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microdosing-candies-finally-recalled-after-psychoactive-muscimol-found

Microdosing candies finally recalled after psychoactive muscimol found

Finally —

Muscimol, found in the candy, is from hallucinogenic Amanita muscaria mushrooms.

Microdosing candies finally recalled after psychoactive muscimol found

After weeks of reports of severe illnesses across the country, the maker of Diamond Shruumz microdosing chocolates, gummies, and candy cones has finally issued a recall. It covers all lots and all flavors of all the brand’s products.

The illnesses have been marked by several severe symptoms, which notably include seizures, loss of consciousness, and the need for intubation and intensive care. To date, there have been 39 people sickened, including 23 hospitalizations across 20 states, according to the Food and Drug Administration and the Centers for Disease Control and Prevention. The FDA first issued a warning on the brand’s chocolate bars on June 7, when there were reports of eight cases, including six hospitalizations, in four states.

Diamond Shruumz’s parent company, Prophet Premium Blends, said in the recall notice that it had received only two complaints about the products to date and, upon receiving those complaints, reviewed recent laboratory analyses (Certificates of Analysis) of its products. According to the company, those CoAs noted “higher than normal amounts of muscimol,” which is one of two key compounds found in hallucinogenic Amanita mushrooms. Muscimol “could be a potential cause of symptoms consistent with those observed in persons who became ill after eating Diamond Shruumz products,” the company said in the recall notice.

In a statement posted on Diamond Shruumz’s website, Prophet Premium Blends announced the recall and added that it has also ceased production and distribution of all of the brand’s products.

“Due to consumers becoming ill after consuming the entire chocolate bar and some products containing higher levels of Muscimol than normal, it is crucial that all of our consumers refrain from ingesting this product while we, alongside the FDA, continue our investigation as to what is the cause of the serious adverse effects,” Prophet Premium Blends wrote on its website.

Diamond Shruumz has not responded to multiple requests for comment from Ars. Prophet Premium Blends did not respond to a request for comment and a list of questions.

What’s normal?

It’s unclear what amounts of muscimol were found in the company’s products and which products were affected. While the company reported only “higher than normal” amounts, it’s also unclear what the “normal” amount is. Diamond Shruumz posts third-party lab reports on its website, most of which indicate that the products are tested for muscimol. For instance, the reports show muscimol testing for all flavors of Cones and Extreme Gummies. For the brand’s chocolate bars, which the FDA first linked to the illnesses, all the bars except for the dark chocolate flavor showed muscimol results. For the gummies, only the report for the Hawaiian Punch flavor shows muscimol results. Of all the reports that include results for muscimol, all indicate that the amounts are lower than the limit of quantitation, which suggests that they are not supposed to contain any amount of muscimol. All of the reports reviewed by Ars were dated at various times throughout 2023.

Muscimol, along with related ibotenic acid, are both key psychoactive components of some Amanita mushrooms. That includes the hallucinogenic toadstool mushroom A. muscaria var. muscaria, which is notable for its unique bright red-orange caps with white warts. Both muscimol and ibotenic acid resemble neurotransmitters, namely GABA and glutamate, respectively. Muscimol is associated with depression of the central nervous system, while Ibotenic acid is associated with excitation of the central nervous system.

Fuzzy findings

According to the recall notice, it’s possible that the muscimol could cause some of the symptoms in people sickened, which included seizures, agitation, involuntary muscle contractions, loss of consciousness, confusion, sleepiness, nausea and vomiting, abnormal heart rates, and hyper/hypotension. The FDA said in its own update that it was “evaluating this information.”

The agency had previously identified the undisclosed synthetic psychedelic compound 4-AcO-DMT in the company’s chocolates, as well as undisclosed compounds found in a potentially toxic Kava plant (Piper methysticum). It remains unclear if any of those compounds explain the illnesses.

The totality of the ingredients in Diamond Shruumz’s products remains unclear. The company does not list the ingredients on its website, selling the products only with terms indicating they contain psychedelic compounds and the vague, buzzword-loaded description of having a “primo proprietary blend of nootropic and functional mushrooms.”

The CDC warns that such “edibles” are often sold as candies and snack food and might contain undisclosed ingredients, including illicit substances, adulterants, or potentially harmful contaminants. Common marketing terms to look out for include “microdosing,” “adaptogens,” “nootropics,” and “functional mushrooms,” the CDC warns.

Consumers should not eat, sell, or serve any Diamond Shruumz product. For those who have already purchased the products, they can be returned for a full refund to 1019 Arlington St., Orlando, Florida, 32805, according to Diamond Shruumz’s website.

Microdosing candies finally recalled after psychoactive muscimol found Read More »

synthetic-psychedelic-found-in-candies-linked-to-seizures,-intubation

Synthetic psychedelic found in candies linked to seizures, intubation

Toxic trip —

Cases grow to 39, including 23 hospitalizations, across 20 states.

A Diamond Shruumz chocolate bar, which comes in a variety of flavors.

Enlarge / A Diamond Shruumz chocolate bar, which comes in a variety of flavors.

The US Food and Drug Administration has identified a synthetic psychedelic compound as well as compounds from a potentially toxic plant in the Diamond Shruumz-brand microdosing candies linked to a growing number of severe illnesses nationwide that have included seizures, intubation, and admissions to intensive care units.

As of June 25, the case total has grown to 39, including 23 hospitalizations, across 20 states, the FDA and the Centers for Disease Control and Prevention reported.

It remains unclear what is in the candies and what may be causing the severe illnesses. Diamond Shruumz does not provide a full list of ingredients. The term “microdosing” and other marketing used by Diamond Shruumz suggests the candies contain a psychedelic compound, but the company does not name any. To figure it out, the FDA has been analyzing multiple samples of Diamond Shruumz-brand candies, including chocolates, gummies, and candy cones. On Tuesday, the FDA reported finding the synthetic psychedelic compound 4-AcO-DMT in the company’s Dark Chocolate Bar and its Birthday Cake Chocolate Bar.

