Promethazine Effects on Motion Sickness During Altered Gravity Induced by Parabolic Flight
INTRODUCTION: Astronauts commonly experience space motion sickness, which can impair astronaut performance and safety. Pharmaceuticals are frequently used to reduce space motion sickness symptoms but have not been extensively studied in partial gravity. In this research effort, we investigated the impact of oral promethazine on motion sickness during parabolic flight.
METHODS: We collected motion sickness scores from 12 subjects (6 women) during parabolic flight. Each subject participated in two flights—one 0-G flight and one partial g flight—experiencing 10 parabolas at 0 g, 0.25 g, 0.50 g, and 0.75 g. Half of the subjects, counterbalanced by gender, were given 25 mg of oral promethazine before flight and the other half were given a placebo. Motion sickness scores were collected preflight/postflight and during flight.
RESULTS: Pensacola Motion Sickness Questionnaire scores for the placebo group increased from 2.0 (1.55) preflight to 9.17 (5.42) postflight for the 0-G flight, but not for the partial g flight. Subjects in the placebo group reported motion sickness for 51.8% of parabolas compared to 12.6% of parabolas for the promethazine group. All placebo subjects reported some level of motion sickness during flight, while four of the six subjects who received promethazine reported no motion sickness at all.
DISCUSSION: Promethazine was effective at mitigating motion sickness symptoms in both 0 g and partial g. Microgravity conditions (0 g) may be more provocative than partial gravity, possibly due to the greater magnitude of sensory conflict. Further research should continue to investigate motion sickness as a function of hypogravity level.
Abbott R, Weinrich MM, Keller NW, Wright TJ, Dunbar BJ, Denise P, Kennedy DM, Diaz-Artiles A. Promethazine effects on motion sickness during altered gravity induced by parabolic flight. Aerosp Med Hum Perform. 2025; 96(11):976–984.
Space motion sickness (SMS) is a common neurovestibular condition experienced by approximately 50–80% of astronauts upon initial exposure to the space environment.1 Symptoms, including nausea, malaise, increased salivation, cold sweats, stomach awareness, gastrointestinal motility changes, and vomiting, typically emerge within the first few hours of microgravity exposure and persist for 2–3 d.2 However, in some cases, symptoms have been reported to last beyond a week.3 Some individuals can adapt and perform tasks while experiencing SMS, but severe cases can be debilitating,4 posing a significant concern if astronauts must complete critical tasks such as extravehicular activity, vehicle control, or landing maneuvers during or shortly after gravitational transitions.
Two primary theories have been proposed to explain SMS: the fluid shift theory and the sensory conflict theory. The fluid shift theory suggests that the redistribution of bodily fluids in microgravity alters vestibular system responses, though empirical evidence for this hypothesis remains limited.5 Notably, Graybiel and Lackner6 did not find increased susceptibility to provocative motion during head-down tilt, a commonly used analog for spaceflight-induced fluid shifts. The more widely accepted sensory conflict theory posits that SMS arises when sensory inputs, such as those from the otolith organs, semicircular canals, visual system, and proprioceptors, are incongruent and do not align with previously stored neural patterns due to the altered gravity environment.7
Pharmaceutical interventions are the primary treatment for SMS. Numerous antimotion sickness drugs have been evaluated in both flight and ground-based studies.8 Among these, promethazine and scopolamine are among the most effective options. Promethazine has demonstrated efficacy in laboratory, clinical, and field studies, including parabolic flight.9 Historically, intramuscular injections of promethazine have been the pharmaceutical countermeasure of choice to mitigate SMS.10 However, promethazine can induce undesirable side effects such as drowsiness and impaired sensorimotor coordination and perception.8,11
Notably, motion sickness and promethazine have primarily been studied in terrestrial analogs and microgravity (0 g) environments during spaceflight or parabolic flight and less is known about promethazine’s impact on motion sickness in partial gravity environments (i.e., greater than 0 g but less than 1 g). With NASA’s current plans for future exploration missions, astronauts may have to complete mission critical tasks at 0.16 g on the Moon and 0.38 g on Mars. Thus, it is critical to characterize motion sickness in partial gravity as well as microgravity.
