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titled the Potent, Promises and Perils of Modern Cannabis. These days, pot is more popular and more powerful than ever before, and it's being used and studied in ways that are prompting fresh and surprising discoveries. Here we tackle some of the most critical questions being raised by today's stronger, stranger,

ever more accessible weed. How cannabis chemists engineer a superior high by Rosecrans Baldwin, Enterprising weed scientists are remixing marijuana into startlingly the powerful concentrates, leading consumers into heady new realms where buds can't take them. In a white walled lab inside the vast manufacturing facility of California cannabis company Raw Garden, the bouquet of marijuana is unmistakable even without

a plant or bud in sight. Technicians in lab coats monitor armoire sized machines that rattle as they refine flask after a multi liter flask of amber colored cannabis scented oil in a room around the corner near a row of vacuum ovens, the same extracted oil has been used to make an array of concoctions set out on still tables, in trays, jars, and pyrux dishes. They range from viscous semi liquids that ooze like tree sap to creamy paste

resembling peanut butter. A few trays contain glass like golden shards, and there's a crystallizing substance akin to aging honey. Together, the products represent a substance antil shift in how Americans consume pot. Year after year, they are smoking proportionally less of it and instead embracing more products made with its

extracted oil. These include edibles like gummies and beverages, but also new types of high potency concentrates that are consumed not by smoking but by vaping or what's known as dabbing flash vaporizing dabs of thick extract, and these concentrates are radically altering the experience of getting high. Like other modern cannabis companies. Raw gardens still grows weed, but it is primarily a raw material, something to be processed into

goop for an arguably heightened experience. If you think the heart of the United States roughly thirty two billion dollar cannabis industry looks like a farm or a grow room, think again. It increasingly looks like these industrial cam labs full of scientists imagining new frontiers of mind blowing offerings. Such cannabis concentrates are often named for their textures sauce, wax, shatter, diamonds,

and more. They are dizzingly more potent potent than the joint you might have smoked twenty or forty years ago, and of course, they are now legal in many states as policy shifts have helped launch a space race in the cannabis industry, with entrepreneurs developing more sophisticated techniques to alchemize plant matter into a kaleidoscope of forms and flavors. The rise of the high potency concentrates market comes at a time when marijuana flower traditional smokable cannabis, is already

pretty darn powerful. Thanks to advances in crop science, pot grown in the US has been bred to be substantially stronger than it was a few decades back. Potency in cannabis products is typically expressed as a concentration of delta nine tetra hydro cannabinol or th HC, the comp compound in marijuana that is primarily, though not exclusively, responsible for its psychoactive effects. While precise numbers are tricky to combine, studies suggest the THHC levels in marijuana sold in the

US thirty years ago averaged somewhere in the single digits. Today, at a time when many states require lab verified potency labels on legal products, the average is somewhere between fifteen and twenty percent. Cannabis concentrates, however, results from an extraction process that isolates only the desired compounds, prominently including THHC

from pesky plant matter. Raw Garden advertises a product called Live Sauce, a golden goo described as having an apple sauce consistency at around seventy percent THHC potency depending on the strain used to make it. The company's refined live resin diamonds, which look like something you'd find at a gem show, can tap out above eighty five percent for some The THHC content and hence the rapidity and intensity

of the buzz is the point. High potency vapes and dabs get users high with smaller amounts than other means of ingesting cannabis, but the draw also has to do with the subtlety of flavors and precision of one's intake, says Rawgarden Chief brand officer Dmitri Siegel. It's a purity thing, he says, where you're either getting a really distilled high or you're getting a really distilled flavor. You're not burning

a whole lot of organic matter. Handheld vaporizers are also less conspicuous, notes cannabis industry analyst and consultant Tom Adams, president of Adam's Research. Some concentrate users are enticed by the discreetness of taking a quick toque off a small amount of oil or apple sauce like gel. It just seems odd as an adult to be taking weed out of a bag, crushing it up and rolling it, he says.

