Psy­che­delics have ex­pe­ri­enced a re­nais­sance in re­cent years amid a tor­rent of pre­clin­i­cal and clin­i­cal re­search sug­gest­ing it might pro­vide a path to treat mood dis­or­ders con­ven­tion­al reme­dies have on­ly scraped at. Now a pre­clin­i­cal tri­al from a young biotech sug­gests at least one psy­che­del­ic com­pound has ef­fects be­yond the mind, and — if you be­lieve the still very, very ear­ly hype — could pro­vide the first sin­gle rem­e­dy for some of the main com­pli­ca­tions of obe­si­ty.

A study in mice fund­ed by Eleu­sis and pub­lished in Sci­en­tif­ic Re­ports found a long-known drug called (R)-DOI could be used to treat car­dio­vas­cu­lar dis­ease, re­duc­ing in­flam­ma­tion in the aor­ta, de­creas­ing over­all and HDL cho­les­terol lev­els, and po­ten­tial­ly curb­ing di­a­betes by in­creas­ing glu­cose tol­er­ance.

Lead au­thor Charles Nichols says di­a­betes and high cho­les­terol, though of­ten re­sults of the same un­der­ly­ing con­di­tion, re­quire sep­a­rate drugs and a re­strict­ed di­et.

“This mod­el that treats car­dio­vas­cu­lar dis­ease and meta­bol­ic dis­ease — it’s all-en­com­pass­ing,” Nichols, a pro­fes­sor of phar­ma­col­o­gy at LSU, told End­points News. “Trans­lat­ed in­to the clin­ic in hu­mans, it would be as if some­one was obese, had di­a­betes, had high cho­les­terol, and was able to take a low dose of this drug at a sub-be­hav­ioral lev­el and re­al­ly treat sev­er­al dif­fer­ent as­pects of the com­pli­ca­tions of be­ing obese.”

They’re bold words, though al­most mut­ed in a psy­che­del­ic field brim­ming with hype. Re­searchers have called the re­sults of some psy­chi­atric stud­ies “mind-blow­ing” as clin­i­cal tri­als hint at the pow­er of psilo­cy­bin (the chem­i­cal in mag­ic mush­rooms) to al­le­vi­ate de­pres­sion and MD­MA to re­lieve PTSD.

David Nichols Pur­due

The no­tion that the same class of drugs might have oth­er phys­i­o­log­i­cal and specif­i­cal­ly an­ti-in­flam­ma­to­ry ef­fects is new­er. Nichols, the son of long­time psy­che­del­ic re­search pro­po­nent David Nichols, un­der­stands the rhetoric can get rosy but points out that the tri­al was tar­get­ed. They test­ed DOI in oth­er types of tis­sue and when it had lit­tle ef­fect, fo­cused on vas­cu­lar in­di­ca­tions.

“This is not a com­plete panacea,” said Nichols, who ear­li­er tout­ed his an­i­mal stud­ies in­di­cat­ing DOI’s po­ten­tial in asth­ma.

Nichols dis­cov­ered that sero­tonin 5-HT_2A re­cep­tor ag­o­nists, fol­low­ing a well-un­der­stood path­way psy­che­delics act on, can re­duce in­flam­ma­tion by ac­ci­dent in his LSU lab in 2008. Lat­er, he got a cold call from Shlo­mi Raz, a for­mer Wall Street ex­ec­u­tive who went on to get a mas­ter’s in psy­chol­o­gy at NYU.

Shlo­mi Raz

Eleu­sis launched in 2013 with a mis­sion, Raz told End­points, of ex­plor­ing the broad pos­si­bil­i­ties for these ag­o­nists, with their work so far rang­ing from a tri­al on the ef­fects of ‘mi­cro-dos­ing’ LSD on time per­cep­tion to fil­ing a patent for the treat­ment of Alzheimer’s with LSD. Nichols has pub­lished sev­er­al pre­vi­ous stud­ies on psy­che­delics and an­ti-in­flam­ma­to­ries, but this was no­table in its abil­i­ty to on­ramp in­to clin­i­cal tri­als.