Spaceflight analogs are often used to investigate SMS and countermeasures as opportunities for spaceflight studies are scarce. Common ground-based analogs include rotary chair testing and centrifugation.8 While these methods are accessible and frequently used, they lack the fundamental absence of a gravitational vector, a key characteristic distinguishing SMS from terrestrial motion sickness. Parabolic flight provides a more adequate analog by generating short periods of microgravity that more closely replicates the spaceflight environment.12
Given the impacts of motion sickness on spaceflight operations, this study aims to expand our understanding of the effects of promethazine—the primary SMS countermeasure currently used by astronauts—on motion sickness symptoms over a range of hypogravity levels (0 g, 0.25 g, 0.50 g, 0.75 g) during parabolic flight. In this exploratory analysis, we seek to characterize the time course of motion sickness development and its potential variation across different gravity levels. We hypothesize that motion sickness will increase as gravity level decreases, deviating further from Earth’s 1 g and resulting in more sensory conflict. Since antimotion sickness medication is commonly used in parabolic flight investigations,13 it represents a frequent confounding factor. Typically, subjects are given the choice of opting in/out of using medication before each flight, which introduces variability that can obscure experimental outcomes. Considering the scientific interest in understanding the effects of promethazine under partial gravity conditions, we chose to control for medication in the context of a bimanual coordination parabolic flight study by allowing only half of the subjects to take antimotion sickness medication.
METHODS
Subjects
Potential subjects were screened using the Motion Sickness Susceptibility Questionnaire (MSSQ)14 to exclude individuals with extreme susceptibility to motion sickness (>95th percentile), as this could interfere with their ability to complete the experiment. The MSSQ evaluates how often an individual has experienced nausea or sickness during various modes of transportation or entertainment, such as cars, aircraft, and swings. Total MSSQ scores were converted to percentiles, where values greater than 50% indicate that an individual is more susceptible to motion sickness than half of the general population. Additionally, preference was also given to subjects with prior parabolic flight experience without antimotion sickness medication. Three subjects in the placebo group and four subjects in the promethazine group had prior parabolic flight experience without antimotion sickness medication.
A total of 12 subjects (6 women/6 men; 40.2 ± 8.7 yr old) in good general health participated in the study, and they were divided into a placebo group (3 women/3 men) and a promethazine group (3 women/3 men). All but two men (one in the placebo group and one in the promethazine group) had previous experience with parabolic flight. This study was approved by the NASA Johnson Space Center Institutional Review Board (STUDY00000329), the Texas A&M University Institutional Review Board (STUDY2024-0425), and the Comité de Protection des Personnes Nord Ouest II (Avis no. 22.04602.000171). All procedures complied with the Declaration of Helsinki. Written informed consent was obtained from all subjects before data collection.
Procedure
This study was conducted during the 82nd European Space Agency parabolic flight (PFC82) campaign in June 2023 aboard the Airbus A-310 Zero-G aircraft. The campaign spanned 4 flight days, consisting of: 1) one microgravity (0 g) flight with 31 parabolas organized into 3 sets (the first set contained 11 parabolas, while the remaining 2 contained 10 each); 2) 3 partial gravity flights, each with 1 set of parabolas at 0.25 g, 0.50 g, and 0.75 g (see Fig. 1). Subjects were placed into one of three flight groups: flight group A (subjects A, D, G, J); flight group B (subjects C, F, H, I); and flight group C (subjects B, E, K, L). The sequence of partial gravity levels varied across the 3 d to minimize order effects. For example, flight group C experienced 0.75 g for parabolas 0–10, 0.25 g for parabolas 11–20, and 0.50 g for parabolas 21–30.
Citation: Aerospace Medicine and Human Performance 96, 11; 10.3357/AMHP.6669.2025
Each parabola consisted of an initial hypergravity phase at 1.8 g during the pull-up maneuver (∼20 s), followed by a microgravity or partial gravity phase, and concluded with another 1.8 g hypergravity phase during the pull-out maneuver (∼20 s). The duration of the reduced gravity phases varied depending on the gravitational condition: 0-g and 0.25-g phases lasted approximately 20 s, while the 0.50-g and 0.75-g phases lasted 40 s and 50 s, respectively. The average acceleration measured during the 0-g phases was 0.016 g.
Each subject experienced at least 10 parabolas at each gravity level (0 g, 0.25 g, 0.50 g, 0.75 g). Subjects took part in 2 flights: 1 microgravity flight with a single set of 10 parabolas (or 11, if they were part of the first set) and 1 partial gravity flight consisting of all 31 parabolas. Since there was only one microgravity flight, all subjects completed a single set of 0-G parabolas on that day, while the remaining two sets were allocated to other studies. Each flight lasted approximately 3 h.
