Ancient Cannabis Enzymes Reveal How THC and CBD First Evolved

Scientists are taking a deeper look at the origins of cannabis chemistry by reconstructing enzymes from ancient plants, offering new insight into how cannabis first developed the ability to produce compounds like THC and CBD.

In a recent study published in Plant Biotechnology Journal, researchers at Wageningen University & Research rebuilt molecular structures that existed millions of years ago, revealing that ancient forms of cannabis enzymes were more flexible and robust than those found in modern plants.

The team behind the research says they have successfully traced the evolution of cannabinoid chemistry and identified molecular tools that could improve the biotechnological production of modern medicinal cannabinoids.

The Origin of Cannabinoids

In modern cannabis plants, specialized enzymes are responsible for making individual cannabinoids like THC or CBD. Each enzyme is highly efficient at producing one specific compound. The new study shows that this precision is a recent development in cannabis evolution, rather than something that existed from the start.

Early ancestors of cannabis used versatile enzymes that could create several cannabinoids at once. These enzymes became more specialized over time as gene duplication occurred. This led to the distinct chemical profiles seen in cannabis plants today.

The research team provided direct evidence for this evolutionary process by reconstructing ancient cannabis enzymes in the lab. Their results show that the pathways for creating specific cannabinoids like THC appeared relatively recently and became more specialized over time through natural selection.

Rebuilding Lost Enzymes

The team relied on ancestral sequence reconstruction to study this evolutionary history. They compared DNA from modern cannabis and related species to determine what cannabinoid-producing enzymes looked like millions of years ago.

The researchers synthesized the predicted enzymes and tested their functions in the lab. Many of the reconstructed enzymes converted precursor molecules into several different cannabinoids, unlike the more specialized modern enzymes.

These experiments enabled the team to directly test evolutionary hypotheses that had previously relied solely on genetic comparisons.

Ancient Enzymes as Biotech Tools

The most immediate implications of the study are for biotechnology rather than evolutionary biology. When the researchers expressed ancient enzymes in microbial systems, they found that the reconstructed enzymes were often easier to use than those found in modern cannabis plants.

“What once seemed evolutionarily ‘unfinished’ turns out to be highly useful,” said Robin van Velzen, who led the study with colleague Cloé Villard. “These ancestral enzymes are more robust and flexible than their descendants, which makes them very attractive starting points for new applications in biotechnology and pharmaceutical research.”

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Florida Lawmakers Approve Bill To Ban Public Marijuana Smoking Ahead Of Possible Legalization Vote On The Ballot

A Florida Senate panel has advanced legislation to ban smoking or vaping marijuana in public places, a development that comes as an industry-funded campaign is seeking to place a recreational cannabis legalization initiative on the November ballot.

The Senate Regulated Industries Committee on Tuesday approved the bill, which defines a public place as “a place to which the public has access, including, but not limited to, streets; sidewalks; highways; public parks; public beaches; and the common areas, both inside and outside, of schools, hospitals, government buildings, apartment buildings, office buildings, lodging establishments, restaurants, transportation facilities, and retail shops.”

The measure from Sen. Joe Gruters (R), who is also chairman of the Republican National Committee, would specify that marijuana cannot be smoked or vaped in customs smoking rooms at airports.

Sen. Ana Maria Rodriguez (R) presented the bill, SB 986, on Gruters’s behalf at the committee hearing.

“There is currently no prohibition on smoking marijuana in public places if adult use is approved by the voters,” she saidaccording to Florida Politics. “By banning public smoking of marijuana, we are protecting community health and quality of life, as well as protecting certain outdoor spaces from marijuana smoke such as beaches and parks.”

Rep. Alex Andrade (R) is sponsoring a similar bill to ban public cannabis smoking in the House of Representatives.

The proposals are among a growing list of cannabis legislation that lawmakers are introducing for consideration next year.

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OSU study: Compounds in hemp block COVID-19 from entering human cells

Compounds found in hemp “show the ability to prevent the virus that causes COVID-19 from entering human cells,” Oregon State University says.

New OSU research on hemp and COVID-19 was published Tuesday in the Journal of Natural Products.

Richard van Breemen, a researcher with Oregon State’s Global Hemp Innovation Center in the College of Pharmacy and Linus Pauling Institute, led the study.

