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.
Teen Marijuana Treatment Admissions Fell Sharply In States That Legalized, Federal Report Shows
States that have legalized marijuana for recreational use have seen sharp declines in youth treatment admission rates for the drug, according to a new federal report that also shows teen admission rates for cannabis misuse fell nationwide by nearly half during the 2008-2017 period.
Medical cannabis laws, meanwhile, appear to have no connection to teen treatment rates, according to the peer-reviewed research published on Thursday by the U.S. Centers for Disease Control and Prevention.
The data seem to refute warnings by legalization critics who predicted that ending prohibition would lead to ballooning rates of youth substance misuse.
“Consistent with prior research on medical marijuana and adolescent marijuana use, medical legalization status does not appear to correspond to treatment admission trends,” says study, published in the CDC journal GIS Reports. “Notably, however, 7 of 8 states with recreational legalization during the study period fall into the class with the steepest level of admissions decline.”
Author Jeremy Mennis, a professor at Temple University, assembled the report by collecting state-level data on teen treatment admissions where the primary substance used was marijuana. Dividing the annual admissions numbers by the number of adolescents in each state, obtained through U.S. Census data, allowed him to determine each state’s admission rate over time.
Mennis then displayed the state-by-state data on a map, taking into account both the state admissions rates themselves and the direction each was trending over time.
“The map depicts both the slope of the admissions rate (ie, admissions rate gain or loss) and the mean of the admissions rate (ie, admissions rate magnitude) for each state,” the report says.
Nationwide, the average annual admissions rate over the study period “declined over the study period by nearly half, from 60 (admissions per 10,000 adolescents) in 2008 to 31 in 2017,” according to the CDC study.
While some states saw increases in admissions rates over that period, states that had the highest rates of treatment admissions all experienced declines. All three states on the West Coast, for example, had among the highest treatment admissions rates during the period studied—but also showed the steepest declines in admissions over that time. California, Oregon and Washington State have all legalized cannabis for adult-use.
“All 12 states in the high mean admissions rate class sustained admissions declines,” the report says, “with 10 of those states having declines in the steepest category (states colored darkest blue).”
Some states—Wisconsin, Indiana and South Carolina—had too much missing data to include in the report.
What’s behind the trends isn’t immediately clear from the data. Mennis writes that possible causes for the declines, as well for the variation between states, “include changes in attitudes toward marijuana, as well as differences in marijuana use and incidence of CUD [cannabis use disorder], as well as in socioeconomic status, treatment availability, and health insurance.”
“Whatever the causes of the observed patterns,” the report says, “this research suggests that a precipitious national decline in adolescent treatment admissions, particularly in states legalizing recreational marijuana use, is occurring simultaneously within a period of increased permissiveness, decreasing perception of harm, and increasing adult use.”
The findings generally align with past studies looking at teen marijuana use in legal states, which have found that youth consumption has remained steady or fallen even as the perception of harm caused by marijuana has decreased.
In a presentation to lawmakers in North Dakota this summer, the deputy coordinator for the federal High Intensity Drug Trafficking Area (HIDTA) program’s National Marijuana Initiative, Dale Quigley, acknowledged that teen use was falling both nationally and in legal states.
“For some reason, the use rate among this age bracket is going down,” said Quigley, who lives in Colorado. “We’re not 100 percent sure why it’s going down. It’s a good thing that it’s going down, but we don’t understand why.”
Another study, released by Colorado officials in August, showed that youth cannabis consumption in the state “has not significantly changed since legalization” in 2012.
A CDC report published the same month, meanwhile, found that cannabis use by high school students has fallen in recent years after an earlier increase. Youth lifetime marijuana use “increased during 2009–2013 and then decreased during 2013–2019,” the report found.
“We are reassured by the latest results from the 2019 Youth Risk Behavior Survey because they show that youth marijuana use has not increased over the past decade, even as more states across the country have passed progressive marijuana laws,” Sheila Vakharia, deputy director of the department of research and academic engagement for the Drug Policy Alliance, said in a statement at the time.
