances of FDA testing. In 2016, the FDA tested several “CBD oils,” ultimately issuing warnings to eight companies. Some of those oils were found to contain no or barely any CBD, and many contained illegal quantities of THC. For example, Healthy Hemp Oil’s “Herbal Renewals 25% CBD Hemp Oil Gold Label” contained 8.4 mg/g of THC. Sana Te Premium Oils, which sold 25 mg “CBD oil” capsules on Etsy, contained between 13 and 19 mg/g of THC and less than 0.1 mg/g of CBD.

This isn’t simply an issue of legality, but one of safety. “If you have just, say, 8 mg of THC, that’ll have an effect,” says Blessing. “That’ll get you high. That could impair driving.”

Blessing also notes that in lower doses, like 5 mg or even less, THC does about the same thing that CBD does in very high doses: lightly stimulates that CB1 receptor. It is not impossible that if you’re actually feeling something from a CBD supplement, it’s because that supplement contains some THC. Or who knows what else!

Blessing’s clinical manager contacts did not perform formal studies on CBD. They didn’t want to open themselves up to legal challenges from the CBD companies, and in any case saw very little reason to bother challenging a product with a name like “100% Pure organic cbd oil hemp seed oil for skin with cheap price” that ships in bulk from Alibaba. They see a market littered with items like this and assume that no customer would reasonably assume it’s of high quality.

They’re wrong, of course, because this stuff sells like gangbusters.

Researchers like Blessing are legitimately excited about CBD. It shows real promise in treating previously intractable disorders like schizophrenia, and without the destructive side effects of existing drugs. Still, that doesn’t mean CBD is harmless. Research on drug interactions with CBD is in its infancy, but what is known within the medical community is that CBD can cause serious problems for people taking certain classes of drugs, namely SSRIs (a group of antidepressants including Zoloft and Prozac) and opioids.

“CBD inhibits the cytochrome P450 enzymes that break down important psychiatric drugs,” says Blessing. CBD isn’t the only substance that messes with the body’s ability to metabolize these drugs — both St. John’s wort and the humble grapefruit are unfriendly — but CBD is comparatively poorly studied. The way CBD inhibits those enzymes could dramatically raise the levels of SSRIs or opioids in the system, potentially leading to an overdose.

Clancy readily admits that potential interactions could be dangerous and says that educating customers is a major part of the Alchemist Kitchen’s approach: “We want to make sure that [our customers] have a well-rounded understanding of the medicinal applications of CBD, because right now it’s being thrown in everything, as I’m sure you’re aware.”

CBD has drug interactions with SSRIs and opioids.
Jeremy Sachs Michaels/Hudson Hemp

The Alchemist’s Kitchen makes it a point to tell customers everything they know, or think they know, about CBD, and to emphasize that if CBD is going to be a regular part of their lives, they should consult with a doctor to make sure they won’t have any adverse reactions. Your bodega guy, who’s selling a little jar of CBD oil right next to the Dentyne Ice gum, almost certainly isn’t doing the same.

“If you’re taking Prozac or some other medication, you really need to think carefully about what you’re doing, because it can harm you, and you should talk to your doctor about it,” says Blessing. Blessing does note that while the drug interactions are potentially very serious, the doses in consumer CBD products are so low that the risk is likely minimal. Regardless, the fact that CBD has drug interactions should indicate that it is, at least sometimes, in some doses, actually doing something.

And that’s what’s maddening and fascinating about CBD: It isn’t bullshit. Crystals are bullshit. Himalayan salt ionizers are bullshit. SugarBearHair apparently doesn’t contain what it says it does, though it wouldn’t work better than a well-balanced diet even if it did. CBD, though wildly understudied, is not bullshit. In fact, the FDA just approved its very first cannabis-derived drug, a CBD-based epilepsy treatment called Epidiolex. The dosage for Epidiolex starts at around 2.5 mg/kg and is increased to 5 mg/kg, so a 150-pound adult would settle onto a dose of just over 340 mg per day, though the diseases it targets start in childhood.

Even some of the claims made by recreational CBD sellers aren’t bullshit, in the abstract. CBD really does show some anti-inflammatory properties. It really does have anxiolytic effects, in certain situations. Of course, it’s the scammy nature of herbal supplements that a seller can say something like “CBD has been indicated to reduce anxiety” (a true statement!), even though the actual product you’ve got in your hand has never been indicated to do so. Nutmeg, for example, will act as a dangerous psychoactive drug at high levels, but it would be deranged to put “scientific research has shown that nutmeg can get you high as hell” on a pumpkin spice latte. It’s correct, but it’s also incredibly misleading.

We don’t know how CBD affects the brain in any kind of depth. We don’t know which doses and delivery methods are best for different outcomes. We don’t know how CBD interacts with most other drugs or foods. We don’t know the differences between the effects of isolates and full-spectrum preparations. We don’t even know how many cannabinoids there are. California, for what it’s worth, seems aware and concerned about this whole thing.

But a lack of data does not hinder capitalism; it is, rather, a huge help. When nobody knows anything, you can say — or imply — anything. More importantly, you can sell everything.

Source: https://www.vox.com/the-goods/2018/11/1/18024806/cbd-oil-vape-hemp

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