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The Danger of Synthetic Cannabis

September 9, 2022 Published by

On the potentially lethal subject of synthetic weed, the news, since legalization, is better, but still not great.

Though not wholly harmless, cannabis itself hasn’t killed anyone through overdose or misadventure. But cannabis prohibition absolutely has a body count. Between 2016 and 2019, at least 61 Americans died after exposure to synthetic cannabinoids, according to recent research conducted by scientists at Washington State University and published in the journal Clinical Toxicology.

Many more have become violently ill or wracked with disturbing mental or psychological trauma after using synthetic cannabis, with more than 64 percent of 7,600 documented exposures over that time frame requiring medical attention, the study found. (These figures don’t capture the full scope of the problem; synthetic cannabinoids are difficult to detect and use is often only detected after the user is in the hospital or the morgue.)

A broad term used generally to describe a range of potent chemicals, intended to mimic natural plant-based cannabinoids and to bind to many of the same receptors—but in some cases, up to 100 times more powerful; the difference in impact comparable “to the difference between a hose hooked up to a fire hydrant versus a faucet with a slow drip,” in the words of Dr. Patricia Frye, a Maryland-based physician and cannabis expert. “Synthetic cannabis” is banned under federal and most state law. (Plant-derived cannabis products created via chemical synthesis, including Delta-8 THC and Delta-10 THC, aren’t in this product category.)

Though not a priority for law enforcement, who still arrested hundreds of thousands of Americans for marijuana possession in 2020, synthetic cannabis is notorious stuff. Most often appearing in large cities, fake weed was the ultimate culprit behind a so-called “zombie outbreak” in 2016 in New York City, after several dozen people exhibited the same troubling dis-associative symptoms after smoking a particularly nasty “incense” product called “AK-47” Karat Gold.

Why would anyone use such dangerous and toxic stuff? And how can policymakers discourage such self-harm and solve what researchers described to Cannabis Now as a “serious health threat”?

The obvious answer will not shock you.

Nobody Really Likes Synthetic Weed, But…

Initially created in labs to understand how cannabinoid receptors work, synthetic cannabis was never intended for use in humans. And perhaps owing to the nasty side effects, synthetic cannabis use isn’t widespread.

Natural cannabis is far more popular. Even the estimated 0.2 to 0.4 percent of the population who do admit to using synthetic weed say they’d prefer natural cannabis.

However, there’s some societal “encouragement” for synthetic cannabis use: synthetic weed prohibition turns out to be difficult to enforce. Synthetic cannabis doesn’t contain THC. Users won’t show THC metabolites on a urine screening, and so drug tests can’t detect synthetic cannabis, the study noted. Thus, anyone in a position to want a buzz and avoid punishment for weed, including US service members, may decide that fake cannabis is worth the risk.

Users profiled in another recent study, from researchers based in Spain, confirm this ready common-sense explanation: Because drug tests don’t search for synthetic cannabinoids, meaning people worried about losing employment, housing, or other opportunities for a positive drug test are willing to risk serious consequences to achieve something like a weed-like buzz.

In other words, drug laws encourage drug users to risk great bodily and mental harm they wouldn’t otherwise risk. They say so themselves.

Synthetic cannabinoids “exist as a by-product of prohibition,” said Dr. Ethan Russo, a physician, neurologist and prominent researcher and author.

“Following the law of unintended consequences, the continued pervasiveness of urine drug screening for employment has stimulated the popular appeal of synthetic cannabinoids, which are not detectable on routine laboratory tests,” Russo told Cannabis Now. “The result is considerable attendant morbidity and mortality.”

In some places, this situation is getting worse. According to the researchers’ findings, published in the journal Frontiers in Psychiatry, “synthetic cannabinoids are increasingly gaining popularity and replacing traditional cannabis.”

However, that’s not the case in the US, where a simple and popular policy intervention leads to a decline in synthetic cannabinoid exposure (and related deaths and hospitalizations) of more than 37%. Only 5.5% of the synthetic cannabinoid poisonings tracked in the study occurred in states with legalization laws.

This magic public-health solution is allowing people to use cannabis safely and legally.

With Synthetic Cannabis, Legalization Saves Lives

As the Washington state researchers noted, synthetic cannabinoid exposures declined in the US starting in 2016—the same year that four states (California, Maine, Massachusetts and Nevada) legalized adult-use cannabis for adults 18 and over.

Of the exposures that were recorded, most–-56%–-occurred in states “with restrictive cannabis policies at the time of the exposure,” the researchers wrote. When a state passed a law with a more “permissive cannabis policy,” synthetic cannabinoid exposures reduced by 37%, they added.

