- About 4% of the global population lives with an anxiety disorder, such as generalized anxiety disorder (GAD).
- While there are currently treatment options available for GAD, past studies show that about 50% of people will not respond to first-line treatments like antidepressant therapy.
- A new study reports the results of a phase 2b clinical trial of an LSD medication that shows promise in treating anxiety.
- The drug, called MM120, is an oral pharmaceutical form of LSD, the hallucinogenic drug also known as acid.
According to the World Health Organization (WHO), an estimated
Common symptoms of GAD include continuous worrying about everyday things, fatigue, restlessness, headaches, muscle cramps, concentration issues, shortness of breath, and sleeping problems.
Current treatment options for GAD include psychotherapy, medications like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), and certain lifestyle changes like getting enough sleep, learning relaxation techniques, and avoiding foods that can raise anxiety levels, like caffeine.
An estimated 8.6 million American adults experience GAD, and statistics show that only 4.3% receive treatment. Reid Robison, MD, psychiatrist, chief medical officer, and co-founder of Inner Space Research, told Medical News Today that despite these high numbers, “no new treatments have been approved for the condition since 2007.”
“While currently approved therapies offer relief to many, there are still too many patients who do not experience sustained relief, with approximately 50% inadequately responding to first-line treatments. Further, current treatments come with their own side effects, especially those that require daily use,” he said.
Robison is the principal investigator of a new study recently published in the
This new study reports phase 2b clinical trial results for MM120 ODT (lysergide D-tartrate, LSD) — a novel medication candidate produced by MindMed.
“MM120 is a medical form of LSD (that) MindMed is investigating for the treatment of GAD,” Robison explained. “MM120 works by increasing connections between areas of the brain that aren’t normally connected, enabling changes that could potentially help treat the underlying cause of anxiety, along with other conditions such as depression.”
How LSD changes the brain“Broadly, LSD produces a period of neuroplasticity, making the brain more susceptible to change during and following a session. We also know that people who are in these LSD controlled sessions have experiences that they report as being profound and meaningful and that these experiences contribute to change.”
— Reid Robison, MD
“When it comes to treating conditions like anxiety, I think there’s a component of both, that the profound experiences people have during the session contribute to the rapid and robust improvement, and that those improvements are consolidated and solidified and persist durably because of this period of neuroplasticity,” Robison added.
For this clinical trial, researchers recruited 198 adults with an average age of about 41 with moderate to severe GAD. Study participants were randomly given one of four doses of MM120 — 25, 50, 100, or 200 micrograms — or a placebo.
At the clinical trial’s conclusion, scientists found that study participants receiving the 100 microgram dose of MM120 achieved a 7.6-point larger reduction in their Hamilton Anxiety Rating Scale (HAM-A) scores at week four of the study, compared to placebo, as well as a 65% clinical response rate and 48% clinical remission rate sustained to week 12.
“The 7.6-point reduction shows both a clinically and statistically significant reduction, as the minimal clinically important difference is 2.5 points,” Robison said. “In addition, 100mg and 200mg demonstrated these sustained rapid, clinically meaningful, and statistically significant improvements starting at week one and continuing through week 12.”
Real results or power of suggestion?“What’s more, this is in contrast to the response in patients in the two lower dose arms of the trial. Across all four arms of the trial, the majority of patients correctly guessed they received [an] active drug, but only those on the two higher doses showed a clinically meaningful reduction in anxiety. That clear dose-response pattern points to a real pharmacological effect, not just the power of suggestion.”
— Reid Robison, MD
Additionally, Robison and his team found that study participants given the 100 µg dose of MM120 also improved their Clinical Global Impression-Severity (CGI-S) and Montgomery-Åsberg Depression Rating Scale (MADRS) scores.
“Improvements in both the CGI-S and MADRS scores further support the clinical and statistical significance of the data,” Robison explained. “Importantly, change in severity of depression symptoms as measured by MADRS was a key secondary endpoint. GAD and major depressive disorder (MDD) have a large amount of overlap; often, individuals with anxiety also have co-occurring depressive symptoms and/or have been diagnosed with depression. The co-occurrence and potential for similar benefits are promising for patients living with this disease.”
“These results highlight the promise of psychedelics in psychiatric medicine and demonstrate that psychedelic treatments can be evaluated with care and scientific rigor. This study represents a critical step toward expanding effective options for those who are suffering. I am eager to see continued development of MM120, a treatment that is clinically meaningful and presents a potentially paradigm-shifting option for the millions affected by GAD.”
— Reid Robison, MD
“MindMed’s focus is now on Phase 3 trials, which will test MM120 in even more patients, to fully understand its safety and efficacy,” Robison added.
MNT spoke with Greg Fonzo, PhD, co-director of the McGill Center for Psychedelic Research & Therapy and assistant professor in the Department of Psychiatry & Behavioral Sciences at The University of Texas at Austin Dell Medical School, about this study.
Fonzo commented that he was very impressed by the magnitude and durability of treatment benefit that participants demonstrated in the 100 and 200 microgram dosing groups, especially with a single dose of MM120.
“These results are very promising but need to be replicated in larger [s]amples,” he explained. “This study is also one of the first, large-scale modern psychedelic treatment studies to explicitly prohibit psychotherapeutic interventions by the dosing session monitors and remove any psychotherapy in the phase following treatment, which helps to boost confidence in attributing treatment effects to the drug and not a drug/psychotherapy combination.”
Moving forward, Fonzo said it will be important for researchers to assess the drug’s safety and efficacy in larger and more sociodemographically varied samples with the 100-microgram dose, which the company has chosen to move forward with as the indicated treatment dose.
“These Phase 3 studies are currently ongoing. It will also be important and helpful to follow individuals for longer periods of time after treatment (e.g., six to 12 months) to determine how long the effects of a single dose are maintained and when individuals may need to undergo retreatment.
— Greg Fonzo, PhD
“Finally, assessing how retreatment may or may not show different patterns of efficacy and durability will also be helpful in guiding treatment decision-making should the drug one day be FDA-approved,” he added.
MNT also spoke with Stacy Doumas, MD, chair of the Department of Psychiatry at Hackensack Meridian Jersey Shore University Medical Center in New Jersey, about this study.
“I am always encouraged to see new treatments being explored for mental health conditions, especially for disorders like GAD, where many patients continue to suffer despite the availability of existing options,” Doumas commented. “Any potential new treatment is of great interest.”
What about the LSD-psychosis link?“However, I also felt a significant degree of hesitation regarding the use of LSD in this context. It seems somewhat counterintuitive to treat anxiety with a psychedelic substance known to induce altered states of consciousness, and in some cases, psychosis. Additionally, while the study may show promise, the possibility of psychological dependence is not insignificant. The adverse event profile — including reports of psychosis and nausea — is another reason for caution.”
— Stacy Doumas, MD
“Despite the availability of multiple treatment options, many individuals with moderate to severe GAD continue to suffer due to treatments that are ineffective, only partially effective, poorly tolerated, or inaccessible,” Doumas continued. “Given these limitations, it is critical for researchers to continue exploring new, safe, and effective treatment options for GAD.”
“While the study represents an exciting step forward in exploring novel treatment avenues for GAD, I would approach its findings with both interest and a healthy degree of skepticism,” she said.
“Ultimately, while the potential of psychedelic-assisted therapy for anxiety is intriguing, the bar for safety, ethical oversight, and scientific rigor must be set high. Only through comprehensive, transparent, and methodologically sound research can we determine whether the benefits of LSD in treating GAD truly outweigh the risks — and for whom,” she added.
