Phase I Hydroxylated Metabolites of the K2 Synthetic Cannabinoid JWH-018 Retain In Vitro and In Vivo Cannabinoid 1 Receptor Affinity and Activity
2011

Effects of JWH-018 and Its Metabolites on Cannabinoid Receptors

publication 10 minutes Evidence: moderate

Author Information

Author(s): Lisa K. Brents, Emily E. Reichard, Sarah M. Zimmerman, Jeffery H. Moran, William E. Fantegrossi, Paul L. Prather

Primary Institution: University of Arkansas for Medical Sciences

Hypothesis

The high adverse effect occurrence associated with K2 products is due, at least in part, to distinct JWH-018 metabolite activity at the cannabinoid 1 receptor (CB1R).

Conclusion

JWH-018 and its hydroxylated metabolites retain significant activity at CB1Rs, which may explain the greater prevalence of adverse effects observed with K2 products compared to cannabis.

Supporting Evidence

  • JWH-018 and its metabolites showed high affinity for CB1Rs.
  • The metabolites produced full agonist levels of activation at CB1Rs.
  • JWH-018 and its metabolites caused significant decreases in locomotor activity and core body temperature in mice.

Takeaway

This study found that a synthetic drug called JWH-018 and its breakdown products can strongly affect brain receptors, which might make people feel worse than using regular marijuana.

Methodology

The study used competition binding assays and G-protein activation assays in mouse brain homogenates to evaluate the affinity and efficacy of JWH-018 and its metabolites at CB1Rs.

Limitations

The study primarily focused on in vitro and in vivo effects in mice, which may not fully translate to human responses.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0021917

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