Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity

Abstract

Limited evidence has suggested that terpenes found in Cannabis sativa are analgesic, and could produce an “entourage effect” whereby they modulate cannabinoids to result in improved outcomes. However this hypothesis is controversial, with limited evidence. We thus investigated Cannabis sativa terpenes alone and with the cannabinoid agonist WIN55,212 using in vitro and in vivo approaches. We found that the terpenes α-humulene, geraniol, linalool, and β-pinene produced cannabinoid tetrad behaviors in mice, suggesting cannabimimetic activity. Some behaviors could be blocked by cannabinoid or adenosine receptor antagonists, suggesting a mixed mechanism of action. These behavioral effects were selectively additive with WIN55,212, suggesting terpenes can boost cannabinoid activity. In vitro experiments showed that all terpenes activated the CB1R, while some activated other targets. Our findings suggest that these Cannabis terpenes are multifunctional cannabimimetic ligands that provide conceptual support for the entourage effect hypothesis and could be used to enhance the therapeutic properties of cannabinoids.

Potential impacts of soil microbiota manipulation on secondary metabolites production in cannabis

“…Cannabis plants have attracted much attention for medical uses due to the importance of secondary metabolites, for which demand increased in the last decade following the discovery of the main compound present in Cannabis sativa — cannabinoids. Cannabinoids, a class of compounds specific to cannabis, are responsible for the vast majority of its medicinal activity (Gaoni and Mechoulam, 1964 ; Gorelick and Bernstein, 2017 ; Freeman, et al, 2019 ; Nelson, et al, 2020 ; LaVigne, et al, 2021 ). Here, we will simplify the potential of microbes for cannabinoid production, and how they could be manipulated for the stabilization of biosynthesis of different cannabinoids.…”

Discovery of Novel Delta Opioid Receptor (DOR) Inverse Agonist and Irreversible (Non-Competitive) Antagonists

“…Radioligand binding was generally carried out as reported in our previous work (e.g., [15,[27][28][29]). Briefly, 30 µg of cell membrane protein was combined with 0.89 nM of 3 Hdiprenorphine (PerkinElmer, #NET1121250UC) and concentration curves of experimental ligand or reference drug (see Figure Legends for details) in a 200 µL reaction volume.…”

Novel Solventless Extraction Technique to Preserve Cannabinoid and Terpenoid Profiles of Fresh Cannabis Inflorescence

“…Two recent studies have demonstrated a lack of interaction among common terpenoids on CB 1 receptors [ 13 , 14 ] but without accounting for other mechanisms of action that might produce such synergy, whether by boosting therapeutic effects or reducing adverse events attributable to THC [ 2 ]. A recent study did show cannabimimetic effects by common cannabis terpenoids [ 15 ] but at concentrations at or above 100 µM. It is highly likely that consumers distinguish differences in the subjective experience that they experience from different cannabis chemovars [ 9 ].…”