Orally Active Peptide Vector Allows Using Cannabis to Fight Pain While Avoiding Side Effects.

ABSTRACT: The activation of cannabinoid CB₁ receptors (CB₁R) by Δ⁹-tetrahydrocannabinol (THC), the main component of Cannabis sativa, induces analgesia. CB₁R activation, however, also causes cognitive impairment via the serotonin 5HT_2A receptor (5HT_2AR), a component of a CB₁R-5HT_2AR heteromer, posing a serious drawback for cannabinoid therapeutic use. We have shown that peptides reproducing CB₁R transmembrane (TM) helices 5 and 6, fused to a cell-penetrating sequence (CPP), can alter the structure of the CB₁R-5HT_2AR heteromer and avert THC cognitive impairment while preserving analgesia. Here, we report the optimization of these prototypes into drug-like leads by (i)

SUBMITTER: Gallo M 

PROVIDER: S-EPMC8486167 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature