Acetaminophen (best known as Tylenol) is one of the most frequently used over-the-counter medications for pain and fever. Yet for decades, the medical community has had only a vague understanding of how it actually works. Now, recent research may finally provide answers, and they involve the same system medical cannabis uses to relieve pain: the endocannabinoid system (ECS).
At ECS Wellness, we use emerging science like this to help patients find effective, personalized treatments that work with the body’s natural systems—not against them.
The Endocannabinoid System: Cannabis and Pain Regulation
The endocannabinoid system (ECS) is a complex signaling network that regulates inflammation, pain, appetite, sleep, and mood. It includes cannabinoid receptors (such as CB1 and CB2), naturally occurring cannabinoids like 2-AG and anandamide, and the enzymes that synthesize and break down those compounds.
Cannabis-based medicines work by modulating this system. THC binds primarily to CB1 receptors in the brain and nervous system, often providing effective pain relief, especially for chronic pain conditions.
But the ECS is not always a system that should be “turned up.” Sometimes, relief comes from reducing endocannabinoid activity in very specific areas of the nervous system.
How Acetaminophen Uses the ECS to Relieve Pain
A groundbreaking 2025 study found that acetaminophen reduces pain by acting on the ECS, not by fighting inflammation or dulling perception as once believed.
Researchers discovered that acetaminophen inhibits an enzyme called DAGLα, which is responsible for producing 2-AG, a major endocannabinoid. With lower 2-AG levels, there’s less activation of CB1 receptors in certain pain-related neural circuits. Interestingly, this reduction in CB1 activity led to less pain—not more.
This effect is highly circuit-specific. In some parts of the nervous system, activating CB1 blocks pain. In others, CB1 activation may actually facilitate pain signals. This explains why acetaminophen’s effects disappear in lab animals that lack CB1 receptors.
Just as Percocet is a combination of oxycodone and acetaminophen, cannabis can be effective when used in combination therapies. ECS Wellness specialists help their patients find the right dose of medication and cannabis to achieve optimal health through a completely balanced ECS.
What This Means for Medical Cannabis Patients
Many people assume that medical cannabis works simply by boosting cannabinoid activity. But this new research suggests that selectively modulating the ECS—sometimes turning it down, not just up—may be the key to optimal pain control.
This is why one-size-fits-all dosing or strain recommendations often fall short. At ECS Wellness, our physicians design individualized cannabis therapy plans based on patient symptoms, goals, and ECS response. We often explore integrative strategies where cannabis is used alongside traditional medications like acetaminophen to support safe, evidence-based care.
Acetaminophen and Cannabis: Different Paths to the Same Goal
The idea that acetaminophen and cannabis both interact with the ECS shows us that pain relief is not limited to one molecule or mechanism. Instead, the ECS offers a versatile framework for developing targeted therapies.
Future medications may include cannabinoid formulations that suppress DAGLα activity, synthetic cannabinoids with localized effects, or novel drug combinations that minimize opioid dependence and reduce side effects.
This insight also opens the door to new types of clinical research focused on ECS modulation for chronic pain, fibromyalgia, neuropathy, and inflammatory conditions.
Smarter Pain Management Through Personalized Care
Understanding how the endocannabinoid system works is essential to offering more effective and more personalized treatment plans. At ECS Wellness, we take a science-first approach to medical cannabis by helping patients discover how cannabinoids, and even non-cannabis medications like acetaminophen, can be used strategically to restore balance and promote healing.
If you are exploring medical cannabis for chronic pain, anxiety, or inflammation, our experienced clinicians are here to guide you.
Schedule your consultation today at www.ecswellness.com and discover how integrative cannabinoid care can help you live better, backed by science, not guesswork.
Dr. Ryan Zaklin is a board-certified Internal Medicine physician and a Harvard-trained expert in Integrative and Functional Medicine. He brings deep experience from his work at Massachusetts General Hospital and the Spaulding Rehabilitation Network. As founder of ECS Wellness, Dr. Zaklin leads the clinical strategy with a focus on the endocannabinoid system, mind-body medicine, and plant-based therapies. He regularly educates medical professionals and the public on cannabis therapeutics and continues to advance research and innovation in integrative care.
