The Effects of Cannabidiol and Tetrahydrocannabinol on Motion‐Induced Emesis in Suncus murinus

Abstract

The effect of cannabinoids on motion-induced emesis is unknown. The present study investigated the action of phytocannabinoids against motion-induced emesis in Suncus murinus . Suncus murinus were injected intraperitoneally with either cannabidiol (CBD) (0.5, 1, 2, 5, 10, 20 and 40 mg/kg), ∆ 9 -tetrahydrocannabinol ( ∆ 9 -THC; 0.5, 3, 5 and 10 mg/kg) or vehicle 45 min. before exposure to a 10-min. horizontal motion stimulus (amplitude 40 mm, frequency 1 Hz). In further investigations, the CB 1 receptor antagonist, N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1 Hpyrazole-3-carboxamide (AM 251; 5 mg/kg), was injected 15 min. prior to an injection of ∆ 9 -THC (3 mg/kg). The motion stimulus was applied 45 min. later. The number of emetic episodes and latency of onset to the first emetic episode were recorded. Pre-treatment with the above doses of CBD did not modify the emetic response to the motion stimulus as compared to the vehicle-treated controls. Application of the higher doses of ∆ 9 -THC induced emesis in its own right, which was inhibited by AM 251. Furthermore, pre-treatment with ∆ 9 -THC dose-dependently attenuated motion-induced emesis, an effect that was inhibited by AM 251. AM 251 neither induced an emetic response nor modified motion-induced emesis. The present study indicates that ∆ 9 -THC, acting via the CB 1 receptors, is anti-emetic to motion, and that CBD has no effect on motion-induced emesis in Suncus murinus .The signs and symptoms of motion sickness including vomiting, nausea, pallor and general malaise are seen, to some degree, in most people on sufficient exposure to a motion stimulus [1]. As such, motion sickness is a significant problem not only in civilian transport, but also in military training and travel, and also in space travel. The most widely accepted hypothesis regarding the initiation of motion sickness is the sensory conflict or sensory mismatch theory [2].It is proposed that sensory conflict occurs when vestibular, visual and non-vestibular information from somatosensory receptors concerning motion and balance of the body do not relate to each other or to what is anticipated from previous exposure; this leads to motion sickness. The neuronal pathways and the degree of their involvement in the mediation of motion sickness are not fully known. Experiments involving deaf-mutes [3] were the first to show that a functional vestibular system is critical for the development of motion sickness. This was confirmed when labyrinthine-defective individuals [4,5] and labyrinthectomized dogs [6] were shown to possess a total immunity to seasickness. Following discrete removal of the area postrema (the chemosensitive trigger zone for emesis), it was demonstrated that although this structure is involved in the development of motion-induced emesis, it is not an essential component [7]. The vestibulocerebellum conveys information from the vestibular system regarding the position of the head and is involved in the generation of reflex eye movements and changes in ...

Regulation of nausea and vomiting by cannabinoids

“…potentiating toxin‐induced vomiting in the S. murinus (Parker et al ., 2004; Kwiatkowska et al ., 2004), but a dose as high as 20 mg·kg −1 of CBD had no effect on 2‐AG‐induced emesis in the least shrew (Darmani, 2002). A wide range of doses was not effective in reducing motion‐induced emesis in the S. murinus (Cluny et al ., 2008), which may reflect a different mechanism of action of motion and toxin‐induced vomiting (Cluny et al ., 2008).…”

Mechanisms of Broad-Spectrum Antiemetic Efficacy of Cannabinoids against Chemotherapy-Induced Acute and Delayed Vomiting

“…2-methylserotonin) and nonselective (e.g. 5-HT) 5-HT 3 receptor agonists [80]; (iv) the DA precursor L-DOPA and the dopaminergic D 2 /D 3 –receptor selective (quinpirole, quinelorane or 7-(OH) DPAT) and nonselective (apomorphine) agonists [108,109]; (v) the endocannabinoid 2-AG [11]; (vi) arachidonic acid [11]; (vii) radiation [110]; (viii) SP [111]; (ix) morphine or morphine-6-glucuronide [6,112]; (x) motion [113]; and (xi) Staphylococcus enterotoxin [114]. Cannabinoids’ broad-spectrum antiemetic properties against the miscellaneous central- and peripheral-acting emetogens in general, and their effectiveness against both acute- and delayed-phase CINV in animals [5] and cancer patients [107], propels this class of agonist antiemetics to the forefront of research in terms of mechanisms of action as well as sites of action.…”

Tetrahydrocannabinolic acid reduces nausea‐induced conditioned gaping in rats and vomiting in Suncus murinus

“…In animal models, THC reduces vomiting in ferrets (Van Sickle et al ., ) and has been shown to suppress acute vomiting induced by cisplatin (Darmani, ), SR141716 (SR), a cannabinoid 1 (CB 1 ) receptor antagonist (Darmani, ), radiation (Darmani et al ., ) and 5‐hydroxytryptophan (an indirect 5‐HT receptor agonist, Darmani and Johnson, ) in Cryptotis parva (least shrews), a well‐established animal model for assessing vomiting (see Darmani, ). In another animal model for assessing vomiting, Suncus murinus (house musk shrew), THC reduces cisplatin‐ (Kwiatkowska et al ., ), LiCl‐ (Parker et al ., ) and motion‐induced vomiting (Cluny et al ., ). Additionally, the administration of THC prior to reintroduction to a context previously associated with illness suppressed the expression of conditioned retching in shrews (Parker and Kemp, ; Parker et al ., ).…”