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.”

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.