Raz be­lieves what is com­mon­ly called psy­che­delics have a broad ar­ray of im­pacts be­yond their “psy­che­del­ic” func­tion. He says he has peer-re­viewed re­search com­ing soon that will help bol­ster that claim, and that the cen­tral ques­tion is how to un­lock those ef­fects with­out trig­ger­ing the psy­cho­log­i­cal im­pact.

“If you think of it as an ice­berg,” Raz said, “maybe the tip of the ice­berg is the psy­chi­atrics and the part be­low the sur­face is not psy­chi­atric.”

The vas­cu­lar study showed phys­i­o­log­i­cal with­out any psy­cho­log­i­cal ef­fects (mice giv­en a psy­che­del­ic can some­times show be­hav­ior con­sis­tent with psy­chosis). The re­searchers fat­tened up mice on the “West­ern di­et” for four months and at in­ter­vals ad­min­is­tered DOI to one group and saline to a con­trol.

They found that vas­cu­lar in­flam­ma­tion was low­er in the DOI, as they an­tic­i­pat­ed. They hadn’t an­tic­i­pat­ed that cho­les­terol would be down and glu­cose tol­er­ance up, and they’re still not sure why.

Nichols, though, said the study was trans­lat­able to a clin­i­cal tri­al, and he was hope­ful there would be a drug with­in 10 to 20 years. Reg­u­la­tion, more than the sci­ence, was the bar­ri­er. Raz was mum about what’s next, both in terms of oth­er ap­pli­ca­tions and in busi­ness mod­el, but he left one clue:

“I can tell you it’s not a pill,” he said, “at first.”

Finally freed from the restraints of a partial FDA clinical hold on its lead HER2-positive solid tumor candidate, Pieris Pharmaceuticals is now racing toward Phase II.

The FDA slapped a partial hold on Pieris’ PRS-343 back in July, restricting the biotech from enrolling new patients in a Phase I trial. While Pieris was allowed to continue dosing patients who were already enrolled, the agency requested they conduct an additional “in-use and compatibility study” before recruiting any more.

It’s time for a new FDA commissioner to come on board, a rite of passage for Joe Biden’s administration that should help seal the new president’s rep on seeking out the experts to lead the government over the next 4 years.

As of now, the competition for the top job appears to have narrowed down to 2 people: The longtime CDER chief Janet Woodcock and Joshua Sharfstein, the former principal deputy at the FDA under Peggy Hamburg. Both were appointed by Barack Obama.

Two weeks after joining Verastem Oncology as chief medical officer, Frank Neumann is leaving the company for another job.

Neumann had joined Verastem after leaving bluebird bio, which surprisingly split into two companies last week, one in oncology and one in rare diseases. It’s not yet clear to where Neumann is headed next, but he noted in a statement that Verastem’s data and strategy were “truly exciting.”

A month after filing the IND application for its human extracellular matrix designed to regenerate knee cartilage, Histogen has hit a roadblock.

The FDA on Tuesday verbally notified the San Diego-based biotech that it was placing a clinical hold on the planned Phase I/II clinical trial of HST-003 due to pending CMC information and additional questions needed to complete their review.

Histogen had planned to test the safety and efficacy of implanting hECM within microfracture interstices and related cartilage defects to regenerate that cartilage in conjunction with a microfracture procedure. The company said in a press release that it expects to receive written notice of the clinical hold from the FDA by Feb 12.

Gritstone Oncology has had a big week, and it’s only Wednesday.

On Tuesday, the biotech revealed plans to start clinical testing of an experimental Covid-19 vaccine — in tandem with NIAID — that can also target other coronaviruses, with the goal of preventing future pandemics should SARS-CoV-2 prove difficult to cure with current vaccines. Then, on Wednesday morning, Gritstone licensed lipid nanoparticle technology from Genevant Sciences to develop what it’s calling “self-amplifying RNA vaccines” against Covid-19.