As Ars reported previously, 4-AcO-DMT (aka 4- acetoxy-N,N-dimethyltryptamine, O-acetylpsilocin, or psilacetin) is a common synthetic tryptamine used in psychedelics and was previously suspected to be in the Diamond Shruumz candies. The psychoactive drug has a chemical structure similar to the most notable mushroom-derived psychedelic, psilocybin, as well as LSD. Though safety data on the compound is scant, it is not known to be linked to some of the severe symptoms seen in the current string of illnesses. People who use 4-Aco-DMT describe it as producing effects similar to psilocybin, but without some of the unpleasant side effects noted with natural mushrooms, such as nausea. Still, according to the CDC, some people who use it could experience nausea, vomiting, fast heart rate, anxiety, agitation, lightheadedness, or tremor.

Additionally, the FDA found three compounds from the Kava plant (Piper methysticum) in the company’s dark chocolate bar, though not the birthday-cake flavored bar. The compounds are kavalactones—desmethoxyyangonin, dihydrokavain, and kavain.

Concerning kava

Kava is a plant found on some Pacific Islands and is used in traditional herbal remedies for the treatment of anxiety, insomnia, stress, and other ailments. But, over the years, it has also occasionally been linked to severe liver toxicity. In the early 2000s, this led to warnings, withdrawals, and even bans in several countries, including Germany, Switzerland, France, Canada, and the UK. In 2002, the FDA issued an advisory of its own over the associated liver injuries, which include hepatitis, cirrhosis, and liver failure. Later that same year, researchers published case reports of 11 people (two in the US and nine in Europe) who developed liver failure after using kava products and needed subsequent liver transplants.

In an update on the illnesses linked to Diamond Shruumz candies, the CDC noted that kava can cause numbness of the mouth and skin, loss of coordination, dizziness, sedation, and gastrointestinal effects, such as nausea and vomiting. Consuming kava products alongside alcohol or drugs like benzodiazepines (e.g. Valium and Xanax) can heighten the sedative effects. But, the CDC seemed to downplay the risk of liver toxicity here, noting that it has only occasionally been associated with chronic or heavy ingestion of kava.

In all, it’s still unclear if the compounds the FDA identified in the Diamond Shruumz chocolate bars so far can explain the illnesses seen in the linked cases. The CDC lists the severe and common symptoms from those cases as including seizures, decreased level of consciousness, respiratory failure, nausea, vomiting, abdominal pain, hallucinations, uncontrolled movements, abnormal heart rate (e.g., too fast or too slow), high or low blood pressure, excessive sweating or secretions, and flushed skin.

The FDA said testing of other Diamond Shruumz products is still in progress. The agency noted that there can be differences across products and batches. In the meantime, the agency advises consumers not to eat, sell, or serve any of the company’s products and, instead, discard them.

There is still no recall of the candies. Diamond Shruumz has not responded to multiple inquiries from Ars. The FDA said Tuesday that the agency has “been in contact with the firm about a possible voluntary recall,” but to date, Diamond Shruumz has not initiated one.

Synthetic psychedelic found in candies linked to seizures, intubation Read More »

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Top FDA official overrules staff to approve gene therapy that failed trial

Internal conflict —

Peter Marks overruled three teams and two top directors.

Dr. Peter Marks, Director of the Center for Biologics Evaluation and Research within the Food and Drug Administration on March 18, 2021 in Washington, DC.

Enlarge / Dr. Peter Marks, Director of the Center for Biologics Evaluation and Research within the Food and Drug Administration on March 18, 2021 in Washington, DC.

The Food and Drug Administration (FDA) on Thursday announced expanded approval for a gene therapy to treat Duchenne muscular dystrophy (DMD)—despite the fact that it failed a Phase III clinical trial last year and that the approval came over the objections of three of FDA’s own expert review teams and two of its directors.

In fact, the decision to expand the approval of the therapy—called Elevidys (delandistrogene moxeparvovec-rokl)—appears to have been decided almost entirely by Peter Marks, Director of the FDA’s Center for Biologics Evaluation and Research.

Elevidys initially gained an FDA approval last year, also over objections from staff. The therapy intravenously delivers a transgene that codes for select portions of a protein called dystrophin in healthy muscle cells; the protein is mutated in patients with DMD. Last year’s initial approval occurred under an accelerated approval process and was only for use in DMD patients ages 4 and 5 who are able to walk. In the actions Thursday, the FDA granted a traditional approval for the therapy and opened access to DMD patients of all ages, regardless of ambulatory status.

“Today’s approval broadens the spectrum of patients with Duchenne muscular dystrophy eligible for this therapy, helping to address the ongoing, urgent treatment need for patients with this devastating and life-threatening disease,” Marks said in the announcement Thursday. “We remain steadfast in our commitment to help advance safe and effective treatments for patients who desperately need them.”

Criticism

The move, which follows a string of controversies in recent years of the FDA issuing questionable approvals over the assessments of advisors and its own staff, has quickly drawn criticism from agency watchers.

In a blog post Friday, a notable pharmaceutical industry expert and commentator, Derek Lowe, admonished the approval. Lowe expressed concern that the agency seems to be tilting toward emotional rhetoric and the will of patient advocates over scientific and medical evidence.

“It appears that all you need is a friend high up in the agency and your clinical failures just aren’t an issue any more,” he wrote. “Review committees aren’t convinced? Statisticians don’t buy your arguments? Who cares! Peter Marks is here to deliver hot, steaming takeout containers full of Hope. … And while I realize that this may make me sound like a heartless SOB, I think this is a huge mistake that we will be paying for for a long time.”

