WEBVTT 1 00:00:00.640 --> 00:00:03.640 Welcome. This is Marsha for Radio I, and today I 2 00:00:03.680 --> 00:00:08.599 will be reading National Geographic magazine dated September twenty twenty five, 3 00:00:08.720 --> 00:00:12.519 which is donated by the publisher as a reminder. RADIOI 4 00:00:12.759 --> 00:00:15.640 is a reading service intended for people who are blind 5 00:00:15.720 --> 00:00:18.399 or have other disabilities that make it difficult to read 6 00:00:18.440 --> 00:00:22.120 printed material. Please join me now for the first article 7 00:00:22.199 --> 00:00:30.760 titled the Potent, Promises and Perils of Modern Cannabis. These days, 8 00:00:30.839 --> 00:00:33.719 pot is more popular and more powerful than ever before, 9 00:00:34.119 --> 00:00:36.359 and it's being used and studied in ways that are 10 00:00:36.399 --> 00:00:40.359 prompting fresh and surprising discoveries. Here we tackle some of 11 00:00:40.359 --> 00:00:44.799 the most critical questions being raised by today's stronger, stranger, 12 00:00:45.200 --> 00:00:51.119 ever more accessible weed. How cannabis chemists engineer a superior 13 00:00:51.240 --> 00:00:59.039 high by Rosecrans Baldwin, Enterprising weed scientists are remixing marijuana 14 00:00:59.119 --> 00:01:03.520 into startlingly the powerful concentrates, leading consumers into heady new 15 00:01:03.560 --> 00:01:08.799 realms where buds can't take them. In a white walled 16 00:01:08.879 --> 00:01:13.239 lab inside the vast manufacturing facility of California cannabis company 17 00:01:13.359 --> 00:01:17.799 Raw Garden, the bouquet of marijuana is unmistakable even without 18 00:01:17.840 --> 00:01:21.000 a plant or bud in sight. Technicians in lab coats 19 00:01:21.079 --> 00:01:25.480 monitor armoire sized machines that rattle as they refine flask 20 00:01:25.560 --> 00:01:29.599 after a multi liter flask of amber colored cannabis scented 21 00:01:29.680 --> 00:01:32.640 oil in a room around the corner near a row 22 00:01:32.680 --> 00:01:36.159 of vacuum ovens, the same extracted oil has been used 23 00:01:36.159 --> 00:01:39.760 to make an array of concoctions set out on still tables, 24 00:01:39.799 --> 00:01:44.400 in trays, jars, and pyrux dishes. They range from viscous 25 00:01:44.439 --> 00:01:48.040 semi liquids that ooze like tree sap to creamy paste 26 00:01:48.200 --> 00:01:53.519 resembling peanut butter. A few trays contain glass like golden shards, 27 00:01:53.560 --> 00:01:58.040 and there's a crystallizing substance akin to aging honey. Together, 28 00:01:58.120 --> 00:02:01.840 the products represent a substance antil shift in how Americans 29 00:02:01.879 --> 00:02:05.599 consume pot. Year after year, they are smoking proportionally less 30 00:02:05.640 --> 00:02:09.479 of it and instead embracing more products made with its 31 00:02:09.680 --> 00:02:15.400 extracted oil. These include edibles like gummies and beverages, but 32 00:02:15.479 --> 00:02:18.719 also new types of high potency concentrates that are consumed 33 00:02:19.080 --> 00:02:22.159 not by smoking but by vaping or what's known as 34 00:02:22.280 --> 00:02:27.639 dabbing flash vaporizing dabs of thick extract, and these concentrates 35 00:02:27.680 --> 00:02:31.960 are radically altering the experience of getting high. Like other 36 00:02:32.039 --> 00:02:35.919 modern cannabis companies. Raw gardens still grows weed, but it 37 00:02:36.000 --> 00:02:40.120 is primarily a raw material, something to be processed into 38 00:02:40.159 --> 00:02:44.159 goop for an arguably heightened experience. If you think the 39 00:02:44.199 --> 00:02:47.199 heart of the United States roughly thirty two billion dollar 40 00:02:48.319 --> 00:02:51.520 cannabis industry looks like a farm or a grow room, 41 00:02:51.639 --> 00:02:55.319 think again. It increasingly looks like these industrial cam labs 42 00:02:55.680 --> 00:02:59.599 full of scientists imagining new frontiers of mind blowing offerings. 43 00:03:00.560 --> 00:03:06.840 Such cannabis concentrates are often named for their textures sauce, wax, shatter, diamonds, 44 00:03:06.840 --> 00:03:10.360 and more. They are dizzingly more potent potent than the 45 00:03:10.439 --> 00:03:13.240 joint you might have smoked twenty or forty years ago, 46 00:03:13.759 --> 00:03:16.120 and of course, they are now legal in many states 47 00:03:16.439 --> 00:03:21.000 as policy shifts have helped launch a space race in 48 00:03:21.039 --> 00:03:26.280 the cannabis industry, with entrepreneurs developing more sophisticated techniques to 49 00:03:26.439 --> 00:03:30.199 alchemize plant matter into a kaleidoscope of forms and flavors. 