An interventional study of Nepalese Pepper (Zanthoxylum Armatum DC) extract 275mg and Placebo in Cognition, Mood and Gaming Performance, sponsored by Northumbria University. Not yet recruiting at 1 site in United Kingdom. Open to participants aged 16 Years to 39 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-07.
Sponsored by Northumbria University · Not applicable, Interventional, and Basic science
The goal of this clinical trial is to learn if daily supplementation with a Nepalese Pepper Extract (Zanthoxylum Armatum, ZA) can improve cognitive performance and gaming performance in action video gamers aged 16 to 39, when taken over an extended period. The main questions it aims to answer are:
Does chronic (42-day) daily ZA supplementation improve speed of cognitive performance and reduce subjective mental fatigue? Do these effects translate into objective and self-reported improvements in gaming performance? Are there additional acute (within-session) effects at the end of a chronic supplementation period, on top of any chronic effect?
Researchers will compare 275mg daily ZA supplementation to placebo to see if chronic ZA produces better cognitive performance and lower fatigue than placebo. Participants will:
Complete a screening call and a training visit on the computerised cognitive tasks and gaming tasks Take a daily capsule (either ZA or placebo, depending on treatment order) each morning with food for 42 days, then switch to the other treatment for a further 42 days after a 2-week washout Attend four testing visits at the research centre: a baseline and an endpoint visit for each 42-day treatment period Avoid alcohol and energy drinks for 24 hours before each testing visit, and caffeine from waking Complete cognitive tests before dosing and 1 hour after dosing at each testing visit Complete mood and sleep questionnaires Wear a heart rate monitor at rest on arrival at each visit Complete gaming-specific tasks (aim training, MOBA character control, multi-tasking, finger tapping, Fitts' Law, multiple object tracking, collision prediction) Play their action video game of choice at home throughout each 42-day period and complete performance questionnaires
Zanthoxylum armatum DC (ZA), also known as Nepalese pepper, contains numerous active chemicals throughout all parts of the organism. Traditionally used in the treatment of intestinal disorders, depression and as topical treatment for toothache, it is commonly ingested through the form of Daikenchuto, a traditional combination of the Zanthoxylum fruit with ginseng root, ginger rhizome and rice gluten. In recent years it has been established that ZA also possesses cognitive enhancing properties, with the primary active component revealed to be the fatty acid amide hydroxy α-sanshool. Additionally, ZA is rich in monoterpenes which have also been shown to positively affect cognition, and the combination of these compounds may lead to numerous improvements in brain function.
Through a double-blind placebo-controlled study, acute single dose administration of 80mg of ZA was shown to improve cognitive performance in 'Speed of Attention' and Rapid Visual Information Processing, a sustained attention task. In the same study, chronic (56 day) administration resulted in overall improvement in 'Speed of Performance', with more correct Serial 3 subtractions 3h post dose and lower mental fatigue compared to placebo during performance of the Cognitive Demand Battery (CDB). In both acute and chronic cases, the mechanisms underpinning the effects are currently unknown. For the acute effects there may be a cholinergic mechanism at play, with previous research suggesting a cholinesterase inhibitory effect from ZA. Meanwhile, the observed chronic improvements suggest a more general improvement in neural efficiency and processing speeds rather than the memory/attention benefits generally expected from cholinergic agents.
An increasing area of interest for performance research is in the world of Esports and competitive gaming, where cognitive abilities are paramount. Esport competition incurs physical and mental demands, including motor skills, mental agility, processing speed, motivation, executive function and, to a lower degree, physical exertion. Success hinges on mastering cognitive tasks such as visuospatial processing, cognitive workload, attention and cognitive control, hand-eye coordination, fast reaction times and quick decision-making. Within esports, viewership is overwhelmingly dominated by Massive Online Battle Arenas (MOBA) and First Person Shooters (FPS); despite sharing a similarly fast-paced, high-intensity element, the contrast in player character control mechanisms between these genres creates distinct performance metrics, meaning studies analysing game performance across genres should incorporate genre-specific measurement tools.
One aspect common to all esports players is the prolonged nature of training and gameplay, requiring sustained attention and resulting in high mental demand and fatigue. Energy drink consumption is high within gamers, and an emerging area of research considers the potential to enhance gaming performance via various nootropics, primarily highly caffeinated products. However, the high caffeine content in these products is linked to undesirable side effects including jitteriness, tension, and decreased sleep duration and quality, which can negatively impact both short- and long-term gaming performance. As gaming becomes a more viable career, gamers are likely to seek healthier alternatives, sparking interest in non-caffeinated options to combat mental fatigue and enhance gaming performance.
