Compass points to the bank; 2nd Generation Psychedelics; Mushroom Orchard
COMPASS: “Excuse me, which way to the bank?”
From Monday’s press release:
“COMPASS Pathways, a mental health care company, announced today that it has completed a successful $80m Series B investment round.”
No, COMPASS will not be using this money to come after the grow kit in your closet.
“This funding will expand upon COMPASS's lead programme in psilocybin therapy for treatment-resistant depression, supporting research into additional indications for psilocybin therapy, advancing the company's preclinical pipeline, developing digital technologies, and establishing new academic and clinical research partnerships.”
The first questions that I can think of:
What additional indications will COMPASS look to develop?
And by establishing new clinical research partnerships can they accelerate the timeline to bring future indications to market?
I am not sure the second question makes sense, but let’s think this through.
Breakthrough Therapy Designation
COMPASS has already gained a Breakthrough Therapy Designation (BTD) which is a more direct relationship with the FDA so they will look for other indications for which they can leverage the power of psilocybin for another BTD.
Remember, Breakthrough Therapy means the FDA thinks a drug has the potential to “treat a serious or life-threatening disease or condition, and [has] preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over existing therapies.”
So they’ll be looking at other serious/life-threatening conditions that have a large patient population and shitty treatment options. In other words, almost anything for which Cognitive Behavioral Therapy (CBT) is the first-line treatment.
A few candidates come to mind:
Substance Abuse Disorder
(Please indulge a rant: Evidence-Based sticklers love CBT because it is well researched, straightforward, clean, and cognitive. It has its place, for sure. But psychiatry’s reliance on CBT and psychopharmacology has gotten us to a point where emotions are considered noise. CBT doesn’t teach people how to feel and work with their emotions.
But it’s validated.
Unfortunately, as Bessell Van Der Kolk points out:
“CBT has accumulated the most research support, even though we know that the whole cognitive part of the brain shuts down when people are traumatized, triggering the primitive survival part of the brain.”
Van Der Kolk again referring to trauma here but the principle can be applied more broadly:
“Trauma has nothing whatsoever to do with cognition,” he says. “It has to do with your body being reset to interpret the world as a dangerous place.” That reset begins in the deep recesses of the brain with its most primitive structures, regions that… no cognitive therapy can access. “It’s not something you can talk yourself out of.” That view places him on the fringes of the psychiatric mainstream.
The excitement of psychedelic based interventions is the hope that the unmeasurable, messy, feelings, emotions, and all the shit that doesn’t fit into the current evidence-based framework can be returned to the clinical encounter in a way that is effective and scientifically appreciated. Psychedelic Assisted Therapy is like the exact opposite of CBT.
How’s that for a rant?
That said, I bet CBT’s cognitive focus would complement psychedelic’s effect on the hidden parts of ourselves. Throw in physical practice and that looks pretty good.
Back to COMPASS.
My understanding is that the advantage of using the same drug for multiple indications will ultimately reduce costs and speed up timelines. Plus, preclinical safety and toxicity data is accounted for, Phase I healthy normals is done, relationships with vendors, clinics, Primary Investigators, etc. all in place.
They will look for indications that have lousy treatment options and a large patient population. They’ll want to partner with academic institutions that have done preliminary non-commercial IND stuff for these conditions.
Second Generation Psychedelics: PharmaBro & Patient Approved
Srinivas Rao, CEO of Entheogenix Biosciences was featured in an article this week about the company and the problem they are trying to solve.
Two problems, actually
Trips are a time commitment
The small cardiovascular risk associated with psychedelics
Innovation, Delivery, and Access
Some will see the attempt to shorten the duration of psychedelic trips as another tactic from the big pharma playbook.
Tweak a functional group, slap a patent on it, jack up the price, AND the patient volume. Pharma bro approved.
While big pharma shenanigans are a real thing, there’s also the perspective that if human ingenuity can develop molecules that allow patients and therapists the chance to have a lunch break then it is worth exploring.
I don’t know about you but I want to live in a world where I can leave the office, go to my doctor, kill my ego for 30 minutes and experience nondual oneness with God herself, process it and pick up a sandwich on the way back to work.
Sign me up.
“an FDA-approved psychedelic drug that lasts less than an hour could be dispatched to clinicians in rural areas who could then administer the drugs, provide treatment, and send patients on their merry way back home in the span of a couple of hours. “A lot of people are suffering,” said Dr. Rao, adding, “Psilocybin will be very successful, but we’re looking at getting to the small towns.”
5-HT-2B Cardiac Valve Risk
The other issue is that most of the Classic Psychedelics act on the serotonin system, specifically the 5-HT2 system and mostly on the 5-HT2a receptors, which are abundant in the cortex. (This paper from the Johns Hopkins homies will take you into the weeds and makes for light bedtime reading if you’re up for it.)
However, the classic psychedelics also act on other receptors including the 5-HT-2b. The 2b system affects cardiac function and here’s the bummer part:
The 5-HT2B receptor stimulation can also lead to pathological proliferation of cardiac valves fibroblasts, which with chronic overstimulation of 5-HT2B can lead to a severe valvulopathy.
This is the unknown risk that comes with more and more people taking psychedelics.
The cardiac risk with psilocybin is as Donald Rumsfeld would say an “unknown unknown” and as more people use these molecules we don't know how pervasive this negative effect will be.
I saw the below tweet yesterday. I first thought this was a non-profit pharmaceutical that was planning to crowdsource funds for clinical research.
“That’s ambitious,” I thought.
But if such a group were successful it would go along way to supporting our pharmaceutical bootstrapping hypothesis.
Turns out Orchard is an advocacy group for Obsessive Compulsive Disorder and they will be raising funds for a study that will evaluate psilocybin for OCD. Not as groundbreaking as I fist thought but who knows what it could turn into?
This will be interesting to follow this project for the next few years. Can this kind of grassroots effort grow into a PBC/Non-profit drug developer? Do they want to? It looks like an interesting group.
I will link to their Kickstarter page when they make it available.
Turn On, Tune In, Cash In: Sizing up the commercial and therapeutic prospects for the psychedelic revival
“And Matthew Johnson at Hopkins, ever the pragmatic realist, reminds me: “No medication has ever come to market and remained on market through a nonprofit model.” Drug trials and testing regimes require big money.”
“Following my brother’s passing and knowing the transformative potential of psychedelics, I set out to assemble a team that would include those already leading psychedelic research and consult with them to develop a product to help people like my brother."
Digital Event Season Cont’d
Digital psychedelic conferences are like golf tournaments, there’s one every weekend, they last too long, and its mostly white dudes.
There are two to choose from this weekend.
Upcoming Digital Events less than 8 hours
Thanks for reading, thanks for sharing, stay safe, and take care of each other.