psychedelic

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Synthetic psychedelic found in candies linked to seizures, intubation

4-AcO-DMT, candies, CDC, chocolate, diamond shruumz, fda, kava, piper methysticum, psilocybin, psychedelic, Science / /

Toxic trip —

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

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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.

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

CDC, chocolate, cones, diamond shruumz, fda, gummies, intubation, microdosing, outbreak, psychedelic, recall, Science, seizures / /

No recall —

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

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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.

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Chemical tweaks to a toad hallucinogen turns it into a potential drug

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No licking toads! —

Targets a different serotonin receptor from other popular hallucinogens.

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Image of the face of a large toad.

Enlarge / The Colorado River toad, also known as the Sonoran Desert Toad.

It is becoming increasingly accepted that classic psychedelics like LSD, psilocybin, ayahuasca, and mescaline can act as antidepressants and anti-anxiety treatments in addition to causing hallucinations. They act by binding to a serotonin receptor. But there are 14 known types of serotonin receptors, and most of the research into these compounds has focused on only one of them—the one these molecules like, called 5-HT2A. (5-HT, short for 5-hydroxytryptamine, is the chemical name for serotonin.)

The Colorado River toad (Incilius alvarius), also known as the Sonoran Desert toad, secretes a psychedelic compound that likes to bind to a different serotonin receptor subtype called 5-HT1A. And that difference may be the key to developing an entirely distinct class of antidepressants.

Uncovering novel biology

Like other psychedelics, the one the toad produces decreases depression and anxiety and induces meaningful and spiritually significant experiences. It has been used clinically to treat vets with post-traumatic stress disorder and is being developed as a treatment for other neurological disorders and drug abuse. 5-HT1A is a validated therapeutic target, as approved drugs, including the antidepressant Viibryd and the anti-anxiety med Buspar, bind to it. But little is known about how psychedelics engage with this receptor and which effects it mediates, so Daniel Wacker’s lab decided to look into it.

The researchers started by making chemical modifications to the frog psychedelic and noting how each of the tweaked molecules bound to both 5-HT2A  and 5-HT1A. As a group, these psychedelics are known as “designer tryptamines”—that’s tryp with a “y”, mind you—because they are metabolites of the amino acid tryptophan.

The lab made 10 variants and found one that is more than 800-fold selective about sticking to 5-HT1A as compared to 5-HT2A. That makes it a great research tool for elucidating the structure-activity relationship of the 5-HT1A receptor, as well as the molecular mechanisms behind the pharmacology of the drugs on the market that bind to it. The lab used it to explore both of those avenues. However, the variant’s ultimate utility might be as a new therapeutic for psychiatric disorders, so they tested it in mice.

Improving the lives of mice

The compound did not induce hallucinations in mice, as measured by the “head-twitch response.” But it did alleviate depression, as measured by a “chronic social defeat stress model.” In this model, for 10 days in a row, the experimental mouse was introduced to an “aggressor mouse” for “10-minute defeat bouts”; essentially, it got beat up by a bully at recess for two weeks. Understandably, after this experience, the experimental mouse tended not to be that friendly with new mice, as controls usually are. But when injected with the modified toad psychedelic, the bullied mice were more likely to interact positively with new mice they met.

Depressed mice, like depressed people, also suffer from anhedonia: a reduced ability to experience pleasure. In mice, this manifests in not taking advantage of drinking sugar water when given the opportunity. But treated bullied mice regained their preference for the sweet drink. About a third of mice seem to be “stress-resilient” in this model; the bullying doesn’t seem to phase them. The drug increased the number of resilient mice.

The 5-HT2A receptor has hogged all of the research love because it mediates the hallucinogenic effects of many popular psychedelics, so people assumed that it must mediate their therapeutic effects, too. However, Wacker argues that there is little evidence supporting this assumption. Wacker’s new toad-based psychedelic variant and its preference for the 5-HT1A receptor will help elucidate the complementary roles these two receptor subtypes play in mediating the cellular and psychological effects of psychedelic molecules. And it might provide the basis for a new tryptamine-based mental health treatment as well—one without hallucinatory side effects, disappointing as that may be to some.

Nature, 2024.  DOI: 10.1038/s41586-024-07403-2

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