At the University of California, San Francisco (UCSF), neuroscientist Jennifer Mitchell, PhD, is leading research into innovative treatments for conditions such as anxiety, depression, PTSD, impulsivity, stress, and addiction. She believes a new approach could help where standard therapies fall short -- and early results are encouraging.

This potential breakthrough treatment? A carefully developed pharmaceutical form of LSD.

What is generalized anxiety disorder?

Generalized anxiety disorder is a persistent and excessive form of anxiety that feels out of proportion to actual events or situations. It interferes with daily functioning, affecting relationships, work, and overall quality of life.

People living with GAD may struggle to focus, make decisions, or remember information, making it difficult to manage responsibilities at work or home. The condition can also lead to fatigue, irritability, and secondary depression. Many individuals hesitate to leave their homes for fear of feeling trapped, embarrassed, or helpless in social or public settings.

How is it different from day-to-day anxiety?

A hallmark of generalized anxiety disorder is that it manifests as physical symptoms. Persistent worry activates the body's fight-or-flight response, triggering stress hormones that cause physical effects. Patients may have muscle tension and rapid breathing, and report symptoms like headaches and insomnia, ringing in the ears, and cardiovascular, respiratory, and gastrointestinal issues.

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 with 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.