Exogenous Delta9-Tetrahydrocannabinol Influences Circulating Endogenous Cannabinoids in Humans

Abstract

Delta⁹-tetrahydrocannabinol (THC) competes with the endogenous cannabinoids arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol (2-AG) at cannabinoid receptors. This may cause adaptive changes in the endocannabinoid signaling cascade with possible consequences for the biological functions of the endocannabinoid system. We show that administration of a single oral dose of 20 mg THC to 30 healthy volunteers resulted in higher circulating concentrations of anandamide, 2-AG, palmitoyl ethanolamide, and oleoylethanolamide at 2 and 3 hours after administration as compared with placebo. At 2 hours after THC administration, changes in oleoylethanolamide plasma concentrations from baseline were linearly related to the THC plasma concentrations. In rats, treatment with the CB₁/CB₂ agonist WIN 55,212 also increased plasma endocannabinoid concentrations. However, this was associated with a decrease of ethanolamide endocannabinoids in specific brain regions including spinal cord, cortex, and hypothalamus; whereas 2-arachidonoyl glycerol increased in the cortex. Thus, administration of THC to human volunteers influenced the concentrations of circulating endocannabinoids, which was mimicked by WIN-55,212 in rats, suggesting that exogenous cannabinoids may lead to changes in the endocannabinoid system that can be detected in plasma.

Disrupted Gamma-Band Neural Oscillations During Coherent Motion Perception in Heavy Cannabis Users

“…effect was corroborated in a second experiment in rats with the synthetic cannabinoid WIN-55,212 (Walter et al, 2013). However, the fact that the present study examined induced gamma oscillations at a mean of 42.9 h after last cannabis exposure makes this mechanism unlikely.…”

“…First, as THC competes with endocannabinoid transmitters at the CB1R, recent cannabis exposure may cause a compensatory increase in the synthesis and release of endocannabinoids such as anandamide and 2-arachidonoyl glycerol (2-AG). Indeed, a recent study in humans demonstrated that a single oral dose of 20 mg THC resulted in significant increases in anandamide, 2-AG, palmitoyl ethanolamide, and oleoylethanolamide for several hours after administration (Walter et al, 2013). This Figure 2 Grand-averaged time  frequency plots demonstrating mean trial power (MTP) for midline electrodes during the incoherent motion condition for the healthy control and cannabis groups.…”

Fatty Acid-binding Proteins (FABPs) Are Intracellular Carriers for Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD)

“…A recent study reported that CBD alleviates the psychotic symptoms of schizophrenia, possibly in part by elevating levels of AEA and N-acylethanolamines in humans (17). Another report showed that administration of a single oral dose of 20 mg of THC to 30 healthy volunteers resulted in higher circulating concentrations of anandamide, 2-AG, palmitoyl ethanolamide, and oleoylethanolamide (61). Therefore, it is tempting to speculate that phytocannabinoids modulate the endocannabinoid tone by targeting FABPs in humans (Fig.…”

Brain Mapping-Based Model of Δ9-Tetrahydrocannabinol Effects on Connectivity in the Pain Matrix

“…Measurements took place before (baseline) and 2 h post medication (THC or placebo) when maximum pharmacological effects were expected (Hollister et al, 1981). During measurements after THC administration, plasma concentrations of THC and its metabolites THC-OH and THC-COOH were 6.4 ± 3.9 ng/ml, 6 ± 3.2 ng/ml, and 43.3 ± 20.2 ng/ml (mean ± standard deviation), respectively (for further details, see Walter et al, 2013).…”