50 00:03:31.879 --> 00:03:35.599 The rise of the high potency concentrates market comes at 51 00:03:35.639 --> 00:03:40.240 a time when marijuana flower traditional smokable cannabis, is already 52 00:03:40.280 --> 00:03:44.080 pretty darn powerful. Thanks to advances in crop science, pot 53 00:03:44.159 --> 00:03:47.120 grown in the US has been bred to be substantially 54 00:03:47.120 --> 00:03:50.199 stronger than it was a few decades back. Potency in 55 00:03:50.240 --> 00:03:54.159 cannabis products is typically expressed as a concentration of delta 56 00:03:54.280 --> 00:04:00.759 nine tetra hydro cannabinol or th HC, the comp compound 57 00:04:00.800 --> 00:04:04.919 in marijuana that is primarily, though not exclusively, responsible for 58 00:04:04.960 --> 00:04:10.120 its psychoactive effects. While precise numbers are tricky to combine, 59 00:04:10.280 --> 00:04:14.120 studies suggest the THHC levels in marijuana sold in the 60 00:04:14.240 --> 00:04:18.680 US thirty years ago averaged somewhere in the single digits. Today, 61 00:04:18.720 --> 00:04:21.800 at a time when many states require lab verified potency 62 00:04:21.879 --> 00:04:25.959 labels on legal products, the average is somewhere between fifteen 63 00:04:25.959 --> 00:04:31.160 and twenty percent. Cannabis concentrates, however, results from an extraction 64 00:04:31.319 --> 00:04:36.600 process that isolates only the desired compounds, prominently including THHC 65 00:04:37.120 --> 00:04:41.600 from pesky plant matter. Raw Garden advertises a product called 66 00:04:41.759 --> 00:04:45.680 Live Sauce, a golden goo described as having an apple 67 00:04:45.720 --> 00:04:50.519 sauce consistency at around seventy percent THHC potency depending on 68 00:04:50.560 --> 00:04:53.959 the strain used to make it. The company's refined live 69 00:04:54.160 --> 00:04:56.959 resin diamonds, which look like something you'd find at a 70 00:04:57.000 --> 00:05:01.319 gem show, can tap out above eighty five percent for 71 00:05:01.439 --> 00:05:05.600 some The THHC content and hence the rapidity and intensity 72 00:05:05.600 --> 00:05:08.959 of the buzz is the point. High potency vapes and 73 00:05:09.040 --> 00:05:12.399 dabs get users high with smaller amounts than other means 74 00:05:12.399 --> 00:05:15.560 of ingesting cannabis, but the draw also has to do 75 00:05:15.879 --> 00:05:18.839 with the subtlety of flavors and precision of one's intake, 76 00:05:19.360 --> 00:05:24.480 says Rawgarden Chief brand officer Dmitri Siegel. It's a purity thing, 77 00:05:24.519 --> 00:05:27.839 he says, where you're either getting a really distilled high 78 00:05:28.079 --> 00:05:31.199 or you're getting a really distilled flavor. You're not burning 79 00:05:31.199 --> 00:05:36.600 a whole lot of organic matter. Handheld vaporizers are also 80 00:05:36.759 --> 00:05:41.920 less conspicuous, notes cannabis industry analyst and consultant Tom Adams, 81 00:05:42.279 --> 00:05:46.399 president of Adam's Research. Some concentrate users are enticed by 82 00:05:46.439 --> 00:05:49.560 the discreetness of taking a quick toque off a small 83 00:05:49.560 --> 00:05:53.480 amount of oil or apple sauce like gel. It just 84 00:05:53.560 --> 00:05:56.240 seems odd as an adult to be taking weed out 85 00:05:56.279 --> 00:05:58.600 of a bag, crushing it up and rolling it, he says. 86 00:05:58.879 --> 00:06:02.480 What am I a cowboy Atoms, who has analyzed the 87 00:06:02.560 --> 00:06:06.519 legal cannabis market since twenty fifteen, says demand for legal 88 00:06:06.600 --> 00:06:11.120 concentrates originated in the first medical dispensaries smoking can be 89 00:06:11.160 --> 00:06:16.240 impractical for those looking to consume hundreds of milligrams of 90 00:06:16.319 --> 00:06:20.480 THHC each day, a substantial amount, but which may nonetheless 91 00:06:20.680 --> 00:06:24.720 be what brings relief to chemotherapy patients or sufferers of 92 00:06:24.800 --> 00:06:28.800 chronic pain. Edibles can pose problems for patients with appetite 93 00:06:29.160 --> 00:06:33.600 or gastro intestinal issues, and concentrates, whether for medical or 94 00:06:33.639 --> 00:06:38.439 recreational use, arguably make it easier to regulate dosage sure 95 00:06:38.519 --> 00:06:41.920 Atoms allows pre rolled joints with measured amounts of flour 96 00:06:42.319 --> 00:06:46.040 offer some consistency, but even that is less predictable than 97 00:06:46.079 --> 00:06:50.000 the cleaned up scientifically produced to concentrate that you know 98 00:06:50.079 --> 00:06:52.759 exactly what the impact is going to be, he says. 99 00:06:53.319 --> 00:06:57.439 Rolling your own stuffing erratic hunks of vegetable matter into 100 00:06:57.480 --> 00:07:00.800 a pipe, it's a hard