One dose, twelve weeks: an LSD-based drug clears a second phase 3 for anxiety

One session, and the effect was still there at twelve weeks

Definium Therapeutics said on Wednesday that its LSD-based drug worked in generalized anxiety disorder [1][2]. The 214-patient Voyage trial compared one psychoactive session with DT120, an orally dissolving tablet, against a placebo [1].

Twelve weeks later, scores on the Hamilton Anxiety Rating Scale had fallen 11.6 points on the drug and 6.2 points on placebo [1]. That 5.4-point gap is the number the company is betting on. “We have never seen a pivotal study deliver greater than five-point placebo-adjusted change,” chief executive Robert Barrow told Fierce Biotech [1].

It is Definium’s second phase 3 win in two months. The first was in major depression [1]. Anxiety has had no significant new drug since Eli Lilly’s Cymbalta was cleared for it in 2007 [1].

The caveats are real. One of two anxiety trials has reported, the data are the company’s, and no regulator has seen them. Psychedelic trials are also hard to blind, because people usually know whether they took the drug. A third trial, Panorama, reads out next month [1]. It adds a second control arm using a lower dose of the same drug, so patients who feel something cannot be sure it was real [1].

What is unusual is not the effect size. It is the schedule

The drugs this would compete with are taken every day, and their own labels are blunt about what that costs.

Benzodiazepines - lorazepam, diazepam and their relatives - carry an FDA-approved medication guide that warns against stopping suddenly [3]. Doing so can cause seizures and other life-threatening effects. Symptoms can last “several weeks to more than 12 months” [3]. The same guide draws a line most people miss: physical dependence is not the same as addiction [3]. A body can rebuild itself around a drug taken exactly as prescribed.

That rebuilding is measurable. Almost all of these drugs act on receptors, the docking points on a cell’s surface that hormones and signals normally use. Hold one open long enough and the cell reacts. Over minutes it uncouples the receptor from the machinery behind it. Over hours to days it pulls receptors inside, digests some, and makes fewer new ones [4][5]. In cultured brain neurons, 24 hours of benzodiazepine exposure cut the surface density of one class of GABA-A receptor to roughly 59% of normal [6]. A closely related class barely moved [6].

Psychedelics show the same process at its most extreme. Give LSD daily and by the fourth day the effects vanish, as the serotonin receptors it works through are pulled off the cell surface [7]. That is a large part of why nobody designs an LSD drug you take each morning.

A whole treatment system built around an adapted body

Opioid medicine is where this is handled most openly. On Friday, STAT reported the first real report card on US methadone clinics since a 2024 rules overhaul [8].

A survey of 241 clinics - about 10% of the country’s opioid treatment programs - found more than 70% had adopted at least half of the recommended changes, including more take-home doses [8]. The share of patients still in treatment three months after starting rose an average of 17% [8]. The survey is small and industry-collected, so treat it as a signal, not a settled result.

Sustained opioid exposure chemically tags the mu-opioid receptor and pulls it inside the cell, cutting how many are left working on the surface [4]. Estimates of that loss run as high as 80% to 95% [4]. Methadone maintenance does not try to undo that quickly. It gives an adapted body something steady to stand on.

The other direction: a drug you can stop

Not every long-running drug leaves an adaptation behind. A French trial published on Tuesday in The Lancet Healthy Longevity randomised 1,160 people, average age 80, who had taken statins for years with no history of heart disease [9][10]. Stopping did not increase deaths [9].

The authors are careful. They do not tell doctors to tear up prescriptions [9]. France also has universal health care and the lowest cardiovascular death rate among rich countries, so the result may not carry over [9]. For most American patients over 75 the trial “will not change anything,” cardiologist Romit Bhattacharya told STAT [9].

The rest of the week

A new class in myeloma. The FDA approved Bristol Myers Squibb’s iberdomide, sold as Zenbexus, for advanced multiple myeloma on Thursday [11][12]. It is the debut of a new drug class for the blood cancer and the first drug cleared using a more sensitive measure of remission [11]. It is a pill, taken with Darzalex and dexamethasone [11].

Lung cancer. Taiho and Cullinan said zipalertinib plus chemotherapy beat chemotherapy alone in a 285-patient first-line trial, hitting its main goal at a planned interim look [13]. The actual numbers have not been released [13]. The drug is aimed at one specific gene fault, found in a small slice of lung tumours, and would challenge Johnson and Johnson’s Rybrevant [13][14].

Obesity drugs. Britain’s regulator authorised Lilly’s pill Foundayo for weight management and type 2 diabetes on Monday, the first clearance in Europe, though it is not available on the NHS [15]. Separately, a phase 2 trial of aleniglipron, another once-daily pill in the same weight-loss family as Ozempic, reported up to 12.1% weight loss over 36 weeks in Nature Medicine [16]. A consultancy analysis published Saturday found a British user needs about 97,500 pounds left after tax and essentials before grocery savings cover the drug’s 1,200-pound annual cost [17].

Duchenne. Capricor shares more than doubled after the FDA agreed to review new 24-month data on its muscular dystrophy drug deramiocel [18]. An advisory panel had voted nine to three against the drug’s effectiveness data a month earlier [18].