Jet Lag

Environmental MONDO:0024381 Pathograph 14 Show in embeddings browser Circadian Rhythm Sleep Disorder Sleep-Wake Disorder

Jet lag is an acquired circadian rhythm sleep-wake disorder caused by rapid travel across time zones, in which the endogenous circadian system is misaligned with the destination light-dark and sleep-wake schedule. The typical burden is transient but functionally disruptive, with daytime fatigue, sleep disturbance, impaired mental efficiency, weakness, irritability, and excessive sleepiness after multi-time-zone travel. The core mechanism is circadian desynchronization rather than a primary genetic clock disorder.

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3
Pathophys.
6
Phenotypes
14
Pathograph
5
Medical Actions
2
Datasets
3
Trials
3
References
⚙

Pathophysiology

3
Rapid Transmeridian Light-Dark Shift
The initiating event is abrupt displacement of local clock time and light-dark exposure relative to the traveler's entrained internal circadian phase.
Entrainment of circadian clock GO:0009649 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Entrainment of circadian clock (GO:0009649). GO:0009649 is a biological process from the Gene Ontology.
Downstream
Circadian Desynchronization The shifted external light-dark schedule places internal rhythms out of phase with the destination schedule.
Show evidence (1 reference)
PMID:12076414 SUPPORT Human Clinical
"Jet-lag commonly affects air travellers who cross several time zones. It results from the body's internal rhythms being out of step with the day-night cycle at the destination."
Establishes the time-zone crossing and external day-night mismatch that initiate jet lag.
Circadian Desynchronization
The endogenous circadian system becomes misaligned with the destination day-night cycle, so sleep propensity, alertness, melatonin timing, and other rhythmic physiology occur at inappropriate local times.
Circadian rhythm GO:0007623 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Circadian rhythm (GO:0007623). GO:0007623 is a biological process from the Gene Ontology.
Downstream
Sleep-Wake Symptom Cluster Circadian misalignment and travel-related sleep loss produce the clinical sleep and daytime-function manifestations.
Show evidence (1 reference)
PMID:12076414 SUPPORT Human Clinical
"Jet lag is caused by desynchronization between the body's circadian system and the new day‐night cycle at the traveller's destination."
Directly states the core pathophysiologic mechanism as circadian-system desynchronization from the destination day-night cycle.
Sleep-Wake Symptom Cluster
Misaligned circadian phase and acute sleep loss produce the characteristic symptom cluster of sleep disturbance, daytime fatigue, excessive sleepiness, impaired mental efficiency, weakness, and irritability.
Sleep GO:0030431 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Sleep (GO:0030431). GO:0030431 is a biological process from the Gene Ontology.
Downstream
Fatigue Daytime fatigue is a primary manifestation of the symptom cluster.
Cognitive Impairment Loss of mental efficiency is a recognized daytime manifestation.
Asthenia Weakness is a recognized manifestation of the symptom cluster.
Sleep Disturbance Sleep disturbance is a primary manifestation of the symptom cluster.
Irritability Irritability is a recognized downstream manifestation.
Show evidence (1 reference)
PMID:12076414 SUPPORT Human Clinical
"The symptoms of jet lag are primarily daytime fatigue and sleep disturbance, but also include loss of mental efficiency , weakness and irritability"
Summarizes the characteristic downstream clinical symptom cluster.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Jet Lag Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

6
Nervous System 4
Cognitive Impairment HP:0100543 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cognitive impairment (HP:0100543). HP:0100543 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:12076414 SUPPORT Human Clinical
"The symptoms of jet lag are primarily daytime fatigue and sleep disturbance, but also include loss of mental efficiency , weakness and irritability"
Identifies loss of mental efficiency as part of the jet-lag symptom cluster.
Sleep Disturbance HP:0002360 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Sleep disturbance (HP:0002360). HP:0002360 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:12076414 SUPPORT Human Clinical
"The symptoms of jet lag are primarily daytime fatigue and sleep disturbance, but also include loss of mental efficiency , weakness and irritability"
Identifies sleep disturbance as a primary symptom of jet lag.
Excessive Daytime Somnolence HP:0001262 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Excessive daytime somnolence (HP:0001262). HP:0001262 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:20530317 SUPPORT Human Clinical
"Adults with a history of jet lag symptoms on previous flights through multiple time zones flew from the United States to France (a 6-hour time zone change) for a 3-day laboratory-based study period."
The armodafinil trial enrolled travelers with jet-lag symptoms after a six-hour time-zone shift and evaluated excessive sleepiness as the target symptom domain.
Irritability HP:0000737 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Irritability (HP:0000737). HP:0000737 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:12076414 SUPPORT Human Clinical
"The symptoms of jet lag are primarily daytime fatigue and sleep disturbance, but also include loss of mental efficiency , weakness and irritability"
Identifies irritability as part of the jet-lag symptom cluster.
Constitutional 1
Fatigue HP:0012378 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fatigue (HP:0012378). HP:0012378 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:12076414 SUPPORT Human Clinical
"The symptoms of jet lag are primarily daytime fatigue and sleep disturbance, but also include loss of mental efficiency , weakness and irritability"
Identifies daytime fatigue as a primary symptom of jet lag.
Other 1
Asthenia HP:0025406 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Asthenia (HP:0025406). HP:0025406 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:12076414 SUPPORT Human Clinical
"The symptoms of jet lag are primarily daytime fatigue and sleep disturbance, but also include loss of mental efficiency , weakness and irritability"
Identifies weakness as part of the jet-lag symptom cluster.
💊

