Motion Sickness, Stress and the Endocannabinoid System

Abstract

BackgroundA substantial number of individuals are at risk for the development of motion sickness induced nausea and vomiting (N&V) during road, air or sea travel. Motion sickness can be extremely stressful but the neurobiologic mechanisms leading to motion sickness are not clear. The endocannabinoid system (ECS) represents an important neuromodulator of stress and N&V. Inhibitory effects of the ECS on N&V are mediated by endocannabinoid-receptor activation.Methodology/Principal FindingsWe studied the activity of the ECS in human volunteers (n = 21) during parabolic flight maneuvers (PFs). During PFs, microgravity conditions (<10−2 g) are generated for approximately 22 s which results in a profound kinetic stimulus. Blood endocannabinoids (anandamide and 2-arachidonoylglycerol, 2-AG) were measured from blood samples taken in-flight before start of the parabolic maneuvers, after 10, 20, and 30 parabolas, in-flight after termination of PFs and 24 h later. Volunteers who developed acute motion sickness (n = 7) showed significantly higher stress scores but lower endocannabinoid levels during PFs. After 20 parabolas, blood anandamide levels had dropped significantly in volunteers with motion sickness (from 0.39±0.40 to 0.22±0.25 ng/ml) but increased in participants without the condition (from 0.43±0.23 to 0.60±0.38 ng/ml) resulting in significantly higher anandamide levels in participants without motion sickness (p = 0.02). 2-AG levels in individuals with motion sickness were low and almost unchanged throughout the experiment but showed a robust increase in participants without motion sickness. Cannabinoid-receptor 1 (CB1) but not cannabinoid-receptor 2 (CB2) mRNA expression in leucocytes 4 h after the experiment was significantly lower in volunteers with motion sickness than in participants without N&V.Conclusions/SignificanceThese findings demonstrate that stress and motion sickness in humans are associated with impaired endocannabinoid activity. Enhancing ECS signaling may represent an alternative therapeutic strategy for motion sickness in individuals who do not respond to currently available treatments.

Variants in the CNR1 gene predispose to headache with nausea in the presence of life stress

“…It is interesting to note, that migraineurs are more susceptible to motion sickness than controls probably due to the ineffective top‐down control on relevant brainstem areas in response to excessive or stressful sensory inputs (Cuomo‐Granston & Drummond 2010). Regarding motion sickness, it has been demonstrated that those who respond with acute motion sickness to parabola flight have significantly higher stress scores accompanied by increased salivary cortisol concentration, lower whole blood endocannabinoid levels and decreased CB1 mRNA leukocyte expression compared to those with no motion sickness (Chouker et al 2010). …”

Effects of parabolic flight and spaceflight on the endocannabinoid system in humans

“…Those severe, fast-changing conditions heavily impact on the human sense of balance, leaving the subjects with only little control of their well-being and no possibility to escape the situation and therefore causing acute stress (Schneider et al, 2007(Schneider et al, , 2009Chouker et al, 2010).…”

“…On the ISS, blood vials were stored at -80 ° C until downloaded to Earth and analyzed ( Figure 5 ). The details of the high-performance liquid chromatography tandem mass spectrometry technique used for EC quantification are described elsewhere (Vogeser et al, 2006;Chouker et al, 2010).…”

“…Free cortisol was quantified by an automated immunoassay system based on the principle of electrochemiluminescence (Elecsys Cortisol, Roche Diagnostics, Mannheim, Germany; Chouker et al, 2010). During the PFC, salivary and blood samples were taken at the time points T0 -T5 [inflight before the start of the parabolic maneuvers (T0); after 10 (T1), 20 (T2), and 30 (T3) parabolas; in-flight after the end of the parabolic maneuvers (T4); and 24 h later (T5)].…”

Diagnostic Value of Concentration Profiles of Glucocorticosteroids and Endocannabinoids in Hair

“…27 A recent study has suggested a negative relationship between the concentrations of plasma endocannabinoids and the activity of the HPA axis in stressed humans. 36 Several studies in animals have shown that increased glucocorticoid concentrations in several stress-activated brain areas were associated with reduced AEA concentrations in these regions. 37,38 In this work, a validated analytical method to detect cortisol, cortisone, AEA, and 2AG in hair samples is presented.…”