Dose response effects of theacrine on cognitive performance and subsequent sleep

Abstract

Psychostimulants can be employed as a countermeasure to cognitive declines resulting from insufficient sleep. Although caffeine is the most consumed psychostimulant, consumption can cause adverse side-effects, including sleep disturbance. Therefore, there is interest in identifying alternative supplements that improve cognitive performance without compromising subsequent sleep. Here we investigate the influence of the dose and timing of theacrine consumption on cognitive performance and subsequent sleep using conditions that replicate a low (100 mg) and high (400 mg) dose consumed in the morning (12 h prior to bedtime), afternoon (eight hours prior to bedtime), and evening (four hours prior to bedtime). We found no significant effect of the low or high theacrine dose on subsequent sleep although the high dose showed small non-significant effects on sleep efficiency and wake after sleep onset at each timepoint of consumption. However, consuming theacrine within eight hours of bedtime improved next-morning cognitive performance, with the 400 mg dose reducing the number of lapses on the Psychomotor Vigilance Task, although there were no significant effects on reaction time. Our findings provide initial scientific evidence suggesting that theacrine consumption may improve some aspects of next-morning cognitive performance but not others, with small non-significant effects on nighttime sleep.

Keywords: Adenosine; Alertness; Caffeine; Sleep disruption; Sleepiness; Vigilance.

Fig. 1

Experimental phase of the protocol. Participants completed seven conditions (C1-C7) in a randomised manner with a six-day washout period between each. On each control day (con) and condition day, participants consumed a standardised dose of caffeine (3 mg∙kg^-1) within 30 to 60 min of waking in capsule form. Three capsules (placebo or theacrine) were administered at 12, eight, and four hours prior to bedtime in line with the assigned condition. Participants completed a set of five visual analogue scales followed by the Psychomotor Vigilance Task and Simon task 15 min post waking, 10, six, and two hours prior to bedtime, and 15 min post waking the following day. Immediately prior to bedtime, participants applied the Somfit device and completed the Karolinska Sleepiness Scale. Upon waking, participants removed the Somfit device, recorded their perception of the condition, and completed the sleep diary.

Fig. 2

Change in objective sleep measures: (A) total sleep time (minutes); (B) sleep efficiency (%); (C) sleep onset latency (minutes); (D) wake after sleep onset (minutes); (E) proportion of N1 & N2 sleep (%); and (F) proportion of N3 sleep (%) for placebo, 100 mg of theacrine, and 400 mg of theacrine consumed 12, eight, and four hours prior to bedtime. †indicates a significant difference compared to the 100 mg dose of theacrine within the same timepoint. Error bars represent adjusted 95% confidence intervals.

Fig. 3

Change in subjective sleep measures: (A) total sleep time (minutes); (B) sleep quality (units); (C) sleep onset latency (minutes); (D) wake after sleep onset (WASO) (minutes); (E) Karolinska Sleepiness Scale (units); and (F) pre-sleep alertness (units) for placebo, 100 mg of theacrine, and 400 mg of theacrine consumed 12, eight, and four hours prior to bedtime. *indicates a significant difference to the placebo within the same timepoint. Error bars represent adjusted 95% confidence intervals.

Fig. 4

Change in cognitive performance outcomes assessed 15-min upon waking the following morning: (A) Psychomotor Vigilance Task (PVT) mean reaction time (ms); (B) PVT number of lapses (count); (C) PVT range mean reaction time (ms); (D) Simon task overall proportion of correct responses (%); (E) Simon task congruent proportion of correct responses (%); and (F) Simon task incongruent proportion of correct responses (%) for placebo, 100 mg of theacrine, and 400 mg of theacrine consumed 12, eight, and four hours prior to bedtime. *indicates a significant difference to the placebo within the same timepoint. Error bars represent adjusted 95% confidence intervals.

Fig. 5

A summary of the effects of 100 mg of theacrine and 400 mg of theacrine consumed 12, eight, and four hours prior to bedtime on subsequent sleep outcomes (left) of total sleep time (TST), sleep efficiency (SE), sleep onset latency (SOL), wake after sleep onset (WASO), non-rapid eye movement (NREM) stage one (N1) and two (N2) sleep, NREM stage three (N3) sleep, rapid eye movement (REM) sleep, subjective sleep quality, and subjective SOL and on cognitive perfomance assessed 15 min upon waking the following morning for outcomes (right) of Psychomotor Vigilance Task (PVT) mean reaction time (mean RT), PVT range mean reaction time (range RT); PVT number of lapses (no. lapses), Simon task overall proportion of correct responses and mean reaction time of responses (overall correct and overall RT, respectively), Simon task congruent proportion of correct responses and mean reaction time of responses (congruent correct and congruent RT, respectively), and Simon task incongruent proportion of correct responses and mean reaction time of responses (incongruent correct and incongruent RT, respectively. The effect size scale ranges from -0.8 to 0.8 (large effect), with a red effect indicating a negative influence on the sleep or cognitive performance outcome and a green effect indicating a positive influence on the sleep or cognitive outcome.