Medical Actions

5
Timed Melatonin
Category: Therapeutic Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: melatonin CHEBI:16796 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses melatonin (CHEBI:16796). CHEBI:16796 is a therapeutic agent from Chemical Entities of Biological Interest.
Melatonin timed close to the destination bedtime is used to shift circadian phase and reduce jet-lag symptoms after crossing multiple time zones. Timing is central to the mechanism because mistimed dosing can delay adaptation.
Mechanism Target:
MODULATES Circadian Desynchronization — Timed exogenous melatonin helps re-align bodily rhythms with the destination schedule.
Target Phenotypes: Sleep disturbance HP:0002360 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Sleep disturbance (HP:0002360). HP:0002360 is a phenotype from the Human Phenotype Ontology. Fatigue HP:0012378 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Fatigue (HP:0012378). HP:0012378 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:12076414 SUPPORT Human Clinical
"Nine of the ten trials found that melatonin, taken close to the target bedtime at the destination (10pm to midnight), decreased jet-lag from flights crossing five or more time zones."
Systematic-review evidence supports timed melatonin for reducing jet lag after multi-time-zone flights.
PMID:12076414 SUPPORT Human Clinical
"The timing of the melatonin dose is important: if it is taken at the wrong time, early in the day, it is liable to cause sleepiness and delay adaptation to local time."
Supports modeling melatonin as a timing-sensitive circadian intervention rather than simply a sedative.
Prescribed Sleep Scheduling
Category: Therapeutic Action: Behavioral InterventionNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Behavioral Intervention (NCIT:C15184). NCIT:C15184 is a clinical intervention from the NCI Thesaurus. NCIT:C15184
Planned sleep-wake scheduling before or after travel is a behavioral intervention intended to reduce circadian misalignment and improve adaptation to destination time.
Mechanism Target:
MODULATES Circadian Desynchronization — Scheduling changes alter sleep timing relative to the shifted external light-dark cycle.
Show evidence (1 reference)
PMID:18041480 SUPPORT Human Clinical
"Treatment interventions fall into three broad categories: 1) prescribed sleep scheduling, 2) circadian phase shifting ("resetting the clock"), and 3) symptomatic treatment using hypnotic and stimulant medications."
AASM review frames prescribed sleep scheduling as one of the core treatment categories for jet lag disorder.
Circadian Phase Shifting With Timed Light and Dark Scheduling
Category: Therapeutic Action: Behavioral InterventionNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Behavioral Intervention (NCIT:C15184). NCIT:C15184 is a clinical intervention from the NCI Thesaurus. NCIT:C15184
Timed bright-light exposure and light avoidance can be used as circadian phase-shifting tools to accelerate adaptation to destination time.
Mechanism Target:
MODULATES Circadian Desynchronization — Timed light and dark exposure changes the phase relationship between the endogenous circadian system and destination clock time.
Show evidence (2 references)
PMID:18041480 SUPPORT Human Clinical
"Treatment interventions fall into three broad categories: 1) prescribed sleep scheduling, 2) circadian phase shifting ("resetting the clock"), and 3) symptomatic treatment using hypnotic and stimulant medications."
Supports phase-shifting interventions as a core jet-lag treatment category.
clinicaltrials:NCT00387179 SUPPORT Human Clinical
"This study will evaluate the combined effectiveness of light and non-light therapies at regulating sleep cycles and improving sleep quality."
ClinicalTrials.gov documents research into light and non-light circadian interventions relevant to jet lag and sleep-cycle regulation.
Symptomatic Hypnotic Pharmacotherapy
Category: Therapeutic Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Short-term hypnotic medication is a symptomatic approach for destination-night sleep disturbance. It is modeled as symptom management rather than a re-entrainment mechanism.
Target Phenotypes: Sleep disturbance HP:0002360 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Sleep disturbance (HP:0002360). HP:0002360 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:18041480 SUPPORT Human Clinical
"Treatment interventions fall into three broad categories: 1) prescribed sleep scheduling, 2) circadian phase shifting ("resetting the clock"), and 3) symptomatic treatment using hypnotic and stimulant medications."
Supports hypnotic medication as a symptomatic treatment category for jet lag disorder, without asserting circadian re-entrainment.
Armodafinil for Jet-Lag-Associated Excessive Sleepiness
Category: Therapeutic Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: armodafinil CHEBI:77590 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses armodafinil (CHEBI:77590). CHEBI:77590 is a therapeutic agent from Chemical Entities of Biological Interest.
Armodafinil, the R-enantiomer of modafinil, is a wake-promoting symptomatic treatment studied for excessive sleepiness after eastward transmeridian travel. It should be distinguished from racemic modafinil, which contains both R- and S-modafinil.
Target Phenotypes: Excessive daytime somnolence HP:0001262 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Excessive daytime somnolence (HP:0001262). HP:0001262 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:20530317 SUPPORT Human Clinical
"Armodafinil at 150 mg/d provided a significant benefit in sleep latency on the MSLT (days 1-2: mean, 11.7 minutes vs 4.8 minutes for placebo; P<.001)"
Phase 3 trial evidence supports armodafinil improving objective wakefulness in jet-lag-associated excessive sleepiness.
PMID:20530317 SUPPORT Human Clinical
"CONCLUSION: Armodafinil increased wakefulness after eastward travel through 6 time zones."
Confirms the studied clinical effect as increased wakefulness after eastward travel.
🌍

