Cannabis (Cannabis sativa L.) has been the topic of a lot of discussion in the U.S., not just in recent decades but for more than a century. It’s been one of the most controversial plants worldwide, arguably more than poppies and peyote.

What’s hard to argue with, however, are the clinical findings that the pain-relieving effects of the cannabis plant are 30 times more potent than aspirin for decreasing inflammation, according to scientists at the University of Guelph in Ontario, Canada, a country where cannabis use became legal as of October 17, 2018.1

Tariq Akhtar and Steven Rothstein, professors in the molecular and cellular biology department at McGill University Health Center, worked with five colleagues on the study, observing that besides the psychoactive aspects of tetrahydrocannabinol (THC) and the pharmacological features of cannabinoids such as cannabidiol (CBD) derived from C. sativa varieties, there’s potential for numerous medicinal uses.

One of the points made by the study, published by the journal Phytochemistry,2 is the plant’s “medicinal versatility,” and its focus on two specific molecules, cannflavin A and cannflavin B. Interestingly, the research notes that cannflavins A and B first came to light in 1985 when the benefits were compared to acetylsalicylic acid, the product sold as “aspirin.”

Because research on cannabis has been regulated diligently in Canada, not to mention the U.S., decades of stymied opportunities for discovery were lost due to the ban on its use. Once the ban was lifted, however, Akhtar and Rothstein proceeded, further armed with advanced genomic research.

What’s next: Engineering the molecules

The team’s stated objective was to “better understand how these molecules are made,” Akhtar noted. “There are many sequenced genomes that are publicly available, including the genome of Cannabis sativa, which can be mined for information. If you know what you’re looking for, one can bring genes to life, so to speak, and piece together how molecules like cannflavins A and B are assembled.”3

To identify the biosynthesis producing the two “medicinally relevant cannabis compounds,” the scientists explained:

“Evidence is presented for an O-methyltransferase (CsOMT21) encoded within the C. sativagenome that specifically converts the widespread plant flavone known as luteolin to chrysoeriol, both of which accumulate in C. sativa. These results therefore imply the following reaction sequence for cannflavins A and B biosynthesis: luteolin ► chrysoeriol ► cannflavin A and cannflavin B.”4

Separate studies establish that flavones serve as antioxidant,5 neuroprotective6 and anticancer7 resources when ingested. It’s worth noting that while other plants have been examined to determine similar biosynthetic pathways, oddly, cannabis had not until recently.8

Now, however, the team is working with Canadian company Anahit International Corp., which holds a licensed patent from the university, to develop a “biological system to create these molecules, which would give us the opportunity to engineer large quantities,”9 Rothstein said.

Anahit executives said the company plans to work further with the researchers to “develop effective and safe anti-inflammatory medicines from cannabis phytochemicals that would provide an alternative to non-steroidal anti-inflammatory drugs,” according to chief operating officer Darren Carrigan, who explained what will come next:

“Anahit will commercialize the application of cannflavin A and B to be accessible to consumers through a variety of medical and athletic products such as creams, pills, sports drinks, transdermal patches and other innovative options.”10

The reason that’s important, is that currently in the U.S., people looking for pain relief often turn to opioids, popular because they can effectively block the pain receptors in your brain, but there are two major downsides: numerous side effects and a very real likelihood of addiction.

The continuing case for cannabis

Cannflavins A and B were also discussed in a collaborative study in 2014, which found the foundational source of their potent action came from “two pro-inflammatory mediators, prostaglandin E2 and the leukotrienes.”11 The seeds were found to lack the usual phenolics found in hemp leaves and flower heads, and sprouting them produced cannflavins A and B, they did not trigger cannabinoids. Further:

“Hemp seeds are of great nutritional value, containing all essential amino acids and fatty acids in sufficient amount and ratio to meet the dietary human demand. Hemp seeds do not contain cannabinoids, and because of their high contents of ω fatty acids, are enjoying a growing popularity as a super-food to beneficially affect chronic inflammation.”12

In 2018, another Canadian study produced by McGill University Health Center and led by Gabriella Gobbi, professor of psychiatry and researcher in the Brain Repair and Integrative Neuroscience (BRaIN) Program at McGill, reported that CBD, being free from side effects, is a safe alternative to prescription drugs for pain relief, without the “high” associated with THC.

