Exogenous delta⁹-tetrahydrocannabinol influences circulating endogenous cannabinoids in humans

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Delta-9-tetrahydrocannabinol (THC) interacts with cannabinoid receptors, potentially altering the endocannabinoid system.
• The endocannabinoid system regulates various biological functions through endogenous cannabinoids like anandamide and 2-arachidonoyl glycerol.

Purpose of the Study:

• To investigate the effects of THC administration on circulating endocannabinoid levels in humans.
• To explore whether exogenous cannabinoids induce adaptive changes in the endocannabinoid signaling cascade.

Main Methods:

• Administered a single 20 mg oral dose of THC to 30 healthy volunteers and measured plasma endocannabinoid concentrations.
• Compared THC effects to placebo and analyzed the relationship between THC and oleoylethanolamide plasma levels.
• Used rats treated with a CB₁/CB₂ agonist (WIN 55,212) to investigate brain region-specific endocannabinoid changes.

Main Results:

• THC administration significantly increased plasma concentrations of anandamide, 2-AG, palmitoylethanolamide, and oleoylethanolamide compared to placebo.
• Plasma oleoylethanolamide levels showed a linear correlation with THC concentrations at 2 hours post-administration.
• WIN 55,212 treatment in rats decreased certain endocannabinoids in brain regions but increased 2-AG in the cortex.

Conclusions:

• THC administration influences circulating endocannabinoid concentrations in humans.
• Exogenous cannabinoids can induce detectable changes in the endocannabinoid system, observable in plasma.
• Findings suggest potential adaptive responses within the endocannabinoid system following exposure to exogenous cannabinoids.