Cannabinoid system
The endocannabinoid system developed 500 million years ago.1 It goes back to the unicellular common ancestor of animals and plants, as the metabolic apparatus for building up and breaking down these lipids can be found throughout the animal kingdom. This is unique among neurotransmitter systems.
Endocannabinoids, i.e. cannabinoids produced by the body itself, act as neurotransmitters. The cannabinoid 1 receptor (CB1R) is closely linked to the ADHD symptoms of hyperactivity and impulsivity. CB2R is closely linked to the immune system.
The endocannabinoid system was only discovered in 1992.23
In the meantime, an extended cannabinoid system has been described, the endocannabinoidome.456 Its endocannabinoid-like mediators are not part of the cannabinoid system in the narrower sense.
We have not yet found any other neurotransmitter system that is as closely linked to the dopamine system as the endocannabinoid system.
We recommend reading the very comprehensive review by Kumar from 2024.7
Sagheddu C, Muntoni AL, Pistis M, Melis M (2015): Endocannabinoid Signaling in Motivation, Reward, and Addiction: Influences on Mesocorticolimbic Dopamine Function. Int Rev Neurobiol. 2015;125:257-302. doi: 10.1016/bs.irn.2015.10.004. PMID: 26638769. REVIEW ↥
Parrella NF, Hill AT, Enticott PG, Barhoun P, Bower IS, Ford TC (2023): A systematic review of cannabidiol trials in neurodevelopmental disorders. Pharmacol Biochem Behav. 2023 Aug 3:173607. doi: 10.1016/j.pbb.2023.173607. PMID: 37543051. ↥
Di Marzo V, Melck D, Bisogno T, De Petrocellis L (1998): Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action. Trends Neurosci. 1998 Dec;21(12):521-8. doi: 10.1016/s0166-2236(98)01283-1. Erratum in: Trends Neurosci 1999 Feb;22(2):80. PMID: 9881850. REVIEW ↥
Di Marzo V (2020): The endocannabinoidome as a substrate for noneuphoric phytocannabinoid action and gut microbiome dysfunction in neuropsychiatric disorders . Dialogues Clin Neurosci. 2020 Sep;22(3):259-269. doi: 10.31887/DCNS.2020.22.3/vdimarzo. PMID: 33162769; PMCID: PMC7605024. REVIEW ↥
Cristino L, Bisogno T, Di Marzo V (2020): Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nat Rev Neurol. 2020 Jan;16(1):9-29. doi: 10.1038/s41582-019-0284-z. PMID: 31831863. REVIEW ↥
Veilleux A, Di Marzo V, Silvestri C (2019): The Expanded Endocannabinoid System/Endocannabinoidome as a Potential Target for Treating Diabetes Mellitus. Curr Diab Rep. 2019 Nov 4;19(11):117. doi: 10.1007/s11892-019-1248-9. PMID: 31686231. REVIEW ↥
Kumar U (2024): Cannabinoids: Role in Neurological Diseases and Psychiatric Disorders. Int J Mol Sci. 2024 Dec 27;26(1):152. doi: 10.3390/ijms26010152. PMID: 39796008; PMCID: PMC11720483. REVIEW ↥