People in states where recreational marijuana is legal were significantly less likely to experience vaping-related lung injuries than those in states where cannabis is prohibited, according to a new study published in an American Medical Association journal.
The finding seems to affirm what many reform advocates said during the peak of the e-cigarette or vaping product use-associated lung injury (EVALI) crisis last year. With thousands being hospitalized over EVALI, it became clear that contaminated vape cartridges were the source and that contamination was more common in illicit, unregulated markets where consumers can’t walk into retail stores and buy tested and labeled marijuana products.
By analyzing Centers for Disease Control and Prevention (CDC) data on EVALI cases, the prevalence of e-cigarette use and the population in each state from June 2019 to January 2020, researchers were able to confirm that.
The research letter, published by the JAMA Network Open on Monday, shows that states with recreational marijuana shops had 1.7 EVALI cases per million population compared to 8.1 cases per million in prohibition states. There was no statistically significant difference between criminalized and medical cannabis states, which experienced 8.8 cases per million population.
“The data suggest that EVALI cases were concentrated in states where consumers do not have legal access to recreational marijuana dispensaries,” the letter states. “This association was not driven by state-level differences in e-cigarette use, and EVALI case rates were not associated with state-level prevalence of e-cigarette use. One possible inference from our results is that the presence of legal markets for marijuana has helped mitigate or may be protective against EVALI.”
“Recreational marijuana states had among the lowest EVALI rates of all states.”
Cross-sectional study finds states with legal recreational marijuana had fewer cases of e-cig/vaping associated lung injury #EVALI. @aaronecarroll @ajhollingsworth @AshleyCBradford @coady_wing #VisualAbstract https://t.co/9dXGchag16 pic.twitter.com/nIoeV7v39b
— JAMA Network Open (@JAMANetworkOpen) April 7, 2020
While the researchers said the reason for the association isn’t clear yet, they surmised that it’s “possible that in recreational states, people tend to purchase marijuana products at legal dispensaries, which may be less likely to sell the contaminated products that are thought to cause EVALI.”
That has been the working theory of many industry observers, who have argued that legalization is an important safeguard to public health by ensuring compliance with quality control standards in cannabis products. It should be noted, however, that there are select reports of instances where people seemed to develop a lung injury after obtaining marijuana vaping products from licensed dispensaries in Oregon.
“It appears states that have legal access to marijuana have lower rates of EVALI cases, which is consistent with the hypothesis that people have demand for marijuana products, and in states where they don’t have access to them in this regulatory fashion, they end up purchasing them elsewhere,” study co-author Alex Hollingsworth told MedPage Today.
NORML Executive Director Erik Altieri said the findings “come as little surprise.”
“In jurisdictions where cannabis is legally regulated, consumers gravitate toward the above-ground retail marketplace where they can access lab-tested products manufactured by licensed businesses,” he said. “Just like alcohol prohibition gave rise to the illicit production of dangerous ‘bathtub gin,’ marijuana prohibition provides bad actors, not licensed businesses, the opportunity to fulfill consumers’ demand—sometimes with tragic results.”
In a historical commentary on the new study also published by the American Medical Association Journal, a separate set of researchers drew a parallel to the era of alcohol prohibition—from which an underground industry of bootleggers emerged.
“Bootleggers fortified their distillates with methanol to increase apparent potency, causing blindness and death in unwary consumers,” they said, noting that industrial ethanol, which was exempt from prohibition, was sometimes used despite the fact that government officials directed it to be adulterated with poisonous substances to deter consumption. “The resulting concoctions, known as denatured alcohol, were responsible for thousands of deaths during the 14 years that Prohibition was in effect. The history of Prohibition thus serves as a cautionary tale about unintended and unforeseen consequences of legislation regulating substances that affect public health.”
“Bootlegging was rampant and criminal syndicates proliferated, fueling a wave of organized crime.”
Commentary: EVALI rates are lower in states that have legalized recreational marijuana. Is legalizing marijuana protective against EVALI as there is less incentive to dilute THC in states where raw THC material is readily available without legal risk? https://t.co/Bd5Z8wYbjQ
— JAMA Network Open (@JAMANetworkOpen) April 7, 2020
EVALI similarly appears to be strongly associated with a specific contaminant in illicit markets, vitamin E acetate (VEA), which is used to dilute or stretch cannabis concentrates —”a scenario reminiscent of the unscrupulous bootleggers of the Prohibition era.”
