Psy­che­del­ic re­search gains mo­men­tum, as ear­ly tri­al sug­gests mi­cro-dos­ing LSD is safe

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.

Neilo­u­far Fam­i­ly

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.”

The da­ta sup­port fur­ther clin­i­cal de­vel­op­ment of LSD, whose psy­choac­tiv­i­ty is un­der­stood to be me­di­at­ed pri­mar­i­ly through the 5-HT2A re­cep­tor, Eleu­sis said. The com­pa­ny even plans to de­vel­op the drug to treat and pre­vent Alzheimer’s dis­ease, a field lit­tered with fail­ure and a pauci­ty of promis­ing ther­a­peu­tics in the late-stage pipeline.

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.

Shlo­mi Raz

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.”

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

Biohaven CEO Vlad Coric (Photo Credit: Andrew Venditti)

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