The chemistry and pharmacology of synthetic cannabinoid receptor agonists as new psychoactive substances: evolution

Samuel D. Banister, Mark Connor

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Synthetic cannabinoid receptor agonists (SCRAs) are the largest and most structurally diverse class of new psychoactive substances (NPS). Although the earliest SCRA NPS were simply repurposed from historical academic manuscripts or pharmaceutical patents describing cannabinoid ligands, recent examples bear hallmarks of rational design. SCRA NPS manufacturers have applied traditional medicinal chemistry strategies (such as molecular hybridization, bioisosteric replacement, and scaffold hopping) to existing cannabinoid templates in order to generate new molecules that circumvent structure-based legislation. Most SCRAs potently activate cannabinoid type 1 and type 2 receptors (CB1 and CB2, respectively), with the former contributing to the psychoactivity of these substances. SCRAs are generally more toxic than the Δ9-tetrahydrocannabinol (Δ9-THC) found in cannabis, and this may be due to ligand bias, metabolism, or off-target activity. This chapter will chart the evolution of recently identified SCRA NPS chemotypes, as well as their putative manufacturing by-products and thermolytic degradants, and describe structure-activity relationships within each class.
Original languageEnglish
Title of host publicationNew psychoactive substances
Subtitle of host publicationpharmacology, clinical, forensic and analytical toxicology
EditorsHans H. Maurer, Simon D. Brandt
Place of PublicationCham
PublisherSpringer, Springer Nature
Number of pages36
ISBN (Electronic)9783030105617
ISBN (Print)9783030105600
Publication statusPublished - 2018

Publication series

NameHandbook of Experimental Pharmacology
PublisherSpringer Nature
ISSN (Print)1865-0325
ISSN (Electronic)0171-2004


  • Δ9 -Tetrahydrocannabinol
  • Cannabinoid
  • CP 55,940
  • JWH-018
  • NPS
  • XLR-11


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