Subjects were evenly divided into a control group and a promethazine group, with an equal number of men and women in each group. Medications were administered in a double-blind fashion by medical staff at approximately 07:00 on the morning of each flight. The control group received a placebo, while the promethazine group received 25 mg of oral promethazine, which has a peak plasma concentration between 2–3 h after administration.15 The first set of parabolas began around 10:00, the second set at 11:00, and the third set at 12:00, approximately 3–5 h after promethazine/placebo administration.
During the microgravity or partial gravity phase and for 15 s into the subsequent hypergravity phase, subjects also performed bimanual coordination tasks while seated in modified commercial airline seats. Subjects were seated in the upright position with arms at their sides and elbows bent at a 90° angle. Through force sensors placed under their wrists, subjects controlled a cursor on a screen—the cursor moved horizontally when force was applied with the right limb and moved vertically when force was applied with the left limb. Subjects were instructed to perform different coordination patterns by tracing a template shape on the screen with their cursor. A head-mounted display was used to provide visual feedback and minimize external distractions. Researchers instructed subjects to keep their heads still throughout the experiment. Motion sickness assessments were conducted before and after each parabolic flight, as well as after each individual parabola.
Materials
To assess motion sickness before, during, and after each flight, three validated surveys were administered: the Motion Sickness Assessment Questionnaire (MSAQ),16 the Pensacola Motion Sickness Questionnaire (MSQ),17 and the Misery Scale (MISC).18 Both the MSAQ and MSQ were completed under 1-g conditions before and after each subject’s two flights. The MSAQ asked subjects to rate how accurately 16 statements (e.g., I feel sick to my stomach) described their experience on a scale from 1 (not at all) to 9 (severely). From these responses, four subscales—central, gastrointestinal, peripheral, and sopite-related—as well as an overall motion sickness score were calculated, expressed as the percentage of the total possible points. As the response scale is anchored at 1 instead of 0, the minimum possible MSAQ score is 11.11 (no motion sickness) and the maximum possible MSAQ score is 100 (severe motion sickness). Similarly, the MSQ contained 28 items measuring various motion sickness symptoms, such as nausea and headache, with subjects rating the severity of each symptom on a scale from 0 (none) to 3 (severe). A total MSQ (ranging from 0–84) was calculated as the sum of all responses. The change in motion sickness scores (MSAQ and MSQ) before and after the parabolic flights (i.e., Δ motion sickness score) was also calculated by subtracting preflight scores from postflight scores.
Finally, during the flight, subjects reported their motion sickness levels after each parabola using the MISC, a single-item scale ranging from 0 (no problem) to 10 (vomiting). The datasets analyzed for this study are publicly available and a repository can be found on GitHub (https://github.com/BHP-Lab/BimCoord/tree/main/Parabolic_Flight_Motion_Sickness/Data).
Statistical Analysis
Motion sickness data from the MSAQ and MSQ were summarized by group (placebo or promethazine), gravity condition (0 g or partial g), and time point (preflight or postflight). The Shapiro-Wilk test was used to determine normality. Paired t-tests (or paired Wilcoxon signed-rank tests for nonnormal data) were used to compare: 1) preflight vs. postflight scores for each group at each gravity condition; and 2) 0-g vs. partial g scores for each group at each time point. In addition, Mann-Whitney U-tests were conducted to compare: 1) placebo vs. promethazine groups at each time point (preflight and postflight) in each gravity condition; and 2) change in motion sickness ratings between the placebo and promethazine groups in each gravity condition. A Benjamini-Hochberg false discovery rate correction was implemented to adjust for multiple comparisons. However, due to the very low number of subjects included in the study, we report both the unadjusted and adjusted results. Effect sizes (Cohen’s d for parametric tests and r for nonparametric tests) are also reported and statistical significance was set at α = 0.05. Descriptive statistics in the text are reported as means (SD) and percentages, as appropriate. In the figures, central tendency is represented by the median (50th percentile) due to the mixed distribution of the data (both normal and nonnormal). All statistical analyses were conducted using R (version 4.4.2, The R Project).
