BACKGROUND AND PURPOSE To determine the minimally effective dose of cannabidiolic acid (CBDA) that effectively reduces lithium chloride (LiCl)-induced conditioned gaping reactions (nausea-induced behaviour) in rats and to determine if these low systemic doses of CBDA (5–0.1 mg·kg-1 ) relative to those of CBD could potentiate the anti-nausea effects of the classic 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, ondansetron (OND).   EXPERIMENTAL APPROACH We investigated the efficacy of low doses of CBDA to suppress acute nausea, assessed by the establishment of conditioned gaping to a LiCl-paired flavour in rats. The potential of threshold and subthreshold doses of CBDA to enhance the reduction of nausea-induced conditioned...

ABSTRACT: As a complement to vaccines, small-molecule therapeutic agents are needed to treat or prevent infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants, which cause COVID-19. Affinity selection−mass spectrometry was used for the discovery of botanical ligands to the SARS-CoV-2 spike protein. Cannabinoid acids from hemp (Cannabis sativa) were found to be allosteric as well as orthosteric ligands with micromolar affinity for the spike protein. In follow-up virus neutralization assays, cannabigerolic acid and cannabidiolic acid prevented infection of human epithelial cells by a pseudovirus expressing the SARS-CoV-2 spike protein and prevented entry of live SARS-CoV-2 into cells. Importantly, cannabigerolic acid and...

ABSTRACT   Cannabis sativa produces a complex mixture of many bioactive molecules including terpenophenolic compounds known as phytocannabinoids. Phytocannabinoids come in neutral forms (e.g., Δ9 - tetrahydrocannabinol, THC; cannabidiol, CBD; etc.) or as acid precursors, which are dominant in the plant (e.g., Δ9 -tetrahydrocannabinolic acid, THCA; cannabidiolic acid, CBDA; etc.). There is increasing interest in unlocking the therapeutic applications of the phytocannabinoid acids; however, the present understanding of the basic pharmacology of phytocannabinoid acids is limited. Herein the brain and plasma pharmacokinetic profiles of CBDA, THCA, cannabichromenic acid (CBCA), cannabidivarinic acid (CBDVA), cannabigerolic acid (CBGA), and cannabigerovarinic acid (CBGVA) were examined following intraperitoneal administration...

Abstract   Cannabidiolic acid (CBDA) is the main phytocannabinoid in fiber and seed-oil hemp (Cannabis sativa L.) plants, but its potential health-related capabilities have been masked for years by a greater scientific interest towards its neutral derivative cannabidiol (CBD). This review aims to collect from the literature and critically discuss all the information about this molecule, starting from its biosynthesis, and focusing on its bioactivity, as an anti-inflammatory, anti-emetic, anti-convulsant, and anti-cancerogenic drug. Furthermore, in the awareness that, despite its multiple bioactive effects, currently poor efforts have been made to achieve its reliable purification, herein, we propose a relatively simple, fast, and inexpensive procedure for...

ABSTRACT:   In the present study it was revealed that cannabidiolic acid (CBDA) selectively inhibited cyclooxygenase (COX)-2 activity with an IC50 value (50% inhibition concentration) around 2 􏰀M, having 9-fold higher selectivity than COX-1 inhibition. In contrast, 􏰁9-tetrahydro- cannabinolic acid (􏰁9-THCA) was a much less potent inhibitor of COX-2 (IC50 > 100 􏰀M). Nonsteroidal anti-inflammatory drugs con- taining a carboxyl group in their chemical structures such as salicylic acid are known to inhibit nonselectively both COX-1 and COX-2. CBDA and 􏰁9-THCA have a salicylic acid moiety in their structures. Thus, the structural requirements for the CBDA- mediated COX-2 inhibition were next studied. There is...

Abstract: The cellular microenvironment plays a critical role in the maintenance of bone marrow-derived mesenchymal stem cells (BM-MSCs) and their subsequent cell lineage differentiation. Recent studies suggested that individuals with adipocyte-related metabolic disorders have altered function and adipogenic potential of adipose stem cell subpopulations, primarily BM-MSCs, increasing the risk of heart attack, stroke or diabetes. In this study, we explored the potential therapeutic effect of some of the most abundant non-euphoric compounds derived from the Cannabis sativa plant (or phytocannabinoids) including tetrahydrocannabivarin (THCV), cannabidiol (CBD), cannabigerol (CBG), cannabidiolic acid (CBDA) and cannabigerolic acid (CBGA), by analysing their pharmacological activity on viability of endogenous BM-MSCs...

Abstract Background and purpose: To evaluate the ability of cannabidiolic acid (CBDA) to reduce nausea and vomiting and enhance 5-HT(1A) receptor activation in animal models. Experimental approach: We investigated the effect of CBDA on (i) lithium chloride (LiCl)-induced conditioned gaping to a flavour (nausea-induced behaviour) or a context (model of anticipatory nausea) in rats; (ii) saccharin palatability in rats; (iii) motion-, LiCl- or cisplatin-induced vomiting in house musk shrews (Suncus murinus); and (iv) rat brainstem 5-HT(1A) receptor activation by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and mouse whole brain CB(1) receptor activation by CP55940, using [³⁵S]GTPγS-binding assays. Key results: In shrews, CBDA (0.1 and/or 0.5 mg·kg⁻¹ i.p.) reduced toxin- and motion-induced...