What am I a cowboy Atoms, who has analyzed the legal cannabis market since twenty fifteen, says demand for legal concentrates originated in the first medical dispensaries smoking can be impractical for those looking to consume hundreds of milligrams of THHC each day, a substantial amount, but which may nonetheless be what brings relief to chemotherapy patients or sufferers of

chronic pain. Edibles can pose problems for patients with appetite or gastro intestinal issues, and concentrates, whether for medical or recreational use, arguably make it easier to regulate dosage sure Atoms allows pre rolled joints with measured amounts of flour offer some consistency, but even that is less predictable than the cleaned up scientifically produced to concentrate that you know exactly what the impact is going to be, he says.

Rolling your own stuffing erratic hunks of vegetable matter into a pipe, it's a hard cell, says Atoms. Consumers are just not used to the primitiveness. The quest to concentrate the psychoactive components of cannabis goes back to at least the eleventh century, when hashish caught on recreationally in the Arab world. Hasheesh is made from plant glands now known as tricombs, which early hashmakers rubbed or sieved off the surface of cannabis leaves and buds, then pressed into a

sort of cake. Tricombs are rich in bioactive compounds called cannabinoids, the most well known of which are THHC and cannabidial or CBD. They also contain other specialized compounds, such as chirpenes, the hydrocarbons responsible for plants, aromas, and flavors. Today, cannabis processors have built on medieval methods, finding new efficient ways to isolate those prized compounds. Among the most common is hydrocarbon extraction, in which a solvent separates desired chemicals from

raw plant material. Butane and propane are the industry standard solvents, and, prior to widespread legalization, back when extraction was an underground hobby, use of these combustible materials occasionally resulted in hotel rooms

and apartments blowing up. FEMA went so far as to issue a bulletin in twenty thirteen warning hash oil explosions increasing across US, but during the wave of state legislation that has swept the country since, cannabis extraction has gone mainstream, and today companies like raw Garden are subject to licensure regulations and inspections. The basis of nearly all raw garden products is the oily substance known as live resin a cannabis extract that aims to capture a wide array of

those cannabinoids and terpen terpenes. Some extraction processes, by contrast, isolate only a single compon pound, usually THHC or CBD, but before they become oil. All of the company's offerings start out as plants on fifty four acres of farmland in the Santa Barbara wine country. At harvest time, the plants are cut, then the buds are removed and immediately flash frozen with liquid nitrogen in a cryogenic tunnel, preserving

all those volatile organic compounds from the farm. The pot is trucked to a cold storage warehouse in nearby Lombach, where it's placed in a deep freeze. When any given strain is up for extraction, the frozen buds are moved to a manufacturing facility up the road, where they're loaded into six foot tall stainless steel columns, each of which can hold about eighteen pounds of pot. Inside, they're saturated with pressurized solvent that dissolves the desired chemicals and leaves

behind unwanted biomass. Later stages for some project products include one in which the crude extract is purified with fats, waxes, lipids, and other solids filtered out other products, cooked for twenty four to thirty six hours in a vacuum oven to purge away residual solvent. The pressure inside the oven lowered so that the solvent evaporates without any of the good stuff boiling off. Using solvents isn't the only way to

make an extract. Raw Garden sends a small amount of its harvest to a partner facility where it's turned into a hashish like product called rosin via a similar process using only ice, water, heat, and pressure. But hydrocarbon extraction is scalable and highly efficient. Raw Gardens facility process processes around twenty twelve hundred pounds of cannabis a day and has plans to expand. This isn't to say there's no

art to it. A concentrates consistency, That is, whether the live resin turns into something creamier crispier oily results from the strain one starts with, as well as small inspired interventions during extraction. What if we whipped the extract before

purging it. What if we cured it so that crystal's form extract bound for vape cartridges sometimes involves an additional step in which terpenes are evaporated and collecting in a distillation column, then selectively reinserted to achieve specific scent and flavor profiles in raw gardens vape lab A colorful aroma wheel shows one hundred plus fragrances one might allegedly encounter in cannabis, like apricot, sage, pine tyran, espresso. We're taking

aromatic compounds from plants. As vice President of Agricultural Operations Casey Birthisle, there's a lot here that's parallel to the perfume industry. Some medical professionals see more alarming parallels, however, to drugs ostensibly harder than cannabis. The sky high potency of concentrates has raised red flags, as multiple epidemiological studies have found correlations between their frequent use and increased risks of psychoses and cannabis use disorder, a form of dependence.