In a comment to Stat News, former FDA chief scientist Luciana Borio echoed concerns about how decisions like this will affect the agency in the longer term.

“I don’t know what to say. Peter Marks makes a mockery of scientific reasoning and approval standards that have served patients well over decades,” said Borio, who has also opposed earlier controversial approvals. “This type of action also promotes the growing mistrust in scientific institutions like the FDA.”

Internal dissent

In a series of review documents and memos released by the FDA, the divide between Marks and agency staff is abundantly clear. A review by FDA statisticians concluded that the collective clinical trial results “do not suggest there is substantial evidence to support the effectiveness of [Elevidys] for the expanded indication to all DMD patients and do not support the conversion of accelerated to traditional approval.”

A joint review from the agency’s Clinical and Clinical Pharmacology teams likewise concluded that the “totality of the data does not provide substantial evidence of effectiveness of Elevidys for treatment of ambulatory DMD patients of any age” and that the results “argue against” expanding access.

In a memo, Lola Fashoyin-Aje, Director of the Office of Clinical Evaluation in the Office of Therapeutic Products (OTP), and Dr. Nicole Verdun, Super Office Director of the OTP, concluded that the clinical results “cast significant uncertainty regarding the benefits of treatment of DMD with Elevidys.” The two directors found the primary clinical trial endpoint results were “not statistically significant” and smaller analyses looking at secondary endpoints of specific patient measures—such as the time it takes patients to rise from the floor or walk 10 meters—were “inconclusive,” in some cases “conflicting,” and overall illustrated the “unreliability of exploratory analyses to support regulatory decision-making.”

In a memo of his own, Marks agreed that primary endpoint result of the trial—based on scores on a standardized assessment of motor function in patients—did not show a statistically significant benefit. But he argued that the secondary endpoints were convincing enough for him. Marks wrote:

Specifically, although acknowledging that the Applicant’s randomized study of Elevidys failed to meet its statistical primary endpoint … I find that the observations regarding the secondary endpoints and exploratory endpoints are compelling and, combined with other data provided in the efficacy supplement and the original [Biologics License Application], meet the substantial evidence of effectiveness standard …

If Marks had not overruled the agency’s reviewers and directors, Fashoyin-Aje wrote that she would have recommended the therapy’s maker, Sarepta, conduct “an additional adequate and well-controlled study of Elevidys in the subgroup(s) of patients for which [Sarepta] believes the effects of Elevidys to be most promising.” However, Marks’ decision to approve renders the possibility of such a trial “highly infeasible to explore in a post-approval setting,” she wrote.

Top FDA official overrules staff to approve gene therapy that failed trial Read More »

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Microdosing candy-linked illnesses double; possible recall in “discussions”

No recall —

Of the 26 cases identified so far, 25 sought medical care and 16 were hospitalized.

Microdosing candy-linked illnesses double; possible recall in “discussions”

Cases of illnesses linked to microdosing candies have more than doubled, with reports of seizures and the need for intubation, mechanical ventilation, and intensive care stays. But, there remains no recall of the products—microdosing chocolates, gummies, and candy cones by Diamond Shruumz—linked to the severe and life-threatening illnesses. In the latest update from the Food and Drug Administration late Tuesday, the agency said that it “has been in contact with the firm about a possible voluntary recall, but these discussions are still ongoing.”

In the update, the FDA reported 26 cases across 16 states, up from 12 cases in eight states last week. Of the 26 reported cases, 25 sought medical care and 16 were hospitalized. No deaths have been reported.

Last week, the Centers for Disease Control and Prevention released a health alert about the candies. The agency noted that as of June 11, the people sickened after eating Diamond Shruumz candies presented to health care providers with a host of severe symptoms. Those include: central nervous system depression with sedation, seizures, muscle rigidity, clonus (abnormal reflex responses), tremor, abnormal heart rate (bradycardia or tachycardia), abnormal blood pressure (hypotension or hypertension), gastrointestinal effects (nausea, vomiting, or abdominal pain), skin flushing, diaphoresis (excessive sweating), and metabolic acidosis with increased anion gap (an acid-based disorder linked to poisonings).

At the time of the CDC alert, 10 patients had been hospitalized, and “several required intubation, mechanical ventilation, and admission to an intensive care unit,” the agency reported.

It remains unclear what ingredient in the candies could be causing the poisonings. The FDA reports that it has worked with state partners to collect multiple samples of Diamond Shruumz products so they can be analyzed for potential toxic components. That analysis is still ongoing, the agency said.

Diamond Shruumz has not responded to multiple requests for comment from Ars.

Untold toxic ingredients

Diamond Shruumz does not list the ingredients of its products on its website. They are sold as “microdosing” candies, a term that typically suggests a small amount of a psychedelic compound is present. The company describes its chocolates, gummies, and cones as “trippy,” “psychedelic,” and “hallucinogenic,” and also claims they contain a “primo proprietary blend of nootropic and functional mushrooms.” But, it’s unclear what, if any, psychoactive compound is present in the candies.

The CDC notes that products like these “might contain undisclosed ingredients, including illicit substances, other adulterants, or potentially harmful contaminants that are not approved for use in food.”

Diamond Shruumz posted documents on its website from third-party laboratories claiming to indicate that the candies do not contain the most notable mushroom-derived psychedelic compound, psilocybin. The reports also indicate that some of the products do not contain cannabinoids or compounds from the hallucinogenic Amanita muscaria mushroom. Additionally, the company said in a blog post that its products contain a blend of Lion’s mane, Reishi, and Chaga mushrooms, but these are all non-hallucinogenic mushrooms used in herbal and traditional medicines and supplements.