cell, says Atoms. Consumers are 101 00:07:01.160 --> 00:07:05.759 just not used to the primitiveness. The quest to concentrate 102 00:07:05.920 --> 00:07:09.519 the psychoactive components of cannabis goes back to at least 103 00:07:09.519 --> 00:07:14.160 the eleventh century, when hashish caught on recreationally in the 104 00:07:14.160 --> 00:07:17.959 Arab world. Hasheesh is made from plant glands now known 105 00:07:18.079 --> 00:07:23.240 as tricombs, which early hashmakers rubbed or sieved off the 106 00:07:23.279 --> 00:07:26.959 surface of cannabis leaves and buds, then pressed into a 107 00:07:26.959 --> 00:07:32.439 sort of cake. Tricombs are rich in bioactive compounds called cannabinoids, 108 00:07:32.959 --> 00:07:37.680 the most well known of which are THHC and cannabidial 109 00:07:37.959 --> 00:07:43.199 or CBD. They also contain other specialized compounds, such as chirpenes, 110 00:07:43.319 --> 00:07:49.199 the hydrocarbons responsible for plants, aromas, and flavors. Today, cannabis 111 00:07:49.240 --> 00:07:53.279 processors have built on medieval methods, finding new efficient ways 112 00:07:53.319 --> 00:07:57.199 to isolate those prized compounds. Among the most common is 113 00:07:57.240 --> 00:08:02.160 hydrocarbon extraction, in which a solvent separates desired chemicals from 114 00:08:02.399 --> 00:08:07.839 raw plant material. Butane and propane are the industry standard solvents, and, 115 00:08:07.959 --> 00:08:12.839 prior to widespread legalization, back when extraction was an underground hobby, 116 00:08:13.319 --> 00:08:18.040 use of these combustible materials occasionally resulted in hotel rooms 117 00:08:18.040 --> 00:08:22.040 and apartments blowing up. FEMA went so far as to 118 00:08:22.079 --> 00:08:26.079 issue a bulletin in twenty thirteen warning hash oil explosions 119 00:08:26.160 --> 00:08:30.560 increasing across US, but during the wave of state legislation 120 00:08:30.680 --> 00:08:34.759 that has swept the country since, cannabis extraction has gone mainstream, 121 00:08:35.200 --> 00:08:38.679 and today companies like raw Garden are subject to licensure 122 00:08:38.840 --> 00:08:43.120 regulations and inspections. The basis of nearly all raw garden 123 00:08:43.200 --> 00:08:46.960 products is the oily substance known as live resin a 124 00:08:47.000 --> 00:08:50.399 cannabis extract that aims to capture a wide array of 125 00:08:50.480 --> 00:08:58.000 those cannabinoids and terpen terpenes. Some extraction processes, by contrast, 126 00:08:58.519 --> 00:09:02.759 isolate only a single compon pound, usually THHC or CBD, 127 00:09:03.480 --> 00:09:06.399 but before they become oil. All of the company's offerings 128 00:09:06.759 --> 00:09:09.600 start out as plants on fifty four acres of farmland 129 00:09:09.960 --> 00:09:13.200 in the Santa Barbara wine country. At harvest time, the 130 00:09:13.240 --> 00:09:16.200 plants are cut, then the buds are removed and immediately 131 00:09:16.240 --> 00:09:21.120 flash frozen with liquid nitrogen in a cryogenic tunnel, preserving 132 00:09:21.200 --> 00:09:25.320 all those volatile organic compounds from the farm. The pot 133 00:09:25.399 --> 00:09:29.159 is trucked to a cold storage warehouse in nearby Lombach, 134 00:09:29.519 --> 00:09:32.240 where it's placed in a deep freeze. When any given 135 00:09:32.320 --> 00:09:35.399 strain is up for extraction, the frozen buds are moved 136 00:09:35.440 --> 00:09:38.919 to a manufacturing facility up the road, where they're loaded 137 00:09:38.960 --> 00:09:42.840 into six foot tall stainless steel columns, each of which 138 00:09:42.919 --> 00:09:47.679 can hold about eighteen pounds of pot. Inside, they're saturated 139 00:09:47.720 --> 00:09:51.679 with pressurized solvent that dissolves the desired chemicals and leaves 140 00:09:52.000 --> 00:09:57.919 behind unwanted biomass. Later stages for some project products include 141 00:09:57.960 --> 00:10:02.600 one in which the crude extract is purified with fats, waxes, lipids, 142 00:10:02.600 --> 00:10:06.039 and other solids filtered out other products, cooked for twenty 143 00:10:06.080 --> 00:10:08.960 four to thirty six hours in a vacuum oven to 144 00:10:09.039 --> 00:10:13.679 purge away residual solvent. The pressure inside the oven lowered 145 00:10:13.720 --> 00:10:16.519 so that the solvent evaporates without any of the good 146 00:10:16.519 --> 00:10:20.320 stuff boiling off. Using solvents isn't the only way to 147 00:10:20.360 --> 00:10:23.240 make an extract. Raw Garden sends a small amount of 148 00:10:23.240 --> 00:10:26.480 its harvest to a partner facility where it's turned into 149 00:10:26.480 --> 00:10:31.399 a hashish like product