Effects of super-class cannabis terpenes beta-caryophyllene and alpha-pinene on zebrafish behavioural biomarkers

Abstract

Terpenes possess a wide range of medicinal properties and are potential therapeutics for a variety of pathological conditions. This study investigated the acute effects of two cannabis terpenes, β-caryophyllene and α-pinene, on zebrafish locomotion, anxiety-like, and boldness behaviour using the open field exploration and novel object approach tests. β-caryophyllene was administered in 0.02%, 0.2%, 2.0%, and 4% doses. α-pinene was administered in 0.01%, 0.02%, and 0.1% doses. As α-pinene is a racemic compound, we also tested its (+) and (−) enantiomers to observe any differential effects. β-caryophyllene had only a sedative effect at the highest dose tested. α-pinene had differing dose-dependent effects on anxiety-like and motor variables. Specifically, (+)-α-pinene and (−)-α-pinene had significant effects on anxiety measures, time spent in the thigmotaxis (outer) or center zone, in the open field test, as well as locomotor variables, swimming velocity and immobility. (+ /−)-α-pinene showed only a small effect on the open field test on immobility at the 0.1% dose. This study demonstrates that α-pinene can have a sedative or anxiolytic effect in zebrafish and may have different medicinal properties when isolated into its (+) or (−) enantiomers.

Chemical Composition of Commercial Cannabis

“…Our terpenoid analysis demonstrated that the six cultivars have very different terpenoid compositions, which could explain the varied aromas and flavors associated with each cultivar (Table ). The values found with these cannabis terpenoids agree with those published elsewhere. , …”

“…The values found with these cannabis terpenoids agree with those published elsewhere. 55,56 For the untargeted GC−MS terpenoid assay, the analytes were putatively identified at a confidence level of two. The identification criteria were based on a combination of the RIs and matching the experimental electron impact (EI)−MS fragmentation patterns of the corresponding compounds with the EI−MS spectra in the NIST20 GC−MS library.…”

Beta-Caryophyllene, a Cannabinoid Receptor Type 2 Selective Agonist, in Emotional and Cognitive Disorders

“…When used in zebrafish behavioral assays, including an open field-exploration test and a novel object approach test, BCP revealed no effect on anxiety and swimming velocity, while decreasing immobility ( Table 1 ). BCP had only a sedative effect at the highest dose tested [ 109 ]. Taken together, the results of this study indicated a potential dose-dependent downward trend in anxiety levels, which may require an increased dosage.…”

“… Mice DSS-induced anxiety ↓ Anxiety [ 108 ] BCP (chronic; 0.02, 0.2, 2, 4%; p.o. in dosing beaker) Zebrafish Acute stress ↓ Immobility at the highest dose used (i.e., 4%) No effect on anxiety [ 109 ] BCP (chronic; 10 mg/kg; p.o.) BALB/c mice STZ-induced diabetes ↓ Depressive-like behavior ↓ IL-1β ↓ TNFα ↓ IL-6 [ 110 ] …”

Antitumor Effects of Cannabis sativa Bioactive Compounds on Colorectal Carcinogenesis

“…Particularly in C. sativa, Chacon and coworkers found that terpenes may vary between 0.001 and 14.8 mg/g of the dry weight of the plant [39] and are in general rich in mono-and sesquiterpenes [34]. Monoterpenes, structurally characterized by a skeleton with two molecules of isoprene, are more volatile and contribute to the flavor and aroma of the plant, while sesquiterpenes (structure containing three molecules of isoprene) are more stable and contribute to the therapeutical benefits of the plant [40]. The monoterpene β-myrcene and the sesquiterpenes β-caryophyllene and α-humulene have been identified in most cannabis species, including C. sativa.…”