Mushrooms: The Original Christmas Miracle?
Ancient mushroom outperforms expectations in FDA trials...
Amanita muscaria is a distinctive mushroom species. It has a striking red cap and is covered with white dots.
The mushrooms would grow on the ground in the Arctic, often under birch or pine trees. They are quite toxic, especially when fresh, and thus need to be “processed” by drying them out before they can be safely ingested. One could hang them in a sock over the fire, I suppose? That might do it. The other option is to let the reindeer have the first nibble—they didn’t seem phased by the toxins! The potent hallucinogenic compounds would pass through into the reindeer's urine. If so inclined, one could safely drink that urine for a shamanic experience. And, it turns out, the antidepressant effects might have combated the lack of daylight in the long winter.
These are Christmas magic… mushrooms.
These are not the same as psilocybin, of course. Different species. But this holiday season, we had another Christmas miracle…
Compass Pathways is the biotech company bringing its psilocybin analog, Comp360, to market. We have already seen published data on depression, which I will get back to in a second. This holiday season, we were greeted with this drug development gem from their PTSD study of the same compound:
Patients in the trial were monitored 24 hours after administering a single 25mg dose of COMP360. The safety profile was as expected with no serious treatment-emergent adverse events, according to Compass.
The rationale for therapists during the administration is a little perplexing to me, given this description of the administration of the compound:
COMP360 is combined with psychotherapy in the trials. After building a relationship with the therapist, the patient’s dosing session involves lying down, taking the drug capsule, listening to a specially designed music playlist while wearing an eye mask. The session lasts six to eight hours under the supervision of a therapist.
Which sounds less like therapy during administration and more like patiently waiting for my kids not to freak out before opening their presents on Christmas morning, which also requires adult supervision?
Be that as it may, the data in the phase 2b treatment-resistant depression studies already published in the New England Journal of Medicine is remarkable.
FDA Phases: A Review
Phase 1 trials are drugs administered to healthy human subjects to determine safety and dose-finding. In a Phase 2 trial, humans with the studied disease get the study drug. Typically, these are a few hundred individuals, and, quoting the FDA now:
In Phase 2 studies, researchers administer the drug to a group of patients with the disease or condition for which the drug is being developed. Typically involving a few hundred patients, these studies aren't large enough to show whether the drug will be beneficial.
Instead, Phase 2 studies provide researchers with additional safety data. Researchers use these data to refine research questions, develop research methods, and design new Phase 3 research protocols.
In summary, Phase 2 trials are not powered to show the drug is effective. It’s usually too few people. We have an entire other phase of drug development for that, phase 3. Thus, my eyebrows go up when I see a phase 2 study result demonstrating statistical superiority. These phase 2 studies were not powered—that is, they have not enrolled enough subjects—to show that difference!
It is the drug development version of a Christmas Miracle:
After a single 25mg dose of COMP360 psilocybin, in combination with psychological support, 29.1% of participants with TRD were in remission by week 3 (p<0.002)
That statistical difference? We don't usually see that in a phase 2 trial. They aren’t designed to show a difference. The big difference we see? It’s a hint that the drug is much more powerful than we suspected when deciding how many people to enroll.
There are phase 3 differences in phase 2 size trials. That is a big deal. No wonder ancient Santas were willing to drink reindeer pee to get a dose of what was in those mushrooms! There is still a lot of research to be done before these become well-established medicines. I look forward to the kinds of risk mitigation measures needed to reduce harm to humans with serious health conditions. Those include depression and PTSD. But this Christmas, I am hopeful we will have new and powerful treatments for depression under the tree in the near future!
🍄