called rosin via a similar process 150 00:10:31.840 --> 00:10:36.360 using only ice, water, heat, and pressure. But hydrocarbon extraction 151 00:10:36.519 --> 00:10:41.679 is scalable and highly efficient. Raw Gardens facility process processes 152 00:10:42.039 --> 00:10:45.720 around twenty twelve hundred pounds of cannabis a day and 153 00:10:45.759 --> 00:10:48.879 has plans to expand. This isn't to say there's no 154 00:10:49.039 --> 00:10:52.440 art to it. A concentrates consistency, That is, whether the 155 00:10:52.480 --> 00:10:57.120 live resin turns into something creamier crispier oily results from 156 00:10:57.159 --> 00:11:00.519 the strain one starts with, as well as small inspired 157 00:11:00.600 --> 00:11:04.639 interventions during extraction. What if we whipped the extract before 158 00:11:04.679 --> 00:11:07.440 purging it. What if we cured it so that crystal's 159 00:11:07.440 --> 00:11:12.240 form extract bound for vape cartridges sometimes involves an additional 160 00:11:12.399 --> 00:11:16.759 step in which terpenes are evaporated and collecting in a 161 00:11:16.799 --> 00:11:21.840 distillation column, then selectively reinserted to achieve specific scent and 162 00:11:21.919 --> 00:11:27.000 flavor profiles in raw gardens vape lab A colorful aroma 163 00:11:27.039 --> 00:11:31.360 wheel shows one hundred plus fragrances one might allegedly encounter 164 00:11:31.799 --> 00:11:36.759 in cannabis, like apricot, sage, pine tyran, espresso. We're taking 165 00:11:36.799 --> 00:11:41.559 aromatic compounds from plants. As vice President of Agricultural Operations 166 00:11:41.639 --> 00:11:46.200 Casey Birthisle, there's a lot here that's parallel to the 167 00:11:46.240 --> 00:11:51.240 perfume industry. Some medical professionals see more alarming parallels, however, 168 00:11:51.679 --> 00:11:55.919 to drugs ostensibly harder than cannabis. The sky high potency 169 00:11:55.919 --> 00:12:00.600 of concentrates has raised red flags, as multiple epidemiological studies 170 00:12:00.639 --> 00:12:04.639 have found correlations between their frequent use and increased risks 171 00:12:04.919 --> 00:12:09.799 of psychoses and cannabis use disorder, a form of dependence. 172 00:12:10.360 --> 00:12:14.720 Those risks seem particularly acute for teenagers. Colorado and Washington, 173 00:12:14.799 --> 00:12:18.519 the first states to legalize recreational pot are among the 174 00:12:18.519 --> 00:12:22.320 states where bills to limit THHC potency have been introduced, 175 00:12:22.639 --> 00:12:28.159 then rejected or withdrawn amid industry pushback. Meanwhile, according to 176 00:12:28.200 --> 00:12:32.080 analyst Atoms, sales of marijuana flour made up about seventy 177 00:12:32.120 --> 00:12:36.000 percent of the recreational market when the first legal retailers 178 00:12:36.320 --> 00:12:40.279 opened in Colorado in twenty fourteen. Today, according to point 179 00:12:40.279 --> 00:12:44.360 of sale data from Atoms and market research firm BDSA, 180 00:12:44.879 --> 00:12:48.200 that number has dropped to forty percent. In the same span, 181 00:12:48.639 --> 00:12:53.080 sales of vaping and dada being products have climbed from 182 00:12:53.080 --> 00:12:56.600 around fifteen percent of the legal market to thirty two percent, 183 00:12:57.039 --> 00:12:59.720 though the pace of that growth now seems to be slowing. 184 00:13:00.399 --> 00:13:03.200 It's all a function, Adam says, of a reunion of 185 00:13:03.240 --> 00:13:08.320 technology in cannabis brought about by legalization. Ironically, what excites 186 00:13:08.399 --> 00:13:11.440 him most about the future of extraction has nothing to 187 00:13:11.480 --> 00:13:15.000 do with t h C. The next big things in cannabis, 188 00:13:15.000 --> 00:13:19.519 Adams suggests, might derive from the industry's ability to efficiently 189 00:13:19.600 --> 00:13:23.320 isolate all those other compounds. What new effects are there 190 00:13:23.399 --> 00:13:27.279 to discover from the terpenes or from the more then 191 00:13:27.519 --> 00:13:32.480 a hundred other little researched cannabinoids that aren't t h 192 00:13:32.559 --> 00:13:37.200 C or CBD. We are totally revolutionizing the view of 193 00:13:37.200 --> 00:13:40.080 what the compounds in the plant can do through the 194 00:13:40.120 --> 00:13:44.240 concentrates side of the market. He says that opens up 195 00:13:44.240 --> 00:13:46.679 the uses to all sorts of things other than sitting 196 00:13:47.000 --> 00:13:52.639 on the couch watching Netflix. Modern cannabis, explained, consuming pot 197 00:13:52.720 --> 00:13:56.679 mostly used to means smoking it, rolling a joint, or 198 00:13:56.720 --> 00:13:59.679 packing a pipe owl. How is vaping it any different? 