According to OSU:

Hemp, known scientifically as Cannabis sativa, is a source of fiber, food and animal feed, and multiple hemp extracts and compounds are added to cosmetics, body lotions, dietary supplements and food, van Breemen said.

Van Breemen and collaborators, including scientists at Oregon Health & Science University, found that a pair of cannabinoid acids bind to the SARS-CoV-2 spike protein, blocking a critical step in the process the virus uses to infect people.

The compounds are cannabigerolic acid, or CBGA, and cannabidiolic acid, CBDA, and the spike protein is the same drug target used in COVID-19 vaccines and antibody therapy. A drug target is any molecule critical to the process a disease follows, meaning its disruption can thwart infection or disease progression.

“These cannabinoid acids are abundant in hemp and in many hemp extracts,” van Breemen said. “They are not controlled substances like THC, the psychoactive ingredient in marijuana, and have a good safety profile in humans. And our research showed the hemp compounds were equally effective against variants of SARS-CoV-2, including variant B.1.1.7, which was first detected in the United Kingdom, and variant B.1.351, first detected in South Africa.”

OSU said those two variants are also known as alpha and beta.

According to OSU:

Characterized by crown-like protrusions on its outer surface, SARS-CoV-2 features RNA strands that encode its four main structural proteins – spike, envelope, membrane and nucleocapsid – as well as 16 nonstructural proteins and several “accessory” proteins, van Breemen said.

“Any part of the infection and replication cycle is a potential target for antiviral intervention, and the connection of the spike protein’s receptor binding domain to the human cell surface receptor ACE2 is a critical step in that cycle,” he said. “That means cell entry inhibitors, like the acids from hemp, could be used to prevent SARS-CoV-2 infection and also to shorten infections by preventing virus particles from infecting human cells. They bind to the spike proteins so those proteins can’t bind to the ACE2 enzyme, which is abundant on the outer membrane of endothelial cells in the lungs and other organs.”

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Dutch scientists discover ancient cannabis enzyme with pain-relief potential

Researchers at Wageningen University & Research (WUR) reported a discovery that an ancient ancestor of the cannabis plant produced a compound with anti-inflammatory and pain-relieving properties, opening potential new avenues for medical use.

The team investigated how compounds like THC, CBD, and CBC emerged in cannabis. To do this, they reconstructed extinct enzymes that were active millions of years ago in the plant’s ancestors. These enzymes are crucial in producing cannabinoid compounds.

“In modern cannabis plants, specific enzymes produce cannabinoids such as THC, CBD, and CBC,” WUR researcher Robin van Velzen told NU.nl. “But the ancestral enzymes could produce multiple cannabinoids simultaneously.”

These “ancestral enzymes” are simpler to produce in microorganisms, such as yeast, compared with their modern counterparts, making them easier to harness.

“These ancestral enzymes are more robust and flexible than their descendants, making them very attractive starting points for biotechnology and medicine,” Velzen said.

One enzyme of particular interest produces a high level of CBC, a cannabinoid known for anti-inflammatory and pain-relieving effects. “Currently, no cannabis plant produces high levels of CBC, so introducing this enzyme into a plant could lead to innovative medicinal varieties,” Van Velzen said.

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Marijuana Users Are Being Unjustly Jailed For Allegedly Driving Under The Influence, Government-Funded Study Shows

Laws aimed at preventing marijuana-impaired driving in almost 20 states are causing innocent people who show no signs of impairment to be criminalized and imprisoned for allegedly operating vehicles while under the influence, a new government-funded study shows.

Lawmakers and regulators aiming to reduce drug-impaired driving have long sought to apply a familiar strategy from alcohol enforcement: setting a numerical limit of THC in the bloodstream beyond which a driver is presumed to be impaired, commonly referred to as a “per se” amount.

But the new study suggests that approach may be badly misaligned with the science related to impairment from cannabis, the components and metabolites of which can remain in the body day or weeks after use—when impairment is no longer an issue.

“Many regular users of cannabis exceed zero tolerance and per se THC cutpoint concentrations days after their last use, risking legal consequences despite no evidence of impairment,” the study, which was published in the scientific journal Clinical Chemistry and partially funded by the National Institutes of Health and the State of California, found.

The findings echo earlier research showing weak or inconsistent links between THC blood levels and crash risk. Large epidemiological studies have found that while marijuana use may slightly increase collision risk, the effect is far smaller than that of alcohol use.