This amounted to an “association” between “liberal policies (legalization) for natural cannabis and declines in reported synthetic cannabinoid poisonings,” they concluded. “This finding suggests a potential effect of policy change on substance use behaviors that may have long-term public health implications.”

Tracy Klein, the lead researcher and a professor in Washington State University’s College of Nursing, didn’t respond to a request for comment. But other experts, including Frye and Russo and Peter Grinspoon, a Boston-based physician and lecturer at Harvard Medical School, accepted the findings as a strong endorsement for cannabis legalization as a public-health intervention.

Synthetic cannabis harms people, but people don’t want to use it when natural cannabis is available. When natural cannabis is available, people don’t use it. Legalization saves lives. Could there be a simpler proposition?

“The rules of society have created this problem,” Russo said, “one that should no longer exist once a legal and regulated market for cannabis is established.”

“Legalizing cannabis, in the adult-use market, would certainly eliminate the need for experimenting with these potentially deadly chemicals,” Frye said.

The post The Danger of Synthetic Cannabis appeared first on Cannabis Now.

‘3x Stronger’ Than THC? The Latest Cannabinoid THC-O Arrives

October 8, 2021 Published by

Although his Higher Life dispensary is located in the midwestern U.S. state of Indiana, where adult-use cannabis is still illegal, owner Brandon Howard has added one new product after another over the past few months.

Earlier this year, all the rage was over hemp-derived Delta-8 THC products: federally legal under the 2018 Farm Bill, and psychoactive enough to produce a high similar enough to regular old (and banned) plant-derived THC to move markets. But with the federal government and the states cracking down on Delta-8, Howard started offering edibles and vaporizer cartridges featuring yet another “new” cannabinoid (or new to consumers, at least): THC-O, or THC-O acetate.

What is THC-O?

First discovered by chemists decades ago (and first observed by the U.S. Drug Enforcement Administration in 1978) THC-O is an analogue of “regular” plant-derived Delta-9 THC, meaning its chemical structure is similar. More specifically, THC-O is a “prodrug,” meaning after the body metabolizes THC-O, it becomes THC.

THC-O can be derived from Delta-8 THC, which is obtained from CBD—which in turn comes from hemp, which is legal to cultivate, sell, and tinker with. In April, the U.S. Patent and Trade Office issued Nextleaf Solutions, what they believe is the first patent for a THC-O extraction process. This is why THC-O is important to Howard—as well as any other business or entrepreneur eager to participate in the greater cannabis industry, while staying outside of  regulated adult-use markets—because it means he can sell it in Indiana.

So far, the reception is encouraging, he told Cannabis Now recently.

“I’ve had customers tell me it helps with their appetite,” he said. Others say using THC-O is like eating “way too many gummies,” he added, describing the effect in turn as “a slight feeling of being on psychedelics” and “an indica and a sativa feeling.” 

One thing THC-O is not, he said, is weak.

‘Three Times Stronger’ Than THC

THC-O is supposedly up to three times stronger than “normal” Delta-9 THC, something close to “weed on steroids,” as Westword put it in a December 2019 article. “It hits you in waves,” Howard said. “Just when you think you’re coming down, it hits you again.”

It’s safe, he said, but “I highly suggest starting with a low dose.”

Not everyone agrees.

THC-O’s critics include prominent cannabis researchers as well as some businesses and entrepreneurs. In their analysis, THC-O is merely the latest synthetic substitute for what customers really want—regular old cannabis.

“Industry businesses are constantly looking for the next value proposition to stick on their product box so they can stand out in a highly saturated and competitive Delta 8 market,” said Ashley Dellinger, the owner of The Hemp Collect, a Texas-based CBD wholesaler that deals with Delta-8 THC—but not THC-O. “I don’t see a lot of people deep diving into the repercussions of consumption of these compounds insomuch as they are obsessed with not missing out on another potentially large revenue opportunity.”

Exactly what a concentrated, semi-synthetic product like THC-O will do to the human brain and body is still unclear, but more menacing are the methods with which THC-O is extracted from its source material.

How is THC-O Extracted?

In an August interview with Hempgrower.com, Dr. Ethan Russo, one of the most respected experts and researchers in cannabis science, suggested that the THC-O extraction process might not be entirely legal. Under a 1986 law passed by Congress called the Federal Analogue Act, any compound that’s an analogue of a banned compound is subject to the same bans. For now, Delta-8 THC, named because it has one less carbon bond than Delta-9 THC, may escape this snare.

