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The Other Cannabinoids

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Cannabinoids are a diverse set of chemicals used by the endocannabinoid system, one of the largest neurotransmission systems in the bodies of all mammals. Whether the cannabinoids are produced by our bodies (endocannabinoids) or are obtained from external sources like cannabis (ectocannabinoids), they have profound effects on regulating appetite, mood, motor control, immunity, reproduction, pain, memory and sleep, to name a few.

The cannabinoids produced in our bodies are not the exact same cannabinoids found in cannabis, but they all interact with the body’s endocannabinoid system in a very similar way and consequently produce very similar effects.

There are over 100 cannabinoids, but the only ones that make headlines are the two cannabis-produced cannabinoids tetrahydrocannabinol (THC) and cannabidiol (CBD). Both are known for many health benefits such as relieving pain, mitigating depression, inducing sleep and fighting cancer, but THC is notorious for the psychoactive high it produces. As a consequence, THC and CBD eclipse the “other cannabinoids” in name recognition. The rarely mentioned and less-researched “other cannabinoids” have health benefits that deserve serious consideration.

“The cannabinoids produced in our bodies are not the exact same cannabinoids found in cannabis, but they all interact with the body’s endocannabinoid system in a very similar way and consequently produce very similar effects.”

 

Cannabigerol (CBG) is found abundantly in immature plants, but as the plant matures it all but disappears as it is broken down by specific enzymes into other cannabinoids—mainly THC and CBD. CBG has been shown to provide relief from irritable bowel syndrome, reduce intraocular eye pressure in glaucoma patients, inhibit the growth of cancer cells and act as an antibacterial agent. As a consequence of these multiple health benefits, geneticists are working to develop cannabis strains that retain high levels of CBG.

 

Cannabichromene (CBC) is also a derivative of CBG. Of interest is that CBC is reported to provide pain relief by binding with receptors outside the endocannabinoid system leading to increased levels of the body’s natural THC like cannabinoid—anandamide. CBC has also been shown to possess anti-inflammatory, anti-fungal and antibiotic properties.

 

Tetrahydrocannabivarin (THCV) has a similar molecular structure to THC, but medical studies have produced conflicting results on whether it has the same psychoactive properties as THC, with some studies finding enhanced psychoactive properties while others found it to reduce THC’s psychoactive effects. As for health benefits, positive results have been demonstrated in treating diabetes, as THCV has been shown to reduce insulin resistance and regulate blood sugar levels. Research has also shown its potential to lessen anxiety in post-traumatic stress disorder patients and reduce the tremors, brain lesions and loss of motor control associated with Alzheimer’s disease.

 

Cannabinol (CBN) is formed from the exposure of THC to light and air. With minimal psychoactive effects, the high produced by cannabis decreases when THC degrades into CBN due to improper storage. Although CBN will not produce a psychoactive effect, studies have shown an ability to reduce insomnia, fight infections and provide relief from pain.

 

Cannabidivarin (CBDV) is similar in structure and function to CBD. Studies have demonstrated the ability of CBDV to heighten the anti-convulsive properties of CBD. GW Pharmaceuticals, the maker of Epidiolex, the first cannabis-based medicine to be approved by the U.S. Food and Drug Administration, undertook research studies to document the ability of CBDV to treat adults with seizures and autism. Even though the studies did not produce the desired results, GW Pharmaceuticals is continuing the research as its totally non-psychoactive properties make CBDV an ideal candidate for treating these disorders.

 

Delta-8-Tetrahydrocannabinol (Delta-8-THC) has the same atomic composition as traditional THC, but the atoms are arranged differently. Somewhat less psychoactive, it has shown great promise in treating cancer patients as research has demonstrated its ability to kill cancer cells and reduce tumors in mice. Studies have confirmed the research undertaken with mice as Israeli researchers have reported successful cancer treatments utilizing Delta-8-THC in 480 patients. In addition, it has been shown to significantly reduce nausea and vomiting, which would benefit cancer patients experiencing the debilitating side effects of chemo and radioactive therapies.

