Cannabinoid receptor signaling (Homo sapiens)

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1CYP3A4CYP2C194endogenous cannabinoidsCBD catabolismPKARelevant MAPK subtypesNeuronal cell of CNS(hyppocampus, cerebellum or basal ganglia)inactiveInhibition of Glutamate or GABA release in synaptic cleftLeukocytes, spleen, thymus, bone marrowand other tissues associated with immune functionsHepG2 cellsPRKAR1BMAPK9MAPK14ADCY1MAPK13MAPK12PRKAR2BMAPK3MAPK1PRKAR1AMAPK11MAPK10MAPK8PRKACBPRKACAPRKAR2APRKACGCNR1CYP2C911-OH-THCMAPK PhosphatidylethanolamineDAGLBcAMP AHRNAPEPLD5ADCY76NAPEDAGLA5Arachidonic acidTHC1''-hydroxycannabidiol42-arachidonoylglycerolprotein tyrosine kinasesFAAH5GlutamateADORA2A2CNR2CalciumGABA CBDATPAEAAnti-inflammatory pathwaysCOOH-THC7CYP1A13ATPcAMP CBD2''-hydroxycannabidiol 43''-hydroxycannabidiol 44''-hydroxycannabidiol 45''-hydroxycannabidiol 46a-hydroxycannabidiol 46b-hydroxycannabidiol 47-hydroxycannabidiol endogeneous cannabinoid synthesis4PRKACBPRKACAPRKAR1APRKAR2BPRKAR1BPRKACGPRKAR2APKA regulatory subunit type IPKAcatalytic subunitPKA regulatory subunit type IIPRKACBPRKACAPRKAR1APRKAR2BPRKAR1BPRKACGPRKAR2APKA


Endogenous cannabinoid receptors belong to the endocannabinoid system and are located in the mammalian brain and throughout the central and peripheral nervous systems, consisting of neuromodulatory lipids and their receptors. The endocannabinoid system is involved in a variety of physiological processes including appetite, pain-sensation, mood, and memory, and in mediating the psychoactive effects of cannabis. Two primary endocannabinoid receptors have been identified: CNR1 and CNR2. CNR1 is found predominantly in the brain and nervous system, as well as in peripheral organs and tissues, and are the main molecular target of the endocannabinoid ligand (binding molecule), Anandamide, as well as its mimetic phytocannabinoid, THC (tetrahydrocannabinol). One other main endocannabinoid is 2-Arachidonoylglycerol (2-AG) which is active at both cannabinoid receptors, along with its own mimetic phytocannabinoid, CBD (cannabidiol). 2-AG and CBD are involved in the regulation of appetite, immune system functions and pain management.


Not all MAPK subtypes are relevant for this pathway. The relevant types have been separately added on the right side of the pathway.

Source: Howlett A.C. Cannabinoid Receptor Signaling. In: Pertwee R.G. (eds) Cannabinoids. Handbook of Experimental Pharmacology, vol 168. Springer, Berlin, Heidelberg, 2005

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  1. Laprairie RB, Bagher AM, Kelly ME, Denovan-Wright EM; ''Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor.''; Br J Pharmacol, 2015 PubMed
  2. Carrier EJ, Auchampach JA, Hillard CJ; ''Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression.''; Proc Natl Acad Sci U S A, 2006 PubMed
  3. Yamaori S, Kinugasa Y, Jiang R, Takeda S, Yamamoto I, Watanabe K; ''Cannabidiol induces expression of human cytochrome P450 1A1 that is possibly mediated through aryl hydrocarbon receptor signaling in HepG2 cells.''; Life Sci, 2015 PubMed
  4. Jiang R, Yamaori S, Takeda S, Yamamoto I, Watanabe K; ''Identification of cytochrome P450 enzymes responsible for metabolism of cannabidiol by human liver microsomes.''; Life Sci, 2011 PubMed
  5. Díaz-Alonso J, Guzmán M, Galve-Roperh I; ''Endocannabinoids via CB� receptors act as neurogenic niche cues during cortical development.''; Philos Trans R Soc Lond B Biol Sci, 2012 PubMed
  6.; ''''; ,
  7. Anderson GD, Chan LN; ''Pharmacokinetic Drug Interactions with Tobacco, Cannabinoids and Smoking Cessation Products.''; Clin Pharmacokinet, 2016 PubMed