RESULTS
Figure 2A shows MSAQ individual subscales and overall scores preflight and postflight for the 0-G flight and partial g flight separated by group (placebo vs. promethazine). A paired t-test indicated that overall MSAQ scores for the placebo group tended to increase from 14.0 (1.78) at preflight to 21.3 (6.83) at postflight with a large effect size [t(5) = 2.39, P = 0.063, padj = 0.49, d = 0.97] on the 0-G flight day, but not on the partial g flight day [t(5) = 1.34, P = 0.24, padj = 0.56, d = 0.55]. MSAQ central, gastrointestinal, peripheral, and sopite subscales were not significantly different between preflight and postflight for either group for either gravity condition. Overall MSAQ scores and the central, gastrointestinal, peripheral, and sopite-related subscales were not significantly different between the two gravity conditions (0 g vs. partial g) for either group at either time point according to paired t-tests and Wilcoxon signed-rank tests.
Citation: Aerospace Medicine and Human Performance 96, 11; 10.3357/AMHP.6669.2025
A Mann-Whitney U-test indicated that the placebo group had significantly (unadjusted P-value) higher MSAQ scores than the promethazine group for the following measures: central 0 g postflight [U = −2.19, P = 0.028, padj = 0.11, r = 0.66], gastrointestinal 0 g postflight [U = −2.26, P = 0.024, padj = 0.11, r = 0.68], overall 0 g preflight [U = −2.55, P = 0.011, padj = 0.11, r = 0.76], overall 0 g postflight [U = −2.34, P = 0.019, padj = 0.11, r = 0.69], and gastrointestinal partial g postflight [U = −2.19, P = 0.028, padj = 0.11, r = 0.66].
Δ MSAQ scores, calculated as postflight–preflight, are shown in Fig. 2B. Positive values indicate that motion sickness was greater after the parabolic flight than before the parabolic flight. A Mann-Whitney U-test indicated that Δ MSAQ central was significantly greater (unadjusted P-value) for the placebo group than the promethazine group, but only for the 0-g condition [U = −2.19, P = 0.028, padj = 0.28, r = 0.66]. Similarly, Δ MSAQ gastrointestinal was generally higher for the placebo group than the promethazine group for the 0-g condition [U = −1.88, P = 0.059, padj = 0.29, r = 0.57].
MSQ scores generally tended to increase from preflight to postflight across both groups (see Fig. 3A). A paired t-test test indicated that the MSQ scores significantly increased from 2.0 (1.55) preflight to 9.17 (5.42) postflight for the placebo group in the 0-g condition [t(5)=3.19, P = 0.024, padj = 0.048, d = 1.30]. MSQ scores also significantly increased from 0.67 (0.82) preflight to 4.33 (2.25) postflight for the promethazine group in the partial g condition [t(5)=5.50, P = 0.002, padj = 0.01, d = 2.24]. MSQ scores preflight or postflight were not significantly different between the 0-g and partial g flights for the placebo or promethazine group according to a paired t-test. According to a Mann-Whitney U-test, MSQ scores in the 0-G condition postflight were significantly higher (unadjusted P-value) for the placebo group than the promethazine group [U = −2.18, P = 0.029, padj = 0.12, r = 0.65].
Citation: Aerospace Medicine and Human Performance 96, 11; 10.3357/AMHP.6669.2025
Δ MSQ scores, calculated as postflight–preflight, are shown in Fig. 3B. There was no significant difference in Δ MSQ score between the placebo and promethazine group for the 0-g [U = −1.54, P = 0.124, padj = 0.25, r = 0.47] or partial g [U = −0.57, P = 0.572, padj = 0.572, r = 0.18] conditions.
MISC scores for each subject over the course of the 0-G flight and the partial g flight are shown in Fig. 4. Note that during the 0-G flight, subjects only reported MISC scores for 1 set of 10 (or 11, if subjects participated in the first set) parabolas. The median MISC score across all gravity levels was 1 (range = 0–5) for the placebo group and 0 (range = 0–4) for the promethazine group. Median MISC scores for the placebo group at each gravity level were 1 (range = 0–5) at 0 g, 0 (range = 0–2) at 0.25 g and 0.50 g, and 1 (range = 0–4) at 0.75 g. Median MISC scores for the promethazine group at each gravity level were 0 (range = 0–4) at 0 g, 0 (range = 0–1) at 0.25 g, 0 (range = 0) at 0.50 g, and 0 (range = 0–1) for 0.75 g.