Environmental Factors

1
Rapid Transmeridian Travel
transmeridian travel ECTO:6000033 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is transmeridian travel, annotated with exposure to travel (ECTO:6000033). ECTO:6000033 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
Rapid air travel across several time zones shifts the external light-dark and social sleep-wake schedule faster than the endogenous circadian system can re-entrain.
Show evidence (1 reference)
PMID:12076414 SUPPORT Human Clinical
"Jet-lag commonly affects air travellers who cross several time zones. It results from the body's internal rhythms being out of step with the day-night cycle at the destination."
Identifies transmeridian air travel and destination day-night mismatch as the defining exposure context.
⚖️

Clinical Burden

Low
Typical jet lag is self-limited over days after travel and does not usually impose long-term morbidity, intensive management, or mortality risk. It is still clinically relevant because the transient sleep and daytime-function disruption can affect travel, work performance, and safety.
Show evidence (1 reference)
PMID:12076414 SUPPORT Human Clinical
"After a flight through six or more time zones most travellers will take 4‐6 days to re‐establish a normal sleeping pattern and not to feel tired during the day."
The typical course is measured in days after major time-zone travel, supporting low disease-level burden while acknowledging temporary daytime impairment.
📊

Related Datasets

2
Transcriptional profiling of mouse prefrontal cortex and nucleus accumbens under chronic jet lag geo:GSE153540
Chronic jet lag (CJL) induced by shifting light-dark cycles repeatedly is a commonly used protocol to mimic the environmental light/dark changes encountered by shift workers. We conducted RNA sequencing using prefrontal cortex (PFC) and nucleus accumbens (NAc) tissues from these animals, which are brains regions strongly implicated in the pathology of various neurological and psychiatric conditions. Our results reveal the alterations of brain activities and systematic reprogramming of gene expression in brain tissues under CJL, building hypothesis for how CJL increases the susceptibility to neurological and psychiatric diseases.
mouse BULK RNA SEQ n=24
PMID:33087702
Identified by GEO DataSets index search for Jet Lag (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Effect of 8-weeks of chronic jet lag lighting (CJL) on gene expression in the livers of Eu-MYC mice geo:GSE242159
Background: Disruption of natural diurnal light cycles, such as that experienced by shift workers, is linked to enhanced cancer incidence. Several mouse models of cancer have been shown to develop more severe disease when exposed to irregular light/dark cycles, further supporting the connection between circadian disruption and increased cancer risk. Cryptochrome 2 (CRY2), a repressive component of the molecular circadian clock, facilitates the turnover of the oncoprotein c-MYC, one mechanism that may link the molecular clock to tumorigenesis.
mouse BULK RNA SEQ n=26
Identified by GEO DataSets index search for Jet Lag (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
🔬

Clinical Trials

3
NCT00758498 PHASE_III COMPLETED
Randomized, double-blind, placebo-controlled study of armodafinil 50 or 150 mg/day in healthy subjects with excessive sleepiness associated with jet lag disorder.
Target Phenotypes: Excessive daytime somnolence HP:0001262 Human Phenotype Ontology (HP) Relation: this clinical trial targets this phenotype This clinical trial targets Excessive daytime somnolence (HP:0001262). HP:0001262 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
clinicaltrials:NCT00758498 SUPPORT Human Clinical
"This is a randomized, double-blind, placebo-controlled, parallel-group study of armodafinil and placebo treatment in healthy subjects with excessive sleepiness associated with jet lag disorder."
ClinicalTrials.gov documents the armodafinil jet-lag-disorder trial.
PMID:20530317 SUPPORT Human Clinical
"TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00758498."
Published trial registration links the phase 3 armodafinil study to NCT00758498.
NCT00387179 COMPLETED
Study of photic and non-photic stimuli, including light and non-light therapies, for regulating sleep cycles and improving sleep quality in jet lag and related sleep disorders.
Target Phenotypes: Sleep disturbance HP:0002360 Human Phenotype Ontology (HP) Relation: this clinical trial targets this phenotype This clinical trial targets Sleep disturbance (HP:0002360). HP:0002360 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
clinicaltrials:NCT00387179 SUPPORT Human Clinical
"Jet lag and some sleep disorders are caused by a disruption in an individual's "internal clock.""
Trial registry framing supports this as circadian-intervention research relevant to jet lag.
clinicaltrials:NCT00387179 SUPPORT Human Clinical
"This study will evaluate the combined effectiveness of light and non-light therapies at regulating sleep cycles and improving sleep quality."
Documents research into combined photic and non-photic circadian interventions.
NCT00097474 COMPLETED
Study of hydrocortisone, melatonin, combined hydrocortisone/melatonin, and placebo for symptoms and circadian re-establishment after eastward travel.
Target Phenotypes: Sleep disturbance HP:0002360 Human Phenotype Ontology (HP) Relation: this clinical trial targets this phenotype This clinical trial targets Sleep disturbance (HP:0002360). HP:0002360 is a phenotype from the Human Phenotype Ontology. Fatigue HP:0012378 Human Phenotype Ontology (HP) Relation: this clinical trial targets this phenotype This clinical trial targets Fatigue (HP:0012378). HP:0012378 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
clinicaltrials:NCT00097474 SUPPORT Human Clinical
"This study will examine the effects of cortisol (hydrocortisone), melatonin, a combination of cortisol and melatonin, and placebo (an inactive substance) on jet lag symptoms."
ClinicalTrials.gov documents hydrocortisone and melatonin research for jet lag symptoms.
clinicaltrials:NCT00097474 SUPPORT Human Clinical
"This study will test whether taking cortisol, melatonin, or both can help re-establish the body's day-night cycle and result in less jet lag."
Captures a research question focused on endocrine/circadian re-establishment after travel.
{ }

