Abstract BACKGROUND AND PURPOSE The cannabinoid 1 (CB1) receptor inverse agonists/antagonists, rimonabant (SR141716, SR) and AM251, produce nausea and potentiate toxin-induced nausea by inverse agonism (rather than antagonism) of the CB1 receptor. Here, we evaluated two phytocannabinoids, cannabidivarin (CBDV) and Δ9-tetrahydrocannabivarin (THCV), for their ability to produce these behavioural effect characteristics of CB1 receptor inverse agonism in rats. EXPERIMENTAL APPROACH In experiment 1, we investigated the potential of THCV and CBDV to produce conditioned gaping (measure of nausea-induced behaviour) in the same manner as SR and AM251. In experiment 2, we investigated the potential of THCV and CBDV to enhance conditioned gaping produced by a toxin...

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 Background: Hyperemesis Gravidarum (HG) responds only partially to standard antiemetic medications. Cannabis has been known to possess antiemetic effects and there are several medicinal cannabinoids used as anti -emetics for cancer chemotherapy. Its favorable use for HG has been described in social media, but not in the medical literature. Methods: We evaluated 4 women with HG counseled by the Motherisk Program, before and following the use of cannabis. Using the validated Pregnancy Unique Quantification of Emesis (PUQE) scoring system and employing the Student’s paired t test, we compared changes in symptoms following initiation of cannabis. Results: There was a highly significant improvement in...

Abstract Considerable evidence demonstrates that manipulation of the endocannabinoid system regulates nausea and vomiting in humans and other animals. The anti-emetic effect of cannabinoids has been shown across a wide variety of animals that are capable of vomiting in response to a toxic challenge. CB1 agonism suppresses vomiting, which is reversed by CB1 antagonism, and CB1 inverse agonism promotes vomiting. Recently, evidence from animal experiments suggests that cannabinoids may be especially useful in treating the more difficult to control symptoms of nausea and anticipatory nausea in chemotherapy patients, which are less well controlled by the currently available conventional pharmaceutical agents. Although rats and mice are incapable of...

Abstract Background and purpose: To evaluate the hypothesis that activation of somatodendritic 5-HT(1A) autoreceptors in the dorsal raphe nucleus (DRN) produces the anti-emetic/anti-nausea effects of cannabidiol (CBD), a primary non-psychoactive cannabinoid found in cannabis. Experimental approach: The potential of systemic and intra-DRN administration of 5-HT(1A) receptor antagonists, WAY100135 or WAY100635, to prevent the anti-emetic effect of CBD in shrews (Suncus murinus) and the anti-nausea-like effects of CBD (conditioned gaping) in rats were evaluated. Also, the ability of intra-DRN administration of CBD to produce anti-nausea-like effects (and reversal by systemic WAY100635) was assessed. In vitro studies evaluated the potential of CBD to directly target 5-HT(1A) receptors and...

The present paper describes the historical use of cannabis, starting with its use in Assyria and China. Recent advances in the understanding of the molecular basis of cannabis action are explained, including the identification of the cannabinoid receptors CB(1) and CB(2), as well as the isolation of endogenous cannabinoids from the brain and periphery. The use of delta(9)-tetrahydrocannabinol as an anti-vomiting and anti-nausea drug for cancer chemotherapy, and as an appetite-enhancing agent is described. Clinical work in multiple sclerosis, which may lead to the approval of tetrahydrocannabinol as a drug for this condition, is presented. Preclinical and clinical investigations with cannabidiol, a non-psychotropic cannabis...

Rationale - The interaction between two non-psychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG), which have been reported to act as a 5-hydroxytryptamine 1A (5-HT1A) agonist and antagonist, respectively, was evaluated. Objective - To evaluate the potential of CBG to reverse the anti-nausea, anti-emetic effects of CBD. Materials and methods In experiment 1, rats were pre-treated with CBG (0.0, 1, 5, and 10 mg/kg, ip), 15 min prior to being treated with CBD (experiment 1a: VEH or 5 mg/kg, ip) or 8- OH-DPAT (experiment 1b: VEH or 0.01 mg/kg, ip). Thirty minutes later, all rats received a pairing of 0.1% saccharin solution and LiCl (20...

Abstract Chemotherapy-induced nausea is one of the most distressing symptoms reported by patients undergoing treatment, and even with the introduction of newer antiemetics such as ondansetron and aprepitant, nausea remains problematic in the clinic. Indeed, when acute nausea is not properly managed, the cues of the clinic can become associated with this distressing symptom resulting in anticipatory nausea for which no effective treatments are available. Clinical trials exploring the potential of exogenous or endogenous cannabinoids to reduce chemotherapy-induced nausea are sparse; therefore, we must rely on the data from pre-clinical rat models of nausea. In this review, we explore the human and pre-clinical animal...

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...