TRPV1 is part of the transient receptor potential family and is one of the non-GPCR cannabinoid receptors. TRPV1 is involved in thermoregulation and pain detection (nociception).

Chemical Name: 
Transient receptor potential cation channel subfamily V member 1/Vanilloid receptor 1.
IUPHAR entry: 
Wikipedia entry: 

TRPV1 is found in dorsal root ganglia, brain, kidney, pancreas, testes, uterus, spleen, stomach, small intestine, lung and liver.

Literature Discussion: 


Anandamide anti cancer properties depend on TRPV1 and not on CB1 or CB2 (Contassot et al., 2004; Ramer and Hinz, 2008).


Bone Cancer

Research shows that bone cancer cells express TRPV1 receptor  (Kawamata et al., 2010). 

Cervical Cancer

cannabinoid receptors CB1CB2 and TRPV1 are expressed in the cervix (Ayakannu et al., 2015).


CBD modulates Id-1 gene and targets receptors CB1, CB2, TRPV-1 and TRPV-2 (Solinas et al., 2013; Soroceanu et al., 2013)

Lung Cancer

In three different cancer cell lines (A549, H358 and H460) CBD dose dependently (1nM-3μM) increased ICAM-1 and TIMP-1 through TRPV1. In mice carrying human lung cancer xenografts, CBD increased ICAM-1 and TIMP-1 2.6-3.0-fold, inhibiting lung cancer cell invasion and metastasis (Ramer et al., 2012)


OEA reduced food intake and weight gain in rodents via PPARα and TRPV1 (Overton et al., 2006).

Functional Gastro-intestinal disorders

Apart from CB1 and CB2, there is evidence for the involvement of PPARγ and TRPV1 in Crohn’s Disease (de Fontgalland et al., 2014; Schicho and Storr, 2014)

CB1 and TRPV1 signaling are both required for the development of stress-induced visceral hyperalgesia and TRPV4 and TRPA1 may also be involved (Lin et al., 2013).


In a rat study, Anandamide was found to induce bladder inflammation pain through TRPV1 suggesting this receptor might be a therapeutic target (Dinis et al., 2004).


In an experimental mouse model of Eczema endocannabinoids AEA and PEA were increased and TRPV1 and PPARα were upregulated (Petrosino et al., 2010). PEA enhances AEA activity at CB1CB2 and TRPV1 receptors and protects against keratinocyte inflammation in a TRPV1-, but not CB1CB2 or PPARα-dependent way.


In mice, stimulating CB1 receptors (ACEA) or blocking TRPV1 receptors (capsazepine) protected against PTZ-induced seizures (Naderi et al., 2015). Interestingly, co-administration of both compounds attenuated the anti-convulsive effect, suggesting an interaction between CB1 and TRPV1 mediated signaling.


CBD would act as an inhibitor of Anandamide uptake through TPRV1 receptor, suggesting a role in sleep (Bisogno et al., 2001; Mechoulam et al., 1997)


TRPV1 has also been implicated in the pathophysiology of migraine. Interestingly, blocking TRPV1 function has no effect but stimulating these receptors offers pain relief; in fact transient activation is followed by prolonged de-sensitization and thus effective pain relief. TRPV1-mediated antinociception is thought to work in synergy with CB1-mediated neuronal inhibition in pain management (Hoffmann et al., 2012).


OEA reduced food intake and weight gain in rodents via PPARα and TRPV1 (Overton et al., 2006).


TRP receptors (TRPV1-4, TRPA1TRPM8) are classically known for their role in pain sensation. TRPs bind to most plant cannabinoids and endocannabinoids with varying affinities (De Petrocellis et al., 2011, 2012), tentatively making TRPs excellent targets and plant cannabinoids excellent substrates for pain management.


In one study, Anandamide was found to reduce dopamine release via TRPV1 receptors (de Lago et al., 2004) suggesting their involvement in movement behaviour. In another study, OEA reduced L-dopa-induced-dyskinesia in a TRPV1-dependent way (González-Aparicio and Moratalla, 2014).


CBD and CBG do not function through classical CB receptors and none of the phytocannabinoids depended on TRPV1 for their effect (in contrast to endocannabinoid function below), but PPARγ and GPR55 may be involved in the effect of cannainoids in Psoriasis (Wilkinson and Williamson, 2007).


Ayakannu, T., Taylor, A.H., Willets, J.M., and Konje, J.C. (2015). The evolving role of the endocannabinoid system in gynaecological cancer. Hum. Reprod. Update 21, 517–535.

Bisogno, T., Hanuš, L., De Petrocellis, L., Tchilibon, S., Ponde, D.E., Brandi, I., Moriello, A.S., Davis, J.B., Mechoulam, R., and Di Marzo, V. (2001). Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of Anandamide. Br. J. Pharmacol. 134, 845–852.

Contassot, E., Tenan, M., Schnüriger, V., Pelte, M.-F., and Dietrich, P.-Y. (2004). Arachidonyl ethanolamide induces apoptosis of uterine cervix cancer cells via aberrantly expressed vanilloid receptor-1. Gynecol. Oncol. 93, 182–188.