The team was able to demonstrate that CBD doesn’t work on CB1 cannabinoid receptors in the way THC does, but rather through the specific receptor mechanisms concerned with anxiety, called serotonin 5-HT1A, as well as pain, known as vanilloid TRPV1.

The scientists also extrapolated the precise dosage of CBD for analgesic and anxiety relief, as well as for chronic back, sciatica, diabetic, cancer and other types of pain. Postdoctoral fellow at McGill University and the study’s first author, Danilo De Gregorio, added, “We found in animal models of chronic pain that low doses of CBD administered for seven days alleviate both pain and anxiety, two symptoms often associated in neuropathic or chronic pain.”13

Gobbi called the research a “new advancement for an evidence-based application of cannabis in medicine”14 — pain relief without the euphoria, and more importantly, without the risk of addiction. Notably, the FDA approved CBD oil15 in a purified form known as Epidiolex by prescription for two types of epilepsy.

The crucial difference between cannabis and hemp

While cannabis and hemp are often referred to interchangeably, important distinctions need to be made. Both come from Cannabis sativa and both contain cannabidiol (CBD), but the amount of CBD is the big difference, and that difference is crucial.

Researchers from the University of Minnesota’s College of Biological Sciences and College of Food, Agricultural and Natural Resource Sciences are one of the few groups of scientists in the U.S. given federal authorization to study cannabis.

Following 12 years of study, published online at New Phytologist, U of M plant biologist George Weiblen explained, “While marijuana is rich in psychoactive tetrahydrocannabinol (THC), hemp produces mostly a noneuphoric cannabidiol (CBD).”16 The implications of decades of confusion on the part of the medical community, legislators and the public at large were addressed by EurekAlert:

“The discovery of a single gene distinguishing the two varieties, which according to Weiblen took more than 12 years of research, could strengthen hemp producers’ argument that their products should not be subject to the same narcotics laws as hemp’s cannabinoid cousin.

The market for hemp seed and fiber in the U.S. surpassed $600 million last year alone. But despite the plant’s surging popularity as an ingredient in food, personal care products, clothing and even construction, commercial hemp cultivation is prohibited by the federal government. Currently, all hemp products are imported to the U.S.”17

March 22, 2019, the Congressional Research Service (CRS),18 which serves implicitly at the behest of the U.S. Congress, submitted a fact sheet to define hemp, comparing the differences in chemical and genetic composition from marijuana, as well as its production and use. As deputy director of the North Carolina Cooperative Extension Service, Tom Melton succinctly explains:

“The difference is that hemp plants contain no more than 0.3 percent (by dry weight) of THC (tetrahydrocannabinol), the psychoactive substance found in marijuana. By comparison, marijuana typically contains 5 to 20 percent THC. You can’t get high on hemp.”19

Brief history of hemp in the US

As previously stated, the U.S. has a long history of confusion and misinformation when it comes to the cannabis plant. A brief timeline from Origins,20 published by the history departments at Miami University and The Ohio State University, to show how different areas and legislatures viewed cannabis and its constituents:

In 1862, hashish candy was advertised in Vanity Fair as a pleasurable and harmless stimulant and a way to treat “nervousness and melancholy,” along with the hype that “under its influence all classes seem to gather new inspiration and energy.”
The first effort at establishing federal marijuana regulations were made June 2, 1906, when the Pure Food and Drug Act was passed.21
Between 1914 and 1925, 26 states passed laws prohibiting the plant.
Congress passed the Comprehensive Drug Abuse Prevention and Control Act in 1970, placing marijuana “in the most restrictive category of drugs having no permissible use in medical practice.”
Medical marijuana laws were passed in California in 1996, statewide, while Colorado became the first state to allow marijuana dispensaries to market marijuana for recreational use in 2014.