Those risks seem particularly acute for teenagers. Colorado and Washington, the first states to legalize recreational pot are among the states where bills to limit THHC potency have been introduced, then rejected or withdrawn amid industry pushback. Meanwhile, according to analyst Atoms, sales of marijuana flour made up about seventy percent of the recreational market when the first legal retailers

opened in Colorado in twenty fourteen. Today, according to point of sale data from Atoms and market research firm BDSA, that number has dropped to forty percent. In the same span, sales of vaping and dada being products have climbed from around fifteen percent of the legal market to thirty two percent, though the pace of that growth now seems to be slowing. It's all a function, Adam says, of a reunion of

technology in cannabis brought about by legalization. Ironically, what excites him most about the future of extraction has nothing to do with t h C. The next big things in cannabis, Adams suggests, might derive from the industry's ability to efficiently isolate all those other compounds. What new effects are there to discover from the terpenes or from the more then a hundred other little researched cannabinoids that aren't t h

C or CBD. We are totally revolutionizing the view of what the compounds in the plant can do through the concentrates side of the market. He says that opens up the uses to all sorts of things other than sitting on the couch watching Netflix. Modern cannabis, explained, consuming pot mostly used to means smoking it, rolling a joint, or packing a pipe owl. How is vaping it any different?

Like smoking? Vaping cannabis involves heating up some manner of marijuana and inhaling the results, but without setting anything on fire. Some vaping devices can be loaded with dry herb or cannabis flour, while others are used for high potency concentrates like oil or live resin. At the touch of a button, a battery powered element heats the bud or oil just enough to release compounds like THHC and other cannabinoids in an aerosol or vapor without any burning plant material. The

experience may seem less harsh than smoking. It's also arguably more convenient. Hand Held devices like vappens are portable and discrete, leaving less odor than smoking. Many pens are disposable, and for those seeking to reduce electronic waste. Other styles can be reloaded with prefilled cartridges of cannabis oil, known as vape carts. Studies suggest that vaping flour rather than smoking it can reduce your exposure to toxins and carbon monoxide,

but that doesn't mean it's entirely safe. Vaping, especially with concentrates, comes with its own lung disease risks. For people interested in more of a THHC jolt, there's the form of vaporization called dabbing, which involves heating up thicker cannabis concentrates like wax, a gooey form of hash oil, or shatter a solid glass like version. This takes a different tool, known as a dab rig, a kind of water pipe

that's more elaborate and less portable than most vapes. Users typically apply a small hand held torch to a heating element called a nail, then use a wand like tool to touch a dollop of concentrate to it, inhaling its vapor through a chamber of cooling water. Hand Held dab pens are a simpler alternative, but some dab fans suggest dab pens can sacrifice flavor, making such devices smaller, simpler and cheaper is a major focus of the increasingly innovation

driven industry. A new tool in the Fight against chronic pain by Devon Powell. For decades, scientists have sought a non addictive means of treating people in ongoing agony. Now cannabis is inspiring a safer way forward. They call it the holy Grail of pain relief research, a medicine that is comparable to the strongest opioids but lacks their potentially

devastating side effects. When biophysicist and structural biologist Kavya Krishna Kumar set out looking for a novel way to develop one, she knew she needed to start with a substance that hit the body incredibly hard. So she took to the seatier corners of the online forum read It, where she learned about an illicit street drug with a reputation for making people both very high and very sick. It's out of this world potent, read one recreational user's poach post.