199 00:14:00.279 --> 00:14:03.600 Like smoking? Vaping cannabis involves heating up some manner of 200 00:14:03.639 --> 00:14:08.080 marijuana and inhaling the results, but without setting anything on fire. 201 00:14:08.559 --> 00:14:11.360 Some vaping devices can be loaded with dry herb or 202 00:14:11.399 --> 00:14:15.200 cannabis flour, while others are used for high potency concentrates 203 00:14:15.519 --> 00:14:18.399 like oil or live resin. At the touch of a button, 204 00:14:18.440 --> 00:14:21.440 a battery powered element heats the bud or oil just 205 00:14:21.559 --> 00:14:25.559 enough to release compounds like THHC and other cannabinoids in 206 00:14:25.639 --> 00:14:29.320 an aerosol or vapor without any burning plant material. The 207 00:14:29.399 --> 00:14:33.799 experience may seem less harsh than smoking. It's also arguably 208 00:14:33.879 --> 00:14:38.720 more convenient. Hand Held devices like vappens are portable and discrete, 209 00:14:38.960 --> 00:14:43.559 leaving less odor than smoking. Many pens are disposable, and 210 00:14:43.639 --> 00:14:47.480 for those seeking to reduce electronic waste. Other styles can 211 00:14:47.519 --> 00:14:51.519 be reloaded with prefilled cartridges of cannabis oil, known as 212 00:14:51.639 --> 00:14:56.159 vape carts. Studies suggest that vaping flour rather than smoking 213 00:14:56.200 --> 00:15:00.039 it can reduce your exposure to toxins and carbon monoxide, 214 00:15:00.159 --> 00:15:04.559 but that doesn't mean it's entirely safe. Vaping, especially with concentrates, 215 00:15:04.840 --> 00:15:09.159 comes with its own lung disease risks. For people interested 216 00:15:09.240 --> 00:15:11.840 in more of a THHC jolt, there's the form of 217 00:15:11.919 --> 00:15:16.559 vaporization called dabbing, which involves heating up thicker cannabis concentrates 218 00:15:16.600 --> 00:15:20.440 like wax, a gooey form of hash oil, or shatter 219 00:15:20.879 --> 00:15:24.440 a solid glass like version. This takes a different tool, 220 00:15:24.600 --> 00:15:27.519 known as a dab rig, a kind of water pipe 221 00:15:27.600 --> 00:15:31.440 that's more elaborate and less portable than most vapes. Users 222 00:15:31.440 --> 00:15:34.679 typically apply a small hand held torch to a heating 223 00:15:34.720 --> 00:15:38.399 element called a nail, then use a wand like tool 224 00:15:38.600 --> 00:15:41.879 to touch a dollop of concentrate to it, inhaling its 225 00:15:41.960 --> 00:15:45.200 vapor through a chamber of cooling water. Hand Held dab 226 00:15:45.240 --> 00:15:49.759 pens are a simpler alternative, but some dab fans suggest 227 00:15:49.919 --> 00:15:54.480 dab pens can sacrifice flavor, making such devices smaller, simpler 228 00:15:54.480 --> 00:15:58.960 and cheaper is a major focus of the increasingly innovation 229 00:15:59.120 --> 00:16:03.080 driven industry. A new tool in the Fight against chronic 230 00:16:03.120 --> 00:16:08.000 pain by Devon Powell. For decades, scientists have sought a 231 00:16:08.120 --> 00:16:12.039 non addictive means of treating people in ongoing agony. Now 232 00:16:12.080 --> 00:16:16.639 cannabis is inspiring a safer way forward. They call it 233 00:16:16.720 --> 00:16:19.759 the holy Grail of pain relief research, a medicine that 234 00:16:19.840 --> 00:16:23.399 is comparable to the strongest opioids but lacks their potentially 235 00:16:23.399 --> 00:16:29.879 devastating side effects. When biophysicist and structural biologist Kavya Krishna 236 00:16:30.000 --> 00:16:33.320 Kumar set out looking for a novel way to develop one, 237 00:16:33.559 --> 00:16:35.799 she knew she needed to start with a substance that 238 00:16:35.879 --> 00:16:38.600 hit the body incredibly hard. So she took to the 239 00:16:38.600 --> 00:16:41.759 seatier corners of the online forum read It, where she 240 00:16:41.879 --> 00:16:45.039 learned about an illicit street drug with a reputation for 241 00:16:45.159 --> 00:16:48.240 making people both very high and very sick. It's out 242 00:16:48.279 --> 00:16:52.840 of this world potent, read one recreational user's poach post. 243 00:16:53.279 --> 00:16:57.000 A very very small, almost invisible amount of powder sky 244 00:16:57.159 --> 00:17:02.279 rockets you into stoned euphoria. The drug is called fubinacca, 245 00:17:02.519 --> 00:17:06.680 and it's what's known as a synthetic cannabinoid A molecule 246 00:17:06.759 --> 00:17:08.920 designed in a lab to target the same parts of 247 00:17:08.960 --> 00:17:14.480 the nervous system affected by tetra hydro cannabinol or THHC, 248 00:17:15.119 --> 00:17:19.640 the main psychoactive compound in cannabis. Underground chemists have been 249 00:17:19.640 --> 00:17:22.680 making drugs like it since the early two thousands, when 250 00:17:22.720 --> 00:17:26.759 recreational marijuana was still criminalized in the United States and 251 00:17:26.839 --> 00:17:32.400 synthetic cannabinoids began catching on as a cheap quasi legal alternatives. 