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The Transcriptional Signature of a Runner’s High


Medicine & Science in Sports & Exercise: May 2019 - Volume 51 - Issue 5 - p 970–978
doi: 10.1249/MSS.0000000000001865

Introduction Endorphins, endocannabinoids, monoamines, and neurotrophins have all been implicated in the euphoric response to endurance running, known as a runner’s high (RH). The epitranscriptional mechanisms regulating this effect have not been defined. Here, we investigate peripheral micro–ribonucleic acid (miRNA) changes unique to athletes experiencing postrun euphoria, yielding insights into gene networks that control an RH.

Methods A cohort study involving 25 collegiate runners (48% females, age = 20 ± 1 yr) examined salivary RNA levels before and after a long-distance run. Participants were divided into RH and nonrunner’s high (NRH) groups based on surveys of four criteria (mood, lost sense of time, run quality, and euphoria). Physiological measures were also recorded (temperature, heart rate, blood pressure, pupillary dilatation, and salivary serotonin). Levels of miRNAs and their messenger RNA targets were compared across pre- and postrun samples from RH and NRH groups with two-way ANOVA. Representation of opioid, gamma-aminobutyic acid (GABA), endocannabinoid, neurotrophin, serotonergic, and dopaminergic pathways was assessed in DIANA miRPath. Pearson’s correlation analyses examined relationships between miRNAs and RH indices.

Results RH participants (n = 13) demonstrated postrun mydriasis (P = 0.046) and hypothermia (P = 0.043) relative to NRH participants (n = 12) but had no difference in serotonin dynamics (P = 0.88). Six miRNAs (miR-194-5p, miR-4676-3p, miR-4254, miR-4425, miR-1273-3p, miR-6743-5p) exhibited significant effects (false discovery rate P value < 0.05) across pre- or postrun and RH/NRH groups. These miRNAs displayed target enrichment for opioid (P = 2.74E−06) and GABA (P = 0.00016) pathways. miR-1237-3p levels were related with lost sense of time (R = 0.40). Mitogen-activated protein kinase (MAPK11), an endocannabinoid target of miR-1273-3p, was nominally elevated in RH participants (false discovery rate P value = 0.11).

Conclusions Unique dynamics in miRNA concentration occur in athletes with subjective/objective evidence of RH, targeting genes implicated endorphin, endocannabinoid, and GABAergic signaling.

1Department of Pediatrics, Penn State College of Medicine, Hershey, PA;

2Department of Biology, Marist College, Poughkeepsie, NY; and

3Departments of Neuroscience and Physiology, Biochemistry and Molecular Biology, Pediatrics, and Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY

Address for correspondence: Steven D. Hicks, M.D., Ph.D., Assistant Professor of Pediatrics, Penn State College of Medicine, 500 University Drive, Mail Code HS83, Hershey PA, 17033; E-mail:

Submitted for publication August 2018.

Accepted for publication November 2018.

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© 2019 American College of Sports Medicine