Citation: Aerospace Medicine and Human Performance 96, 11; 10.3357/AMHP.6669.2025
Motion sickness was reported (i.e., MISC score ≥1) at least once by all subjects in the placebo group. In contrast, four of six subjects in the promethazine group experienced no motion sickness symptoms at all during flight, and subject J in the promethazine group only reported after one single parabola. Four subjects in the placebo group and one in the promethazine group (subject H) reported MISC scores greater than 1 at some point during their flights. None of the 12 subjects reported any nausea during flight (i.e., MISC score ≥6). The highest MISC score was 5, indicating severe symptoms except nausea, reported by subject F (from the placebo group) during the 0-G flight. On average, placebo group subjects reported motion sickness (MISC score ≥1) in 51.8% of parabolas, compared to only 12.6% of parabolas in the promethazine group.
MISC scores remained at or below 1 during the first 10 parabolas for all subjects except subject F (from the placebo group), who also reported the most severe motion sickness symptoms overall. The highest MISC scores for each subject occurred in the second half of the flight (parabolas 16–31). This suggests that motion sickness severity often increased over the duration of the flight, likely because of the prolonged exposure to a provocative environment. On average, motion sickness was reported with slightly higher frequency during the 0-G flight (55.9% of parabolas in the placebo group and 16.7% in the promethazine group) than during the partial g flight (50.5% of parabolas in the placebo group and 11.3% in the promethazine group). MSSQ percentiles were normally distributed for each group and the average MSSQ percentile for the placebo group (5.5 ± 5.2) was not significantly different than the promethazine group (21.8 ± 21.7) [independent samples t-test with unequal variance; t(5.5) = −1.79, P = 0.13].
DISCUSSION
Motion sickness scores generally increased from preflight to postflight for both groups, with more pronounced changes observed in the placebo group. Most subjects who received promethazine were remarkedly absent of any motion sickness symptoms preflight, during flight, or postflight. While results were inconsistent regarding changes in motion sickness between the two groups, postflight motion sickness scores were higher in the placebo group compared to the promethazine group across several measures. Even though this study has several limitations, further discussed later in this section, and conclusions should be drawn with caution, the data presented offer valuable insights due to the scarcity of knowledge regarding motion sickness in partial gravity.
The MSAQ provides a multidimensional assessment of motion sickness, providing a more complete representation of the subjects’ state. The gastrointestinal subscale, encompassing symptoms like queasiness and nausea, was the most affected, with two placebo subjects and one promethazine subject reporting moderate to severe gastrointestinal symptoms postflight. Central subscale scores, which include symptoms such as feeling disoriented, dizzy, and lightheaded, also increased postflight for the placebo group and less so for the promethazine group. Thus, promethazine appears to alleviate motion sickness symptoms, particularly in the gastrointestinal and central subscales, likely due to its role as a central nervous system depressant. It antagonizes histamine and acetylcholine—two of the three neurotransmitters (histamine, acetylcholine, and noradrenaline) associated with motion sickness. Additionally, promethazine exhibits antidopaminergic properties.15 Its antimotion sickness effects are believed to result from the blockage of central acetylcholine/muscarinic receptors, while its antiemetic properties may stem from dopaminergic receptor inhibition in the chemoreceptor trigger zone of the medulla, a key neural structure involved in motion sickness.19 Furthermore, promethazine’s H1 receptor blockade contributes to reducing symptoms such as nausea and vomiting.15 Plasma concentrations of promethazine were not measured in this study, but given the approximately 12–15 h elimination half-life of oral promethazine,15 future work incorporating pharmacokinetic data could clarify whether temporal variations in drug levels influence motion sickness symptoms across the duration of the flight.
The MSAQ also includes sopite-related symptoms, which are often overlooked yet can persist for hours or days even in the absence of nausea. Sopite syndrome, first described by Graybiel and Knepton, is characterized by yawning, drowsiness, lack of motivation, and social withdrawal.20 Drowsiness, a common symptom of motion sickness, likely contributed to the relatively high incidence of sopite-related symptoms in both groups. Additionally, drowsiness is a known side effect of promethazine and it is used as a sedative at higher doses. Due to its sedating properties, promethazine is often combined with stimulants to counteract its effects.10 However, in the present study, we did not find any significant difference in sopite-related symptoms between the placebo and promethazine groups. Furthermore, there was no difference in preflight sopite symptoms between the 0-G and partial g flight; thus, sopite symptoms did not appear to carry over from prior flights in this instance.
