09/23/2026
A conversation with a friend recently reminded me of something I probably don’t talk about enough.
He had gone down a research rabbit hole on some of the cannabinoids we use, found a study that raised a question, and brought it to me.
I loved it.
Because my answer wasn’t simply:
“Yes, there’s a study.”
It was:
“Where does that study sit on the evidence ladder?”
People tend to talk about science like evidence is binary.
There’s a study or there isn’t.
Something works or it doesn’t.
That’s not really how science works.
Evidence exists in layers, and each layer allows us to say something different with a different degree of confidence.
This is especially important in my world because cannabinoid formulation often lives somewhere in the lower and middle portions of this ladder.
So, let’s climb it. 🪜
1. PATIENT EXPERIENCE & REAL-WORLD OBSERVATION
Sometimes science begins with someone saying:
“Something changed.”
My pain improved. I slept better. My appetite came back. This worked differently than that.
One person reporting something is an observation.
When the same thing starts showing up independently across many patients?
Now we are paying attention.
Patient-reported outcomes can identify patterns and generate incredibly valuable questions. Formal, validated patient-reported outcome measures can make those observations much more rigorous.
But observation alone cannot prove why something happened.
Placebo effects, expectation, other medications, lifestyle changes, natural changes in disease and dozens of other variables exist.
So patient experience doesn’t give me a conclusion.
It gives me something incredibly valuable:
A signal.
And a reason to ask:
Why?
2. MECHANISTIC & LABORATORY EVIDENCE
Now we take that question into the biology.
What receptors does this compound interact with?
What signaling pathways does it influence?
What happens to inflammation, neurotransmission, immune signaling, bone metabolism, cell proliferation, etc.?
Then researchers can test those ideas in cells and tissues.
This is where we start establishing biological plausibility.
We can begin saying:
There is a mechanism through which this could make sense.
But here’s the limitation:
A mechanism isn’t a treatment, and a petri dish isn’t a person.
A concentration that produces an incredible effect on a cell in a laboratory may never even be achievable in human tissue.
This rung can tell us a tremendous amount about how something might work.
It cannot yet tell us that it actually will.
3. ANIMAL / PRECLINICAL EVIDENCE
Now we move from cells into an entire living organism.
Suddenly absorption, metabolism, circulation, immune response and interacting biological systems matter.
That’s a huge step.
We can begin studying dose-response relationships, toxicity, pharmacokinetics and whether the biological mechanism actually survives the chaos of a living body.
But:
A mouse isn’t a tiny human.
Different species metabolize compounds differently. Receptor systems differ. Disease models aren’t perfect copies of human disease.
Animal studies can make a hypothesis considerably stronger.
They still don’t prove the same thing will happen in us.
But they give us another reason to think it might.
4. HUMAN OBSERVATIONAL EVIDENCE
Now we’re finally looking at actual humans.
Case reports, case series and larger observational studies can show us whether the signal we’re chasing appears in people.
And when human observations start agreeing with the mechanism, the cell research and the animal research?
Now things get really interesting.
But observational research still has a causation problem.
Maybe the people using something also exercise more.
Maybe they’re younger.
Maybe they’re taking another medication.
Maybe there’s some variable nobody measured.
Human observation can strengthen a hypothesis, but humans also introduce a LOT more variables.
Correlation does not automatically prove causation.
5. CONTROLLED HUMAN TRIALS
Now we deliberately test the question.
Defined dose.
Defined population.
Defined outcome.
Comparison groups.
Randomization, blinding and placebo controls can further reduce bias and confounding.
This is where our ability to make causal statements becomes MUCH stronger.
But even here, “there was a clinical trial” isn’t enough.
How many people?
What dose?
For how long?
What population?
Was the effect statistically significant?
Was it actually large enough to matter?
Did anyone replicate it?
One RCT, or randomized controlled trial, isn’t scientific scripture.
It’s a very powerful piece of evidence answering a very specific question.
6. SYSTEMATIC REVIEWS & META-ANALYSES
Eventually we stop asking:
“What did this study find?”
and start asking:
“What does the body of evidence show?”
Researchers systematically evaluate multiple studies and, when appropriate, combine their results.
When independent researchers, different populations and multiple well-designed studies keep arriving at similar answers, our confidence grows.
This is near the top of the evidence ladder.
But even here:
Garbage in, garbage out.
A meta-analysis of weak studies doesn’t magically become strong science because we put them together.
AND HERE’S WHERE FORMULATION GETS WEIRD…
Weird Science. 😂
As we climb the evidence ladder, studies generally become better at answering a question.
But the question often becomes narrower.
That’s intentional.
Science likes isolating variables.
Researchers may study one cannabinoid, at one dose, for one outcome.
That’s how we figure out whether X actually caused Y.
But modern formulation often asks a completely different question.
I may not be asking:
“What does C*D do?”
I may be asking:
“What happens when C*D, CBG, CBC and CBN are used together at specific ratios, through a particular delivery system, possibly alongside other botanicals?”
Now we’re studying a system rather than a single molecule.
Those compounds may affect different biological targets.
They may overlap.
They may oppose each other.
They may affect one another’s absorption or metabolism.
Their effects could be additive, synergistic, antagonistic or completely independent.
And here’s the important part:
We don’t get to assume which one.
Strong evidence for A + strong evidence for B does NOT automatically equal strong evidence for A+B.
The combination itself is a new scientific question.
That is one of the biggest challenges of formulation.
The highest-quality research available may answer only individual pieces of the question we’re actually trying to solve.
So what do I do as a formulator?
I work backwards.
What is happening in the body?
What systems are involved?
What signals need to change?
What receptors or pathways influence those signals?
What cannabinoids or botanicals could potentially influence them?
Then:
What evidence do we actually have?
Patient experience?
Mechanism?
Cellular?
Animal?
Human observational?
Clinical?
And one of the biggest things I’m looking for is:
CONVERGENCE.
If patient observations point one direction…
The biology of the condition points the same direction…
The receptor pharmacology makes sense…
Cellular research supports it…
Animal research supports it…
And human evidence begins pointing that direction too…
That doesn’t magically turn a hypothesis into a proven treatment.
But it does make it a much better-supported hypothesis.
And THAT is where I think people misunderstand the evidence ladder.
It isn’t simply:
BAD EVIDENCE → GOOD EVIDENCE
Every rung answers a different question.
The mistake is asking one level of evidence to tell us something it can’t.
A cell study cannot prove clinical efficacy.
An animal study cannot prove a human outcome.
Patient feedback cannot establish causation.
And an RCT of one isolated cannabinoid cannot automatically tell me what a complex multi-compound formulation will do.
They are pieces of the same puzzle.
As a formulator, my job isn’t to pretend the missing pieces aren’t missing.
It’s to understand exactly which pieces I have, what each one tells me, and how confidently I’m allowed to speak because of them.
That’s the line I try very hard to respect:
What we know.
What the evidence suggests.
What is biologically plausible.
What we’re observing.
What the available evidence tells us about safety.
And what we still don’t know.
Science isn’t just the collection of things humanity has already proven.
It’s the process we use to investigate everything we haven’t.
So when someone tells me:
“There’s a study that says…”
My answer is almost always:
Awesome. Send it to me.
Then let’s ask the question that matters:
Where does it sit on the evidence ladder, and what does that actually allow us to say?
Because finding a study isn’t the end of scientific thinking.
It’s where it begins.
And it’s a whole ass vibe. 🪜😂
- Joshua
**Photo included is a free use stock photo. Post is for informational and educational purposes only.**