 

Although cannabinoids can provide benefits on their own, research has established that the cannabinoids found in cannabis work best in the presence of other cannabinoids and not in isolation. Known as “The Entourage Effect,” whole-plant cannabis used in its natural form with its cornucopia of cannabinoids intact remains effective and is perhaps one of the best ways to obtain the health and medical benefits of cannabis.

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Riveting Research

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Eleven states, with a combined population of 77 million people and representing roughly one-fourth of America, have legalized the adult-use of cannabis for any reason. Another 120 million live in states that have legalized some form of medical cannabis. This makes for a grand total of 197 million or over 60 percent of the country.

Based on the predictions of drug warrior groups opposing cannabis legalization, we should be experiencing substantial increases in youth consumption, increased driving fatalities from impaired drivers and dramatic increases in physical and mental health ailments.

Far from their sky is falling pronouncements, the results published in peer-reviewed evidentiary-based medical journals have found that all states that legalized the medical and adult-use of cannabis have experienced positive benefits. It’s not to say that there haven’t been some problems, but overall, the effects are beneficial for public health.

A study published in the October 2019 The American Journal of Drug and Alcohol Abuse found that “medical cannabis laws increase adult but not adolescent cannabis use,” although the report did caution that “provisions of the laws associated with less regulated supply may increase adult cannabis use disorders.” The same proved true for recreational cannabis laws as the report noted their “findings suggest little impact on the prevalence of adolescent cannabis use, potential increases in college student use, and unknown effects on other substance use.” The study went on to recognize that “these laws may reduce some opioid-related harms, while their impacts on alcohol and tobacco use remain uncertain.”

“Reducing opioid-related harm is one of the major public benefits of legalizing cannabis.”

 

Reducing opioid-related harm is one of the major public benefits of legalizing cannabis. Multiple research studies substantiate its pain-relieving abilities with medical researchers reporting in a 2018 study published by the American Medical Association that “marijuana liberalization may serve as a component of a comprehensive package to tackle the opioid epidemic.”

As for the ability of cannabis to reduce alcohol consumption, another recent study also published in October 2019 in the Forum for Health Economics & Policy examined the impact of medical cannabis laws and the prevalence of “active and legally protected dispensaries” reporting that “medical marijuana laws have harm reduction effects across a variety of outcomes related to risky health behaviors.”

Elaborating on this conclusion and highlighting the need for legal access, the study reported “strong improvements in health among non-white individuals, those reporting chronic pain, and those with a high school degree, driven predominately by whether or not the state had active and legally protected dispensaries.” Most importantly, the study concluded “that the aforementioned demographic groups experience large reductions in alcohol consumption after the implementation of a medical marijuana law.”

Even a modest reduction in alcohol consumption from the use of cannabis will provide substantial public health benefits.

As for bloodbaths on the highways, The National Highway Transportation Safety Administration and the AAA Foundation for Traffic Safety have all found that, unlike alcohol’s contribution to highway mayhem, there is no evidence of any relationship between THC levels in the bloodstream and impairment.

A September 2019 study published in the medical journal Cureus concluded, “There is no clear or stated correlation between the legalization of cannabis and crash rates.” The article substantiated that conclusion finding, “The correlation between alcohol and crash risk is clear and the findings are so consistent. Some research shows that THC only causes minimal impairment and has a little contribution to crash risk.”

A 2015 study published by the University of Chicago Law School found that “the legalization of medical cannabis is associated with reduced alcohol consumption, especially among young adults.” Cannabis is not going to make you a better driver, but unlike alcohol, it is not going to make you a menace on the highway.