Earlier studies looking at teen use rates after legalization have found similar declines or a lack of evidence of an increase.
Last year, for example, a study took data from Washington State and determined that declines in youth cannabis consumption could be explained by replacing the illicit market with regulations or the “loss of novelty appeal among youths.”
Another study from last year showed declining youth cannabis consumption in legalized states but didn’t suggest possible explanations.
Photo by Sharon McCutcheon on Unsplash
FDA Is Hosting A Conference On CBD, Sex And Gender This Week
As the federal government continues to develop regulations around CBD, the Food and Drug Administration (FDA) will host a public conference on Thursday to highlight how the cannabinoid’s use and effects may differ based on sex and gender.
The daylong meeting, organized by FDA’s Office of Women’s Health, will include presentations on “sex differences in the effects of CBD and other cannabinoids, use of CBD and other cannabinoids in pregnancy, and government agency perspectives on CBD research and evaluation,” according to an agency description.
“Researchers, educators, clinicians, and patients may benefit from attending this multidisciplinary scientific conference,” it says.
The @FDAWomen will host a free virtual public meeting on Thurs., 11/19 to discuss potential sex & gender differences in use and responses to cannabidiol (CBD) and other cannabinoids. @NCCIH_David & Dr. Inna Belfer, NCCIH program director, will participate. https://t.co/KEbSsT9O56 https://t.co/ERD8SCpqPq
— NIH NCCIH (@NIH_NCCIH) November 12, 2020
(A Federal Register notice from September indicated a registration deadline of Monday, but the system was still accepting new sign-ups as of Tuesday morning.)
In addition to remarks by FDA officials, the event will feature four panels throughout the day:
- 9:30 a.m. — Use of CBD and Other Cannabinoids: Perspectives from Patients and Healthcare Professionals
- 10:45 a.m. — Sex Differences in the Effects of CBD and Other Cannabinoids
- 1 p.m. — Use of CBD and Other Cannabinoids in Pregnancy
- 2:30 p.m. — Government Agency Perspectives on CBD Research and Evaluation
Speakers include an array of academics, researchers and other health professionals, such as professors from research departments at the University of Colorado at Boulder and Johns Hopkins University, among others. On the government side are panelists from FDA and the National Institutes of Health.
Each panel discussion will include a Q&A session to respond to questions from attendees, FDA said in September.
Sex and gender are important factors to consider in CBD regulation not only because the compound could affect people’s bodies differently—such as in the case of pregnancy—FDA says, but also because of what the agency calls “psychosocial,” or gender-based, differences.
“Conditions for which CBD is often marketed, such as chronic pain, anxiety, depression, and sleep disturbances, are more prevalent in women than men,” the event listing says. “Therefore, consideration of issues pertaining to the safety of CBD products may be particularly important to address in women.”
— FDAWomen (@FDAWomen) November 6, 2020
FDA has been especially active among federal agencies since Congress legalized hemp and its derivatives through the 2018 Farm Bill. The agency is developing regulations expected to allow for the lawful marketing of CBD products, and it also recently held meetings to promote studies into the cannabis plant and inform researchers and cultivators about opportunities to protect their proprietary information from competitors.
The agency was required by law to give an update on its regulatory approach to CBD, which it did in March, saying that “FDA is currently evaluating issuance of a risk-based enforcement policy that would provide greater transparency and clarity regarding factors FDA intends to take into account in prioritizing enforcement decisions.” In July it submitted draft enforcement guidance to the White House.
“FDA recognizes the significant public interest in cannabis and cannabis-derived compounds, particularly CBD,” says the description of Thursday’s sex and gender event. “However, there are many unanswered questions about the science, safety, and quality of products containing CBD… This public meeting will provide further insight into the scientific evidence suggesting the presence or absence of sex and gender differences in use and responses to CBD and other cannabinoids.”
In the years since hemp became legal, FDA has been using enforcement discretion in its approach to CBD products. The agency has issued warnings to cannabis businesses in certain cases—such as when some companies claimed CBD could treat or cure the virus that causes COVID-19—and provided public notices about recalls.