“One of the primary problems with using THC concentrations in per se legislation is that the pharmacokinetics of THC are much different from ethanol,” the researchers wrote.

The authors noted that alcohol generally cannot be detected 1 to 2 days after last ingestion, whereas THC can be measured up to 30 days after last use because of its lipophilic nature.

To generate the data, researchers studied 190 heavy consumers who were instructed to abstain for 48 hours. Following that several day period, the participants’ blood THC concentrations were measured both before and after cannabis consumption to establish baselines. They were also observed using a driving simulator.

“Current cannabis blood concentrations used to identify impaired drivers could land innocent people in jail,” the Association for Diagnostics & Laboratory Medicine, which publishes the journal that the study appeared in, said in a press release.

“Cannabis blood limit laws lack scientific credibility and are not an accurate determinant of when drivers should face criminal charges or not.”

The authors of the study concluded that “more work needs to be done to address how to best identify drivers who are under the influence of cannabis and are unsafe to drive.”

“Despite evidence showing no correlation between the detection of THC in the blood and driving impairment, 6 states in the United States have per se laws using 2 or 5 ng/mL of THC as the cut-off point for driving under the influence of cannabis, while 12 have a zero-tolerance law,” the journal’s press release says.

The authors, affiliated with the University of California, San Diego and the Center for Medicinal Cannabis Research cautioned that additional research is needed, saying “at present, the best protocol is a combination of observations in the field and toxicology testing.”

A separate study last year found “no support that marijuana legalization increased tolerant behaviors and attitudes toward driving after marijuana use.” Authored by researchers at Nationwide Children’s Hospital and Ohio State University, the study used data from a national traffic safety survey.

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Microdosing Cannabis Pauses Alzheimer’s Decline in Unprecedented Trial

As the world’s population ages, the number of people living with dementias such as Alzheimer’s disease increases.

Given the lack of curative treatments and the limited effectiveness of available medications, interest in new therapeutic approaches is growing. Among them are cannabinoids from the cannabis plant.

A small new Brazilian study published in the international Journal of Alzheimer’s Disease investigated the effects of microdoses of cannabis extract on patients with mild Alzheimer’s disease. The results found positive effects, without the associated “high” of cannabis.

The logic of microdoses

The study, led by Professor Francisney Nascimento and colleagues at the Federal University of Latin American Integration (UNILA), recruited 24 elderly patients (60-80 years) diagnosed with mild Alzheimer’s.

It evaluated the effects of daily use of an oil prepared from cannabis extract containing THC and CBD in similar proportions and extremely low concentrations (0.3 mg of each cannabinoid). These sub-psychoactive doses do not cause the “high” associated with recreational use of the plant.

The extract used was donated by ABRACE, Brazil’s biggest patient association, and had no contribution from cannabis companies or other funding sources.

“Microdosing” is a term usually associated with recreational use of psychedelics. Given the size of the dose, it would be easy to question whether it could have any effect at all.

Doses below 1 mg of the cannabinoid compounds are not frequently reported in the literature of clinical practice. However, the researchers’ decision to use microdosing did not come out of nowhere.

In 2017, the group led by Andreas Zimmer and Andras Bilkei-Gorzo had already demonstrated that very low doses of THC restored cognition in elderly mice, reversing gene expression patterns and brain synapse density in the hippocampus to levels similar to those of young animals.

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Trump’s Marijuana Executive Order Details Leaked Ahead Of Announcement, Including CBD And Hemp Provisions

President Donald Trump will be signing an executive order on Thursday that will direct the attorney to “expedite” and “complete” the marijuana rescheduling process, throw a lifeline to the hemp industry, allow doctors to prescribe CBD products that would be eligible for Medicare coverage and more, a White House official told reporters at a readout ahead of the signing event.

Marijuana Moment wasn’t invited to attend the background briefing, but obtained the transcript of the conversation.

Many details are consistent with reporting about the plan to move marijuana from Schedule I to Schedule III of the Controlled Substances Act (CSA), but the discussion revealed additional information about the order and how the administration is framing the reform.

The official started by emphasizing that the “common sense” administrative action is “focused on increasing medical research for medical marijuana and CBD” to “better inform patients and doctors.”