In recent decades, hundreds of new synthetic psychoactive substances have hit the market in such products, including many new phenethylamines and tryptamines, which are chemically related to LSD and psilocybin. Some experts and members of the psychedelic community have speculated that Diamond Shruumz products could potentially contain one of the more popular tryptamines, 4-AcO-DMT, often pronounced  “4-akko-DMT,” and also known as 4- acetoxy-N,N-dimethyltryptamine, O-acetylpsilocin, or psilacetin. According to a qualitative 2020 study, users describe 4-AcO-DMT as producing effects similar to psilocybin, but without some of the unpleasant side effects noted with natural mushrooms, such as nausea. Animal experiments have confirmed that 4-AcO-DMT appears to produce psilocybin-like effects.

Still, it’s unclear if such ingredients could explain the symptoms seen in the current outbreak. Though clinical data on 4-AcO-DMT is scant, it has not been linked to such severe symptoms. On the other hand, some novel synthetic compounds, such as Dox and NBOMe, often misrepresented as LSD, are considered dangerous. For instance, NBOMe compounds (N-methoxybenzyl, also called N-bombs or 251), first discovered in 2003, have been linked to overdoses and deaths. In the scientific literature, they’ve been linked to “unpleasant hallucinations, panic, agitation, hypertension, seizures, acute psychosis, and/or excited delirium that can result in cardiac arrest,” according to the 2020 study.

Microdosing candy-linked illnesses double; possible recall in “discussions” Read More »

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More seizures, intubation from microdose candies: 12 sickened, 10 hospitalized

Potent microdoses —

FDA updates alert after the latest case fell ill on June 9.

Diamond Shruumz's

Enlarge / Diamond Shruumz’s “extremely potent” infused cones in “sprinkles” flavor.

More people have reported severe poisonings in an ongoing outbreak marked by people seizing and needing to be intubated after consuming microdose candies made by Diamond Shruumz, the Food and Drug Administration reported Tuesday.

There are now at least 12 reported cases across eight states. All 12 people were ill enough to seek medical care, and 10 needed to be hospitalized. The symptoms reported so far include seizures, central nervous system depression (loss of consciousness, confusion, sleepiness), agitation, abnormal heart rates, hyper/hypotension, nausea, and vomiting, the FDA reported.

In Tuesday’s update, the FDA also expanded the products linked to the illnesses. In addition to all flavors of Diamond Shruumz’s Microdosing Chocolate Bars, the agency’s warning now covers all flavors of the brand’s Infused Cones and Micro Dose and Macro Dose Gummies.

According to the FDA, the most recent case fell ill on June 9. On June 7, the FDA issued its initial warning on Diamond Shruumz’s chocolates, reporting that eight people had been sickened in four states, with six people hospitalized. The agency advised the public not to sell, serve, buy, or consume the chocolates and instead discard them.

The candies are available nationwide. They are sold online—where they remain available for purchase as of Tuesday evening—and can also be found in various retail locations throughout the US, including smoke/vape shops and retailers that sell hemp-derived products.

The current tally of cases includes one from Alabama, four from Arizona, two from Indiana, one from Kentucky, one from Missouri, one from Nevada, one from Pennsylvania, and one from South Carolina.

Diamond Schruumz has not responded to multiple requests for comment from Ars. The New York Times also reported that the company was unresponsive.

It remains unclear what exactly is in the candies and what could cause such severe toxicity. The company does not provide ingredient lists for its products on its website. The term “microdosing” typically suggests a small amount of psychedelic compound is present, and Diamond Shruumz markets its products as “trippy,” “psychedelic,” and “hallucinogenic.” But lab reports posted on Diamond Shruumz’s website indicate that its candies do not contain the notable mushroom-derived psychedelic compound, psilocybin.

The company only says that its candies contain a “primo proprietary blend of nootropic and functional mushrooms.” Nootropics are compounds said to affect cognition, though supplement makers have used the term dubiously in marketing.

In an April 2023 blog, Diamond Shruumz said its chocolate bars contain a blend of Lion’s mane, Reishi, and Chaga mushrooms, which are all non-hallucinogenic mushrooms used in herbal and traditional medicines and supplements. “Lion’s mane is a natural nootropic that can enhance cognitive function, while Reishi is an adaptogen that helps the body adapt to stress and boosts the immune system,” the company claimed. “Finally, Chaga is rich in antioxidants and can help reduce inflammation in the body.”

The FDA, along with America’s Poison Centers and the Centers for Disease Control and Prevention, is still investigating the cases and working to determine the cause. In a response to an inquiry from Ars, the FDA declined to comment on whether it is in contact with the company and if it is recommending a voluntary recall.

6/12/2024 3: 50pm ET: This story was updated to include the response from the FDA. 

More seizures, intubation from microdose candies: 12 sickened, 10 hospitalized Read More »

people-are-seizing,-being-intubated-after-eating-microdose-chocolates

People are seizing, being intubated after eating microdose chocolates

Yikes —

“Extreme caution” urged as at least 8 people in 4 states sickened, 6 hospitalized.

A Diamond Shruumz chocolate bar, which come in a variety of flavors.

Enlarge / A Diamond Shruumz chocolate bar, which come in a variety of flavors.

Various federal and state health officials are sounding the alarm on Diamond Shruumz-brand Microdosing Chocolate Bars. The candy, said to be infused with mushrooms, has been linked to severe illnesses, including seizures, loss of consciousness, confusion, sleepiness, agitation, abnormal heart rates, hyper/hypotension, nausea, and vomiting, according to an outbreak alert released by the Food and Drug Administration on Friday.

So far, eight people across four states have been sickened—four in Arizona, two in Indiana, one in Nevada, and one in Pennsylvania, the FDA reported. Of the eight, six have been hospitalized.

“We are urging the public to use extreme caution due to the very serious effects of these products,” Maureen Roland, director of the Banner Poison and Drug Information Center in Phoenix, said in a press release earlier this week.

