People living with treatment-resistant Depression or chronic anxiety in New York City have more treatment options today than they did even a few years ago. Transcranial magnetic stimulation (TMS), Spravato® (esketamine), and conventional antidepressant medications can all play an important role in treatment. At the same time, researchers are continuing to investigate entirely new approaches for people who do not obtain adequate relief from existing treatments.
One of the most closely watched areas of psychiatric research involves psychedelic medications, including lysergide, commonly known as LSD. Recent studies have examined a pharmaceutical formulation of lysergide called MM120, as well as LSD-assisted therapy for Major Depressive Disorder (MDD).
Two 2025 studies are particularly important. A randomized clinical trial by Robison and colleagues, published in JAMA, evaluated a single dose of MM120 in adults with moderate-to-severe generalized anxiety disorder (GAD). A separate randomized trial by Müller and colleagues, published in Med, investigated different doses of LSD-assisted therapy in people with moderate-to-severe MDD. Together, these studies add to the growing evidence that carefully controlled psychedelic treatments may eventually become part of psychiatric care. Both are early-stage studies with meaningful limits, which we describe below.
What Is MM120?
MM120 is a pharmaceutical formulation of lysergide D-tartrate, an oral form of LSD. Unlike recreational LSD, MM120 is being developed as a standardized pharmaceutical treatment administered in a controlled medical and research environment.
The distinction is important. Researchers studying MM120 are not simply examining recreational psychedelic use. Clinical trials use carefully measured doses, standardized drug formulations, medical screening, monitoring, and structured follow-up.
MM120 is being investigated for generalized anxiety disorder and Major Depressive Disorder. The FDA has granted it Breakthrough Therapy Designation for GAD, a status intended to speed development, and larger Phase 3 trials are underway. It is not currently FDA-approved for treating anxiety or Depression. The recent research is therefore promising but still investigational.
JAMA Study: A Single Dose of MM120 for Generalized Anxiety Disorder
The first study, published in JAMA in September 2025, was a phase 2b randomized, double-blind, placebo-controlled trial involving 198 adults with moderate-to-severe GAD at 22 outpatient research sites in the United States. Participants were assigned to receive a single dose of MM120 at 25, 50, 100, or 200 micrograms, or placebo. Participants did not receive psychotherapy as part of the trial: the protocol prohibited it during dosing sessions so that researchers could assess the drug on its own. Most participants (84%) also had to taper off existing psychiatric medications before dosing.
The investigators were primarily interested in whether there was a dose-response relationship in improvement in anxiety symptoms, measured using the Hamilton Anxiety Rating Scale (HAM-A) at four weeks.
The results demonstrated a statistically significant dose-response relationship. At four weeks, the 100- and 200-microgram groups showed greater reductions in HAM-A scores compared with placebo, while the 25- and 50-microgram groups did not differ significantly from placebo. The 100-microgram dose produced a greater reduction of about 5 points (95% CI, 0.4 to 9.6 points) and the 200-microgram dose about 6 points (95% CI, 2.0 to 9.8 points), measured against a minimal clinically important difference of 2.5 points. Those confidence intervals are wide, which means the true size of the benefit is uncertain.
In exploratory analyses at 12 weeks, 65.0% of the 100-microgram group and 62.5% of the 200-microgram group met criteria for response, compared with 30.8% of the placebo group. Remission rates were 47.5%, 45.0%, and 20.5%, respectively. The placebo group also improved meaningfully, which is common in anxiety and Depression trials. The 200-microgram dose caused more adverse events without added benefit, and the findings supported selection of 100 micrograms as the dose for subsequent pivotal clinical trials.
Interestingly, the study also found evidence of improvement in depressive symptoms. Many people with GAD experience significant depressive symptoms; in this trial, roughly one-third to nearly half of the participants in each group also had co-occurring Major Depressive Disorder. On the Montgomery-Åsberg Depression Rating Scale, the 100- and 200-microgram groups showed greater improvement than placebo beginning at one week and continuing through the 12-week follow-up. These were secondary outcomes that were not adjusted for multiple statistical comparisons, so they are best understood as a signal worth investigating, not a confirmed result.
This does not mean that MM120 has been established as a treatment for Major Depressive Disorder. Rather, the findings provide another reason researchers are studying lysergide across multiple psychiatric conditions.
What About Safety?
The JAMA study also illustrates why psychedelic treatment needs to be distinguished from ordinary outpatient medication treatment. Nearly every participant who received the two higher doses reported at least one adverse event (97.5% at 100 micrograms and 100% at 200 micrograms, compared with 56.4% with placebo), and 98.5% of all adverse events occurred on the dosing day.
The most common adverse effects were visual perceptual changes, including illusions and hallucination-like experiences. These effects were strongly dose-related, reported by 46.2% of participants at 25 micrograms, 75.0% at 50, 92.5% at 100, and 100% at 200, compared with 10.3% with placebo. Nausea occurred in 40.0% of the 100-microgram group and 60.0% of the 200-microgram group, compared with 7.7% with placebo. Headache occurred in 35.0% and 27.5% of those groups, compared with 23.1% with placebo.