252 00:17:33.000 --> 00:17:36.519 From their powdered form, they're typically dissolved into solvents, which 253 00:17:36.519 --> 00:17:40.839 are then sprayed on two plant shreds to be sold 254 00:17:40.880 --> 00:17:45.000 with a wink as incense or pot poiri. Not for 255 00:17:45.079 --> 00:17:48.480 human consumption. The label may read a dodge against regulation. 256 00:17:49.359 --> 00:17:52.839 Sold under monikers like spice or K two, these gray 257 00:17:52.839 --> 00:17:56.319 market synthetics have raised public health alarms for both their 258 00:17:56.359 --> 00:18:01.599 toxicity and their contamination risks. The extract the exact chemicals, 259 00:18:01.599 --> 00:18:05.079 and their concentrations can vary from product to product, with 260 00:18:05.119 --> 00:18:09.559 side effects ranging from mania to heart attacks. But Krishna Kumar, 261 00:18:09.920 --> 00:18:14.680 then at Stanford Medicine, now at wild Cornell Medicine, now 262 00:18:14.839 --> 00:18:19.720 in fubinaka a tool for better understanding how our pain 263 00:18:19.799 --> 00:18:24.359 management system works, and after some clever molecular modeling. She 264 00:18:24.559 --> 00:18:27.759 and a team led by researchers from Stanford and Washington 265 00:18:28.119 --> 00:18:31.960 University School of Medicine in Saint Louis devised an innovative 266 00:18:32.000 --> 00:18:35.519 way of modifying it. Earlier this year, the team published 267 00:18:35.920 --> 00:18:40.759 a study showing a fubinaca derived drug providing a sustained 268 00:18:40.759 --> 00:18:45.599 pain relief in mice, seemingly without psychoactive or tolerance building 269 00:18:45.640 --> 00:18:49.920 side effects. Such side effects have stymied progress on other 270 00:18:50.079 --> 00:18:56.279 would be cannabinoid pain relievers, dampening enthusiasm for what once 271 00:18:56.359 --> 00:19:01.440 seemed like a promising opioid alternative. Now, some scientists hope 272 00:19:01.599 --> 00:19:04.319 the research can breathe new life into that work and 273 00:19:04.400 --> 00:19:10.160 perhaps open up even wider therapeutic frontiers. Fubinaca wasn't always 274 00:19:10.160 --> 00:19:13.359 a street drug. It was developed by Phizer and patented 275 00:19:13.400 --> 00:19:16.200 in two thousand nine, part of an effort to create 276 00:19:16.279 --> 00:19:20.759 a superpowered aspirin with no side effects. According to former 277 00:19:20.799 --> 00:19:28.279 physer chemist Darren Jones, like THHC, synthetic cannabinoids activate a 278 00:19:28.319 --> 00:19:32.640 powerful chemical receptor known as CB one in humans and 279 00:19:32.680 --> 00:19:35.839 other mammals. CB one is found on nerve cells in 280 00:19:35.880 --> 00:19:39.000 the brain and crucially on cells elsewhere in the body. 281 00:19:39.400 --> 00:19:42.319 It's known to influence not only the perception of pain, 282 00:19:42.400 --> 00:19:46.599 but also sleep, metabolism, and memory, making it a promising 283 00:19:46.680 --> 00:19:53.160 target for pharmaceutical research. A second cannabinoid receptor, c B two, 284 00:19:53.240 --> 00:19:57.519 seems mostly to regulate the functions of immune cells. Of course, 285 00:19:57.559 --> 00:20:00.279 the path to market for any new drug it must 286 00:20:00.319 --> 00:20:04.559 take into account future profitability, and while it's unclear just 287 00:20:04.720 --> 00:20:09.240 what scuttled Pfiser's research, Jones theorizes it had to do 288 00:20:09.279 --> 00:20:13.039 with the increasing legality of medical marijuana, which was suddenly 289 00:20:13.119 --> 00:20:18.160 pennies a pound at pro proliferating dispensaries. But when the 290 00:20:18.200 --> 00:20:21.640 company published its patent, that became a blueprint for so 291 00:20:21.680 --> 00:20:26.240 called garage chemists to replicate the formula and create analogs. 292 00:20:26.319 --> 00:20:30.599 The US Drug Enforcement Administration reports that law enforcement has 293 00:20:30.680 --> 00:20:35.680 encountered hundreds of different synthetic cannabinoids, most of them manufactured 294 00:20:35.720 --> 00:20:40.000 in Asia. Variants of Pfiser's fubinaca, the first of which 295 00:20:40.119 --> 00:20:43.559 was detected in Japan in twenty twelve, are known as 296 00:20:43.640 --> 00:20:48.039 most of the most toxic. In twenty fourteen, dozens of 297 00:20:48.079 --> 00:20:53.920 deaths in Russia were linked to an analog called MDMB fubinaca. 