One of the most unambiguous conclusions found in the Cureus and other studies has been the effect on crime and punishment. In every state that has legalized cannabis, arrest rates have plummeted—98 percent in Washington, 81 percent in Colorado, 76 percent in Washington D.C., 96 percent in Oregon and 94 percent in Alaska with comparable reductions in all other legalization states. The public health benefits resulting from the saving of hundreds of millions of dollars and sparing hundreds of thousands of people from being saddled with lifelong criminal records is almost beyond measure.

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Gastrointestinal Distress

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Almost everyone has experienced nausea during their lifetime and most likely will continue to experience nausea sporadically throughout their life. This is because nausea has so many causative factors, and being nauseous on occasion is as likely as experiencing pain on occasion.

Nausea can be acute and last briefly or it can be chronic and incapacitating, leading to debilitating vomiting and interfering with the ability to function on a day-to-day basis. It is not a disease but a symptom of many internally and externally caused ailments such as gastrointestinal imbalances, motion sickness, anxiety, medication reactions, food poisoning and host of other disorders, both physical and psychological.

Whether short-term or recurrent and chronic, there is a cornucopia of nausea medications called antiemetics. One of the most common, bismuth subsalicylate, works by protecting the stomach lining and is found in many over-the-counter medications like Kaopectate and Pepto-Bismol. By blocking H1 receptors in the area of the brain, which create nausea, anti-histamines like Benadryl are effective in treating motion sickness and nausea caused by many medications.

Like most antiemetics, cannabis does not cure the underlying ailment, but mitigates the symptoms. When activated by the THC and CBD cannabinoids found in cannabis, the endocannabinoid receptors located throughout the body produce an anti-emetic response as was noted in a study published in the October 2013 issue of British Journal of Pharmacology finding that THC and CBD “may have therapeutic potential in reducing nausea.”

This was further confirmed in the February 2015 issue of Current Gastroenterology Reports, which reported that “Several cannabinoid receptors, which include the cannabinoid receptor 1 (CB1), CB2 and possibly GPR55, have been identified throughout the GI tract. These receptors may play a role in the regulation of food intake, nausea and emesis.”

“When treating nausea, it is important to determine the THC/CBD content of the cannabis.”

 

More significantly, this anti-nausea property was found to be particularly effective in treating the extreme and debilitating nausea that comes from the chemo and radiation therapies used to treat cancer. As far back as 1975, a study published by The New England Journal of Medicine reported that “oral tetrahydrocannabinol has antiemetic properties and is significantly better than a placebo in reducing vomiting caused by chemotherapeutic agents.”

The Institutes of Medicine’s 1999 groundbreaking study entitled “Marijuana as Medicine” noted “an inhalation (preferably not smoking) cannabinoid drug delivery system would be advantageous for treating chemotherapy-induced nausea.”

Cannabis works to treat nausea and, other than making a person who is feeling poorly feel better, produces far fewer side effects than almost all current antiemetic medications, both over-the-counter and prescribed.

When treating nausea, it is important to determine the THC/CBD content of the cannabis. If you are feeling nauseous you might not want to experience effects that might intensify the feelings of nausea, so you should choose a cannabis with low THC and high CBD.

The route of administration also needs to be one that does not aggravate the nausea. Although inhalation is a quick route to relief, in some people smoking can trigger additional feelings of nausea especially if you are already feeling nauseous. Use of a vaporizer should reduce the likelihood of additional nausea as no smoke is produced when vaporizing.

A method that was possibly used by your grandparent or great-grandparent to treat nausea was tincture of cannabis. Found in medicine cabinets just about everywhere, this solution of cannabis dissolved in alcohol or glycerin is taken sublingually (under-the-tongue) with effects noticed within three to five minutes. Although the taste is not the most pleasant, it is unlikely to antagonize the nausea.

Edibles are a double-edged sword. If the nausea is being generated from or by the gastrointestinal (GI) tract, getting the cannabis directly into the area where the nausea is occurring could be very beneficial. At the same time, the introduction of food products into the GI tract can intensify the ongoing nausea episode.

