Biased agonism refers to the process in which a signaling pathway is chosen for activation over other pathways by a drug. Biased agonism is sometimes also called biased signaling, ligand bias, or functional selectivity. Lysergic acid diethylamide (LSD) is an example of a biased ligand.

Biased agonism refers to a ligand’s ability to trigger a certain signaling pathway. A ligand is a molecule that binds to a receptor in your body. A receptor is a protein that receives information and then acts based on the information it receives. This binding process can be either reversible or irreversible. A ligand can be a hormone, a neurotransmitter, or a drug.

Different ligands react with different receptors. When a ligand shows a high affinity for one receptor over another, this is considered biased agonism.

Since biased ligands are able to activate one pathway over another, they have gained attention for their potential therapeutic properties. Biased agonism is so attractive because it means beneficial pathways are activated, and pathways associated with negative effects are avoided.

Biased Agonism And Hallucinogens

Hallucinogens like mescaline, LSD, and psilocybin all have a high preference for serotonin 5-HT2A receptors. It’s believed that this interaction between psychedelic substances and the serotonin 2A receptors is what actually produces a hallucinogenic experience.

References

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948287/
  2. https://academic.oup.com/ijnp/article/21/10/962/5066769
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756147/
  4. https://www.researchgate.net/figure/Illustration-of-the-biased-agonist-action-of-the-hallucinogenic-5-HT2A-agonists-LSD-and_fig2_262611841
  5. https://www.ncbi.nlm.nih.gov/books/NBK482407/
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549660/
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750957/
  8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756147/
  9. https://www.researchgate.net/publication/345769878_Identification_of_psychedelic_new_psychoactive_substances_NPS_showing_biased_agonism_at_the_5-HT_2A_R_through_simultaneous_use_of_b-arrestin_2_and_miniGa_q_bioassays