298 00:20:54.200 --> 00:20:57.279 Two years later, another variant was behind a mass overdose 299 00:20:57.319 --> 00:21:00.440 in Brooklyn, New York that the media characterized as a 300 00:21:00.559 --> 00:21:04.680 zombie outbreak. But Krishna Kumar hoped to pick up where 301 00:21:04.680 --> 00:21:09.359 Pfizer left off harnessing that potency. First, she examined how 302 00:21:10.039 --> 00:21:14.440 MDMB fubinaca attached to human CB I receptors in the 303 00:21:14.519 --> 00:21:19.279 dish compared to other synthetic cabin cannabinoids. She found it 304 00:21:19.440 --> 00:21:23.880 held tighter and activated effects more powerfully. Then, using a 305 00:21:23.920 --> 00:21:30.640 Nobel Prize winning technology called cryoelectron microscopy cryo e M, 306 00:21:31.119 --> 00:21:36.039 she flashes that she flash froze that fubinaca molecule while 307 00:21:36.160 --> 00:21:39.640 it was affixed to CB one and scanned the conjoined 308 00:21:39.720 --> 00:21:43.119 pair with a beam of electrons. The result was a 309 00:21:43.160 --> 00:21:47.319 three D picture, down to individual atoms, of how the 310 00:21:47.400 --> 00:21:50.240 drug fits so well into a pocket or binding sight 311 00:21:50.480 --> 00:21:53.359 on the receptor's surface like a key in a lock. 312 00:21:53.880 --> 00:21:58.559 That image provided a starting point for designing new versions 313 00:21:58.559 --> 00:22:02.480 of fubinaca that might, by stimulating the receptor in new ways, 314 00:22:02.880 --> 00:22:07.839 keep the original's potency while limiting side effects. For that, 315 00:22:08.039 --> 00:22:14.200 Krishna Kumar turned to Sasruta Majumdar, a Washington university chemist 316 00:22:14.640 --> 00:22:19.039 and pharmacologist whose lab had previously shown that activating a 317 00:22:19.039 --> 00:22:24.720 particular site on an opioid receptor could inhibit chemical reactions 318 00:22:24.759 --> 00:22:28.759 that led to tolerance. Might this be possible for CEB one. 319 00:22:29.559 --> 00:22:32.160 The researchers knew that CEB one, a cousin to that 320 00:22:32.319 --> 00:22:36.519 opioid receptor, had a potential binding site with similar qualities, 321 00:22:36.759 --> 00:22:39.359 but it was deep inside the receptor and in Krishna 322 00:22:39.440 --> 00:22:44.440 Kumar's cryo em snapshot, blocked by clusters of atoms. It 323 00:22:44.720 --> 00:22:49.000 was also the wrong shape to fit Fubinaka, So Majumdar's 324 00:22:49.240 --> 00:22:54.960 team started sketching bespoke attachments for the cannabinoid chains of 325 00:22:55.000 --> 00:22:59.640 atoms that might help the molecule worm its way in. Meanwhile, 326 00:23:00.000 --> 00:23:04.640 Truford scientists took another approach, animating the statics napshot using 327 00:23:04.759 --> 00:23:08.680 computer simulations showing how atoms in the drug and the 328 00:23:08.720 --> 00:23:13.680 receptor moved around each other. The simulations revealed something surprising. 329 00:23:14.160 --> 00:23:20.079 The atom clusters blocking blocking the tantalizing sight sporadically moved aside, 330 00:23:20.160 --> 00:23:24.359 opening what biochemists call a cryptic pocket, allowing researchers a 331 00:23:24.400 --> 00:23:30.119 glimpse in tweaking their designs to fit Majumdar's team made 332 00:23:30.200 --> 00:23:34.319 one other crucial adjustment in the hope of nixing fubinacca's 333 00:23:34.640 --> 00:23:38.480 psychoactive side effects. The newly accessible site, it turned out, 334 00:23:38.759 --> 00:23:42.119 could accept a compound with a positive electric charge, which 335 00:23:42.200 --> 00:23:46.119 hinders a molecule from crossing the membrane separating blood from 336 00:23:46.119 --> 00:23:51.039 the brain. By tacking a charged group of atoms onto fubinaca, 337 00:23:51.240 --> 00:23:56.079 researchers confined its activity to CEB one receptors outside the brain, 338 00:23:56.480 --> 00:23:58.920 where it can't get anyone high or act on the 339 00:23:58.960 --> 00:24:04.359 brain's reward circuitry, limiting risks of misuse and abuse. New 340 00:24:04.440 --> 00:24:08.759 versions of fubinaca were injected into rodents experiencing various kinds 341 00:24:08.799 --> 00:24:13.200 of pain, and one variant, which the researchers called VIP 342 00:24:13.400 --> 00:24:18.039 thirty six, showed indicators of relieving chronic pain from three 343 00:24:18.079 --> 00:24:22.799 different sources inflammation, nerve damage, and headaches, even after days 344 00:24:22.839 --> 00:24:28.839 of repeated injections. True, says Washington University neurobiologist Robert Giroux, 345 00:24:29.319 --> 00:24:33.359 all that molecular tinkering had reduced the