A clinical LSD formulation shows promise for severe anxiety. Trials reveal meaningful symptom relief and limited side effects.
Generalized anxiety disorder affects about one in every twenty adults in the United States. In severe cases, individuals may become so withdrawn that they seldom leave their homes, struggle to work, and find it difficult to maintain social connections. Standard medications often provide only limited relief.
At the University of California, San Francisco, neuroscientist Jennifer Mitchell, PhD, studies new treatments for conditions such as drug and alcohol dependence, PTSD, stress, anxiety, impulsivity, and depression. She believes there may be a therapy capable of producing greater results. So far, an experimental drug she is testing has delivered unexpectedly positive outcomes.
What is this mystery new treatment? It is a pharmaceutical version of LSD.
What is generalized anxiety disorder?
Generalized anxiety disorder is a chronic condition marked by excessive anxiety that is out of proportion to the actual circumstances causing it. The disorder can significantly disrupt daily functioning.
People living with generalized anxiety disorder often have trouble focusing, remembering information, or making decisions. These challenges can interfere with their ability to work, manage a household, or care for family members. Many also experience depression brought on by anxiety, along with restlessness, fatigue, and a sense of constant tension. They may avoid leaving home due to fears of feeling trapped, helpless, or embarrassed in public situations.
How is it different from day-to-day anxiety?
Unlike ordinary stress or nervousness, generalized anxiety disorder produces clear physical symptoms. Persistent worry keeps the body’s fight-or-flight system active, releasing stress hormones that cause physiological strain.
Those affected may experience muscle tightness, rapid breathing, headaches, insomnia, ringing in the ears, or issues involving the heart, lungs, and digestive system.
How is generalized anxiety disorder treated?
It’s usually treated with medications like Zoloft and Paxil that boost and stabilize the neurotransmitter serotonin, leading to reduced anxiety and enhanced emotional well-being. These medications have been found to reduce symptoms by an average of 1.25 points on the 56-point anxiety scale — insufficient to make significant difference for at least some patients.
Why LSD?
LSD as well as other psychedelics, have tremendous potential to shift mood and emotions when used in a controlled, therapeutic setting. We have seen this in a previous trial of Ecstasy to treat PTSD.
The pharmaceutical formulation of LSD is MM120. Its primary mechanism is to promote neuroplasticity in the brain, potentially altering negative thought patterns. It also increases communication between brain regions that may address the rigid thinking that underlies GAD.
How effective is MM120?
In an earlier phase of the study, published in JAMA, the effects of a single dose of MM120 were evaluated over a 12-week period in approximately 200 participants with moderate-to-severe generalized anxiety disorder.
The drug significantly alleviated symptoms, reducing them by five to six points on the anxiety scale in addition to the effects of placebo. That’s quite significant and enough to reclassify moderate generalized anxiety disorder as mild in some cases.
Were there side effects?
Participants were carefully monitored by medical staff during the period after the drug was administered. Side effects were generally mild or moderate and included hallucinations, visual distortions, nausea, and headache.
It’s important to note, these were more prevalent using the highest dosage, which we will not be using since it was found to be no more effective. Nausea is a common side effect of psychedelics, but this was reduced by restricting participants to a light breakfast and treating them proactively with an anti-nausea medication.
What challenges do you face recruiting participants for the study?
We are looking for people with moderate-to-severe general anxiety disorder, so typically those with disabling symptoms who are reluctant to leave their home. Ironically, people who would best qualify are least likely to show up. Participants are screened by very skilled clinicians who probe and observe body language and carefully build a rapport. We hope this builds trust and enables participants to be vulnerable and reflective.
Reference: “Single Treatment With MM120 (Lysergide) in Generalized Anxiety Disorder: A Randomized Clinical Trial” by Reid Robison, Robert Barrow, Craig Conant, Eric Foster, Jamie M. Freedman, Paula L. Jacobsen, Jamileh Jemison, Sarah M. Karas, Daniel R. Karlin, Todd M. Solomon, Miri Halperin Wernli and Maurizio Fava, 4 September 2025, JAMA.
DOI: 10.1001/jama.2025.13481
If you are interested in participating in MM120 trial sites at UCSF and other California locations, please check this information.
Details about more MM120 trial sites can be found here.
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