When skin or tissues become more sensitive—when a cut burns or a chili-pepper cream creates an intense warming sensation—it’s likely that TRPV1 is the one “reading” that signal. Specifically, it is an ion channel expressed by sensory neurons that detects high heat, acidity, and certain irritating molecules. Understanding how it works helps us better interpret pain and navigate the evidence on CBD, which maintains a close relationship with TRPV1.

What is the TRPV1 receptor?

The TRPV1 receptor (Transient Receptor Potential Vanilloid 1) is part of the TRP ion channel family, membrane proteins that regulate the passage of ions such as calcium and sodium and that participate in various sensory functions, from heat perception to pain.

Its structure is a tetramer: four subunits, each with six membrane-spanning segments, combine to form a central pore. When the pore opens, calcium and sodium enter the neuron and the electrical signal is triggered.

Why does it open? TRPV1 is polymodal: it integrates different stimuli and decides whether to “raise its hand.” Essentially:

·       Heat: above ~43 °C, the likelihood of opening increases.

·       Acidic pH: during inflammation or ischemia, a more acidic environment facilitates activation.

·       Capsaicin: the spicy compound in chili peppers is a direct agonist of the TRPV1 receptor.

·       Endogenous mediators: lipids and peptides released in damaged tissues can sensitize the channel.

One often overlooked aspect is desensitization: after intense or prolonged stimuli, the channel becomes less responsive. This principle explains why high-capsaicin topical formulations can reduce pain perception after an initial burning phase. In short, the mechanism governing TRPV1 is not limited to activation, it also includes internal brakes that modulate the response.

The Functions of TRPV1 in the Body

Recognizing sensations of pain and heat is only a small part of TRPV1’s functions. These receptors are involved in circuits that connect the periphery to the central nervous system. Specifically:

●      Pain perception: RPV1 is expressed in the sensory fibers of the dorsal root and trigeminal ganglia. When it activates, the neuron releases neuropeptides (substance P, CGRP) and the nociceptive signal is amplified. This is one reason why, in an inflamed joint, even a moderate stimulus hurts: the system is “sensitized”.

●      TRPV1 and inflammation: Channel activation not only transmits pain but also promotes vasodilation and capillary permeability. This creates a bidirectional dialogue between nerves and the immune system. This is why scientific literature often mentions “TRPV1 inflammation”: the channel links harmful perception with tissue response.

●      Thermoregulation: Systemic TRPV1 antagonists tested as analgesics have produced hyperthermia in some clinical studies. This is strong evidence that the receptor contributes to balancing body temperature. Beyond being physiologically interesting, this explains why not all anti-TRPV1 drugs can be used without adjustments.

●      Extra-neuronal expression: TRPV1 has also been detected in the gastrointestinal tract, airways, and cardiovascular system. Here, it plays roles in motility, secretion, and responses to tissue stress. This doesn’t mean it “does everything,” but rather that it is a general-purpose sensor integrated into multiple networks.

This combination of roles clarifies why the TRPV1 receptor is a major target in research on chronic pain and inflammatory conditions: modulating a sensor that integrates so many signals can shift the pain threshold and alter the dynamics of inflammation.

TRPV1 and the Endocannabinoid System

The endocannabinoid system (CB1/CB2 receptors, ligands such as anandamide and 2-AG, and synthesis/degradation enzymes) maintains the balance of functions like pain, immunity, and mood. TRPV1 is part of the dialogue within this circuit.

·       Anandamide can activate TRPV1 as well as modulate CB1: the same molecule interacts with two different nodes, one sensory and one neuromodulatory.

·       In many sensory fibers, TRPV1 is co-expressed with CB1/CB2: this means that endocannabinoid signals can influence not only synaptic transmission but also the channel’s sensitivity.

·       On an applied level, “polypharmacology” that combines CB2 and TRPV1 is being studied to achieve analgesia and inflammation control through a single strategy.

Viewed this way, understanding the structure of the TRPV1 receptor and its modulation dynamics is the foundation for designing targeted—and, above all, predictable—interventions. 

The Role of CBD in the TRPV1 Receptor

Cannabidiol (CBD), which has no psychoactive effects, acts on multiple targets. Its interaction with TRPV1 is documented by preclinical studies.

·       What happens to the channel: CBD can activate TRPV1 at specific concentrations: calcium influx increases and the neuron initially transmits more. Afterwards, desensitization occurs: the channel becomes less responsive, and the cell reduces its excitability. This two-phase dynamic (brief activation followed by attenuation) aligns with analgesic effects observed in models of neuropathic and inflammatory pain.

·       Why this matters clinically: in inflamed tissues, TRPV1 is often hypersensitive; bringing it back to a higher threshold helps limit hyperalgesia and pro-inflammatory signaling. CBD also interacts with other targets (for example 5-HT1A, GPR55); overall, it reduces the likelihood that the neuron will “fire” excessively.

·       What we know in humans: clinical studies vary widely in dose, duration, and route of administration. There are signs of benefit, but larger controlled protocols are needed to draw firmer conclusions. Any evaluation for wellness purposes or as support in painful conditions should be discussed with a physician, also to avoid drug interactions.

To turn this information into more informed choices, consult Eusphera’s section dedicated to CBD oils.