Nausea may be part of life, but it doesn’t have to interfere with life. With preventative care and proper treatment that includes the use of cannabis, nausea can be mitigated, allowing the body to recover, regain strength and return to a state of healthful equilibrium.

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The Science of Edibles

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Even though the perceived effects of inhaled and ingested cannabis can feel so different from one another, it is how the body assimilates and incorporates THC and other cannabinoids found in cannabis that makes for the stark differences between inhaling and ingesting.

There is no psychoactive THC found naturally in cannabis plants. What is actually found in the plant is tetrahydrocannabinolic acid (THCA), which has no psychoactive properties. THCA contains a carboxyl molecule which, when removed by a process called decarboxylation, gives cannabis its famed psychotropic properties.

With temperatures in excess of 350 degrees Fahrenheit, the elevated heat from smoking or vaping will instantly decarboxylate the THCA converting it into Delta-9-THC, the famously celebrated psychoactive cannabinoid of cannabis. When inhaled, the Delta-9-THC is immediately absorbed by the lungs flowing directly into the bloodstream and crossing the blood-brain barrier. The psychoactive effects occur within minutes so you can easily titrate and quickly moderate your intake maintaining levels you are comfortable with.

The decarboxylation of THCA to produce Delta-9-THC can also take place at lower temperatures such as those used for baking. The conversion is not instantaneous, and thus it requires 15 to 45 minutes depending on the temperature. In addition to producing Delta-9-THC for use in edibles, one of the advantages of heating at a lower temperature is the terpenes, which are responsible for the aroma of cannabis, are preserved.

Edibles are not absorbed through the respiratory system, but rather through the digestive system. Therein is the big difference, which accounts for why the potency and length of time of action is greater for cannabis that is eaten versus cannabis that is inhaled.

“The bottom line for edibles is you can always take more, but you can’t take less once you have taken them, so err on the side of caution, and wait at least two hours before consuming more.”

 

When Delta-9-THC goes through the digestive system rather than the respiratory system, it is metabolized in the liver and converted to 11-hydroxy-THC (11-OH-THC). This form of THC crosses the blood-brain barrier more quickly than Delta-9-THC and is considered to be more psychotropic, because it activates specific cannabinoid receptors in the brain more effectively than Delta-9-THC does. This is one of the reasons edibles are believed to be more likely to bring on feelings of anxiety, panic, paranoia and other negative psychotropic reactions.

Although this has been the accepted explanation for why edibles are more potent than smoking or vaping, not all researchers agree. Studies done at GW Pharmaceuticals, according to an article in The Atlantic, have found that the two compounds are basically equivalent and point to a far simpler explanation. The author refers to Dr. Ethan Russo and his skepticism for such an explanation. “Russo says the reason edibles affect people more strongly is simply because more THC—of any kind—gets into the body when pot is eaten. When a joint is smoked, only 10 to 30 percent of the THC is absorbed into the body, he says. A lot—quite literally—just goes up in smoke,” reads the article.

Whether the psychoactive effects of edibles derive from the potency of 11-OH-THC versus Delta-9-THC or the simple fact that you are going to get more psychoactive THC from ingesting than from inhaling, it still calls for more caution when edibles are consumed.

This is why knowing the amount of THC in edibles is critical. Eating someone’s homemade edibles with unknown potencies can be especially risky as beginners are advised to limit their intake of THC to between one and five milligrams. Once accustomed to the effects, dosages can be increased up to 10 milligrams. Most states that have legalized cannabis have set 10 milligrams as a single serving size although very experienced consumers can utilize considerably more with no ill effect.

Along with potency, the time for onset of the effects with edibles is critical with times of onset running from 30 minutes to two hours. Just because you have not felt anything in 60 minutes doesn’t mean you should take more. Overdosing is not going to kill you, but it is very uncomfortable, with some people going to emergency rooms with panic attacks and other distressful symptoms.

The bottom line for edibles is you can always take more, but you can’t take less once you have taken them, so err on the side of caution, and wait at least two hours before consuming more.

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