Cannabinoid receptor signaling (Homo sapiens)

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CYP3A4 CYP2C19 PKA regulatory subunit type I Relevant MAPK subtypes PKA catalytic subunit endogenous cannabinoids CBD catabolism PKA regulatory subunit type II Neuronal cell of CNS (hyppocampus, cerebellum or basal ganglia) inactive Inhibition of Glutamate or GABA release in synaptic cleft Leukocytes, spleen, thymus, bone marrow and other tissues associated with immune functions HepG2 cells ADCY1 MAPK11 MAPK9 MAPK10 MAPK14 MAPK8 MAPK12 MAPK3 MAPK1 MAPK13 PRKACB PRKACA PRKAR1A PRKAR2B PRKAR1B PRKACG PRKAR2A CNR1 CYP2C9 11-OH-THC MAPK Phosphatidylethanolamine DAGLB DAGLA cAMP AHR NAPEPLD ADCY7 NAPE Arachidonic acid THC 1''-hydroxycannabidiol 2''-hydroxycannabidiol 3''-hydroxycannabidiol 4''-hydroxycannabidiol 5''-hydroxycannabidiol 6a-hydroxycannabidiol 6b-hydroxycannabidiol 7-hydroxycannabidiol 2-arachidonoylglycerol AEA protein tyrosine kinases FAAH Glutamate ADORA2A CNR2 Calcium GABA CBD ATP Anti-inflammatory pathways COOH-THC CYP1A1 ATP cAMP CBD endogeneous cannabinoid synthesis PKA regulatory subunit type I PKA catalytic subunit PKA regulatory subunit type II PRKACB PRKACA PRKAR1A PRKAR2B PRKAR1B PRKACG PRKAR2A Name: Cannabinoid receptor signaling Organism: Homo sapiens


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. Source:

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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Ontology Terms



  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. Anderson GD, Chan LN; ''Pharmacokinetic Drug Interactions with Tobacco, Cannabinoids and Smoking Cessation Products.''; Clin Pharmacokinet, 2016 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.; ''''; ,
  5. 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
  6. 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
  7. 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
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97566view 00:39, 25 May 2018IreneHemelModified description
97565view 00:39, 25 May 2018IreneHemelModified description
97564view 00:36, 25 May 2018IreneHemelAddition of relevant MAPK subtypes
97536view 07:31, 24 May 2018IreneHemelSubunits PKA
94926view 04:40, 13 October 2017DeSlOntology Term : 'xenobiotic metabolic pathway' added !
94925view 04:38, 13 October 2017DeSladded ID for 2nd PKA node
94924view 04:37, 13 October 2017DeSladded ID for PKA
94923view 04:36, 13 October 2017DeSladded ID for MAPK
88989view 04:44, 18 August 2016Mkutmonremoved comments
88980view 02:30, 18 August 2016Fehrhartfixed some weird characters
88978view 02:18, 18 August 2016Fehrhartadjusted some lines and added descriptions
88975view 02:12, 18 August 2016Fehrhartaddition of OH-CBDs
88973view 01:36, 18 August 2016FehrhartModified description
88834view 06:13, 15 August 2016Fehrhartwork in progress
88833view 06:10, 15 August 2016FehrhartModified description
88598view 12:51, 11 August 2016Mkutmonfix unconnected lines
88457view 07:38, 9 August 2016Fehrhartwork in progress
88450view 08:07, 8 August 2016Fehrhartwork in progress
88449view 08:02, 8 August 2016Fehrhartadded CYP1A1 stimulation pathway
88389view 06:24, 3 August 2016FehrhartOntology Term : 'leukocyte' added !
88388view 06:24, 3 August 2016FehrhartOntology Term : 'neuron' added !
88387view 06:23, 3 August 2016FehrhartOntology Term : 'cannabinoid signaling pathway' added !
88386view 06:22, 3 August 2016FehrhartWork in progress
88383view 05:53, 3 August 2016FehrhartNew pathway

External references


View all...
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

<cite>No annotated interactions</cite>