In July, FDA submitted a report to Congress on the state of the CBD marketplace, outlining studies the agency has performed on the contents and quality of cannabis-derived products it has tested. The agency is also looking to award a contract to help study CBD.
A proposal from Senate Appropriations Committee last week would further fund FDA’s work with cannabinoids by earmarking $5 million to support the agency’s regulatory activities around cannabis, including “targeted research for cannabis-derived substances, such as cannabidiol.”
Photo by Kimzy Nanney
New FDA Guidance Will Make It Easier To Approve CBD-Based Medicines
The Food and Drug Administration (FDA) is releasing new draft guidelines that are meant to streamline approvals for generic oral CBD medications.
In a notice published in the Federal Register on Wednesday, the agency said it is soliciting public feedback on its guidance to researchers who are interested in submitting abbreviated new drug applications (ANDAs) for CBD solutions.
To expedite the approval process, FDA said applicants can request a waiver of an in vivo bioequivalence study if they meet certain requirements. This guidance comes two years after the agency approved the brand-name CBD-based epilepsy medication Epidiolex from GW Pharmaceuticals.
Going forward, if a drug company wants to produce generic versions of that 100 mg/mL cannabidiol solution, they could follow specific rules to skip the in vivo bioequivalence study step if the draft guidance is finalized. The drug would have to be derived from Cannabis sativa L, contain no more than 0.1 percent THC and have “no inactive ingredient or other change in formulation from the [reference listed drug] that may significantly affect systemic availability.”
Researchers must use “appropriate analytical methods” such as macroscopic or microscopic analysis or DNA bar-coding methods to determine that the solution is being made from cannabis sativa.
“Due to the many cultivars within this species, identification and authentication of plant species should be conducted at the cultivar(s) level if the potential cultivar(s) will be used as a natural source of the [botanical raw material],” FDA said.
Further, when collecting that raw cannabis, the agency said applicants must follow “established good agricultural and collection practices (GACP) procedures to minimize variations in BRM and eventually ensure the batch-to-batch consistency of the drug substance.”
A public comment period on FDA’s draft guidance will last until November 23. FDA also recently closed a comment period on separate draft guidance on developing cannabis-derived medications. However, three other federal agencies are currently accepting input on a variety of other proposed cannabis- and drug-related regulations.
While this latest document isn’t the separate comprehensive CBD guidance that advocates and industry stakeholders have been waiting for, it’s another example of how the scientific landscape around cannabis is changing, with a federal agency helping to facilitate the production of cannabidiol-based drugs.
Separately, FDA announced on Tuesday that it will be hosting a public meeting in November to discuss gender and sex differences in the effects of CBD and other cannabinoids.
The agency also recently held a meeting to help inform cannabis researchers and cultivators about opportunities to protect their proprietary information and promote studies into the plant.
It also recently submitted draft guidance on CBD enforcement to the White House Office of Management and Budget—a long-anticipated move that comes after hemp legalization.
The agency was mandated under appropriations legislation enacted late last year to provide an update on its regulatory approach to CBD, and it did so in March. The update stated that “FDA is currently evaluating issuance of a risk-based enforcement policy that would provide greater transparency and clarity regarding factors FDA intends to take into account in prioritizing enforcement decisions.”
FDA has been using enforcement discretion for CBD in the years since hemp became legal.
The agency has continued to issue warnings to cannabis businesses in certain cases—such as instances in which companies claimed CBD could treat or cure coronavirus—and provide public notices about recalls.
In July, FDA also submitted a report to Congress on the state of the CBD marketplace, and the document outlines studies the agency has performed on the contents and quality of cannabis-derived products that it has tested over the past six years.
Also that month, a congressional spending bill for FDA was released that includes a provision providing “funding to develop a framework for regulating CBD products.”
The agency is also actively looking to award a contract to help study CBD as the agency develops regulations for products containing the non-intoxicating cannabinoid.
Read FDA’s draft guidance on developing CBD medications below:
Photo by Kimzy Nanney.