The previous acute study conducted by our group (53BS2) administered single doses of 150mg and 300mg of a powdered ZA formulation (SaraPepp™ Nu) to assess acute cognitive and mood effects against placebo and caffeine. The main aim of the current study is to investigate the chronic cognitive and mood effects of 275mg ZA administered daily over 42 days in young, healthy action video gamers, building on the chronic findings of Kennedy et al. (2019), in which 56-day ZA administration improved 'Speed of Performance' and reduced subjective mental fatigue relative to placebo. A crossover design with a 2-week washout period will allow for within-participant comparisons while controlling for individual differences. Additional aims include ascertaining whether chronic cognitive improvements translate into objective and subjective in-game performance improvements, deepening understanding of how action video game genres present differing cognitive gameplay requirements, and developing robust methods of assessing gameplay performance over an extended supplementation period.
Primary objectives
The primary objectives of this study are to evaluate the chronic effects of 275mg daily ZA supplementation within a young, healthy population, with focus on:
These were the areas of improvement ascertained under chronic supplementation by Kennedy et al. (2019), and these results will be tested for replicability. Participants will be tested using computerised cognitive tasks (COMPASS) in a randomised, double-blind, placebo-controlled crossover design, with assessments at pre-dose baseline and 1hr post-dose at both the baseline and endpoint visit of each 42-day treatment arm.
Secondary objectives
The secondary objectives of this study are to evaluate other cognitive areas where no significant changes were revealed in the previous study, to test for replication and see if any other changes appear. These include:
To fulfil these objectives, the full battery of COMPASS tasks will be tested at pre-dose baseline and 1hr post-dose on each testing visit, under both treatment conditions.
In addition, subjective alertness and mental fatigue will be assessed following each of 3 completions of the Cognitive Demand Battery (CDB), a 10-minute battery of tasks completed three times in immediate succession (30 minutes continuous). In addition to this, mood and sleep will also be recorded on testing visits through the Positive and Negative Affect Schedule (PANAS), Visual Analogue Mood Scales (VAMS), and the sleep disturbance short form (PROMIS). Heart Rate Variability will also be assessed at rest upon arrival at each testing visit, prior to task performance or supplementation.
Further secondary objectives are to implement gaming tests to assess if any differences can be observed in gameplay-related outcomes following treatment. These include: an aim trainer (Aim Labs), a Massive Online Battle Arena (MOBA) control simulator, a Multi-Tasking Framework (MTF), a Finger Tapping Task (FTT), a Fitts' Law Task (visuomotor speed-accuracy trade-off), a Multiple Object Tracking Task (MOT; divided visual attention), and a Collision Prediction Task (anticipation and trajectory prediction).
In addition to this, gameplay monitoring of at-home play will be implemented as a secondary outcome measure to assess real-world gameplay ability across the 42-day supplementation period, via the Subjective Performance Gameplay Scale and gameplay tracking where possible.
Investigational plan
This study follows a randomised, placebo-controlled, double-blind, crossover design with two treatment arms (275mg ZA, Placebo). Participants attend the lab on five occasions: a screening/training visit, two baseline testing visits, and two endpoint testing visits, following the structure Baseline 1 → 42-day supplementation → Endpoint 1 → 14-day washout → Baseline 2 → 42-day supplementation → Endpoint 2. Total study duration is approximately 20 weeks per participant. A total sample of 70 participants will be recruited.
2,229 studies on the registry are indexed under Fatigue; 426 are open to participants now.
This study's planned enrollment of 70 is above the median of 54 across 1,757 interventional studies indexed under Fatigue.
Browse Fatigue studies →Northumbria University is the lead sponsor of 160 studies on the registry; 22 are open to participants now.
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Exclusion Criteria:
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Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
275mg daily dosage of Nepalese Pepper (Zanthoxylum Armatum) extract (SaraPepp™ Nu) in capsule form, taken once daily for 42 days, to measure chronic effects on cognition, mood and gaming performance.
Dietary Supplement: Nepalese Pepper (Zanthoxylum Armatum DC) extract 275mg
Inert placebo, Microcrystalline Cellulose (MCC), delivered in capsule form, taken once daily each morning with food for 42 days.
Dietary Supplement: Placebo
The intervention is a powdered form of Zanthoxylum Armatum (ZA) extract (SaraPepp™ Nu) delivered in capsule form, taken once daily with food for a 42-day supplementation period. The dosage is 275mg.
Also known as: Timut Pepper, SaraPepp™ Nu
Microcrystalline Cellulose (MCC), delivered in capsule form, taken once daily for a 42-day supplementation period.
Subjective Fatigue
Self-assessed fatigue level following each of three completions of the Cognitive Demand Battery (CDB).
Time frame: Assessed at pre-dose baseline and 1hr post-dose, on the Baseline and Endpoint visit of each 42-day treatment arm.
Speed of Performance
Composite outcome derived from combined performance on Serial 3 Subtractions, Simple Reaction Time, Choice Reaction Time, Numeric Working Memory, RVIP, Delayed Picture Recognition, and Delayed Word Recognition tasks from the COMPASS battery.
Time frame: Assessed at pre-dose baseline and 1hr post-dose, on the Baseline and Endpoint visit of each 42-day treatment arm.
Accuracy of Attention
Score calculated through combined performance on Rapid Visual Information Processing, RVIP, and Choice Reaction Time tasks.