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98007view07:54, 3 July 2018Fehrhartfixed aesthetics
97566view07:39, 25 May 2018IreneHemelModified description
97565view07:39, 25 May 2018IreneHemelModified description
97564view07:36, 25 May 2018IreneHemelAddition of relevant MAPK subtypes
97536view14:31, 24 May 2018IreneHemelSubunits PKA
94926view11:40, 13 October 2017DeSlOntology Term : 'xenobiotic metabolic pathway' added !
94925view11:38, 13 October 2017DeSladded ID for 2nd PKA node
94924view11:37, 13 October 2017DeSladded ID for PKA
94923view11:36, 13 October 2017DeSladded ID for MAPK
88989view11:44, 18 August 2016Mkutmonremoved comments
88980view09:30, 18 August 2016Fehrhartfixed some weird characters
88978view09:18, 18 August 2016Fehrhartadjusted some lines and added descriptions
88975view09:12, 18 August 2016Fehrhartaddition of OH-CBDs
88973view08:36, 18 August 2016FehrhartModified description
88834view13:13, 15 August 2016Fehrhartwork in progress
88833view13:10, 15 August 2016FehrhartModified description
88598view19:51, 11 August 2016Mkutmonfix unconnected lines
88457view14:38, 9 August 2016Fehrhartwork in progress
88450view15:07, 8 August 2016Fehrhartwork in progress
88449view15:02, 8 August 2016Fehrhartadded CYP1A1 stimulation pathway
88389view13:24, 3 August 2016FehrhartOntology Term : 'leukocyte' added !
88388view13:24, 3 August 2016FehrhartOntology Term : 'neuron' added !
88387view13:23, 3 August 2016FehrhartOntology Term : 'cannabinoid signaling pathway' added !
88386view13:22, 3 August 2016FehrhartWork in progress
88383view12:53, 3 August 2016FehrhartNew pathway

External references


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NameTypeDatabase referenceComment
1''-hydroxycannabidiolMetaboliteCHEBI:133056 (ChEBI)
11-OH-THCMetaboliteHMDB60906 (HMDB)
2''-hydroxycannabidiol MetaboliteCHEBI:133058 (ChEBI)
2-arachidonoylglycerolMetaboliteHMDB04666 (HMDB)
3''-hydroxycannabidiol MetaboliteCHEBI:133059 (ChEBI)
4''-hydroxycannabidiol MetaboliteCHEBI:133055 (ChEBI)
5''-hydroxycannabidiol MetaboliteCHEBI:133062 (ChEBI)
6a-hydroxycannabidiol MetaboliteCHEBI:133049 (ChEBI)
6b-hydroxycannabidiol MetaboliteCHEBI:133052 (ChEBI)
7-hydroxycannabidiol MetaboliteCHEBI:133053 (ChEBI)
ADCY1GeneProductENSG00000164742 (Ensembl)
ADCY7GeneProductENSG00000121281 (Ensembl)
ADORA2AGeneProductENSG00000128271 (Ensembl)
AEAMetaboliteHMDB04080 (HMDB)
AHRGeneProductENSG00000106546 (Ensembl)
ATPMetaboliteHMDB00538 (HMDB)
Anti-inflammatory pathwaysPathway
Arachidonic acidMetaboliteHMDB01043 (HMDB)
CBDMetaboliteCHEBI:69478 (ChEBI)
CNR1GeneProductENSG00000118432 (Ensembl)
CNR2GeneProductENSG00000188822 (Ensembl)
COOH-THCMetaboliteCHEBI:77273 (ChEBI)
CYP1A1GeneProductENSG00000140465 (Ensembl)
CYP2C19GeneProductENSG00000165841 (Ensembl)
CYP2C9GeneProductENSG00000138109 (Ensembl)
CYP3A4GeneProductENSG00000160868 (Ensembl)
CalciumMetaboliteHMDB00464 (HMDB)
DAGLAGeneProductENSG00000134780 (Ensembl)
DAGLBGeneProductENSG00000164535 (Ensembl)
FAAHGeneProductENSG00000117480 (Ensembl)
GABA MetaboliteHMDB00112 (HMDB)
GlutamateMetaboliteHMDB00148 (HMDB)
MAPK GeneProduct2.7.11.24 (Enzyme Nomenclature)
MAPK10GeneProductP53779 (Uniprot-TrEMBL)
MAPK11GeneProductQ15759 (Uniprot-TrEMBL)
MAPK12GeneProductP53778 (Uniprot-TrEMBL)
MAPK13GeneProductO15264 (Uniprot-TrEMBL)
MAPK14GeneProductQ16539 (Uniprot-TrEMBL)
MAPK1GeneProductP28482 (Uniprot-TrEMBL)
MAPK3GeneProductP27361 (Uniprot-TrEMBL)
MAPK8GeneProductP45983 (Uniprot-TrEMBL)
MAPK9GeneProductP45984 (Uniprot-TrEMBL)
NAPEMetaboliteCHEBI:61232 (ChEBI)
NAPEPLDGeneProductENSG00000161048 (Ensembl)
PRKACAGeneProductENSG00000072062 (Ensembl)
PRKACBGeneProductENSG00000142875 (Ensembl)
PRKACGGeneProductENSG00000165059 (Ensembl)
PRKAR1AGeneProductENSG00000108946 (Ensembl)
PRKAR1BGeneProductENSG00000188191 (Ensembl)
PRKAR2AGeneProductENSG00000114302 (EMBL)
PRKAR2BGeneProductENSG00000005249 (Ensembl)
PhosphatidylethanolamineMetaboliteHMDB60501 (HMDB)
THCMetaboliteHMDB41865 (HMDB)
cAMP MetaboliteHMDB00058 (HMDB)
protein tyrosine kinasesPathway

Annotated Interactions

No annotated interactions

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