Source YAML

click to show 
name: Jet Lag
creation_date: "2026-07-11T00:00:00Z"
category: Environmental
categories:
- Sleep Disorder
- Circadian Rhythm Sleep-Wake Disorder
- Environmental/Exposure-Related Disorder
parents:
- Circadian Rhythm Sleep Disorder
- Sleep-Wake Disorder
disease_term:
  preferred_term: jet lag
  term:
    id: MONDO:0024381
    label: circadian rhythm sleep disorder, jet lag type
synonyms:
- Jet lag disorder
- Circadian rhythm sleep disorder, jet lag type
- Transmeridian travel-associated circadian misalignment
description: >-
  Jet lag is an acquired circadian rhythm sleep-wake disorder caused by rapid
  travel across time zones, in which the endogenous circadian system is
  misaligned with the destination light-dark and sleep-wake schedule. The
  typical burden is transient but functionally disruptive, with daytime fatigue,
  sleep disturbance, impaired mental efficiency, weakness, irritability, and
  excessive sleepiness after multi-time-zone travel. The core mechanism is
  circadian desynchronization rather than a primary genetic clock disorder.
clinical_burden:
  burden_level: LOW
  rationale: >-
    Typical jet lag is self-limited over days after travel and does not usually
    impose long-term morbidity, intensive management, or mortality risk. It is
    still clinically relevant because the transient sleep and daytime-function
    disruption can affect travel, work performance, and safety.
  evidence:
  - reference: PMID:12076414
    reference_title: "Melatonin for the prevention and treatment of jet lag."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      After a flight through six or more time zones most travellers will take
      4‐6 days to re‐establish a normal sleeping pattern and not to feel tired
      during the day.
    explanation: >-
      The typical course is measured in days after major time-zone travel,
      supporting low disease-level burden while acknowledging temporary daytime
      impairment.
environmental:
- name: Rapid Transmeridian Travel
  exposure_term:
    preferred_term: transmeridian travel
    term:
      id: ECTO:6000033
      label: exposure to travel
  presence: required
  description: >-
    Rapid air travel across several time zones shifts the external light-dark
    and social sleep-wake schedule faster than the endogenous circadian system
    can re-entrain.
  effect: >-
    Produces circadian desynchronization between internal rhythms and the
    destination day-night cycle.
  evidence:
  - reference: PMID:12076414
    reference_title: "Melatonin for the prevention and treatment of jet lag."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Jet-lag commonly affects air travellers who cross several time zones. It
      results from the body's internal rhythms being out of step with the
      day-night cycle at the destination.
    explanation: >-
      Identifies transmeridian air travel and destination day-night mismatch as
      the defining exposure context.
pathophysiology:
- name: Rapid Transmeridian Light-Dark Shift
  role: trigger
  biological_scale: ORGANISM
  conforms_to: "circadian_phase_misalignment#Loss or Mistiming of Photic Entrainment Input"
  description: >-
    The initiating event is abrupt displacement of local clock time and
    light-dark exposure relative to the traveler's entrained internal circadian
    phase.
  biological_processes:
  - preferred_term: Entrainment of circadian clock
    term:
      id: GO:0009649
      label: entrainment of circadian clock
  evidence:
  - reference: PMID:12076414
    reference_title: "Melatonin for the prevention and treatment of jet lag."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Jet-lag commonly affects air travellers who cross several time zones. It
      results from the body's internal rhythms being out of step with the
      day-night cycle at the destination.
    explanation: >-
      Establishes the time-zone crossing and external day-night mismatch that
      initiate jet lag.
  downstream:
  - target: Circadian Desynchronization
    causal_link_type: DIRECT
    description: >-
      The shifted external light-dark schedule places internal rhythms out of
      phase with the destination schedule.
- name: Circadian Desynchronization
  role: central_effector
  biological_scale: ORGANISM
  conforms_to: "circadian_phase_misalignment#Misalignment Between Endogenous Circadian Phase and the Imposed Sleep-Wake Schedule"
  description: >-
    The endogenous circadian system becomes misaligned with the destination
    day-night cycle, so sleep propensity, alertness, melatonin timing, and other
    rhythmic physiology occur at inappropriate local times.
  biological_processes:
  - preferred_term: Circadian rhythm
    term:
      id: GO:0007623
      label: circadian rhythm
  evidence:
  - reference: PMID:12076414
    reference_title: "Melatonin for the prevention and treatment of jet lag."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Jet lag is caused by desynchronization between the body's circadian system
      and the new day‐night cycle at the traveller's destination.
    explanation: >-
      Directly states the core pathophysiologic mechanism as circadian-system
      desynchronization from the destination day-night cycle.
  downstream:
  - target: Sleep-Wake Symptom Cluster
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Mis-timed sleep propensity