But the body doesn’t care about the law. What the body does care about are adulterants and other potentially dangerous additives. Though there’s not one standardized THC-O extraction process, Russo believes most THC-O makers use a reagent called acetic anhydride to convert their source material to THC-O. And acetic anhydride is highly flammable and very dangerous to humans. On top of the dangerous process, Russo added, there’s the potential of an unwelcome reaction in the human body. Most people don’t need huge amounts of THC—and, in fact, getting too high is one of the most common complaints from new (and old!) cannabis users.

“So, between the inherent danger of the process to make it, the potential toxicity of the product, and its illegality, I’ve got to recommend that people forget about it,” Russo said in his interview. “It’s just not something that people should be trying.”

Howard says he is convinced that THC-O is safe. Anyone who doubts him can use their phone to scan his products’ QR code and see the process for themselves. At the least, someone purchasing from Higher Life CBD knows where the product came from; someone buying online or at a gas station or smoke shop might not have that same level of accountability. 

Other entrepreneurs like Dellinger aren’t convinced and want more data. “We are working with the appropriate people to understand the safety of this compound before moving forward and urge other to do their due diligence,” she said. For now, product makers should “[m]aintain the plant’s range of phytochemistry as much as you can in your extractions and formulations,” she added.

The post ‘3x Stronger’ Than THC? The Latest Cannabinoid THC-O Arrives appeared first on Cannabis Now.

The Endocannabinoid System and Clinical Endocannabinoid Deficiency

June 1, 2020 Published by

The discovery of the endocannabinoid system in the mid-1980s was a major breakthrough in modern medicine. Yet, if you looked at the curriculum for most medical schools, you might not know it. The finding would not have been possible without the help of the cannabis plant, which remains illicit in most countries around the world. After wide-spread legalization of medical cannabis and over three decades of research, knowledge about the endocannabinoid system and its associated pathologies, like clinical endocannabinoid deficiency, remain sorely overlooked.

The Endocannabinoid System: The Find of the Century?

Two decades before the discovery of the endocannabinoid system, a team of scientists led by Dr. Raphael Mechoulam, a professor of medical chemistry a the Hebrew University of Jerusalem, had finally isolated the primary psychoactive constituent of the cannabis plant—tetrahydrocannabinol (THC). After the discovery, researchers around the globe began the quest to figure out exactly how the compound worked.  A group led by Dr. Allyn Howlett, a neuroscientist then with St. Louis University, finally cracked the mystery: THC produced its psychoactive effects through engagement with specialized cell receptors.

A cell receptor can be thought of as a lock that is embedded on the surface of a cell membrane. These locks only respond to specific chemical keys. In this case, THC was the key that engaged a cannabinoid receptor. As research would soon reveal, cannabinoid receptors are part of a larger endocannabinoid system (ECS), a neurotransmitter and cell signaling network like none other.  Made up of receptor sites, their respective chemical activators, and the enzymes that deactivate these compounds, scientists quickly unveiled that the ECS was ubiquitous throughout the human body. Cannabinoid receptors are nearly everywhere — connective tissue, the brain, the spinal cord, internal organs, the digestive tract, the skin, and immune cells.

After what surely was many long hours in the lab, Howlett and her team landed on something big. Why on earth would these receptors be found in so many places? Nearly three decades down the line, scientists are still exploring the wide-reaching ramifications of the endocannabinoid system, Howlett included. In the time since its first discovery, the ECS has been found to be a potent regulator of brain activity, hormonal function, and immune response, linking the three main regulatory systems together. It’s this pervasive modulatory network that responds to THC and other cannabis constituents. When a person consumes intoxicating forms of cannabis, THC hijacks the cannabinoid receptor sites that are normally inhabited by compounds that the body produces naturally.

These compounds are called endocannabinoids. The prefix endo- refers to endogenous or internal cannabinoids. In contrast, the cannabinoids found on the cannabis plant are phytocannabinoids with the prefix phyto referring to plants. As it turns out, endocannabinoids are molecules that help maintain a state of equilibrium, or homeostasis, throughout the nervous, endocrine, and immune systems. Endocannabinoids play the part of harmonizers or middlemen, managing how each of these systems responds to stressful stimuli and communicates with the others.

Endocannabinoids are at least in part responsible for regulating the biological clock, managing things like hunger and sleep over the course of the day. Cannabinoid receptors are also highly concentrated in areas of the brain responsible for memory, emotion, and metabolism, giving them regulatory effects over a remarkable number of physiological functions. One endocannabinoid, called anandamide, even takes its name from the Sanskrit word for bliss Ananda thanks to its calming and relaxing effects.