“How could a state’s legalization of recreational marijuana inadvertently protect its citizens against EVALI? The obvious answer is that THC-containing vaping products in states where recreational marijuana is legal are uncontaminated with VEA. If so, another question follows: why would THC products in these states be less likely to be contaminated (ie, diluted) with VEA? One salient possibility is that there is less financial incentive to dilute THC concentrates in states where raw THC material is readily available without legal risk and compensatory markup.”
“If THC concentrates are transported from states where they are legal and can be relatively cheaply mass produced (like industrial ethanol stocks during Prohibition) to other states where they are illegal and must be guarded jealously as a rare and precious commodity, there may be a strong economic inducement to dilute them, thereby increasing profits. Thus, legalization of marijuana may have protective local effects but untoward collateral effects.”
President Trump also seemed to pick up on the failure of prohibition during a meeting on the vaping crisis last year. He acknowledged that simply banning the products wouldn’t work, as people would simply move on to the illicit market, where there aren’t regulations.
What’s worse, the conflict between state and federal marijuana laws actually inhibited research into how to address EVALI cases, complicating shipments of vaping specimens, a top CDC official said.
The same official also suggested that federal cannabis regulations could mitigate the vaping problem. Former Food and Drug Administration Commissioner Scott Gottlieb made a similar argument.
This story was updated to include comment from NORML.
Proof Of Marijuana Use Discovered At Ancient Biblical Site In Israel
An ancient biblical tribe in Israel likely used marijuana to produce hallucinogenic effects as part of cultic rituals, according to a new study that identified cannabis resin on an alter in a shrine built around 750 BCE.
Two alters that appeared near the entrance of the “Holy of Holies” in the Judahite shrine were excavated about 50 years ago and now an analysis of the materials on top of the alters turned up evidence of marijuana combustion at the site.
The study, published Thursday in the journal Tel Aviv, states that “cannabis inflorescences were burnt there, conceivably as part of a ritual that took place in the shrine.”
“It seems feasible to suggest that the use of cannabis on the Arad altar had a deliberate psychoactive role,” the study concluded.
“Cannabis odors are not appealing,” the researchers opined, “and do not justify bringing the inflorescences from afar. The frequent use of hallucinogenic materials for cultic purposes in the Ancient Near East and beyond is well known and goes back as early as prehistoric periods.”
However, this is the first time physical evidence has been identified that indicates the tribe of Judah participated in marijuana-infused ceremonies. Evidence of frankincense being burned was also found at the site.
The team behind the study, from the Israel Museum and the Volcani Center, relied on two common methods of identifying cannabinoids: liquid chromatography and gas chromatography. They found components of marijuana known widely today such as THC, CBD, CBN and various terpenoids.
Researchers said it’s unclear where the ancient tribe obtained cannabis, but they suspect that it “may have been imported from distant origins and were transported as dried resin (commonly known as hashish).”
To burn the marijuana and let out the smoke, it was apparently mixed with animal feces “to enable its mild heating,” the study states.
“It seems likely that cannabis was used at Arad as a deliberate psychoactive, to stimulate ecstasy as part of cultic ceremonies,” it continues. “If so, this is the first such evidence in the cult of Judah.”
“The discovery of cannabis on the smaller altar was a surprise. Arad provides the earliest evidence for the use of cannabis in the Ancient Near East. Hallucinogenic substances are known from various neighboring cultures, but this is the first known evidence of hallucinogenic substance found in the Kingdom of Judah.”
Eran Arie, a curator at the Israel Museum where the excavated shine is housed, told CNN that they “never thought about Judah taking part in these cultic practices.”
“The fact that we found cannabis in an official cult place of Judah says something new about the cult of Judah,” he said.
A separate study released last year documented how people from a diverse range of cultures have been using marijuana for thousands of years—in different forms and for different purposes. For example, cannabis was considered a “holy plant” in Tibet and was used in Tantric Buddhism to “facilitate meditations.” It was also used in Arabic medicine to treat ear infections, skin diseases, flatulence, intestinal worms, neurological pain, fever and vomiting.
Photo courtesy of Brian Shamblen.
THC-Infused Semen Can Be A Side Effect Of Frequent Marijuana Use, Study Finds
Many people have had to take a urine test for cannabis, perhaps as a job requirement. Using the popular procedure, marijuana metabolites can in some cases be detected for weeks after a person’s last use. But here’s a question few may have thought to ask: Can THC be detected in semen?