Time frame: Assessed at pre-dose baseline and 1hr post-dose, on the Baseline and Endpoint visit of each 42-day treatment arm.
Speed of Attention
Score calculated through combined performance on Rapid Visual Information Processing, Simple Reaction Time, and Choice Reaction Time tasks.
Time frame: Assessed at pre-dose baseline and 1hr post-dose, on the Baseline and Endpoint visit of each 42-day treatment arm.
Accuracy of Performance
Score calculated through combined performance on Immediate Word Recall, Choice Reaction Time, Corsi Blocks, Stroop, RVIP, Delayed Word Recall, Delayed Picture Recognition, and Delayed Word Recognition.
Time frame: Assessed at pre-dose baseline and 1hr post-dose, on the Baseline and Endpoint visit of each 42-day treatment arm.
Working Memory
Score calculated through combined performance on Numeric Working Memory and Corsi Blocks tasks.
Time frame: Assessed at pre-dose baseline and 1hr post-dose, on the Baseline and Endpoint visit of each 42-day treatment arm.
Speed of Memory
Score calculated through combined performance on Numeric Working Memory, Delayed Picture Recognition, and Delayed Word Recognition tasks.
Time frame: Assessed at pre-dose baseline and 1hr post-dose, on the Baseline and Endpoint visit of each 42-day treatment arm.
Episodic Memory
Score calculated through combined performance on Immediate Word Recall, Delayed Word Recall, Delayed Picture Recognition, and Delayed Word Recognition tasks.
Time frame: Assessed at pre-dose baseline and 1hr post-dose, on the Baseline and Endpoint visit of each 42-day treatment arm.
Executive Function
Score calculated through performance on Peg and Ball and Stroop interference tasks.
Time frame: Assessed at pre-dose baseline and 1hr post-dose, on the Baseline and Endpoint visit of each 42-day treatment arm.
Mood
Mood rating calculated through answers to the Visual Analogue Mood Scales and the Positive and Negative Affect Schedule.
Time frame: Assessed at pre-dose baseline and 1hr post-dose, on the Baseline and Endpoint visit of each 42-day treatment arm.
Sleep Disturbance
Sleep disturbance score calculated through the PROMIS Sleep Disturbance Short Form (8 items, range 8-40, higher scores indicating greater disturbance).
Time frame: Assessed on the Baseline and Endpoint visit of each 42-day treatment arm.
Heart Rate Variability (HRV)
HRV recorded via a 5-minute resting ECG using Biopac research rings, following 5 minutes of seated rest, prior to any task performance or supplementation.
Time frame: Assessed at rest upon arrival, prior to task performance or supplementation, on the Baseline and Endpoint visit of each 42-day treatment arm.
First Person Shooter Aiming Ability
Aiming performance with a mouse measured through accuracy percentage and reaction time across five Aim Labs challenges (Spidershot, Motionshot, Gridshot, CircleShot, WallPeek).
Time frame: Assessed at pre-dose baseline and 1hr post-dose, on the Baseline and Endpoint visit of each 42-day treatment arm.
MOBA Control Ability
Measure of character control ability using a custom MOBA-style game, indexed by in-game score, reaction time, accuracy, targets hit, distance travelled, and click patterns.
Time frame: Assessed at pre-dose baseline and 1hr post-dose, on the Baseline and Endpoint visit of each 42-day treatment arm.
Multi-Tasking Ability
Multi-tasking ability measured through Multi-Tasking Framework score.
Time frame: Assessed at pre-dose baseline and 1hr post-dose, on the Baseline and Endpoint visit of each 42-day treatment arm.
Finger Tapping Task
Number of finger taps completed in 10 seconds.
Time frame: Assessed at pre-dose baseline and 1hr post-dose, on the Baseline and Endpoint visit of each 42-day treatment arm.
Fitts' Law Task
Visuomotor speed-accuracy trade-off measured through throughput (bits/second; effective index of difficulty divided by movement time, averaged as a mean of condition means), with slope and intercept of the movement-time-on-ID regression as secondary parameters.
Time frame: Assessed at pre-dose baseline and 1hr post-dose, on the Baseline and Endpoint visit of each 42-day treatment arm.
Multiple Object Tracking Task
Divided visual attention measured through threshold tracking speed, estimated via a staircase procedure.
Time frame: Assessed at pre-dose baseline and 1hr post-dose, on the Baseline and Endpoint visit of each 42-day treatment arm.
Collision Prediction Task
Anticipation and trajectory prediction measured through spatial prediction error (Euclidean distance between click position and true collision point, in pixels) and temporal prediction error (absolute deviation between click timing and true collision time, in milliseconds).
Time frame: Assessed at pre-dose baseline and 1hr post-dose, on the Baseline and Endpoint visit of each 42-day treatment arm.
Subjective Gameplay Performance
Subjective Performance Gameplay Scale self-report, completed by participants following evening gameplay sessions.
Time frame: At home, periodically throughout each 42-day supplementation period, following gameplay sessions.
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