Participants were monitored on site for at least 12 hours after dosing, with a physician available, and acute effects had resolved in more than 97% of participants by that point. One serious adverse event occurred: a hospitalization for a panic attack about three months after dosing in the 50-microgram group, which investigators judged unrelated to the drug. Five participants (2.5%) withdrew because of adverse events, and no suicidal behavior was reported.
These findings underscore an important point: even if psychedelic medications eventually receive FDA approval, they are unlikely to be medications that patients simply take at home without supervision. The acute effects of the medication and the need for appropriate patient selection and monitoring will be important considerations.
Limits of the MM120 Findings
Several limits are worth keeping in mind. Because the perceptual effects of MM120 are obvious to the person taking it, blinding was imperfect: about 85% of participants correctly identified that they had received active drug, and more than 65% of placebo recipients correctly guessed they had received placebo. The investigators used independent, blinded raters to reduce the effect on outcome ratings, and they noted that the lower doses were also noticeable yet did not improve symptoms, which argues against unblinding alone explaining the results. Participants were also physically healthy with limited psychiatric comorbidities, were 83% White, and were followed for only 12 weeks, so the findings may not reflect the broader population of people with GAD. Finally, the trial was conducted by MindMed, the company developing MM120, and the company’s chief executive, Robert Barrow, is among the listed authors, a common arrangement in drug development but worth knowing when weighing how the results are presented.
LSD-Assisted Therapy and Major Depressive Disorder
A second 2025 study, conducted at the University of Basel in Switzerland and published in Med, examined LSD-assisted therapy specifically in people with Major Depressive Disorder.
The randomized trial included 61 adults with moderate-to-severe MDD, many with long-standing illness (an average of nearly 17 years) and prior antidepressant treatment. Participants were assigned to either a lower-dose or a higher-dose LSD regimen, with each participant receiving two dosing sessions accompanied by supportive psychotherapy. The higher-dose group received 100 micrograms followed by 200 micrograms (the second dose was increased only if the first was well tolerated and the participant agreed), while the lower-dose group received 25 micrograms at both sessions. The researchers used a low-dose comparison instead of an inactive placebo to improve blinding.
At the primary follow-up two weeks after the second administration, the investigators observed greater reductions in depressive symptoms in the higher-dose group. On the clinician-rated Inventory of Depressive Symptomatology (IDS-C), scores fell by 12.9 points in the higher-dose group compared with 3.6 points in the lower-dose group (p=0.023, which remained significant after correction for the two primary outcomes). On the self-rated version (IDS-SR), the difference (11.8 versus 3.9 points) approached but did not reach statistical significance (p=0.059).
When the researchers adjusted for baseline depression severity and other factors in a sensitivity analysis, the clinician-rated difference was no longer statistically significant (p=0.086). That adjustment matters because the higher-dose group began the trial with more severe symptoms (an average IDS-C score of 35.9 versus 28.9), so regression to the mean may have accounted for part of the observed difference.
At the primary follow-up, 40% (clinician-rated) and 44% (self-rated) of the higher-dose group met criteria for response, compared with 20% of the lower-dose group on both measures. Remission rates were 32% and 36% versus 20%. The numerical improvement in depressive symptoms remained evident through follow-up 12 weeks after the second session. The investigators concluded that the findings support further study of LSD-assisted therapy in a larger phase 3 trial.
This is an important distinction. The study does not establish LSD as an FDA-approved treatment for Depression, nor does it demonstrate that LSD is ready to replace established treatments such as antidepressant medication, TMS, or Spravato. Instead, it provides evidence that warrants additional investigation.
Safety and Limits of the LSD-Assisted Therapy Trial
Adverse events were comparable between the groups, with headache, nausea, dizziness, fatigue, and difficulty concentrating the most common. The most clinically important findings involved two participants in the higher-dose group who left the study after their first session because the acute effects were distressing (dysphoria and anxiety). One of them reported a temporary increase in passive suicidal thoughts, without intent, for three days, and had reported such thoughts before. Overall, roughly one in five participants (12 of 61) left the study, and one participant in the higher-dose group had a systolic blood pressure above 180 mmHg during a dosing session.
Four serious adverse events occurred after dosing: three involved worsening depression with hospitalization (two in the lower-dose group, one in the higher-dose group) and one involved an accident. The investigators judged these unlikely to be related to the drug, citing intervals of weeks to months and other plausible causes. The study team also noted that one participant who had left the study after a single low-dose session died by suicide seven months later. Because this occurred after the participant’s involvement had ended, it was not counted as a serious adverse event, and an independent rater judged it unlikely to be related to the study drug.