According to a new study by a team of Harvard Medical School researchers, the answer is yes—at least sometimes. In a study of 12 participants who regularly consumed marijuana by inhalation, the researchers were able to detect delta-9 THC, the main psychoactive ingredient in cannabis, in two subjects’ semen samples. And at least one metabolite of THC—what’s left over after the body processes the compound—could be detected in all samples capable of being analyzed. “Two semen samples,” the report says, “had insufficient volume to be analyzed.”
Why the focus on THC in semen? In a word, pregnancy. Men of reproductive age, the study’s authors note, “are the most prevalent consumers of marijuana, with 19.4% of men in the USA reporting use.” A 2018 study cited by the authors found that 16.5 percent of men and 11.5 percent of women reported using marijuana while attempting to conceive.
How exactly THC affects reproductive systems and childhood development are questions the Harvard authors don’t attempt to answer in the study. The primary goal of the proof-of-concept research, they explain, “was to determine whether THC can cross the blood-testis barrier.” On that front, they appear to have succeeded.
“In the setting of a growing repository of data surrounding the effects of the endocannabinoid system in the regulation and maintenance of fertility and early pregnancy,” the study says, “ours is the first report that the exogenous cannabinoid THC can be detected in any human reproductive matrix.”
Because of the interest in whether THC could be detected at all, researchers focused on regular, long-term marijuana consumers. All participants indicated they had used the drug between 25 and 30 days of the last month, and most said they had been regular consumers for at least five years. “Consequently,” the team said, “our study findings cannot be generalized to include ever users, light, or moderate users of marijuana.”
Of the two participants whose semen contained detectable levels of THC itself, samples contained 0.97 nanograms per milliliter and 0.87 ng/mL.
But it wasn’t clear what set those two participants apart. There was no correlation between semen THC and concentration of the metabolite THC carboxylic acid in urine, nor with time since last cannabis consumption, participant age or participant body mass index.
“It is puzzling that some, but not all, semen samples tested positive for THC,” the study says. “There were no obvious factors that were strongly associated with detectable semen THC; thus, we can propose few predictors of the presence of THC in human semen. Future directions (of research) include identifying characteristics that may affect semen detectable THC levels.”
How precisely THC affects semen—or the sperm within it, not to mention conception, pregnancy or childhood development—is still hard to say with certainty. As the Harvard researchers note in the study, “Evidence linking marijuana to reproductive outcomes is scarce and to date, often conflicting.”
One study of 1,200 young Danish men, for example, found that those who smoked marijuana regularly had lower sperm counts than those who did not. Another study, of 662 older, subfertile men in Massachusetts, found that men who had ever smoked marijuana had significantly higher sperm counts than those who’d abstained.
As for the effects of THC on sperm, or conception itself, those also remain unclear. “The effect of marijuana on human gametes and fertilization is relatively unknown,” the new paper says. Endocannabinoid receptors have been reported on sperm themselves, but “studies examining the direct effect of THC on human sperm are limited.”
Most research so far has either been observational, by measuring THC through self-reporting or blood testing, or studied the behavior of sperm that had been washed in a laboratory with a THC solution. “Our findings, that THC can be directly quantified in human seminal fluid, lay the groundwork to allow for future studies,” the new study says. “Since THC can be detected in the seminal fluid of some individuals, this might provide a direct method of measurement (rather than relying on self-reporting marijuana use, which is subjective and potentially unreliable, or serum levels which only reflect recent exposure) to bridge real-world clinical studies with the prior staged studies in which THC was directly incubated with washed sperm.”
While the THC-washed sperm showed some concerning effects, including decreased motility and mitochondrial oxygen consumption, the Harvard team acknowledged the concentrations of THC used in those studies were significantly stronger than anything observed in their semen study: “It should be noted that even the lowest concentration of THC with which former studies incubated sperm was over tenfold higher than the concentration of THC detected in the semen of our study subjects.”
In other words, the study is a stepping-stone to further research. And while the top-line findings might elicit some giggles, authors say the study is serious business.
“The ability to quantify cannabinoids in human reproductive tissues and fluids,” they conclude, “gives us the capability to directly study the effects of cannabis on early human reproduction.”
States With Medical Marijuana Laws Saw 20% Drop In Some Opioid Prescriptions
States with active medical marijuana laws saw certain opioid prescription rates drop nearly 20 percent compared to prohibition states, a first-of-its-kind study out of Columbia University’s Irving Medical Center has found. Authors said the findings underscore the importance of providing patients with pain management alternatives, such as cannabis, in efforts to reduce opioid use.
