(A Regulatory Toxicologist’s Take on the Hidden Risk Behind “Natural Relief”)

By Dr. Harriet Kamendi, PhD — Regulatory Toxicologist & CEO, Kandih BioScience

Project CBD recently reported a growing trend in the U.S.:
adults reducing or replacing prescription medications with cannabis, while others add cannabis on top of already complex drug regimens.
(Project CBD)

This is where the story turns from wellness to risk.

 Chronic cannabis use + multiple medications = a pharmacology interaction zone with no referee — and toxicology is the missing discipline.

If you work in healthcare innovation, drug development, wellness products, or cannabinoid science, here’s the one clear idea:

Cannabis isn’t dangerous because it’s “bad.” It’s dangerous because it interacts with medications in ways most people — and many clinicians — don’t understand.

Let me say the quiet part out loud as a toxicologist:

 “Natural” does not mean pharmacologically neutral.
Why Cannabis + Polypharmacy Is a Toxicology Problem

Cannabis doesn’t simply “add” to drug regimens — it rewires the exposure landscape.

1. CYP450 Enzyme Interference: The Chemical Traffic Jam

THC, CBD, CBG, and their metabolites all interact with liver enzymes responsible for breaking down most prescription drugs, especially:

CYP3A4 → metabolizes ~30% of all pharmaceuticals

CYP2C9

CYP2C19

UGT enzymes

When cannabis inhibits these enzymes, drugs build up to higher levels than intended, increasing toxicity risk.

This can amplify or destabilize medications used for:

hypertension

depression or anxiety

diabetes

anticoagulation (blood thinners)

insomnia

pain

seizures

From a toxicologist’s perspective, this isn’t a side note — it is the central safety issue.

2. Cannabis Is Biphasic — A Regulatory Nightmare

Cannabis has opposite effects at different doses:

Low dose → calming, anti-nausea

High dose → anxiety, paranoia, rebound nausea

When combined with medications acting on:

serotonin

dopamine

GABA

the endocannabinoid system

…the results are often unpredictable.
This is mixture toxicology, not single-agent exposure.

Regulators currently do not classify cannabis + meds as a combination product — but biologically, that’s exactly what it is.

3. Chronic Cannabis Use Changes Physiology

Long-term cannabis use can:

influence blood pressure swings

alter appetite hormones

shift opioid receptor sensitivity

increase or destabilize anxiety

disrupt REM sleep

affect glucose control

When layered on top of existing medications, the toxicology landscape isn’t linear — it’s multidimensional.

From a regulatory toxicology standpoint, this is precisely why cannabis should be treated as a pharmacologic exposure, not a casual supplement.

What Product Developers Must Learn — Immediately

Whether you’re formulating edibles, wellness tinctures, CBD oils, or THC beverages, you are already operating in a drug–interaction ecosystem.

1. Build Drug–Cannabinoid Interaction Data Into R&D

Responsible development means:

 Modeling CYP450 interactions

 Using in silico drug–interaction prediction tools

 Testing formulations against commonly co-used medications

If you skip this, you’re flying blind.

2. Prioritize Exposure Science, Not Just Potency

Most companies still design products based on:

taste

experience

potency

branding

But toxicologists care about:

chronic THC/CBD accumulation

metabolite toxicity

slow hepatic clearance

food-effect interactions

tolerance and receptor desensitization

These determine long-term safety, not the label.

3. Labeling Must Catch Up

Hemp/CBD/THC products should include warnings for interactions with:

CNS depressants

SSRIs & SNRIs

benzodiazepines

beta blockers

insulin & hypoglycemics

anticoagulants

antiepileptics

This is not alarmist — it is standard risk communication.

4. Use Real-World Evidence (RWE) as a Surveillance System

Cannabis is not taken in controlled laboratories.
Users stack:

edibles

vapes

alcohol

medications

supplements

RWE + toxicology = early detection of:

cognitive impairment

tachycardia

mood destabilization

hepatotoxicity

bleeding events

hypoglycemia

This should feed directly into product reformulation and labeling.

My Professional Opinion

As a regulatory toxicologist, here’s my frank view:

The cannabis industry has scaled faster than the safety science needed to support it.

Polypharmacy isn’t niche — it is the defining challenge of modern cannabis use.

Older adults are:

the largest group taking multiple medications

one of the fastest-growing groups adopting cannabis

And yet many product developers approach cannabis like aromatherapy.

My stance is simple:

 Cannabis is a pharmacologically active compound.

Treat it with pharmaceutical respect.

Until drug–interaction toxicology is built into every stage of development, the ER visits will continue — and so will preventable harm.

The Bottom Line

The most dangerous side effect of chronic cannabis use in 2025 is not paranoia or cognitive fog.

It’s polypharmacy without toxicological oversight.

If your product interacts with the endocannabinoid system, you’re now in the drug–interaction business.

 Toxicology is not a barrier to innovation.

 It is the infrastructure that lets innovation survive real-world use.

 Separately let us all not forget the terpenes…. A story for another day…. Another blog

 Reference Links
1. Project CBD — Cannabis Instead of Polypharmacy
https://projectcbd.org/safety/cannabis-instead-of-polypharmacy

2. U.S. FDA — Cannabis and Cannabis-Derived Products: Quality Considerations
https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd

3. CDC — Cannabis and Health Effects
https://www.cdc.gov/cannabis/health-effects/index.html

4. Stout SM & Cimino NM. Exogenous Cannabinoids and Drug Interactions. J Clin Pharmacol. 2014
https://www.tandfonline.com/doi/full/10.3109/03602532.2013.849268

5. Huestis MA. Human Cannabinoid Pharmacokinetics. Chem Biodivers. 2007
https://pmc.ncbi.nlm.nih.gov/articles/PMC2689518