Education

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Receptors and channels

Cannabinoids produce effects through a variety of binding places in the body. These binding places is where certain processes occur, which lead to different effects by, for example, activating molecules, or letting ions flow. These binding places are called receptors and ion channels, and there are different types of each. In this chapter, we will describe a few important ones that are relevant for cannabis and the endocannabinoid system: G-coupled protein receptors and ion channels. Binding to or activation of these triggers different effects in our bodies.

G-protein coupled receptors (GPCRs)

G-protein coupled receptors are a family of proteins that detect specific molecules outside of a cell and, upon binding, activate a signaling pathway inside the cell. Important cannabis molecules exert many pharmacological effects by binding and interacting with the GPCRs cannabinoid receptors type 1 and 2 (CB1 and CB2).1, 2, 3 There are also other GPCRs that cannabinoids act upon, including the serotonin receptor, β-adrenergic receptor, and µ-opioid receptor, but these interactions are studied less thoroughly.4, 5

Transient receptor potential (TRP) channels

Besides GCP-receptors, cannabinoids also bind to ion channels, which are pore-shaped proteins in a cell membrane that allow ions {call-out, text:Electrically charged particles} to pass through. This ion movement influences electrical signals that allow communication between cells and thereby effects. One of these ion channels is the Transient Receptor Potential Vanilloid-1 (TRPV-1) channel, belonging to the family of transient receptor potential (TRP) channels. Through TRPV-1, cannabinoids can affect the sensation of pain.6, 7, 8 This channel might be familiar to you under the name capsaicin receptor, and is, indeed, the place that is activated by the hot chili pepper molecule capsaicin as well. Watch a brief summary video about CB1 and CB2 made in collaboration with Enlighten on YouTube or on the screens page. References:
  1. Grotenhermen, Franjo.; Russo, Ethan. (2002). Cannabis and cannabinoids : pharmacology, toxicology, and therapeutic potential. Haworth Integrative Healing Press.
  2. Grotenhermen, Franjo (2003). Clinical Pharmacokinetics of Cannabinoids. Journal of Cannabis Therapeutics, 3(1), 3--51.
  3. Grotenhermen, Franjo (2004). Clinical Pharmacodynamics of Cannabinoids. Journal of Cannabis Therapeutics, 4(1), 29--78.
  4. Mallipeddi, Srikrishnan; Janero, David R.; Zvonok, Nikolai; Makriyannis, Alexandros (2017). Functional selectivity at G-protein coupled receptors: Advancing cannabinoid receptors as drug targets. Biochemical Pharmacology, 128, 1--11.
  5. Pertwee, Roger G. (2014). Handbook of Cannabis. Handbooks in Psychopharmacology, 44(8), 085201.
  6. Costa, Barbara; Giagnoni, Gabriella; Franke, Chiara; Trovato, Anna Elisa; Colleoni, Mariapia (2004). Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation. British Journal of Pharmacology, 143(2), 247--250.
  7. De Petrocellis, Luciano; Ligresti, Alessia; Moriello, Aniello Schiano; Allarà, Marco; Bisogno, Tiziana; Petrosino, Stefania; Stott, Colin G.; Di Marzo, Vincenzo (2011). Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. British Journal of Pharmacology, 163(7), 1479--1494.
  8. Lowin, Torsten; Straub, Rainer H. (2015). Cannabinoid-based drugs targeting CB1 and TRPV1, the sympathetic nervous system, and arthritis. Arthritis Research & Therapy, 17(1), 226.