The truth is that no one knows precisely what any of these molecules are doing to us. It is a case of finding the effects first and working backwards to understand the mechanisms. “There are a number of possible transmitter systems that CBD could act on,” says McGuire. “And it’s not 100% clear which ones are critical for anxiety, or psychosis or schizophrenia. But [the antipsychotic effect] is a different mechanism from existing treatments, which is a big deal because existing treatments aren’t working.”
Selective breeding of cannabis plants has expanded and diversified as commercial and therapeutic markets develop. Some growers in the U.S. succeeded in lowering the proportion of CBD-to-THC to accommodate customers who preferred varietals that were more mind-altering due to the higher THC and lower CBD content. Hemp is classified as any part of the cannabis plant containing no more than 0.3% THC in dry weight form (not liquid or extracted form).
A geneticist, Kane studies cannabis from a unique perspective—he probes its DNA. He’s an affable, outdoorsy guy with a bright face and eyes that wander and dart inquisitively when he talks. He has studied chocolate and for many years the sunflower, eventually mapping its genome, a sequence of more than three and a half billion nucleotides. Now he’s moved on to marijuana. Though its sequence is much shorter, roughly 800 million nucleotides, he considers it a far more intriguing plant.
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The 44,000-square-foot building hulks across from a police station in an industrial part of Denver, along a gritty stretch of converted warehouses that’s come to be known as the Green Mile. There’s nothing to indicate the nature of the enterprise. The door buzzes open, and I’m met by the chief horticulturist of Mindful, one of the largest cannabis companies in the world. A druidlike 38-year-old with keen blue eyes, Phillip Hague wears fatigues, hiking boots, and the incredulous grin of someone who—through a confluence of events he never imagined possible—has found his exact life’s calling.
But it’s Guzmán’s brain tumor research that has captured headlines—and the interest of pharmaceutical companies. Through his years of research he has ascertained that a combination of THC, CBD, and temozolomide (a moderately successful conventional drug) works best in treating brain tumors in mice. A cocktail composed of these three compounds appears to attack brain cancer cells in multiple ways, preventing their spread but also triggering them, in effect, to commit suicide.
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CBD was first discovered in the 1940s by Roger Adams, the former head of the chemistry department at University of Illinois at Champaign-Urbana. In his research, Adams isolated CBD from hemp but couldn’t determine what exactly he’d found. In addition to CBD, Adams also synthesized analogs of THC and another cannabinoid, showing their relationship to CBD.
What makes CBD so appealing is that it’s non-intoxicating, so it won’t get you high, though it “is technically psychoactive, because it can influence things like anxiety,” Jikomes said. Although much of the marketing blitz around CBD centers on the fact that you can take it without getting stoned, there isn’t much research looking at the effects of CBD when used in isolation, with a couple of exceptions. One is the use of CBD to treat seizures: CBD is the active ingredient in the only cannabis product that the Food and Drug Administration has signed off on — a drug called Epidiolex, which is approved for treating two rare forms of epilepsy. Animal models and a few human studies suggest that CBD can help with anxiety, but those are the only conditions with much research on CBD in isolation.
A research conducted by Ethan B Russo, GW Pharmaceuticals, WA, USA, suggests that CBD oil interacts with the protein cells in the body and sends chemical signals to your brain and immune system through a number of stimuli. This helps the cells positively respond to chronic pain. This oil is regularly suggested for people with inflammation and back pain because of its painkilling quality.
As a consumer, you can look at the manufacturer's website to see whether they batch-test their products, or ask them directly. You could also send a sample of your CBD oil to a testing facility yourself, something Bonn-Miller says he would do if he were trying to treat someone with a severe issue such as epilepsy. Testing can also determine whether the product contains pesticides, heavy metals, or other toxins.
Right now, there’s a good chance that you don’t really know what you’re getting from any source. Testing and labeling rules vary by state, but many states that allow legal cannabis also require some kind of testing to verify that the THC and CBD levels listed on the label are accurate. However, this testing is controversial, and results can vary widely between labs, Jikomes said. A study published in March found measurable variations in test results, with some labs consistently reporting higher or lower levels of cannabinoids than others. There are no guarantees that the label accurately reflects what’s in the product. For a 2015 study published in JAMA, researchers tested 75 products purchased in San Francisco, Los Angeles and Seattle and found that only 17 percent were accurately labeled. More than half of the products contained significantly lower levels of cannabinoids than the label promised, and some of them contained only negligible amounts of the compounds. “We need to come up with ways to confidently verify the composition of cannabis products and make this information available to consumers,” Jikomes said.
In order to create a system where oils can be provided to patients when the original prescription is expressed in grams of dried product, each Licensed Producer must provide an ‘Equivalency Factor’. This allows you to see how much oil you can purchase to be in line with your prescription and ensures that you do not go over your prescribed allowance. For example, a 60ml bottle of Blueberry Lamsbread Cannabis Oil, which has an equivalency factor of 12 ml of oil to 1 gram of dried cannabis, will use 5 grams of your possession limit.
According to the American Glaucoma Society, cannabis has demonstrated the ability to lower IOP in both normal individuals and in those with glaucoma, and therefore might be a natural glaucoma treatment. One cautionary fact about cannabis’ ability to lower IOP is that it only works for a short time, so patients would have to use cannabis about every three hours.
Although we’ve packaged our oils in a dark glass bottle to better preserve the active ingredients, we recommend storing your cannabis oil in a cool, dark place. It doesn’t need to be refrigerated, but you also don’t want to set it on a sunny windowsill either. As with any cannabis product, keep your oils out of reach of other family members, especially children.
Both Bonn-Miller and Ward stress that it's up to the consumer to be well-educated about the material they're purchasing and the research that's out there. "The companies that are creating [cannabis oils] are offering lots of claims about its use that are not necessarily substantiated by any research," Bonn-Miller said. So "I think there needs to be, from a consumer standpoint, a lot of vigilance," he added.
A 2016 review of animal studies indicated that cannabidiol has potential as an anxiolytic for relief of anxiety-related disorders and fear. Reviews of preliminary research showed cannabidiol has potential for improving addictive disorders and drug dependence, although as of 2016, they indicated limited high-quality evidence for anti-addictive effects in people.
Kane fingers one of his innocuous-looking plants, expressing mild bemusement at the U.S. ban on commercial hemp cultivation. “Hemp produces fibers of unparalleled quality,” he notes. “It’s a tremendously high biomass crop that replenishes the soil and doesn’t require much in terms of inputs. We import tons and tons of hemp each year from China and even Canada, yet as a matter of federal policy, we can’t legally grow it. There are places where farmers in the U.S. can literally look across the Canadian border and see fields that are yielding huge profits.”
Cannabinoids are a class of compounds that interact with receptors throughout your body. CBD is just one of dozens of cannabinoids found in cannabis, including tetrahydrocannabinol (THC), which is the one responsible for marijuana’s famous high. Medical cannabis is technically any cannabis product used for medicinal purposes, and these can contain THC or CBD or both, said Nick Jikomes, a neuroscientist at Leafly, a website that provides information about legal cannabis. “A common mistake people make is to think that CBD is ‘the medical cannabinoid’ and THC is ‘the recreational cannabinoid.’” That’s inaccurate, he said, because THC is a potent anti-inflammatory and can be helpful for pain.
Typically, pharmaceutical companies making cannabis-based medicines have sought to isolate individual compounds from the plant. But Mechoulam strongly suspects that in some cases those chemicals would work much better in concert with other compounds found in marijuana. He calls this the entourage effect, and it’s just one of the many cannabis mysteries that he says require further study.
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