Steve Dudley, director of the Arizona Poison and Drug Information Center, added that there’s “clearly something toxic occurring” with the chocolates. “We’ve seen the same phenomenon of people eating the chocolate bar then seizing, losing consciousness, and having to be intubated.” Dudley noted that the state is aware of additional cases beyond the eight reported Friday by the FDA. Those cases were reported from Nebraska and Utah.

It’s not entirely clear what is in the chocolates or what could be causing the illnesses. The FDA said it was working with the Centers for Disease Control and Prevention as well as America’s Poison Centers to “determine the cause of these illnesses and is considering the appropriate next steps.”

On its website, Diamond Shruumz says that its chocolate bars contain a “primo proprietary blend of nootropic and functional mushrooms.” The website also contains reports of laboratory analyses on their products, some of which indicate the absence of select known fungal toxins and compounds such as the hallucinogen psilocybin and cannabinoids.

Diamond Shruumz did not immediately respond to Ars’ request for comment.

The chocolate bars are still available for sale online but the FDA said that consumers should not eat, sell, or serve them. Any bars already purchased should be discarded. Likewise, retailers should not sell or distribute them. The FDA noted that, in addition to being available online, the bars are also sold in various retail locations nationwide, including smoke/vape shops and retailers that sell hemp-derived products.

People are seizing, being intubated after eating microdose chocolates Read More »

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FDA’s review of MDMA for PTSD highlights study bias and safety concerns

Complicated —

FDA advisors will meet June 4 to discuss and vote on the therapy’s effectiveness.

MDMA is now in the FDA's hands.

Enlarge / MDMA is now in the FDA’s hands.

The safety and efficacy data on the use of MDMA (aka ecstasy) for post-traumatic stress disorder therapy is “challenging to interpret,” the Food and Drug Administration said in a briefing document posted Friday. The agency noted significant flaws in the design of the underlying clinical trials as well as safety concerns for the drug, particularly cardiovascular harms.

On Tuesday, June 4, the FDA will convene an advisory committee that will review the evidence and vote on MDMA’s efficacy and whether its benefits outweigh its risks. The FDA does not have to follow the committee’s recommendations, but it often does. If the FDA subsequently approves MDMA as part of treatment for PTSD, it would mark a significant shift in the federal government’s stance on MDMA, as well as psychedelics, generally. Currently, the US Drug Enforcement Administration considers MDMA a Schedule I drug, defined as one with “no currently accepted medical use and a high potential for abuse.” It would also offer a new treatment option for patients with PTSD, a disabling psychiatric condition with few treatment options currently.

As Ars has reported previously, the submission of MDMA for approval is based on two clinical trials. The first trial, published in Nature Medicine in 2021, involved 90 participants with moderate PTSD and found that MDMA-assisted psychotherapy significantly improved Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) scores compared with participants who were given psychotherapy along with a placebo. In the second study, published in September in Nature Medicine, the finding held up among 104 participants with moderate or severe PTSD (73 percent had severe PTSD).

In the briefing documents released Friday, the FDA highlighted that there was a high potential for bias to have crept into those results. Though the trials were designed to be double-blind (meaning that therapists and trial participants were not told who received MDMA), the FDA noted that MDMA “produces profound alterations in mood, sensation, suggestibility, and cognition.” Blinding is “nearly impossible,” the FDA wrote.  And indeed, approximately 90 percent of those assigned to take MDMA and 75 percent of those assigned to a placebo were able to accurately guess their treatment assignment, the FDA notes. As such, it is “reasonable to assume” that bias and “expectation bias” affected the results of the trials, the FDA concluded.

The agency also noted concerns that MDMA caused “significant increases in blood pressure and pulse,” which could trigger cardiac events, such as heart attacks. However, the trial data was limited for assessing the risks of these adverse events.

The FDA also dinged the studies for not including data on whether participants experienced effects such as “euphoria” after taking MDMA—an anticipated effect that could indicate the drug’s potential for abuse.

In all, the FDA’s review presented a complicated picture of MDMA’s risk-benefit assessment, one that should make for an interesting discussion Tuesday. The FDA’s criticisms follows an even more critical report released earlier this month by the Institute for Clinical and Economic Review (ICER), which identified “substantial concerns about the validity of the results” from the clinical trials.

Like the FDA, ICER found the trials to be “essentially unblinded.” However, ICER went further, having conducted a number of interviews with trial participants and others involved, finding that the trials largely pulled from an existing community of psychedelic advocates and supporters, introducing significant bias. “Concerns have been raised by some that therapists encouraged favorable reports by patients and discouraged negative reports by patients including discouraging reports of substantial harms, potentially biasing the recording of benefits and harms,” the report said. MDMA is known to induce confusion, depression, and paranoia in some. One participant reported feeling “relentlessly suicidal” after the trial, as a result of participating in it, but that result was not reflected in the trial’s reported results.

Various people told ICER that the community involved in the trials regarded psychedelics “more like a religious movement than like pharmaceutical products.” Some participants felt as though “they could be shunned if they reported bad outcomes or that it could lead to future patients being denied the benefits of MDMA-AP.”

In all, ICER concluded that the evidence available to assess for MDMA treatment is “insufficient.”

Editor’s Note: This story was corrected to report that the participant’s suicidal thoughts occurred after the trial, as a result of participation, not during the trial.

FDA’s review of MDMA for PTSD highlights study bias and safety concerns Read More »

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After mice drink raw H5N1 milk, bird flu virus riddles their organs

Deadly dairy —

No, really, drinking raw milk during the H5N1 outbreak is a bad idea.

Fresh raw milk being poured into a container on a dairy farm on July 29, 2023, in De Lutte, Netherlands.

Enlarge / Fresh raw milk being poured into a container on a dairy farm on July 29, 2023, in De Lutte, Netherlands.

Despite the delusions of the raw milk crowd, drinking unpasteurized milk brimming with infectious avian H5N1 influenza virus is a very bad idea, according to freshly squeezed data published Friday in the New England Journal of Medicine.