    - Altered melatonin timing
    - Acute sleep loss from travel
    description: >-
      Circadian misalignment and travel-related sleep loss produce the clinical
      sleep and daytime-function manifestations.
- name: Sleep-Wake Symptom Cluster
  role: consequence
  biological_scale: ORGANISM
  conforms_to: "circadian_phase_misalignment#Circadian Sleep-Wake Disorder Syndrome"
  description: >-
    Misaligned circadian phase and acute sleep loss produce the characteristic
    symptom cluster of sleep disturbance, daytime fatigue, excessive sleepiness,
    impaired mental efficiency, weakness, and irritability.
  biological_processes:
  - preferred_term: Sleep
    term:
      id: GO:0030431
      label: sleep
  evidence:
  - reference: PMID:12076414
    reference_title: "Melatonin for the prevention and treatment of jet lag."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The symptoms of jet lag are primarily daytime fatigue and sleep
      disturbance, but also include loss of mental efficiency , weakness and
      irritability
    explanation: >-
      Summarizes the characteristic downstream clinical symptom cluster.
  downstream:
  - target: Fatigue
    causal_link_type: DIRECT
    description: Daytime fatigue is a primary manifestation of the symptom cluster.
  - target: Cognitive Impairment
    causal_link_type: DIRECT
    description: Loss of mental efficiency is a recognized daytime manifestation.
  - target: Asthenia
    causal_link_type: DIRECT
    description: Weakness is a recognized manifestation of the symptom cluster.
  - target: Sleep Disturbance
    causal_link_type: DIRECT
    description: Sleep disturbance is a primary manifestation of the symptom cluster.
  - target: Irritability
    causal_link_type: DIRECT
    description: Irritability is a recognized downstream manifestation.
phenotypes:
- name: Fatigue
  category: Constitutional
  description: >-
    Daytime tiredness and low energy after transmeridian travel, typically
    improving as circadian alignment is restored.
  phenotype_term:
    preferred_term: Fatigue
    term:
      id: HP:0012378
      label: Fatigue
  evidence:
  - reference: PMID:12076414
    reference_title: "Melatonin for the prevention and treatment of jet lag."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The symptoms of jet lag are primarily daytime fatigue and sleep
      disturbance, but also include loss of mental efficiency , weakness and
      irritability
    explanation: >-
      Identifies daytime fatigue as a primary symptom of jet lag.
- name: Cognitive Impairment
  category: Cognitive
  description: >-
    Transient loss of mental efficiency can occur during jet lag while the
    circadian system remains misaligned with local time.
  phenotype_term:
    preferred_term: Cognitive impairment
    term:
      id: HP:0100543
      label: Cognitive impairment
  evidence:
  - reference: PMID:12076414
    reference_title: "Melatonin for the prevention and treatment of jet lag."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The symptoms of jet lag are primarily daytime fatigue and sleep
      disturbance, but also include loss of mental efficiency , weakness and
      irritability
    explanation: >-
      Identifies loss of mental efficiency as part of the jet-lag symptom
      cluster.
- name: Asthenia
  category: Constitutional
  description: >-
    Transient weakness can occur as part of the daytime-function symptom
    cluster during jet lag.
  phenotype_term:
    preferred_term: Asthenia
    term:
      id: HP:0025406
      label: Asthenia
  evidence:
  - reference: PMID:12076414
    reference_title: "Melatonin for the prevention and treatment of jet lag."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The symptoms of jet lag are primarily daytime fatigue and sleep
      disturbance, but also include loss of mental efficiency , weakness and
      irritability
    explanation: >-
      Identifies weakness as part of the jet-lag symptom cluster.
- name: Sleep Disturbance
  category: Sleep
  description: >-
    Disrupted sleep timing and quality after time-zone travel, reflecting
    mismatch between local clock time and internal circadian sleep propensity.
  phenotype_term:
    preferred_term: Sleep disturbance
    term:
      id: HP:0002360
      label: Sleep disturbance
  evidence:
  - reference: PMID:12076414
    reference_title: "Melatonin for the prevention and treatment of jet lag."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The symptoms of jet lag are primarily daytime fatigue and sleep
      disturbance, but also include loss of mental efficiency , weakness and
      irritability
    explanation: >-
      Identifies sleep disturbance as a primary symptom of jet lag.
- name: Excessive Daytime Somnolence
  category: Sleep
  description: >-
    Excessive sleepiness during the destination daytime can occur when internal
    circadian sleep propensity remains aligned to the origin time zone.
  phenotype_term:
    preferred_term: Excessive daytime somnolence
    term:
      id: HP:0001262
      label: Excessive daytime somnolence
  evidence:
  - reference: PMID:20530317
    reference_title: >-
      A phase 3, double-blind, randomized, placebo-controlled study of
      armodafinil for excessive sleepiness associated with jet lag disorder.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Adults with a history of jet lag symptoms on previous flights through