While direct comparisons between the 0-G and partial g flight conditions did not yield significant differences in motion sickness scores, significant differences between the placebo and promethazine groups as well as between preflight and postflight were more frequent in the 0-G flight. This suggests that microgravity may be more provocative than partial gravity. According to Oman’s model, susceptibility to motion sickness is influenced by the amount of sensory conflict, among other factors.7 The greater magnitude of acceleration changes in the 0-G flight compared to the partial g flight likely led to greater sensory conflict and, consequently, increased motion sickness. The variation in exposure to each hypogravity level is another factor to consider. Hypogravity exposure during each parabola for 0.50 g and 0.75 g was approximately double the duration for 0 g and 0.25 g. This extended exposure to a provocative environment with conflicting sensory stimuli may have intensified motion sickness at higher hypogravity levels. Furthermore, the cumulative exposure to each gravity level differed: ∼3.3 min for 0.25 g, ∼6.6 min for 0.50 g, ∼8.3 min for 0.75 g, and ∼10.3 min of cumulative exposure to 0 g. The extended cumulative exposure to 0 G may have contributed to the increased incidence of motion sickness after the 0-G flight. However, the cumulative exposure to partial gravity conditions as a whole (∼18.3 min) was almost double the exposure time on the 0-G flight. Despite this, the cumulative exposure to 0 g appears to be more provocative than the cumulative exposure to the partial gravity levels investigated. These results highlight the need to examine whether the larger gravitational transition from 0 g to Martian gravity may induce greater motion sickness compared to the transition from 0 g to lunar gravity.
Parabolic flight is an invaluable tool for hypogravity research. However, no analog can fully replicate spaceflight conditions. The hypergravity periods preceding and following the hypogravity phases are an inherent constraint and confounding factor of parabolic flight. Previous research has shown that head movements during the hypergravity periods of parabolic flight alone can induce motion sickness, with sensory conflict induced by an excess in otolith signals.21 To mitigate this, we instructed participants to remain seated and minimize head movements. However, increased motion-sickness severity as the flight progressed could have been driven by the provocative stimulus from both the hypogravity and hypergravity periods as well as the transition between hyper- and hypogravity, resulting in greater motion sickness overall.
Subjects had significantly lower MSSQ percentiles (mean ± SD = 13.6 ± 17.3) than the general population (mean = 50). All subjects scored below the 58th percentile, with 9 out of 12 subjects scoring at or below the 20th percentile. Similarly, Golding found that parabolic flight subjects had lower-than-average motion sickness susceptibility scores (MSSQ percentile = 27.4 ± 28.0), likely because individuals prone to motion sickness avoid highly provocative environments such as parabolic flight.13 Our subjects had even lower MSSQ scores than those in Golding’s study, likely due to our recruitment criteria: we specifically selected individuals with prior parabolic flight experience, particularly without the use of antimotion sickness medication, ensuring they could complete the bimanual coordination task even without treatment. Additionally, motion sickness susceptibility was not significantly different between the placebo and promethazine groups, simplifying motion sickness comparisons between the two groups.
It should be noted that there is no significant correlation between those who experience motion sickness in parabolic flight vs. orbital flight.22 However, parabolic flight induces periods of 0 g and partial gravity in a way that other spaceflight analogs cannot. Changes in torsional eye position, likely due to a loss of compensation for otolith asymmetry in altered gravity environments, have been found during both parabolic flight23 and orbital flight.24 Furthermore, torsional offsets in parabolic flight have been proposed as a means to predict SMS25 and warrants further investigation. Thus, while generalizations from parabolic flight to orbital flight are limited, this similarity may provide a unique link between motion sickness in parabolic flight and orbital flight that has not been shown in other analogs.
