The Interplay of Exogenous Cannabinoid Use on Anandamide and 2-Arachidonoylglycerol in Anxiety: Results from a Quasi-Experimental Ad Libitum Study

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 17; no. 10; p. 1335
• Main Authors: Martin-Willett, Renée, Skrzynski, Carillon J., Taylor, Ethan M., Sempio, Cristina, Klawitter, Jost, Bidwell, L. Cinnamon
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.10.2024; MDPI
• Subjects: 2-AG; AEA; Antianxiety agents; Anxiety; Cannabidiol; cannabinoid content; CBD; Chemical properties; Dosage and administration; Enzymes; Lipids; Marijuana; Medical marijuana; Nervous system; Testing; Tetrahydrocannabinol; THC; United States; anxiety; CBD; 2-AG; endocannabinoid system; cannabinoid content; AEA; THC
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph17101335

The public is increasingly reporting using cannabis for anxiety relief. Both cannabis use and the endocannabinoid system have been connected with anxiety relief/anxiolytic properties, but these relationships are complex, and the underlying mechanisms for them are unclear. Background/Objectives: Work is needed to understand how the endocannabinoid system, including the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG), may be impacted by the main constituents of cannabis, Δ9-tetrahydrocannabinol (THC), and cannabidiol (CBD). Methods: The current study examined how the ab libitum use of products differing in THC and CBD affected AEA and 2-AG among 292 individuals randomly assigned to THC-dominant use (N = 92), CBD-dominant use (N = 97), THC + CBD use (N = 74), or non-use (N = 29). Results: The findings suggest that AEA levels do not change differently based on 4 weeks of cannabis use or by cannabinoid content, as AEA similarly increased across all conditions from study weeks 2 to 4. In contrast, AEA decreased at an acute administration session with product conditions containing any THC having greater AEA levels on average than the non-use condition. With regard to 2-AG, its levels appeared to primarily be affected by THC-dominant use, both acutely and over 4 weeks, when controlling for baseline cannabis use and examining study product use frequency among use conditions. Conclusions: Overall, the results continue to shed light on the complicated relationship between cannabinoid content and endocannabinoid production, and highlight the need for continued research on their interplay in human subjects.