      multiple time zones flew from the United States to France (a 6-hour time
      zone change) for a 3-day laboratory-based study period.
    explanation: >-
      The armodafinil trial enrolled travelers with jet-lag symptoms after a
      six-hour time-zone shift and evaluated excessive sleepiness as the target
      symptom domain.
- name: Irritability
  category: Behavioral
  description: >-
    Irritability can occur as part of the daytime-function symptom cluster
    during jet lag.
  phenotype_term:
    preferred_term: Irritability
    term:
      id: HP:0000737
      label: Irritability
  evidence:
  - reference: PMID:12076414
    reference_title: "Melatonin for the prevention and treatment of jet lag."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The symptoms of jet lag are primarily daytime fatigue and sleep
      disturbance, but also include loss of mental efficiency , weakness and
      irritability
    explanation: >-
      Identifies irritability as part of the jet-lag symptom cluster.
treatments:
- name: Timed Melatonin
  action_category: THERAPEUTIC
  therapeutic_modality: SMALL_MOLECULE
  description: >-
    Melatonin timed close to the destination bedtime is used to shift circadian
    phase and reduce jet-lag symptoms after crossing multiple time zones. Timing
    is central to the mechanism because mistimed dosing can delay adaptation.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: melatonin
      term:
        id: CHEBI:16796
        label: melatonin
  target_mechanisms:
  - target: Circadian Desynchronization
    treatment_effect: MODULATES
    description: >-
      Timed exogenous melatonin helps re-align bodily rhythms with the
      destination schedule.
  target_phenotypes:
  - preferred_term: Sleep disturbance
    term:
      id: HP:0002360
      label: Sleep disturbance
  - preferred_term: Fatigue
    term:
      id: HP:0012378
      label: Fatigue
  evidence:
  - reference: PMID:12076414
    reference_title: "Melatonin for the prevention and treatment of jet lag."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Nine of the ten trials found that melatonin, taken close to the target
      bedtime at the destination (10pm to midnight), decreased jet-lag from
      flights crossing five or more time zones.
    explanation: >-
      Systematic-review evidence supports timed melatonin for reducing jet lag
      after multi-time-zone flights.
  - reference: PMID:12076414
    reference_title: "Melatonin for the prevention and treatment of jet lag."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The timing of the melatonin dose is important: if it is taken at the wrong
      time, early in the day, it is liable to cause sleepiness and delay
      adaptation to local time.
    explanation: >-
      Supports modeling melatonin as a timing-sensitive circadian intervention
      rather than simply a sedative.
- name: Prescribed Sleep Scheduling
  action_category: THERAPEUTIC
  therapeutic_modality: BEHAVIORAL
  description: >-
    Planned sleep-wake scheduling before or after travel is a behavioral
    intervention intended to reduce circadian misalignment and improve adaptation
    to destination time.
  treatment_term:
    preferred_term: Behavioral Intervention
    term:
      id: NCIT:C15184
      label: Behavioral Intervention
  target_mechanisms:
  - target: Circadian Desynchronization
    treatment_effect: MODULATES
    description: >-
      Scheduling changes alter sleep timing relative to the shifted external
      light-dark cycle.
  evidence:
  - reference: PMID:18041480
    reference_title: >-
      Circadian rhythm sleep disorders: part I, basic principles, shift work and
      jet lag disorders. An American Academy of Sleep Medicine review.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Treatment interventions fall into three broad categories: 1) prescribed
      sleep scheduling, 2) circadian phase shifting ("resetting the clock"), and
      3) symptomatic treatment using hypnotic and stimulant medications.
    explanation: >-
      AASM review frames prescribed sleep scheduling as one of the core treatment
      categories for jet lag disorder.
- name: Circadian Phase Shifting With Timed Light and Dark Scheduling
  action_category: THERAPEUTIC
  therapeutic_modality: BEHAVIORAL
  description: >-
    Timed bright-light exposure and light avoidance can be used as circadian
    phase-shifting tools to accelerate adaptation to destination time.
  notes: >-
    A local NCIT light-therapy term exists but is retired, so this is represented
    with the broader behavioral-intervention action term and the phase-shifting
    mechanism is stated explicitly.
  treatment_term:
    preferred_term: Behavioral Intervention
    term:
      id: NCIT:C15184
      label: Behavioral Intervention
  target_mechanisms:
  - target: Circadian Desynchronization
    treatment_effect: MODULATES
    description: >-
      Timed light and dark exposure changes the phase relationship between the
      endogenous circadian system and destination clock time.
  evidence:
  - reference: PMID:18041480
    reference_title: >-
      Circadian rhythm sleep disorders: part I, basic principles, shift work and
      jet lag disorders. An American Academy of Sleep Medicine review.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Treatment interventions fall into three broad categories: 1) prescribed