The 2018 Farm Bill22 made it legal for farmers to grow industrial hemp for the first time since Franklin D. Roosevelt signed the “Marihuana Tax Act of 1937.” The American Farm Bureau Federation states its own clarification:

“Industrial hemp is not marijuana, although it is a different variety of the same species, a fact that has at times resulted in a negative association and stymied hemp’s growth. That species is Cannabis sativa L., a substance that has historically been classified in the U.S. as a Schedule I controlled substance and regulated under the Controlled Substance Act.

Since the 1990s, varieties of this plant containing low levels of delta-9-tetrahydrocannabinol, or THC, which is the ingredient that lends marijuana is psychoactive properties, have been legalized in many European countries, as well as Canada and Australia. The common threshold level of allowable THC for industrial hemp is 0.3 percent on a dry weight basis.”23

Cannabis used for pain reduces addiction risk

One of the most ironic and thought-provoking points in regard to cannabis use as a remedy for pain and inflammation is this one: Using cannabis, especially when it’s so successful in bringing relief, is that it’s a natural (read: not synthetic) substance that could reduce the out-of-control addiction rates now being acknowledged by both the medical and law enforcement communities. Plus, as noted by Medical News Today side effects from CBD use are neither harmful nor lethal:

“Many small-scale studies have looked into the safety of CBD in adults. They concluded that adults tend to tolerate a wide range of doses well. Researchers have found no significant side effects on the central nervous system, the vital signs, or mood, even among people who used high dosages.

The most common side effect was tiredness. Also, some people reported diarrhea and changes in appetite or weight … There is still a lack of available long-term safety data.”24

According to the Department of Health and Human Services25 the essence of the problem, aptly coined the “opioid crisis,” stemmed initially from drug companies in the 1990s collectively assuring medical entities opioid pain relievers weren’t addictive, so they began prescribing them more often.

That resulted in a cascade of events: First, health care personnel started prescribing them more often, which naturally led to widespread consumption of prescription drugs first, then spilled over to nonprescription opioids before it became apparent that they could indeed be very addictive.

By 2017, HHS announced a public health emergency. Statistics helped flesh out the story; for instance, according to a CDC report in 2016, there were 47,055 drug overdose deaths in the U.S. involving synthetic opioids in 2014 alone. Since 2000, the “age-adjusted drug overdose death rate has more than doubled,” and a “substantial portion … appears to be related to increased availability of illicit fentanyl,” a type of opioid that comes with severe side effects, including death.26

The CDC delineates two types of fentanyl: legal and illegal. Legal fentanyl is described as a “synthetic opioid pain reliever, approved for treating severe pain,”27 usually for end-of-life care. The other type, nonpharmaceutical fentanyl, is defined as “Illicitly manufactured and often mixed with cocaine or heroin,” and “50 times more potent than heroin and 100 times more potent than morphine.”28

Common side effects from opioid use

A list of side effects caused by opioid use is addressed by the American Cancer Society.29 These include sleepiness, making it unsafe to drive or operate machinery. Nausea and/or vomiting; and itching are also common. Constipation or trouble urinating are also side effects people experience with opioid use, as well as mental effects such as confusion, hallucinations and nightmares.

While patients may find certain side effects diminish without further treatment intervention, a combination of side effects, such as swelling in your throat, hives or trouble breathing along with nausea, may be an allergic reaction to a drug.

Patients are cautioned to never stop taking their medications suddenly, and to rely on their health care providers for advice on increases or decreases, or interactions with other drugs they may be taking, which can exacerbate problems. Additionally, people often have different reactions to drugs, including over-the-counter kind, but there’s also the opioid epidemic to consider.

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