The trial has several limits. Blinding was often ineffective: participants and therapists correctly guessed group assignment between 69% and 96% of the time, depending on the group and session. The clinician-rated outcome was assessed by the treating therapist rather than an independent rater, which can introduce bias. The sample was small, excluded people at acute risk of suicide and those with bipolar disorder or psychosis, was composed almost entirely of participants of European ancestry, and did not adjust secondary outcomes for multiple comparisons. The trial was funded by the Gertrud Thalmann Fund for depression research. Its senior author disclosed consulting fees from Mind Medicine, Inc. (MindMed), which licensed know-how and data from the work, although the company had no role in financing, planning, or conducting the study.
How Does This Compare With TMS?
For patients considering treatment for Depression in NYC, it is useful to understand the difference between established neuromodulation treatments and newer psychedelic therapies.
TMS is already an established, FDA-cleared treatment for Major Depressive Disorder under specific indications. TMS uses magnetic pulses to stimulate targeted areas of the brain and does not involve psychedelic intoxication or an altered state of consciousness. We describe how it works in our post on how TMS improves brain connectivity and neuroplasticity.
By contrast, MM120 and LSD-assisted therapy remain investigational treatments. LSD acts on serotonin 5-HT2A receptors, but how it produces antidepressant or anti-anxiety effects has not been established. Hypotheses include the psychological experience during the dosing session and lasting changes in neuroplasticity. Spravato, which is FDA-approved for treatment-resistant Depression, is likewise administered in a supervised setting.
Research into both approaches is asking a similar broad question: can we develop more effective treatments for people whose Depression or anxiety has not responded adequately to conventional approaches? The answer may eventually involve multiple types of treatment rather than a single therapy.
Why This Research Matters for Patients in New York City
Treatment-resistant Depression and difficult-to-treat anxiety can be particularly challenging for people trying multiple medications without achieving sufficient improvement. Patients may also experience medication side effects, incomplete responses, or difficulty maintaining treatment over time.
That is why research into new approaches is important. The MM120 research is particularly interesting because the JAMA study found measurable improvement following a single administration, with effects assessed over 12 weeks. The LSD depression study similarly raises the possibility that relatively limited treatment sessions could produce longer-lasting changes in depressive symptoms.
However, these findings need to be replicated in larger and broader populations. Researchers also need to better understand which patients are most likely to benefit, how long benefits last (neither trial followed participants beyond about three months), what type of psychological support is necessary (the MM120 trial provided none, while the LSD trial paired dosing with supportive psychotherapy), and how psychedelic treatments compare directly with existing therapies. The safety and monitoring requirements, including the 12-hour supervised dosing days used in the MM120 trial, will also be central to determining how these treatments could be delivered in routine psychiatric practice.
Could Mid City TMS Offer This Treatment in the Future?
At Mid City TMS in New York City, we follow new research in psychiatry and neuromodulation because patients deserve access to evidence-based treatment options as the field advances.
Our current treatment approach includes established options such as TMS and Spravato, when clinically appropriate. At the same time, we recognize that psychiatric treatment is changing quickly.
If MM120 or another lysergide-based treatment receives FDA approval, and if the treatment becomes available for appropriate clinical use, Mid City TMS may consider incorporating this treatment option into our practice. Any future use would depend on FDA approval, regulatory requirements, clinical evidence, appropriate patient selection, and the availability of a safe and medically appropriate treatment protocol.
For now, MM120 and LSD-assisted therapy should be considered investigational treatments rather than currently available FDA-approved treatments for Depression or generalized anxiety disorder.
The Future of Depression and Anxiety Treatment
The new research on MM120 and LSD-assisted therapy represents one part of a much larger shift in psychiatry. Researchers are investigating treatments that work through different biological mechanisms, may act more rapidly than traditional antidepressants, or may produce benefits after relatively limited treatment exposure. TMS and other forms of neuromodulation are also advancing, with research examining accelerated protocols, theta-burst stimulation, individualized targeting, and other approaches.
For patients in New York City with Depression or anxiety that has not responded adequately to conventional treatment, this widening range of options is a reason to stay informed. At Mid City TMS, our goal is to evaluate treatments based on the available scientific evidence while continuing to monitor developments that could expand the options available to our patients.
MM120 and LSD-assisted therapy are not yet established clinical treatments. But the recent research offers an important glimpse into what the next generation of psychiatric treatments may look like.
If you or a loved one has Depression that has not responded to medication, learn how Mid City TMS can help and contact us today to schedule a consultation about the options available now.
Sources
Robison R, Barrow R, Conant C, et al. Single Treatment With MM120 (Lysergide) in Generalized Anxiety Disorder: A Randomized Clinical Trial. JAMA. 2025;334(15):1358-1372. doi:10.1001/jama.2025.13481.
Müller F, Zaczek H, Becker A, et al. Efficacy and safety of low- versus high-dose-LSD-assisted therapy in patients with major depression: A randomized trial. Med. 2025;6(9):100725. doi:10.1016/j.medj.2025.100725.