Researchers at the University of Wisconsin-Madison squirted raw H5N1-containing milk from infected cows into the throats of anesthetized laboratory mice, finding that the virus caused systemic infections after the mice were observed swallowing the dose. The illnesses began quickly, with symptoms of lethargy and ruffled fur starting on day 1. On day 4, the animals were euthanized to prevent extended suffering. Subsequent analysis found that the mice had high levels of H5N1 bird flu virus in their respiratory tracts, as well their hearts, kidneys, spleens, livers, mammary glands, and brains.

“Collectively, our data indicate that HPAI [Highly Pathogenic Avian Influenza] A(H5N1) virus in untreated milk can infect susceptible animals that consume it,” the researchers concluded. The researchers also found that raw milk containing H5N1 can remain infectious for weeks when stored at refrigerator temperatures.

Bird flu has not historically been considered a foodborne pathogen, but prior to the unexpected outbreak of H5N1 in US dairy cows discovered in March, it had never been found at high levels in a food product like milk before. While experts have stepped up warnings against drinking raw milk amid the outbreak, the mouse experiment offers some of the first data on the risks of H5N1 from drinking unpasteurized dairy.

Before the mouse data, numerous reports have noted carnivores falling ill with H5N1 after eating infected wild birds. And a study from March in the journal Emerging Infectious Diseases reported that over half of the 24 or so cats on an H5N1-infected dairy farm in Texas died after drinking raw milk from the sick cows. Before their deaths, the cats displayed distressing neurological symptoms, and studies found the virus had invaded their lungs, brains, hearts, and eyes.

While the data cannot definitely determine if humans who drink H5N1-contaminated raw milk will suffer the same fate as the mice and cats, it highlights the very real risk. Still, raw milk enthusiasts have disregarded the concerns. PBS NewsHour reported last week that since March 25, when the H5N1 outbreak in US dairy cows was announced, weekly sales of raw cow’s milk have ticked up 21 percent, to as much as 65 percent compared with the same periods a year ago, according to data shared by market research firm NielsenIQ. Moreover, the founder of California-based Raw Milk Institute, Mark McAfee, told the Los Angeles Times this month that his customers baselessly believe drinking H5N1 will give them immunity to the deadly pathogen.

In normal times, the Centers for Disease Control and Prevention and the Food and Drug Administration strongly discourage drinking raw milk. Without pasteurization, it can easily be contaminated with a wide variety of pathogens, including Campylobacter, Cryptosporidium, E. coli, Listeria, Brucella, and Salmonella.

Fortunately, for the bulk of Americans who heed germ theory, pasteurization appears completely effective at deactivating the virus in milk, according to thorough testing by the FDA. Pasteurized milk is considered safe during the outbreak. The US Department of Agriculture, meanwhile, reports finding no H5N1 in retail beef so far and, in laboratory experiments, beef patties purposefully inoculated with H5N1 had no viable virus in them after the patties were cooked to 145°F (medium) or 160°F (well done).

To date, the USDA has reported that H5N1 has infected at least 58 dairy herds in nine states.

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Raw-milk fans plan to drink up as experts warn of high levels of H5N1 virus

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Raw milk fans called warnings “fear mongering,” despite 52% fatality rate in humans.

A glass of fresh raw milk in the hand of a farmer.

Enlarge / A glass of fresh raw milk in the hand of a farmer.

To drink raw milk at any time is to flirt with dangerous germs. But, amid an unprecedented outbreak of H5N1 bird flu in US dairy cows, the risks have ratcheted up considerably. Health experts have stepped up warnings against drinking raw milk during the outbreak, the scope of which is still unknown.

Yet, raw milk enthusiasts are undaunted by the heightened risk. The California-based Raw Milk Institute called the warnings “clearly fearmongering.” The institute’s founder, Mark McAfee, told the Los Angeles Times this weekend that his customers are, in fact, specifically requesting raw milk from H5N1-infected cows. According to McAfee, his customers believe, without evidence, that directly drinking high levels of the avian influenza virus will give them immunity to the deadly pathogen.

Expert Michael Payne told the LA Times that the idea amounts to “playing Russian roulette with your health.” Payne, a researcher and dairy outreach coordinator at the Western Institute for Food Safety and Security at UC Davis, added, “Deliberately trying to infect yourself with a known pathogen flies in the face of all medical knowledge and common sense.”

Much remains unknown about the biology of avian influenza in cattle. Until March 25, when the US Department of Agriculture confirmed the virus in a dairy herd in Texas, cattle were generally considered virtually resistant to H5N1. But since then, the USDA has tallied 42 herds in nine states that have contracted the virus. Epidemiological data so far suggests that there has been cow-to-cow transmission following a single spillover event and that the 42 outbreak herds are connected by the movement of cattle between farms.

The limited data on the cows so far suggests that the animals largely develop mild illness from the infection and recover in a few weeks. Their mammary glands are the primary target of the virus. A preprint published earlier this month found that cows’ udders are rife with the molecular receptors that bird flu viruses latch onto to spark an infection. Moreover, the glands contain multiple types receptors, including ones targeted by human flu viruses as well as those targeted by bird flu viruses. Thus, dairy cows could potentially act as a mixing vessel for the different types of flu viruses to reassemble into new, outbreak-sparking variants.

With the virus apparently having a field day in cows’ udders, researchers have found raw milk to be brimming with high levels of H5N1 viral particles—and those particles appear readily capable of spilling over to other mammals. In a case study last month, researchers reported that a group of about two dozen farm cats developed severe illness after drinking milk from H5N1-infected cows. Some developed severe neurological symptoms. More than half the cats died in a matter of days.