There are several limitations to this study. A potential confounding factor is that subjects took part in an additional experiment during one set of parabolas on the 0-G flight day. Thus, we did not have any control over the subjects’ activities during those parabolas. When subjects were not participating in an experiment on the 0-G flight, they were instructed to stay seated and avoid any provocative movements that could elicit motion sickness. The sequence of the additional task and the task itself could have influenced in-flight and postflight motion sickness. While we cannot completely disentangle sequence effects, all subjects remained onboard for the entire 0-G flight and the gravitational profile and cumulative effects were the same for all subjects. Additionally, we could not measure motion sickness throughout the entire 0-G flight, limiting our ability to make direct comparisons of the evolution of motion sickness in flight between the partial g and 0-g days. Additionally, promethazine has been shown to exhibit a strong placebo effect,26 which may confound motion sickness assessments. It is also important to note that the route of administration in this study differs from spaceflight operations (i.e., oral vs. intramuscular). Oral promethazine has lower bioavailability (∼25%)15 due to hepatic first-pass metabolism. While this difference may affect the magnitude of physiological responses, the present findings still provide valuable insights into the drug’s effects and support its continued evaluation as a countermeasure. Another limitation of this study is the small sample size, a common constraint in parabolic flight experiments due to limited space on board. However, this reduces the statistical power and generalizability of our results. Similarly, the small sample size prevented statistical analysis of sex differences. The information is still reported, as it may prove useful for future investigations. The small sample size also prevented the use of parametric statistical methods, introducing the limitations associated with nonparametric approaches. Thus, we reported both unadjusted and adjusted statistical results. We acknowledge that the risk of false positives increases with multiple comparisons and adjusted analyses did not retain statistical significance. Due to the small sample size, these results are exploratory and replication with sufficiently powered studies are needed to validate these findings. Nevertheless, we believe that these exploratory data constitute a unique normative dataset that can contribute to future research efforts.
This study enhances our understanding of motion sickness and its modulation by the antimotion sickness drug promethazine across different hypogravity levels in parabolic flight. Our results suggest that motion sickness tends to increase as hypogravity level decreases, deviating further from the 1 g experienced on Earth. However, promethazine effectively mitigated most motion sickness symptoms across all gravity conditions. While this study has limitations that inhibit its generalizability, including a small sample size and the use of parabolic flight rather than orbital flight, it serves as a foundation for future investigations. Further studies are needed to corroborate these findings and explore the relationship between promethazine, motion sickness, and sensorimotor performance. Ultimately, this research effort can contribute to the development of guidelines and countermeasures for SMS in future space exploration missions.
Overview of experimental procedure. Each flight group contained four participants (two women/two men). Subjects received either a placebo or 25 mg of oral promethazine in the morning before each flight, counterbalanced by gender. They completed the Motion Sickness Assessment Questionnaire (MSAQ) and the Pensacola Motion Sickness Questionnaire (MSQ) preflight and postflight. All flight groups participated in the same 0-g flight, with flight group A (subjects A, D, G, J) reporting MIsery SCale (MISC) scores immediately after parabolas 0–10, flight group B (subjects C, F, H, I) for parabolas 11–20, and flight group C (subjects B, E, K, L) for parabolas 21–30. On the partial g flights, one flight group participated in the experiment during the 31 parabolas (e.g., 11 parabolas at 0.25 g, 10 parabolas at 0.50 g, and 10 parabolas at 0.75 g) and they also reported their MISC scores after each parabola. On the partial g flights, the gravity levels (0.25 g, 0.50 g, 0.75 g) were presented in a randomized order. Created in BioRender. Abbott, R. (2025); https://BioRender.com/b21p866.
MSAQ Scores for the placebo group (red) and promethazine group (blue) separated by flight day. A) Preflight and postflight MSAQ scores for the 0-g and partial g flights. B) Change in MSAQ scores calculated as postflight–preflight. Individual subjects are shown as points, and the median (50% quantile) is shown with a solid black line. +P ≤ 0.05 unadjusted, #approaching significance (P = 0.063 unadjusted).
MSQ Scores for the placebo group (red) and promethazine group (blue) separated by flight day. A) Preflight and postflight MSAQ scores for the 0 g and partial g flights. B) Change in MSQ scores calculated as postflight–preflight. Individual subjects are shown as points, and the median (50% quantile) is shown with a solid black line. *P ≤ 0.05; +P ≤ 0.05 unadjusted.
MISC scores, ranging from 0 (no problem) to 10 (vomiting), reported by each subject (A–L) after each parabola. The placebo group is displayed in the top row and the promethazine group is displayed in the bottom row. Women (D, E, F, J, K, and L) are shown as triangles. Colors correspond to the gravity level of the parabola completed immediately before reporting MISC score.
Contributor Notes