drug's potency and 346 00:24:33.440 --> 00:24:37.480 thus its pain relieving effects, but where that might have 347 00:24:37.599 --> 00:24:42.640 left other cannabinoids toothless GIAU says VIP thirty six remained 348 00:24:42.920 --> 00:24:47.359 effective in a range that is useful clinically, precisely because 349 00:24:47.359 --> 00:24:52.640 fubinaca packed such a wallop to begin with. VIP thirty 350 00:24:52.680 --> 00:24:55.200 six is still in its baby steps phase. It has 351 00:24:55.279 --> 00:24:57.839 yet to be tested in humans who have fewer c 352 00:24:57.960 --> 00:25:01.519 B one receptors outside of their brains than rodents do, 353 00:25:02.279 --> 00:25:05.480 and for now the new compound can't be taken orally, 354 00:25:05.559 --> 00:25:09.039 only injected. But even if the drug never reaches your 355 00:25:09.079 --> 00:25:14.079 medicine cabinet, the research could still chart new pharmaceutical paths 356 00:25:14.400 --> 00:25:17.480 for when it might occasion a reassessment from those skeptical 357 00:25:17.559 --> 00:25:23.119 of cannabinoid's potential as medicine, a constituency that includes the 358 00:25:23.119 --> 00:25:28.200 world's largest pain research organization, the International Association for the 359 00:25:28.200 --> 00:25:32.039 Study of Pain, whose official position is that science has 360 00:25:32.039 --> 00:25:35.960 so far failed to prove cannabinoids either safe or effective. 361 00:25:36.400 --> 00:25:39.839 This is the perfect paper to help reput steam into 362 00:25:39.880 --> 00:25:45.160 the cannabinoid field, says Michael Burton, a neuroscientist and cannabinoid 363 00:25:45.200 --> 00:25:49.559 researcher at the University of Dallas at Texas. What's more, 364 00:25:49.960 --> 00:25:53.279 Majumdar says there may be other cryptic pockets in other 365 00:25:53.359 --> 00:25:57.000 receptors related to CB one, many of which have nothing 366 00:25:57.000 --> 00:25:59.880 to do with pain. Some have been linked to heart disease, 367 00:26:00.039 --> 00:26:05.200 for instance, or substance abuse disorders. This opens an enticing possibility. 368 00:26:05.799 --> 00:26:09.160 What the researchers have learned about changing a receptor's behavior 369 00:26:09.640 --> 00:26:12.480 could help them tinker with a whole range of drugs. 370 00:26:13.039 --> 00:26:17.000 Majumdar is already planning to revisit a previous study that 371 00:26:17.160 --> 00:26:22.160 unsuccessfully targeted a hard to reach opioid receptor. He imagines 372 00:26:22.559 --> 00:26:28.200 redesigning antidepressants, maybe cancer drugs targeting diseases beyond pain is 373 00:26:28.480 --> 00:26:31.119 expected in the near future. He says, we are just 374 00:26:31.119 --> 00:26:34.839 scratching the surface. Compared to what law enforcement seized in 375 00:26:34.839 --> 00:26:38.720 the nineteen nineties, cannabis grown in the United States today contains, 376 00:26:38.759 --> 00:26:43.240 on average, far more THHC, the plant's main psychoactive compound. 377 00:26:44.519 --> 00:26:48.039 What are the differences between actual cannabis and synthetic products 378 00:26:48.079 --> 00:26:52.119 like K two spice and Delta eight? Are these legal 379 00:26:52.279 --> 00:26:56.359 really legal? Some of these lab made cannabis substitutes may 380 00:26:56.559 --> 00:26:59.599 indeed be legally sold, but legal isn't the same thing 381 00:26:59.680 --> 00:27:04.039 as SAYE, and synthetic cannabinoids come with risks. What makes 382 00:27:04.079 --> 00:27:07.240 things murky and dangerous? Is that what you might hear 383 00:27:07.440 --> 00:27:10.920 called fake or synthetic pot isn't a single drug, but 384 00:27:11.039 --> 00:27:16.880 whole classes of chemicals. To create synthetic cannabinoids for recreational use, 385 00:27:17.279 --> 00:27:22.359 underground chemists formulate compounds that are chemically distinct from THHC 386 00:27:22.519 --> 00:27:26.640 but act on nerve receptors in similar ways. Since some 387 00:27:26.720 --> 00:27:30.119 of those substances marketed with names like K two and 388 00:27:30.200 --> 00:27:34.599 spice aren't technically illegal, they can be sold at gas stations, 389 00:27:34.720 --> 00:27:38.799 smoke shops, and online stores, as for example, herbal incense, 390 00:27:39.319 --> 00:27:42.839 but many have suggestive branding that alerts consumers to a 391 00:27:42.920 --> 00:27:48.599 potential secondary usage for the chemical laced blends. This concludes 392 00:27:48.640 --> 00:27:52.400 readings from National Geographic Magazine for today. Your reader has 393 00:27:52.440 --> 00:27:55.160 been Marcia. Thank you for listening, Keep on listening, and 394 00:27:55.279 --> 00:27:56.000 have a great day.