A very very small, almost invisible amount of powder sky rockets you into stoned euphoria. The drug is called fubinacca, and it's what's known as a synthetic cannabinoid A molecule designed in a lab to target the same parts of the nervous system affected by tetra hydro cannabinol or THHC,

the main psychoactive compound in cannabis. Underground chemists have been making drugs like it since the early two thousands, when recreational marijuana was still criminalized in the United States and synthetic cannabinoids began catching on as a cheap quasi legal alternatives. From their powdered form, they're typically dissolved into solvents, which are then sprayed on two plant shreds to be sold with a wink as incense or pot poiri. Not for

human consumption. The label may read a dodge against regulation. Sold under monikers like spice or K two, these gray market synthetics have raised public health alarms for both their toxicity and their contamination risks. The extract the exact chemicals, and their concentrations can vary from product to product, with

side effects ranging from mania to heart attacks. But Krishna Kumar, then at Stanford Medicine, now at wild Cornell Medicine, now in fubinaka a tool for better understanding how our pain management system works, and after some clever molecular modeling. She and a team led by researchers from Stanford and Washington University School of Medicine in Saint Louis devised an innovative

way of modifying it. Earlier this year, the team published a study showing a fubinaca derived drug providing a sustained pain relief in mice, seemingly without psychoactive or tolerance building side effects. Such side effects have stymied progress on other would be cannabinoid pain relievers, dampening enthusiasm for what once seemed like a promising opioid alternative. Now, some scientists hope the research can breathe new life into that work and

perhaps open up even wider therapeutic frontiers. Fubinaca wasn't always a street drug. It was developed by Phizer and patented in two thousand nine, part of an effort to create a superpowered aspirin with no side effects. According to former physer chemist Darren Jones, like THHC, synthetic cannabinoids activate a powerful chemical receptor known as CB one in humans and other mammals. CB one is found on nerve cells in the brain and crucially on cells elsewhere in the body.

It's known to influence not only the perception of pain, but also sleep, metabolism, and memory, making it a promising target for pharmaceutical research. A second cannabinoid receptor, c B two,

seems mostly to regulate the functions of immune cells. Of course, the path to market for any new drug it must take into account future profitability, and while it's unclear just what scuttled Pfiser's research, Jones theorizes it had to do with the increasing legality of medical marijuana, which was suddenly

pennies a pound at pro proliferating dispensaries. But when the company published its patent, that became a blueprint for so called garage chemists to replicate the formula and create analogs. The US Drug Enforcement Administration reports that law enforcement has encountered hundreds of different synthetic cannabinoids, most of them manufactured in Asia. Variants of Pfiser's fubinaca, the first of which was detected in Japan in twenty twelve, are known as

most of the most toxic. In twenty fourteen, dozens of deaths in Russia were linked to an analog called MDMB fubinaca. Two years later, another variant was behind a mass overdose in Brooklyn, New York that the media characterized as a zombie outbreak. But Krishna Kumar hoped to pick up where Pfizer left off harnessing that potency. First, she examined how MDMB fubinaca attached to human CB I receptors in the dish compared to other synthetic cabin cannabinoids. She found it

held tighter and activated effects more powerfully. Then, using a Nobel Prize winning technology called cryoelectron microscopy cryo e M, she flashes that she flash froze that fubinaca molecule while it was affixed to CB one and scanned the conjoined pair with a beam of electrons. The result was a three D picture, down to individual atoms, of how the drug fits so well into a pocket or binding sight on the receptor's surface like a key in a lock.

That image provided a starting point for designing new versions of fubinaca that might, by stimulating the receptor in new ways, keep the original's potency while limiting side effects. For that, Krishna Kumar turned to Sasruta Majumdar, a Washington university chemist and pharmacologist whose lab had previously shown that activating a particular site on an opioid receptor could inhibit chemical reactions that led to tolerance. Might this be possible for CEB one.

