Benefits
Faster attention and overall task speed in one maker-sponsored trial
In a single trial of this extract in 82 healthy adults, sponsored by its maker, the registered primary outcome, a memory score at day 56, did not differ from placebo. Among secondary measures, one dose sped up an attention factor and 56 days sped up overall task speed, but one dose also made name-to-face recall less accurate. These results had p values near 0.04 among many outcomes.
Smaller frontal blood-flow response during an attention task
In a single trial whose registered primary memory outcome did not differ from placebo, 41 participants had near-infrared spectroscopy: the frontal-lobe blood-flow response during tasks was lower than on placebo on day 1 and day 56, mainly during one attention task. Resting blood flow and task scores in that sub-group did not differ. The authors read this as greater neural efficiency.
Self-rated fatigue during 30 minutes of demanding tasks
After 56 days, self-rated mental fatigue during a 30-minute demanding task battery was lower than placebo. The extract group had started out significantly more fatigued, and scores were adjusted to that starting point, so a drift back toward average could explain part of the gap. Self-rated alertness did not differ from placebo after one dose 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 the trial authors cite reports that structurally similar alkamides 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. In healthy volunteers, swallowed hydroxy-alpha-sanshool from a related pepper reached peak blood levels within about 30 minutes.
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 trial (NCT03673930) of SaraPEPP Nu, an MCT-oil extract of Timut or Nepalese pepper (Zanthoxylum armatum), on cognitive function, mood and frontal brain blood flow after one dose and after 56 days. Sponsored by Mibelle Group, with a Mibelle co-author; the registry lists Northumbria University as lead sponsor and Mibelle AG as collaborator. (Kennedy et al. 2019, Nutrients)
82 healthy adults aged 30 to 55 taking 4 soft gels a day (2.8 g extract, 7.8 mg hydroxy-alpha-sanshool) or a sunflower oil placebo for 56 days; 41 also had frontal blood-flow measurements.
The registered primary outcome, a secondary memory composite score at day 56, did not differ from placebo, and no other cognitive factor score differed at day 56. A single dose improved a speed-of-attention score but made name-to-face recall less accurate. After 56 days, overall task speed was faster and self-rated mental fatigue lower than placebo, though the extract group started out more fatigued. Self-rated alertness did not differ. In the 41-person sub-group, the frontal blood-flow response during tasks was lower, with resting blood flow unchanged.