Binding of Δ9-tetrahydrocannabinol and diazepam to human serum albumin

Gabriella Fanali, Yu Cao, Paolo Ascenzi, Viviana Trezza, Tiziana Rubino, Daniela Parolaro, Mauro Fasano

Research output: Contribution to journalArticlepeer-review


Cannabis is the most commonly used illicit drug worldwide. Cannabis users also appear to use other psychoactive drugs more frequently than noncannabis users. Here, Δ9- tetrahydrocannabinol (THC) and diazepam binding to human serum albumin (HSA) and HSA-heme is reported. THC binds to two different binding sites of HSA (Kd1 ≤ 10-7 M and Kd2 = 10-3 M) without affecting diazepam binding (Kd = 1.2 × 10-5 M). THC binding to the high-affinity site accounts for the low free fraction of the drug in plasma. Moreover, THC increases the affinity of heme for HSA. Accordingly, the affinity of THC for HSA-heme is higher than that for HSA. THC could bind to FA2 and FA7 sites, as substantiated by docking simulations; nevertheless, the observed allosteric effect(s) suggests that the primary binding site of THC is the FA2 cleft that positively modulates heme affinity. Possibly, the HSA conformational transition(s) induced by THC binding could account for drug delivery to the liver through receptor-mediated endocytosis.

Original languageEnglish
Pages (from-to)446-451
Number of pages6
JournalIUBMB Life
Issue number6
Publication statusPublished - Jun 2011


  • Δ9-tetrahydrocannabinol binding
  • conformational transition(s)
  • diazepam binding
  • human serum albumin
  • pharmacokinetics
  • poly-drug use

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Clinical Biochemistry
  • Molecular Biology
  • Genetics


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