Deadly virus

Data on flu receptors in the two animals may explain the difference between cows and cats. While the cow’s mammary gland had loads of multiple types of flu receptors, those receptors were less common in other parts of the cow, including the respiratory tract and brain. This may explain why they tend to have a mild infection. Cats, on the other hand, appear to have receptors more widely distributed, with infected cats showing viral invasion of the lungs, hearts, eyes, and brains.

Raw milk devotees—who claim without evidence that drinking raw milk provides health benefits over drinking pasteurized milk—dismiss the risk of exposure to H5N1. They confidently argue—also without evidence—that the human digestive system will destroy the virus. And they highlight that there is no documented evidence of a human ever becoming infected with H5N1 from drinking tainted milk.

The latter point on the lack of evidence of milkborne H5N1 transmission is true. However, the current outbreak is the first known spillover of highly pathogenic avian influenza (HPAI) to dairy cow mammary glands. As such, it presents the first known opportunity for such milk-based transmission to occur.

Before pasteurization became routine for commercial milk production, raw milk was a common source of infections, serving up a cornucopia of germs. According to the FDA, in 1938, milkborne outbreaks accounted for 25 percent of all foodborne disease outbreaks. In more recent times, milk has been linked to less than 1 percent of such outbreaks. The Centers for Disease Control and Prevention notes that areas where raw milk was sold legally between 1998 and 2018 had 3.2 times more outbreaks than areas where the sale of raw milk was illegal.

In a Q&A document, the Food and Drug Administration notes that it does “not know at this time if HPAI A (H5N1) viruses can be transmitted through consumption of unpasteurized (raw) milk and products (such as cheese) made from raw milk from infected cows.” However, the agency goes on, because of that lack of data and the potential for infection, the FDA recommends halting all sales of raw milk and raw milk products from H5N1 infected or exposed cattle. In general, the agency recommends against consuming raw milk.

Globally, as of March 28, there have been 888 cases of H5N1 reported in humans in 23 countries. Of those 888 cases, 463 were fatal. That represents a 52 percent fatality rate; however, it’s possible that there are asymptomatic or undiagnosed cases that could alter that rate. In the US, only one human so far is known to have been infected with H5N1 in connection with the dairy cow outbreak—a farm worker who developed pink eye. The man had no respiratory symptoms and recovered. He did not consent to further follow-up, and researchers did not get consent to test the man’s household contacts to see if they, too, were infected.

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Alarming superbug from deadly eyedrop outbreak has spread to dogs

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It’s unclear how the dogs became infected with the same strain in the eyedrops.

A dog gets examined by veterinary technicians in Texas.

Enlarge / A dog gets examined by veterinary technicians in Texas.

Two separately owned dogs in New Jersey tested positive last year for a dreaded, extensively drug resistant bacterial strain spread in the US by contaminated artificial eye drops manufactured in India. Those drops caused a deadly multi-state outbreak in humans over many months last year, with at least 81 people ultimately infected across 18 states. Fourteen people lost their vision, an additional four had eyeballs surgically removed, and four people died.

The preliminary data on the dogs—presented recently at a conference of disease detectives hosted by the Centers for Disease Control and Prevention—highlights that now that the deadly outbreak strain has been introduced around the US, it has the potential to lurk in unexpected places, spread its drug resistance to fellow bacteria, and cause new infections in people and animals who may have never used the drops.

The two dogs in New Jersey were not known to have received the drops linked to the outbreak: EzriCare Artificial Tears and two additional products made by the same manufacturer, which were recalled in February 2023. Such over-the-counter products are sometimes used in animals as well as people. But the dogs’ separate owners said they didn’t recall using the drops either. They also didn’t report any exposures in health care settings or recent international travel that could explain the infections. One of the dogs did, at one point, receive eye drops, but they were not an outbreak-associated brand. The only connection between the two dogs was that they were both treated at the same veterinary hospital, which didn’t stock the outbreak-associated eyedrops.

The dogs’ infections were caught between March and June 2023 when clinicians at the veterinary hospital were working to address a chronic cough in one of the dogs and a stubborn ear infection in the other, according to CBS News, which was present for the CDC’s conference of its Epidemic Intelligence Service in Atlanta. The ear and lung swabs were sent to an academic veterinary laboratory in Pennsylvania, where a microbiologist noticed that bacteria from both swabs had uncommon drug-resistance features. The microbiologist then uploaded genetic sequences of the bacterial strains to a national database, where they caught the attention of the CDC and state health authorities.

The genetic sequences uploaded were of the carbapenemase-producing carbapenem-resistant Pseudomonas aeruginosa (CP-CRPA) strain—and they were highly similar to the bacterial strain identified in the deadly eyedrop outbreak. These bacteria are extensively resistant to antibiotics, resisting even last-line drugs, and can silently colonize animals and humans for months or years. An investigation ensued.

Infection gaps

Emma Price, the CDC epidemic intelligence service officer who presented the investigation’s findings at the conference, suggested it was fortunate they were able to make the connection. “Because [the academic veterinary laboratory] had a grant and a veterinary microbiologist works there, he did his great due diligence and uploaded the results. That’s how we got the notification, because the strain matched the outbreak strain,” Price told CBS News.

However, the disease detectives were ultimately unable to identify exactly how the two dogs became infected. “Shared exposures included treatment in the veterinary hospital’s surgical preparation and recovery areas for both canines and ophthalmology department visits by either the affected canine or another animal in the same household,” Price and colleagues wrote in their findings. But all of the sampling done of the veterinary hospital where the dogs were treated turned up negative for the eyedrop outbreak strain.

In the process of the investigation, the epidemiologists also conducted an infection control assessment of the veterinary hospital, finding a variety of “gaps.” These included problems with hand hygiene practices, personal protective equipment use—including use of gloves—and equipment and environmental cleaning and disinfection at the hospital. Price noted that these problems are not uncommon and that there is a general lack of emphasis on infection control in veterinary settings.