De Fontgalland, D., Brookes, S.J., Gibbins, I., Sia, T.C., and Wattchow, D.A. (2014). The neurochemical changes in the innervation of human colonic mesenteric and submucosal blood vessels in ulcerative colitis and Crohn’s disease. Neurogastroenterol. Motil. Off. J. Eur. Gastrointest. Motil. Soc. 26, 731–744.

de Lago, E., de Miguel, R., Lastres-Becker, I., Ramos, J.A., and Fernández-Ruiz, J. (2004). Involvement of vanilloid-like receptors in the effects of Anandamide on motor behavior and nigrostriatal dopaminergic activity: in vivo and in vitro evidence. Brain Res. 1007, 152–159.

De Petrocellis, L., Ligresti, A., Moriello, A.S., Allarà, M., Bisogno, T., Petrosino, S., Stott, C.G., and Di Marzo, V. (2011). Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br. J. Pharmacol. 163, 1479–1494.

De Petrocellis, L., Orlando, P., Moriello, A.S., Aviello, G., Stott, C., Izzo, A.A., and Di Marzo, V. (2012). cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation. Acta Physiol. Oxf. Engl. 204, 255–266.

Dinis, P., Charrua, A., Avelino, A., Yaqoob, M., Bevan, S., Nagy, I., and Cruz, F. (2004). Anandamide-evoked activation of vanilloid receptor 1 contributes to the development of bladder hyperreflexia and nociceptive transmission to spinal dorsal horn neurons in Cystitis. J. Neurosci. Off. J. Soc. Neurosci. 24, 11253–11263.

González-Aparicio, R., and Moratalla, R. (2014). Oleoylethanolamide reduces L-DOPA-induced dyskinesia via TRPV1 receptor in a mouse model of Parkinson´s disease. Neurobiol. Dis. 62, 416–425

Hoffmann, J., Supronsinchai, W., Andreou, A.P., Summ, O., Akerman, S., and Goadsby, P.J. (2012). Olvanil acts on transient receptor potential vanilloid channel 1 and cannabinoid receptors to modulate neuronal transmission in the trigeminovascular system. pain153, 2226–2232.

Kawamata, T., Niiyama, Y., Yamamoto, J., and Furuse, S. (2010).Reduction of bone cancer pain by CB1 activation and TRPV1 inhibition. J. Anesth. 24, 328–332.

Lin, X.-H., Wang, Y.-Q., Wang, H.-C., Ren, X.-Q., and Li, Y.-Y. (2013). Role of endogenous cannabinoid system in the gut. Sheng Li Xue Bao 65, 451–460.

Mechoulam, R., Fride, E., Hanu, L., Sheskin, T., Bisogno, T., Di Marzo, V., Bayewitch, M., and Vogel, Z. (1997). Anandamide may mediate sleep induction. Nature 389, 25–26.

Naderi, N., Shafieirad, E., Lakpoor, D., Rahimi, A., and Mousavi, Z. (2015). Interaction between cannabinoid Compounds and Capsazepine in Protection against Acute Pentylenetetrazole-induced Seizure in Mice. Iran. J. Pharm. Res. IJPR 14, 115–120.

Overton, H.A., Babbs, A.J., Doel, S.M., Fyfe, M.C.T., Gardner, L.S., Griffin, G., Jackson, H.C., Procter, M.J., Rasamison, C.M., Tang-Christensen, M., et al. (2006). Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metab. 3, 167–175.

Petrosino, S., Cristino, L., Karsak, M., Gaffal, E., Ueda, N., Tüting, T., Bisogno, T., De Filippis, D., D’Amico, A., Saturnino, C., et al. (2010). Protective role of palmitoylethanolamide in contact allergic dermatitis. Allergy 65, 698–711.

Ramer, R., and Hinz, B. (2008). Inhibition of cancer cell invasion by cannabinoids via increased expression of tissue inhibitor of matrix metalloproteinases-1. J. Natl. cancer Inst. 100, 59–69.

Schicho, R., and Storr, M. (2014). Cannabis finds its way into treatment of Crohn’s disease. Pharmacology 93, 1–3.

Solinas, M., Massi, P., Cinquina, V., Valenti, M., Bolognini, D., Gariboldi, M., Monti, E., Rubino, T., and Parolaro, D. (2013). Cannabidiol, a Non-Psychoactive cannabinoid Compound, Inhibits Proliferation and Invasion in U87-MG and T98G Glioma Cells through a Multitarget Effect. PLoS ONE 8.

Soroceanu, L., Murase, R., Limbad, C., Singer, E., Allison, J., Adrados, I., Kawamura, R., Pakdel, A., Fukuyo, Y., Nguyen, D., et al. (2013). Id-1 is a key transcriptional regulator of glioblastoma aggressiveness and a novel therapeutic target. cancer Res. 73, 1559–1569.

Wilkinson, J.D., and Williamson, E.M. (2007). cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of Psoriasis. J. Dermatol. Sci. 45, 87–92.