Drug overdoses remain a leading cause of injury-related death in the United States, and the U.S. Centers for Disease Control and Prevention reports that 68 percent of those deaths involve illicit or prescription opioids. The new study examines opioid prescriptions made specifically by orthopedic surgeons, who it notes are the nation’s third-highest prescribers of opioids.
“Although our study does not support a direct causal relationship, these population-level findings show that legalization of medical cannabis and patient access to dispensaries may be associated with reductions in opioid prescribing by orthopaedic surgeons,” the study’s authors concluded. “The observed trends reported in this study may be a reflection of growing availability of alternative pain management options for patients.”
“We found that overall opioid prescribing by orthopaedic surgeons in this cohort was reduced in states permitting patient access to medical cannabis, compared with those who do not.”
Analyzing nationwide Medicare Part D prescription drug data, researchers measured the aggregate daily doses of opioid medications prescribed by orthopedic surgeons in each state annually. They then looked for associations between that state-level data and the legal status of medical marijuana in each state.
As with past studies examining correlations between medical marijuana and opioid prescriptions, the Columbia analysis found a marked drop in prescriptions among states with medical cannabis laws (MCLs). “State MCLs were associated with a statistically significant reduction in aggregate opioid prescribing of 144,000 daily doses (19.7% reduction) annually,” the study, published this month in the Journal of the American Academy of Orthopaedic Surgeons, says.
Medical cannabis laws “were associated with a statistically significant reduction of 72,000 daily doses of hydrocodone annually.”
Not all state legal marijuana programs operate the same way, of course. It can also take years after a state adopts a medical cannabis law before its program is up and running. So the researchers looked at various specific factors, including when storefront dispensaries opened, whether state laws allowed home cultivation by patients, and whether recreational cannabis was legal for adults in each state.
Of the relationships that the researchers found were statistically significant, two stood out most clearly: States with active medical cannabis laws saw a 19.7 percent reductions in Medicare Part D opioid prescriptions made by orthopedic surgeons compared to states without medical cannabis laws. On a more granular level, states with operating storefront dispensaries saw a 13.1 percent reduction in those prescriptions.
Other relationships found by the researchers were just as likely to be due to chance. States with restrictive medical cannabis laws that allowed access only to low-THC products, for example, saw small, statistically insignificant increases in opioid prescriptions.
Researchers also “did not observe any significant association between total opioid prescriptions and home cultivation–only” medical cannabis laws, and concluded that “no significant association between recreational marijuana legalization and opioid prescribing was found.”
In “states that allow physicians to recommend medical cannabis to patients for any reason, there was a significant reduction in prescriptions for fentanyl…”
Cannabis is a particularly appealing alternative pain medication to study the effect of, the authors wrote, “because of its efficacy in treatment of chronic and acute pain and its potential for replacing and/or reducing opioid treatment.”
Researchers adjusted some of their data to better reflect not just the laws on the books but the actual accessibility of medical marijuana in each state. New York, for example, adopted a medical cannabis law in 2014, but home cultivation was prohibited and dispensaries didn’t open until 2016. “As such,” the authors wrote, “we did not classify New York as an MCL state or a dispensary-based MCL state until 2016.”
The study also cautions that its results only mean so much. Because it relied on population-level data and didn’t track individuals’ opioid or medical marijuana use, “we could not make any conclusions about any direct effect of substitution of opioids for cannabis by patients on prescription trends.” the authors wrote. “As such, our study does not draw conclusions of direct causation, but reports observed associations over time using a nationwide cohort database and multivariable regression analysis.”
Still, the study’s results contribute to a growing body of research indicating that medical cannabis accessibility significantly reduces statewide opioid use—and even opioid deaths. As the Columbia authors note in their report, “Multiple large nationwide database studies have shown that states with the legalization of medical marijuana have seen reductions in the opioid prescription rates and opioid-related mortality rates. The authors of these studies have theorized that in states where medical cannabis is more available, patients are likely to substitute cannabis for opioids in their pain management.”
For example, a meta-study that was recently published also signaled that marijuana shows promise as a treatment option for chronic pain and could serve as an alternative to opioid-based painkillers.
Last month, researchers released a study that found cannabis can mitigate symptoms of opioid withdrawal.
In December, researchers determined that states with legal marijuana access experience decreases in opioid prescriptions, and a separate study released the previous month showed that daily marijuana consumption is associated with reduced opioid consumption among chronic pain patients.