      sleep scheduling, 2) circadian phase shifting ("resetting the clock"), and
      3) symptomatic treatment using hypnotic and stimulant medications.
    explanation: >-
      Supports phase-shifting interventions as a core jet-lag treatment category.
  - reference: clinicaltrials:NCT00387179
    reference_title: Circadian Integration of Photic and Non-photic Stimuli
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This study will evaluate the combined effectiveness of light and non-light
      therapies at regulating sleep cycles and improving sleep quality.
    explanation: >-
      ClinicalTrials.gov documents research into light and non-light circadian
      interventions relevant to jet lag and sleep-cycle regulation.
- name: Symptomatic Hypnotic Pharmacotherapy
  action_category: THERAPEUTIC
  therapeutic_modality: SMALL_MOLECULE
  description: >-
    Short-term hypnotic medication is a symptomatic approach for destination-night
    sleep disturbance. It is modeled as symptom management rather than a
    re-entrainment mechanism.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  target_phenotypes:
  - preferred_term: Sleep disturbance
    term:
      id: HP:0002360
      label: Sleep disturbance
  evidence:
  - reference: PMID:18041480
    reference_title: >-
      Circadian rhythm sleep disorders: part I, basic principles, shift work and
      jet lag disorders. An American Academy of Sleep Medicine review.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Treatment interventions fall into three broad categories: 1) prescribed
      sleep scheduling, 2) circadian phase shifting ("resetting the clock"), and
      3) symptomatic treatment using hypnotic and stimulant medications.
    explanation: >-
      Supports hypnotic medication as a symptomatic treatment category for jet
      lag disorder, without asserting circadian re-entrainment.
- name: Armodafinil for Jet-Lag-Associated Excessive Sleepiness
  action_category: THERAPEUTIC
  therapeutic_modality: SMALL_MOLECULE
  description: >-
    Armodafinil, the R-enantiomer of modafinil, is a wake-promoting symptomatic
    treatment studied for excessive sleepiness after eastward transmeridian
    travel. It should be distinguished from racemic modafinil, which contains
    both R- and S-modafinil.
  mechanism:
  - name: Wake promotion without circadian re-entrainment
    description: >-
      Wake promotion is represented here as symptomatic treatment of sleepiness,
      not correction of the upstream circadian desynchronization. ChEBI separates
      armodafinil (CHEBI:77590) from racemic modafinil (CHEBI:31859), preserving
      the R-enantiomer versus racemate distinction.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: armodafinil
      term:
        id: CHEBI:77590
        label: armodafinil
  target_phenotypes:
  - preferred_term: Excessive daytime somnolence
    term:
      id: HP:0001262
      label: Excessive daytime somnolence
  evidence:
  - reference: PMID:20530317
    reference_title: >-
      A phase 3, double-blind, randomized, placebo-controlled study of
      armodafinil for excessive sleepiness associated with jet lag disorder.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Armodafinil at 150 mg/d provided a significant benefit in sleep latency on
      the MSLT (days 1-2: mean, 11.7 minutes vs 4.8 minutes for placebo; P<.001)
    explanation: >-
      Phase 3 trial evidence supports armodafinil improving objective
      wakefulness in jet-lag-associated excessive sleepiness.
  - reference: PMID:20530317
    reference_title: >-
      A phase 3, double-blind, randomized, placebo-controlled study of
      armodafinil for excessive sleepiness associated with jet lag disorder.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      CONCLUSION: Armodafinil increased wakefulness after eastward travel
      through 6 time zones.
    explanation: >-
      Confirms the studied clinical effect as increased wakefulness after
      eastward travel.
clinical_trials:
- name: NCT00758498
  phase: PHASE_III
  status: COMPLETED
  description: >-
    Randomized, double-blind, placebo-controlled study of armodafinil 50 or
    150 mg/day in healthy subjects with excessive sleepiness associated with jet
    lag disorder.
  target_phenotypes:
  - preferred_term: Excessive daytime somnolence
    term:
      id: HP:0001262
      label: Excessive daytime somnolence
  evidence:
  - reference: clinicaltrials:NCT00758498
    reference_title: >-
      A 3-Day, Randomized, Double-Blind, Placebo-Controlled, Parallel Group
      Study of the Effect of Armodafinil Treatment (50 and 150 mg/Day) in
      Healthy Subjects With Excessive Sleepiness Associated With Jet Lag
      Disorder
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This is a randomized, double-blind, placebo-controlled, parallel-group
      study of armodafinil and placebo treatment in healthy subjects with
      excessive sleepiness associated with jet lag disorder.
    explanation: >-
      ClinicalTrials.gov documents the armodafinil jet-lag-disorder trial.
  - reference: PMID:20530317
    reference_title: >-
      A phase 3, double-blind, randomized, placebo-controlled study of
      armodafinil for excessive sleepiness associated with jet lag disorder.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00758498.
    explanation: >-