With such a profound influence over so many basic bodily commands, it is now theorized that problems in the ECS may contribute to a wide variety of difficult-to-treat pathologies. These potential pathologies include ailments as diverse as migraines and autism.

Clinical Endocannabinoid Deficiency May Contribute to Disease

Howlett and Mechulam may have kicked off the first forays into the endocannabinoid system, but they are far from the only scientists who made serious contributions to this emerging arena of health and medicine. Back in 2001, Ethan Russo, a neurologist and medical researcher, first made the case for clinical endocannabinoid deficiency (CECD). Russo is currently the Director of Research and Development with the International Cannabis and Cannabinoids Institute (ICCI). His theory? That many common diseases stem from deficiencies of the endocannabinoid system.

“Many human disorders relate to deficiencies of neurotransmitter function,” Russo told Cannabis Aficionado. “We know that a lack of acetylcholine, the memory neurotransmitter, is key to dementia in Alzheimer disease and related disorders. Parkinson disease is associated with a lack of dopamine function. Depression is related to problems with serotonin.”

Now, Russo suggests that something similar could occur in the endocannabinoid system. “In 2001,” he explains, “I hypothesized that various human disorders could be related to a lack of endocannabinoids, the natural chemicals within our brain and bodies that are similar in activity to THC, the main psychoactive compound in cannabis.”

Since endocannabinoids have wide-spread functions in the body, a lack or deficiency of these signaling molecules could cause a whole host of trouble. Symptoms like seizures, mood troubles, and generalized pain, nausea, and inflammation are all possible side effects of an endocannabinoid imbalance. Further, the universal nature of the ECS means that ailments which are seemingly unrelated to each other may now be classified together under the endocannabinoid umbrella.

“The prime candidates for clinical endocannabinoid deficiency are migraine, fibromyalgia and irritable bowel syndrome,” says Russo, describing conditions that are currently thought of as distinct and separate pathologies. “All [three] have compelling evidence in the interim that there are deficiencies in endocannabinoid function. Additional evidence has accumulated to include post-traumatic stress, autism, and other disorders.”

It is the ECS that perhaps describes why conditions like migraine and irritable bowel syndrome may share so many overlapping symptoms, including changes in mood, digestive distress, pain, and fatigue. These problems may be genetic in nature or acquired over time. At least one scientist has even gone as far as to describe the endocannabinoid system as a “bridge between body and mind”, connecting the physical reality with an emotional and intellectual one.

Toward Recognition of the ECS

Researchers have been investigating the influence of the endocannabinoid system in disease pathology for the past 30 years. Despite advancements in our understanding about the ECS, however, therapies targeting the endocannabinoid system are still few and far between. While some cannabinoid-based therapies are available to select patients, medical cannabis still remains one of the primary therapies that targets the ECS.

Yet, while the herb has been immensely helpful to patients around the world, both cannabis and endocannabinoid research still suffers from underutilization and harsh political barriers to research. In fact, a 2018 study from the Washington School of Medicine found that only a meager nine percent of medical schools teach their students about medical cannabis. This is despite the fact that the medicinal use of the herb is legal in 33 U.S. states and all of Canada.

“In my opinion, the media attention [on the endocannabinoid system] is not yet sufficient,” says Russo, “as the scientific evidence behind the theory is now quite solid based on serum and cerebrospinal fluid tests and other data.” He is referring to tests conducted in patients with schizophrenia,  migraine, and epilepsy. In each of these conditions, patients exhibited a dysregulation of endocannabinoid molecules in their cerebrospinal fluid. In post-traumatic stress, scientists at the New York University Langone Medical Center made a similar finding back in 2013. Compared with controls, PTSD patients demonstrated reduced endocannabinoid circulation.

“Considering the extreme amount of suffering and economic costs associated with clinical endocannabinoid deficiency disorders, it is necessary to have better research support and clinical investigations,” he presses. Better research and support would enable medical researchers and other scientists to more efficiently establish key therapies and interventions for endocannabinoid disorders. “While it is clear that cannabis in one form or another can be very effective in treating such disorders, certain lifestyle approaches, such as low impact aerobic activity, and dietary manipulations with prebiotics and probiotics may also be effective.”

Unfortunately, nearly 75 percent of medical schools also fail to provide students with the required amount of nutrition education. In a world of quasi-legal remedies and under-acknowledged illnesses, its past time that formal institutions look seriously into endocannabinoid health.

TELL US, have you heard of the endocannbinoid system?

Originally published on Cannabis Aficianado.

The post The Endocannabinoid System and Clinical Endocannabinoid Deficiency appeared first on Cannabis Now.