Benefits
Faster task performance in one sponsor-funded trial
In a randomized, double-blind, placebo-controlled trial (n=82, healthy adults aged 30 to 55), a single dose improved a Speed of Attention factor at 1 and 3 hours after dosing. After 56 days, a global Speed of Performance measure was faster and more Serial 3s subtractions were completed at the 3-hour assessment, while Speed of Attention itself was only a non-significant trend at that point (p = 0.079). The trial's registered primary outcome, a secondary-memory score at 56 days, did not differ from placebo, and neither did the registered working-memory score. Individual memory tasks moved in both directions after a single dose: fewer errors on delayed word recall at 1 hour, but significantly less accurate name-to-face recall at 1 and 3 hours.
More efficient brain blood-flow use
In the near-infrared spectroscopy sub-group (41 of the participants), the frontal-lobe blood-flow response during task performance was lower on the extract than on placebo on both day 1 and day 56, and the effect was most pronounced during one attention task. Task scores within that sub-group did not differ between groups, and resting cerebral blood flow was unchanged. The trial authors read this as greater neural efficiency; that is their interpretation of one dataset, not a separately measured benefit.
Caffeine-free cognitive/energy support
It contains no caffeine. In the trial, self-rated mental fatigue during a demanding cognitive battery was lower than placebo after 56 days, but the extract group happened to start out significantly more mentally fatigued at baseline, which makes that result harder to read. Subjective alertness on the Bond-Lader scales did not differ from placebo, either acutely or after 56 days.
Mechanism of action
Sanshool sensory/TRP signaling
Hydroxy-alpha-sanshool interacts with TRPV1 and TRPA1 channels and with two-pore-domain potassium channels, and structurally similar alkamides are reported to cross the blood-brain barrier. The trial authors offer this, together with the monoterpenes in the extract, as one possible explanation for what they saw. No mechanism was measured in the trial, and in the authors' own screening the extract showed no cannabinoid receptor binding.
Cerebral blood-flow efficiency
A smaller frontal blood-flow response during demanding tasks, with task performance unchanged, is what the trial authors describe as increased neural efficiency. It is an interpretation of one near-infrared spectroscopy dataset in 41 people, not an independently confirmed mechanism.
Clinical trials
Randomized, double-blind, placebo-controlled, parallel-groups design testing a single dose and 56 days of daily use. Kennedy D, Wightman E, Khan J, Grothe T, Jackson P. Nutrients 2019;11(12):3022. Sponsored by Mibelle Group, one of whose employees is a co-author; registered as NCT03673930.
82 healthy men and women aged 30 to 55; 41 of them also completed the cerebral blood-flow measurements
The pre-registered primary outcome, a secondary-memory score after 56 days, did not differ from placebo. A single dose improved a Speed of Attention factor, reduced false alarms on a vigilance task and produced fewer delayed word recall errors at 1 hour, but made name-to-face recall significantly less accurate at 1 and 3 hours. After 56 days, overall task speed was faster, Serial 3s subtractions improved at one assessment, and self-rated mental fatigue was lower, while subjective alertness and anxiety were unchanged. Frontal-lobe blood-flow responses during task performance were reduced on both days in the 41-person sub-group, with resting blood flow unchanged.