First Patient Dosed In Historic Study On Whether LSD Effectively Treats Anxiety

For the first time ever, researchers are administering LSD to patients in a Phase 3 clinical trial. The new study focuses on whether the psychedelic can be used to effectively treat generalized anxiety disorder (GAD).

Drugmaker MindMed says that the trial, dubbed Voyage, is eventually expected to enroll about 200 people in the U.S. and will compare the effects of its proprietary LSD product to a placebo. A second Phase 3 trial, called Panorama, will also be conducted in both the U.S. and Europe and is expected to kick off in the first half of next year.

“Today marks a pivotal moment in our journey towards advancing a novel treatment option for the 20 million people in the U.S. living with GAD,” MindMed’s chief medical officer, Daniel R. Karlin, said in a statement released on Monday. “Building on our scientifically rigorous Phase 2b study, which demonstrated efficacy that far exceeds today’s standard of care and a favorable tolerability profile, our Phase 3 studies are designed to adhere to the highest clinical and ethical standards and are in alignment with guidance from the U.S. Food and Drug Administration.”

In March of this year, the Food and Drug Administration (FDA) granted MindMed’s LSD product “breakthrough therapy” status as a treatment for GAD. That followed a Phase 2 trial showing that a single oral dose of LSD led to “clinically and statistically significant” reductions in anxiety scores 12 weeks after administration, with 65 percent of participants showing a clinical response and 48 percent in clinical remission following the treatment.

Breakthrough drug status is meant to recognize the therapeutic promise of an emerging substance or therapy as well as speed the research and development of treatments that fill an unmet need. MDMA and psilocybin have also previously been awarded the designation.

The new research will use dissolvable oral tablets of the drug, MM120 ODT, or lysergide D-tartrate, which MindMed describes as a “proprietary and pharmaceutically optimized form of LSD.”

The first Phase 3 study, Voyage, will last a year and consist of two parts: a 12-week randomized, double-blind, placebo-controlled study to see how LSD affects anxiety symptoms. That will be followed by a 40-week extension period, during which participants can access open-label treatment with the drug based on the severity of their anxiety symptoms.

LSD has a noticeable subjective effect on sensation and cognition, which means it’s likely participants will know whether they received the psychedelic or a non-psychoactive placebo.

David Feifel, an investigator on the Voyage study and a professor emeritus at the University of California San Diego, said the research design “incorporates best-in-class methodologies to mitigate the impact of functional unblinding, including the use of independent central raters blinded to both treatment assignment and visit number.”

“The studies have also been designed to isolate the standalone drug effect of MM120 ODT from other psychotherapeutic intervention and follow industry best practices for safety monitoring,” added Feifel, who also directs the Kadima Neuropsychiatry Institute in La Jolla.

We announced the first patient dosed in our Phase 3 Voyage study evaluating MM120 ODT for generalized anxiety disorder. Thanks to our investigators, clinical trial sites & patients who will enroll in this groundbreaking research. More: https://t.co/ELRPr6tTIK pic.twitter.com/wGAWWZocrV

— MindMed (@mindmedco) December 16, 2024

He emphasized in a MindMed press release that it’s “critical to continue to develop new and effective treatment options for patients with GAD, a debilitating condition where there is an urgent need for transformational innovation.”

Unlike some other psychedelic-assisted therapies—such as the combination of MDMA and talk therapy to treat PTSD—past trials into the efficacy of MM120 did talk therapy or psychotherapy component. “MM120 was administered as a single dose in a monitored clinical setting with no therapeutic intervention,” MindMed said following the Phase 2 stage.

MindMed’s director and CEO, Robert Barrow, said at the time: “We are committed to bringing MM120 to people living with GAD and delivering on the potential of our pipeline to treat serious brain health disorders.”

According to a media representative for MindMed, MM120 is “a tartrate salt form of lysergide, a synthetic drug commonly known as LSD.”

Karlin, the company’s chief medical officer, previously told CNN that “LSD is difficult to manufacture with high purity and tends to degrade quickly in the presence of light and water.”

“We’re manufacturing it to pharmaceutical industry standards,” he added, describing the product as “a highly pure version that is also shelf stable.”

MindMed said after the Phase 2 trials that the most common adverse events for participants were “illusion, hallucinations, euphoric mood, anxiety, abnormal thinking, headache, paresthesia, dizziness, tremor, nausea, vomiting, feeling abnormal, mydriasis and hyperhidrosis.”

The new trials are the latest in a series of developments around psychedelic-based therapies this year, though most research has focused on other drugs, such as psilocybin or MDMA.

This summer, for example, a scientific review into MDMA found that five out of six studies looking at the substances’ potential to treat for post-traumatic stress disorder (PTSD) “provide evidence for the apparent safety and efficacy” of the therapy.

Authors called the findings “encouraging” but said more robust research is needed before MDMA-assisted therapy (MDMA-AT) sees widespread adoption over currently available forms of treatment.

That review came on the heels of an FDA advisory panel rejecting an application to authorize MDMA-assisted therapy. A group of bipartisan lawmakers and veterans advocates, however, almost immediately pushed back on that decision.

“What we’re asking for the FDA to recognize is the science,” said Rep. Morgan Luttrell (R-TX), who in a June op-ed for Marijuana Moment criticized the FDA Psychopharmacologic Drugs Advisory Committee for recommending against against MDMA-assisted therapy.

In August, meanwhile, a bipartisan coalition of congressional lawmakers emphasized the urgency of authorizing MDMA-assisted therapy, particularly as it concerns veterans with severe mental health conditions.

A total of 80 members of Congress—including 19 senators and 61 representatives from the House—sent separate letters to the Biden administration and the head of FDA.

MDMA is “one of the most promising and available options to provide reprieve for veterans’ endless PTSD cycle,” the Senate letter says, noting that FDA has already designated it as a breakthrough therapy.

A separate report by researchers who gave a dog a dose of LSD in order to treat separation anxiety found that the psychedelic caused no adverse effects and appeared to “significantly” attenuate the animal’s nervous symptoms.

Another report, on the millions of Americans with depression who might qualify for psilocybin-assisted therapy if it becomes widely available, noted that if LSD is approved for treatment of generalized anxiety disorder, doctors might also prescribe it for off-label uses, such as depression.

More recently, researchers published a report on how people cope with challenging psychedelic experiences, suggesting that some ways to manage a bad trip may be more helpful than others.

A separate study published this summer found that pairing psychedelics like LSD with a small dose of MDMA seemed to both reduce those feelings of discomfort and highlight more positive aspects of the experience.

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Featured image courtesy of Catalent.