The week’s most astounding developments from the neobiological frontier.

February 16, 2023

How DMT and mushrooms affect the brain

Researchers at the University of California, Davis, have advanced our understanding of the brain mechanism by which psychedelics like LSD, mescaline, psilocybin, and DMT produce altered states of consciousness and mood. Looking at DMT and psilocin specifically, they showed that when the two drugs activate the serotonin receptor 5-HT2AR, this in turn promotes dendritic growth and increases the spine density of rat cortical neurons. Though more work still needs to be done in defining how these neurological changes map to cognitive processes, the work is an important advance given that psychedelic-assisted therapy is being actively pursued for treating PTSD, substance abuse, and treatment-resistant depression, among other applications. Science

Seminal study for male oral contraceptive

Hope for a non-hormonal, on-demand male birth control pill just got a big boost this week in a study from Weill Cornell Medicine in New York. Doctors there have developed a proof-of-concept for an oral on-demand male contraception based on a single dose of a drug that targets an enzyme essential for sperm motility known as soluble adenylyl cyclase (sAC). In a paper this week, they show that a single dose of sAC inhibitor is safe and renders male mice temporarily infertile—though they don’t lose their normal mating drive. And the rodents’ full fertility returns the next day. Designing contraception for men based on this strategy, they write, “has the potential to provide equity between the sexes and, like the advent of oral birth control for women, revolutionize family planning.” Nature Communications

Drugs approved in the United States but nowhere else

Why do we spend more on prescription drugs in the United States than anywhere else in the world? Part of the explanation is that our market supports pricing extremely high-end drugs for small groups of people whereas markets in other countries do not. Researchers at Kaiser Permanente looked at all new drugs approved by the FDA from 2017–2020 and asked how many were refused authorization or not recommended for reimbursement by agencies in places like Canada, Australia, the E.U., or the U.K. It turns out, quite a few. Almost a quarter of the U.S. drugs approved in those four years were snubbed in sister countries due to unfavorable risk profiles, uncertain clinical benefits, or unacceptably high prices. The median U.S. cost for these drugs is $115,281 per person per year, which reveals a peculiarity of the American marketplace: It doesn’t ultimately matter how much a drug costs, or sometimes even how safe and effective it is. So long as it’s approved, someone will be willing to pay for it. JAMA Internal Medicine

10 percent of recent new drugs approved despite failures

And speaking of how drugs get approved, a study by researchers at Yale School of Medicine shows that 10 percent of new drugs approved by the U.S. Food and Drug Administration (FDA) from 2018–2021 failed to hit one or more primary efficacy endpoints in the pivotal studies upon which their approvals were based—although they all showed enough other evidence of effectiveness to be approved, through surrogate markers or other clinical data. So many approved drugs missing their primary efficacy endpoints is still concerning, however, because as the case of the Alzheimer’s disease drug aducanumab shows, failure to demonstrate such clinical proof led to Medicare and other payers refusing to reimburse for the drug, which has ultimately meant that while the FDA’s approval has made it available to people, it’s done little to bring down its cost. JAMA Internal Medicine

Saliva biomarker for gum inflammation

The current standard for measuring the state of someone’s periodontal gum disease is a laborious poke-and-prod procedure to measure gum tissue recession, how much it bleeds, and to generate a composite index score known as a periodontal inflamed surface area (PISA). But in new experiments with 67 otherwise healthy people with some form of gum disease, researchers at NYU have developed a simple new PISA proxy based on measuring inflammatory proteins in the saliva known as cytokines. This potential biomarker could help track a person’s gum disease, see how it responds to treatment, predict whether it will recur, or detect inflammation related to other systemic disease. (Gum disease is not just a matter of oral health—it’s been linked to cardiovascular disease, kidney dysfunction, Alzheimer’s, and rheumatoid arthritis.) PLOS ONE

Potential treatment for sepsis during pregnancy

Sepsis is the number one cause of preventable deaths worldwide, claiming more than 270,000 lives each year in the United States alone. A mystery involving rare cases of sepsis in pregnant women has long stood unsolved: Why does pregnancy make sepsis outcomes worse and make women with sepsis more likely to die? Doctors at the First People’s Hospital of Foshan and Southern Medical University in Guangzhou, China, hypothesized that since pregnancy alters the gut microbiome, it could cause immune dysfunction and increased susceptibility to sepsis, and it turns out they may be right. Fecal transplants from pregnant mice made non-pregnant mice fare worse in sepsis (and transplants from non-pregnant mice protected pregnant ones). They traced this effect to an anti-inflammatory intestinal bacteria called Parabacteroides merdae, which is reduced during pregnancy. Administering the bacteria to pregnant mice protected them, which suggests a promising new strategy for sepsis treatment in the clinic. Immunity