The researchers knew that CEB one, a cousin to that opioid receptor, had a potential binding site with similar qualities, but it was deep inside the receptor and in Krishna Kumar's cryo em snapshot, blocked by clusters of atoms. It was also the wrong shape to fit Fubinaka, So Majumdar's team started sketching bespoke attachments for the cannabinoid chains of

atoms that might help the molecule worm its way in. Meanwhile, Truford scientists took another approach, animating the statics napshot using computer simulations showing how atoms in the drug and the receptor moved around each other. The simulations revealed something surprising.

The atom clusters blocking blocking the tantalizing sight sporadically moved aside, opening what biochemists call a cryptic pocket, allowing researchers a glimpse in tweaking their designs to fit Majumdar's team made one other crucial adjustment in the hope of nixing fubinacca's psychoactive side effects. The newly accessible site, it turned out, could accept a compound with a positive electric charge, which hinders a molecule from crossing the membrane separating blood from

the brain. By tacking a charged group of atoms onto fubinaca, researchers confined its activity to CEB one receptors outside the brain, where it can't get anyone high or act on the

brain's reward circuitry, limiting risks of misuse and abuse. New versions of fubinaca were injected into rodents experiencing various kinds of pain, and one variant, which the researchers called VIP thirty six, showed indicators of relieving chronic pain from three different sources inflammation, nerve damage, and headaches, even after days

of repeated injections. True, says Washington University neurobiologist Robert Giroux, all that molecular tinkering had reduced the drug's potency and thus its pain relieving effects, but where that might have left other cannabinoids toothless GIAU says VIP thirty six remained effective in a range that is useful clinically, precisely because fubinaca packed such a wallop to begin with. VIP thirty

six is still in its baby steps phase. It has yet to be tested in humans who have fewer c B one receptors outside of their brains than rodents do, and for now the new compound can't be taken orally,

only injected. But even if the drug never reaches your medicine cabinet, the research could still chart new pharmaceutical paths for when it might occasion a reassessment from those skeptical of cannabinoid's potential as medicine, a constituency that includes the world's largest pain research organization, the International Association for the Study of Pain, whose official position is that science has so far failed to prove cannabinoids either safe or effective.

This is the perfect paper to help reput steam into the cannabinoid field, says Michael Burton, a neuroscientist and cannabinoid researcher at the University of Dallas at Texas. What's more, Majumdar says there may be other cryptic pockets in other receptors related to CB one, many of which have nothing to do with pain. Some have been linked to heart disease, for instance, or substance abuse disorders. This opens an enticing possibility.

What the researchers have learned about changing a receptor's behavior could help them tinker with a whole range of drugs. Majumdar is already planning to revisit a previous study that unsuccessfully targeted a hard to reach opioid receptor. He imagines redesigning antidepressants, maybe cancer drugs targeting diseases beyond pain is expected in the near future. He says, we are just

scratching the surface. Compared to what law enforcement seized in the nineteen nineties, cannabis grown in the United States today contains, on average, far more THHC, the plant's main psychoactive compound. What are the differences between actual cannabis and synthetic products like K two spice and Delta eight? Are these legal really legal? Some of these lab made cannabis substitutes may indeed be legally sold, but legal isn't the same thing

as SAYE, and synthetic cannabinoids come with risks. What makes things murky and dangerous? Is that what you might hear called fake or synthetic pot isn't a single drug, but whole classes of chemicals. To create synthetic cannabinoids for recreational use, underground chemists formulate compounds that are chemically distinct from THHC

but act on nerve receptors in similar ways. Since some of those substances marketed with names like K two and spice aren't technically illegal, they can be sold at gas stations, smoke shops, and online stores, as for example, herbal incense, but many have suggestive branding that alerts consumers to a potential secondary usage for the chemical laced blends. This concludes readings from National Geographic Magazine for today. Your reader has

been Marcia. Thank you for listening, Keep on listening, and have a great day.