That means expediting the finalization of a rule to reschedule marijuana, they said. The move wouldn’t legalize cannabis, but it would help promote research while also letting marijuana businesses take federal tax deductions they’ve been barred from under an Internal Revenue Service (IRS) code known as 280E.

Here are new details about Trump’s executive order on cannabis:

  • Direct the attorney general to expedite the completion of the process of rescheduling marijuana to Schedule III of the CSA.
  • Direct top White House staff to work with Congress to give patients access to full-spectrum CBD products, “while still restricting the sale and access to products that cause serious and potentially life threatening health risks.”
  • Urge Congress to examine updating the definition of hemp to ensure that full-spectrum CBD is accessible to patients—a policy change that could mitigate some concerns in the sector about a recent spending bill Trump signed with provisions that would broadly ban consumable hemp products.
  • Direct the U.S. Department of Health and Human Services (HHS) to “develop research methods and models, to utilize real world evidence [and] to improve access to hemp-derived CBD products in accordance with federal law” while informing “standards of care.”

Separate from Trump’s order, Mehmet Oz, administrator for the Centers for Medicare & Medicaid Services (CMS), will also be announcing “a model that will allow a number of CMS beneficiaries to benefit from receiving CBD under doctor recommendation at no cost,” the White House official said.

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CBD Provides Pain Relief, Improves Sleep And Aids Relaxation, Study Involving Olympic Athletes Shows

Elite athletes find cannabidiol, or CBD, useful for soreness and recovery, a new study shows.

Researchers found that top competitors use CBD to manage pain, improve sleep and ease the stress of training at the highest level. But the results suggest that even as many athletes believe the cannabis compound helps them recover, they also worry that using it could jeopardize their careers under international anti-doping rules.

The study, conducted between late 2021 and mid-2023 and published this month in the journal Frontiers in Nutrition, surveyed 80 elite Canadian athletes across 27 national sport organizations. To be included, athletes needed to have experience as part of the country’s Olympic or Paralympic team program.

About 38 percent reported using CBD at some point, and nearly a third of those said they were still using it at the time of the survey.

The participants’ motivations reflect a broader societal trend of relying on CBD for therapeutic benefit. The study found that 96 percent of CBD users said they believed the substance was safe, 93 percent said it improved their sleep, 90 percent said it helped them relax and 77 percent credited it with reducing pain from training.

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Key cannabis compounds may help in the battle against one of the deadliest diseases

Talk about a new joint effort in cancer care.

A promising treatment approach for one of the most dangerous cancers has been identified by a team of researchers in Thailand exploring the effects of key cannabis compounds.

The research team looked at the two most well-known compounds in weed plants — THC and CBD — and discovered that both produced significant anti-cancer activity when tested on ovarian cancer cells.

Each slowed cell growth, formed fewer and smaller clusters and prevented them from spreading.

The results were most notable when CBD and THC were used as a combined treatment, proving highly effective at killing a large number of cancerous cells.

While more research is needed, a medication derived from marijuana could be developed to treat ovarian cancer, the 5th deadliest female cancer in the US, affecting more than 20,000 women each year.

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Feds Launch New Marijuana-Focused Ad Campaign To ‘Challenge The Dangerous Belief’ That People Drive Better While High

The Department of Transportation (DOT) and the Ad Council are rolling out a new campaign to “challenge the dangerous belief that it’s safe to drive after consuming marijuana,” with a disturbing ad that they say depicts a real-life story of a child killed by a driver who was under the influence of cannabis.

In an announcement on Tuesday, the Ad Council promoted the “Tell That to Them” initiative, which includes a 60-second ad showing a person claiming they “focus” better when driving while high and then causing a fatal car accident.

“I actually drive better when I’m high,” the man says. “If anything, I’m more careful, more chill, more relaxed.”

He is then shown driving head-on into an incoming car.

DOT’s National Highway Traffic Safety Administration (NHTSA) partnered with the Ad Council for the campaign.

“Too many young men think marijuana doesn’t affect their driving ability or even makes them safer drivers,” NHTSA Administrator Jonathan Morrison said in a press release. “That couldn’t be further from the truth.”

“Marijuana slows down a driver’s reaction time and impairs their coordination and judgement,” he said. “This new PSA reminds motorists that driving high puts us all at risk and can have deadly consequences.”

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