Psychedelics have been long neglected as the subject of vigorous scientific research after governments branded them as illegal hedonistic compounds with no therapeutic potential. But in recent years, despite tricky regulations, a resurgence of interest from researchers has culminated in an FDA approved ketamine-derived depression treatment, clinical trials testing the potential of psilocybin in ‘magic mushrooms,’ and the setting up of a psychedelic research center at Johns Hopkins.
The colorless, odorless and tasteless drug, lysergic acid diethylamide (LSD) or acid, as it is fondly known is part of this research renaissance. On Wednesday, a small privately held company Eleusis Benefit Corporation unveiled data from an early study in healthy older volunteers that tested its micro-dosing approach with LSD. And if it all goes according to plan never a sure thing in biotech they’ve got plans to target Alzheimer’s with the approach.
In the study, 48 volunteers (mean age = 62.9 years) received either 5 μg, 10 μg, or 20 μg of LSD, or placebo administered in water every four days in six sessions. Overall, the LSD was well tolerated, and the frequency of adverse events was no higher than the placebo, the company said, while claiming this is the first ever publication of clinical study data on micro-dosed LSD.
PK data showed that the half-life of the LSD doses was short. “So at 12 hours post-dose, there was no drug in the blood at any of the doses,” Neiloufar Family, the trial’s lead investigator, told Endpoints News. “And there also wasn’t any drug in the blood at baseline on the sixth dose.”
But the brimming enthusiasm comes with a healthy dose of skepticism. Critics worry that the burgeoning psychedelic research could incentivize unbridled use of non-pharmaceutical versions of these drugs and that clinical trial data could be clouded by the fact that placebo-controlled studies are not necessarily double-blinded, because it is far too easy to determine which group of patients have been given a placebo.
“The one thing that we did expect but is still remarkable is the high placebo response,” Family said. “People were reporting perceptions of psychoactive effects, when later on we found out they were on placebo…but in any case, any perceptions of psychoactive effects were very mild and they subsided by the end of the day, both in the active dose groups and the placebo groups.”
Eleusis has a plan to hedge its Alzheimer’s bet, and to deal with the pesky problem of diversion.
Before diving into a Phase II efficacy study in Alzheimer’s, the company is planning an early-stage study with a compound a “not-so-psychedelic” psychedelic serotonin 5-HT2A agonist in ophthalmology. At the moment, the eye drug is at the preclinical stage of development.
The Phase I trial, which is expected to kick off in early 2021, will provide a key mechanistic insight into how psychedelics could prevent neurodegeneration associated with inflammation, Eleusis chief Shlomi Raz told Endpoints.
“The eye is a window to the soul but also to the brain,” he said.”The retina, in particular, gives us a very neat way of assessing how psychedelics could potentially manage neuroprotection, neuroinflammation and provides us a cost-effective proof-of-concept before going into by all measures what seems to be the most expensive type of clinical trial around, which is in Alzheimer’s disease.”
The hope is to develop an LSD compound for therapeutic use that can be used in the outpatient setting, but psychoactivity is a risk that must be monitored, he said. The company says it is developing a noninvasive safety monitoring technology that will be used in its clinical trials, and if the compound is approved, for patient use.
“In all cases, there’s a calculus of safety, versus unmet need, and clinical utility,” he said. “I think in the case of Alzheimer’s disease, should we demonstrate that LSD in fact, is effective in slowing or halting the progression of the disease, then I think that there’s a clear justification for taking that risk.”