LSD Decreased Depression Symptoms by 50% in New MindMed Study

The article LSD Decreased Depression Symptoms by 50% in New MindMed Study was originally published on Microdose.

On April 14th, psychedelic medicine company MindMed (Nasdaq: MNMD, NEO: MMED) released preliminary data from a Phase 2 clinical trial, which attempted to treat Major Depressive Disorder (MDD) with LSD-assisted psychotherapy.

This trial had 61 patients with moderate to severe depression. Half went into a placebo group that received a low dose of LSD (25 micrograms), and half received two large doses, separated by 4 weeks (100 and 200 micrograms). Both groups received accompanying therapy.

MindMed — which differentiates itself from other psychedelic medicine companies by its focus on LSD as compared to psilocybin or DMT — touted the “positive topline data” in their press release. CEO Rob Barrow extolled the “statistically and clinically significant improvements observed in this study,” which reinforces the “preliminary findings that have shown the clinical potential of lysergide [LSD] in anxiety, depression and other brain health disorders.”

But despite the celebratory tone of the press release, the document itself does very little to put into context just how successful the investigator-initiated trial was.

Study shows LSD is an effective treatment for depression

The main data point shared by MindMed showed that 16 weeks after the initial dosing date, the 29 MDD patients who received at least one large dose of LSD saw the severity of their depression drop by an average of 12.9 points, when measured using a rating scale called the “Clinician-Rated Inventory of Depressive Symptomatology (IDS-C).”  This compared to a drop of only 3.6 points for the low-dose placebo group. 

In other words, those who received LSD saw their symptoms decline —on average — almost four times more than those who took a placebo.

But without context into how the IDS-C rating system works or, more importantly, how many patients improved enough to enter remission or to have seen a “clinically significant reduction” in their symptoms — often defined as a reduction of 50% or more — it was hard to judge how successful the trial actually was.

And while I did some digging on the IDS-C (long story short, patients are ranked from 0-84, with the severity of depression increasing with the rank), without further context from MindMed, it was difficult to judge the success of the trial.

And then I got my hands on a translated copy of the German presentation given by Prof. Matthias Liechti and Dr. Felix —the MindMed collaborators who initiated and ran the study — which explained the results of the trial. In it were lots of juicy tidbits left out in the press release.

And let me just tell you, MindMed definitely undersold the effectiveness of LSD in treating Depression, at least as it relates to this one specific Phase 2 trial.

The most significant stat is that the 12.9-point drop on the IDS-C represented an average decrease in depression symptoms of 50%.

To put it another way, if this trial’s results are valid — and we will have to confirm them in many more studies before we can make this claim — then the average person with Major Depressive Disorder could hope to see the severity of their depression cut in half thanks to LSD-assisted therapy. 

This also points to the number of patients seeing a “clinically significant reduction” in their symptoms being around 50%.

Really, MindMed should have included this stat in the press release, as it not only makes the results of their trial clearer, but it also makes the company look better. 

In its press release, MindMed also highlighted that “Data from the secondary endpoints were also encouraging,” and that the “investigational drug was generally well-tolerated.” But beyond this, the psychedelic medicine company did not offer many specifics in its press release.

But once again, looking at Prof. Matthias Liechti and Dr. Felix’s slideshow, we can get a little more information. First, using two different depression measurement scales — the IDS-SR and the BDI —the reduction in depression symptoms were similar to when measured with the IDS-C. This just helps add to our confidence level in the findings, though of course we will need to see the trial repeated.

Next, we found out that while the press release states the LSD was “generally well-tolerated,” there were 3 patients who had to be hospitalized due to worsening depression — though two of these three patients were in the “low dose” placebo group. Either way, this isn’t something to be overly concerned about. It is common that a medicine does not work for everyone, and the LSD did not put patients in physical harm. Still, this is something to keep an eye on in future trials.

Perhaps the most interesting piece of information found on the slides that isn’t in the press release is the relationship between the effectiveness of the treatment, and whether the patient had a “mystical experience” while under the influence of LSD.

On average, the greater a “mystical experience” a person had, the greater their depression levels, anxiety levels, and craving to smoke decreased. 

This is interesting as it points to the question of where the benefit of psychedelics comes from. Are the benefits to mental health due solely to a chemical reaction in the brain, or the subjective experience a person goes through while on a psychedelic? This trial would hint at the latter, which may be bad news for companies working on “non-psychedelic” psychedelic medicines.

In sum, MindMed’s Phase 2 trial attempting to treat moderate to severe Major Depressive Disorder with LSD-assisted therapy was a success, with an average reduction in symptoms of 50%, 16 weeks after taking the first LSD dose. And while it is surprising that MindMed left this number out of its press release, it bodes well for future LSD clinical trials.

Of course, we will have to wait and see further results before making any definitive statements on how effective LSD is in treating mental health issues. And even if it is effective, we will then need to compare it (on effectiveness, efficiency and cost) to other psychedelics such as psilocybin, to see if MindMed’s LSD bet will pay off.

For more on MindMed’s programs, check out Are LSD and r-MDMA the Future of Psychedelics? MindMed Says Yes

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