Though Price and her colleagues were unable to identify the direct route of infection, they suspect the dogs were likely infected either by exposure to a contaminated product or secondary transmission at the veterinary hospital.

Both dogs have since made full recoveries, but because CRPA strains can silently colonize many body sites on both humans and animals, it’s possible that the bacteria still linger on the dogs or on the other pets and people in their households. Price warned the owners of possible future transmission and recommended they flag this risk to their health care providers. She also noted the potential for the bacteria to spread from dog to dog. It would be ideal to “keep the dogs away from other dogs in the future, which we understand is a difficult thing to do,” she said.

Alarming superbug from deadly eyedrop outbreak has spread to dogs Read More »

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DEA to reclassify marijuana as a lower-risk drug, reports say

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Marijuana to move from Schedule 1, the most dangerous drug group, to Schedule 3.

Medical marijuana growing in a facility in Canada.

Enlarge / Medical marijuana growing in a facility in Canada.

The US Drug Enforcement Administration is preparing to reclassify marijuana to a lower-risk drug category, a major federal policy change that is in line with recommendations from the US health department last year. The upcoming move was first reported by the Associated Press on Tuesday afternoon and has since been confirmed by several other outlets.

The DEA currently designates marijuana as a Schedule 1 drug, defined as drugs “with no currently accepted medical use and a high potential for abuse.” It puts marijuana in league with LSD and heroin. According to the reports today, the DEA is moving to reclassify it as a Schedule 3 drug, defined as having “a moderate to low potential for physical and psychological dependence.” The move would place marijuana in the ranks of ketamine, testosterone, and products containing less than 90 milligrams of codeine.

Marijuana’s rescheduling would be a nod to its potential medical benefits and would shift federal policy in line with many states. To date, 38 states have already legalized medical marijuana.

In August, the Department of Health and Human Services advised the DEA to move marijuana from Schedule 1 to Schedule 3 based on a review of data by the Food and Drug Administration. The recommendation came after the FDA, in August, granted the first approval of a marijuana-based drug. The drug, Epidiolex (cannabidiol), is approved to treat rare and severe forms of epilepsy. The approval was expected to spur the DEA to downgrade marijuana’s scheduling, though some had predicted it would have occurred earlier. Independent expert advisors for the FDA voted unanimously in favor of approval, convinced by data from three high-quality clinical trials that indicated benefits and a “negligible abuse potential.”

The shift may have a limited effect on consumers in states that have already eased access to marijuana. In addition to the 38 states with medical marijuana access, 24 states have legalized recreational use. But, as a Schedule 3 drug, marijuana would still be regulated by the DEA. The Associated Press notes that the rule change means that roughly 15,000 dispensaries would need to register with the DEA, much like pharmacies, and follow strict reporting requirements.

One area that will clearly benefit from the change is scientific research on marijuana’s effects. Many academic scientists are federally funded and, as such, they must follow federal regulations. Researching a Schedule 1 drug carries extensive restrictions and rules, even for researchers in states where marijuana is legalized. A lower scheduling will allow researchers better access to conduct long-awaited studies.

It’s unclear exactly when the move will be announced and finalized. The DEA must get sign-off from the White House Office of Management and Budget (OMB) before proceeding. A source for NBC News said Attorney General Merrick Garland may submit the rescheduling to the OMB as early as Tuesday afternoon. After that, the DEA will open a public comment period before it can finalize the rule.

The US Department of Justice told several outlets that it “continues to work on this rule. We have no further comment at this time.”

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20% of grocery store milk has traces of bird flu, suggesting wider outbreak

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The milk is still considered safe, but disease experts are alarmed by the prevalence.

20% of grocery store milk has traces of bird flu, suggesting wider outbreak

The Food and Drug Administration reported late Thursday that about 20 percent of retail milk samples from around the country tested positive for genetic fragments of the bird flu, aka highly pathogenic avian influenza (HPAI) virus H5N1. While retail milk is still considered to be safe, the finding suggests that the spread of the virus in cows is more extensive than is currently known.

The FDA used a test called quantitative polymerase chain reaction (qPCR), which can only detect the presence of genetic fragments. In pasteurized retail milk, it is highly likely that those genetic snippets are merely remnants of virus particles destroyed during pasteurization. The FDA is currently conducting additional testing using egg inoculation tests, a gold standard for detecting a live virus, to confirm the effectiveness of pasteurization. Meanwhile, the director of the National Institute of Allergy and Infectious Diseases, Jeanne Marrazzo, told reporters Wednesday that tests at the agency’s federal labs so far did not identify live virus from any of its sampling. Additionally, several previous studies have found that pasteurization of eggs—which is done at a lower temperature than it is for milk—was effective at destroying H5N1.

While experts are largely unconcerned with the safety of commercial milk, the potential for wide, unrecognized spread of bird flu in dairy herds is alarming. To date, the US Department of Agriculture has only confirmed infections in 33 herds in eight states. The FDA acknowledged that of its positive samples, “a greater proportion of positive results [are] coming from milk in areas with infected herds.” But with tens of thousands of dairy herds in the US, the finding suggests that infections are being missed. It does not necessarily suggest that 20 percent of all cows are affected, since milk is pooled for commercial distribution. But 33 herds alone are unlikely to explain the high prevalence.

Last week, The New York Times reported that the one dairy herd that tested positive for bird flu in North Carolina did not show any symptoms of the infection. The possibility of asymptomatic spread of the virus among cows will make containment and monitoring far more difficult—and could explain why infections may be easily missed. On Wednesday, the USDA issued a federal order requiring dairy cattle to have a negative H5N1 test before being moved across state lines.

For now, the risk to the public is still considered low by the Centers for Disease Control and Prevention. But the more the bird flu virus spreads among mammals—and mammals with close contact with humans—the more opportunities it has to evolve to jump to and among people, experts warn.

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