Metabolism Altered Convulsive Effects Differently for Two Synthetic Cannabinoids
Two synthetic cannabinoids did not respond identically to a metabolic inhibitor in a mouse experiment. The difference is a reason to avoid treating every synthetic cannabinoid as pharmacologically interchangeable.
The study compared specific compounds
Researchers scored observed convulsive effects of JWH-018 and 5F-AB-PINACA, with THC and pentylenetetrazole included as comparisons. THC did not elicit convulsions in the reported conditions, whereas the two synthetic agonists did. That is an observation about this experiment, not a universal statement about all exposures.
Metabolic inhibition produced a selective finding
Nonselective CYP450 inhibition protected against the convulsive effects of JWH-018 but not those of 5F-AB-PINACA or pentylenetetrazole. Human liver-microsome work also showed a difference in oxidative elimination between the two synthetic cannabinoids.
Receptor and metabolism evidence answer different questions
Rimonabant and selected cannabinoid pretreatments attenuated the synthetic-cannabinoid effects without changing the pentylenetetrazole effects. The findings support receptor involvement while showing that metabolism can modify the outcome for one compound more than another.
The behavioral rating does not itself establish an EEG-confirmed seizure. The microsome experiments are laboratory metabolism studies, not measurements of concentrations in an affected patient. The reported diazepam findings should not be used to dictate emergency treatment in people. A clinical or forensic interpretation requires the actual substance and observed syndrome rather than a generic label such as Spice or cannabis.
Related: interpreting cannabis tolerance claims.
Research cited
Wilson CD; Tai S; Ewing L; Crane J; Lockhart T; Fujiwara R; Radominska-Pandya A; Fantegrossi WE. Convulsant Effects of Abused Synthetic Cannabinoids JWH-018 and 5F-AB-PINACA Are Mediated by Agonist Actions at CB1 Receptors in Mice. The Journal of pharmacology and experimental therapeutics (2019). doi:10.1124/jpet.118.251157. Findings discussed from the study abstract.