      Published trial registration links the phase 3 armodafinil study to
      NCT00758498.
- name: NCT00387179
  status: COMPLETED
  description: >-
    Study of photic and non-photic stimuli, including light and non-light
    therapies, for regulating sleep cycles and improving sleep quality in jet
    lag and related sleep disorders.
  target_phenotypes:
  - preferred_term: Sleep disturbance
    term:
      id: HP:0002360
      label: Sleep disturbance
  evidence:
  - reference: clinicaltrials:NCT00387179
    reference_title: Circadian Integration of Photic and Non-photic Stimuli
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Jet lag and some sleep disorders are caused by a disruption in an
      individual's "internal clock."
    explanation: >-
      Trial registry framing supports this as circadian-intervention research
      relevant to jet lag.
  - reference: clinicaltrials:NCT00387179
    reference_title: Circadian Integration of Photic and Non-photic Stimuli
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This study will evaluate the combined effectiveness of light and non-light
      therapies at regulating sleep cycles and improving sleep quality.
    explanation: >-
      Documents research into combined photic and non-photic circadian
      interventions.
- name: NCT00097474
  status: COMPLETED
  description: >-
    Study of hydrocortisone, melatonin, combined hydrocortisone/melatonin, and
    placebo for symptoms and circadian re-establishment after eastward travel.
  target_phenotypes:
  - preferred_term: Sleep disturbance
    term:
      id: HP:0002360
      label: Sleep disturbance
  - preferred_term: Fatigue
    term:
      id: HP:0012378
      label: Fatigue
  evidence:
  - reference: clinicaltrials:NCT00097474
    reference_title: >-
      The Effects of Hydrocortisone, Melatonin, and Placebo on Symptoms of Jet
      Lag
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This study will examine the effects of cortisol (hydrocortisone),
      melatonin, a combination of cortisol and melatonin, and placebo (an
      inactive substance) on jet lag symptoms.
    explanation: >-
      ClinicalTrials.gov documents hydrocortisone and melatonin research for jet
      lag symptoms.
  - reference: clinicaltrials:NCT00097474
    reference_title: >-
      The Effects of Hydrocortisone, Melatonin, and Placebo on Symptoms of Jet
      Lag
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This study will test whether taking cortisol, melatonin, or both can help
      re-establish the body's day-night cycle and result in less jet lag.
    explanation: >-
      Captures a research question focused on endocrine/circadian
      re-establishment after travel.
references:
- reference: PMID:12076414
  title: "Melatonin for the prevention and treatment of jet lag."
- reference: PMID:18041480
  title: >-
    Circadian rhythm sleep disorders: part I, basic principles, shift work and
    jet lag disorders. An American Academy of Sleep Medicine review.
- reference: PMID:20530317
  title: >-
    A phase 3, double-blind, randomized, placebo-controlled study of armodafinil
    for excessive sleepiness associated with jet lag disorder.
datasets:
- accession: geo:GSE153540
  title: Transcriptional profiling of mouse prefrontal cortex and nucleus accumbens under chronic jet lag
  description: Chronic jet lag (CJL) induced by shifting light-dark cycles repeatedly is a commonly used protocol to mimic the environmental light/dark changes encountered by shift workers. We conducted RNA sequencing using prefrontal cortex (PFC) and nucleus accumbens (NAc) tissues from these animals, which are brains regions strongly implicated in the pathology of various neurological and psychiatric conditions. Our results reveal the alterations of brain activities and systematic reprogramming of gene expression in brain tissues under CJL, building hypothesis for how CJL increases the susceptibility to neurological and psychiatric diseases.
  organism:
    preferred_term: mouse
    term:
      id: NCBITaxon:10090
      label: Mus musculus
  data_type: BULK_RNA_SEQ
  sample_count: 24
  publication: PMID:33087702
  notes: Identified by GEO DataSets index search for Jet Lag (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE242159
  title: Effect of 8-weeks of chronic jet lag lighting (CJL) on gene expression in the livers of Eu-MYC mice
  description: 'Background: Disruption of natural diurnal light cycles, such as that experienced by shift workers, is linked to enhanced cancer incidence. Several mouse models of cancer have been shown to develop more severe disease when exposed to irregular light/dark cycles, further supporting the connection between circadian disruption and increased cancer risk. Cryptochrome 2 (CRY2), a repressive component of the molecular circadian clock, facilitates the turnover of the oncoprotein c-MYC, one mechanism that may link the molecular clock to tumorigenesis.'
  organism:
    preferred_term: mouse
    term:
      id: NCBITaxon:10090
      label: Mus musculus
  data_type: BULK_RNA_SEQ
  sample_count: 26
  notes: Identified by GEO DataSets index search for Jet Lag (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
📚

References & Deep Research

References

3
PMID:12076414
Melatonin for the prevention and treatment of jet lag.
No top-level findings curated for this source.
PMID:18041480
Circadian rhythm sleep disorders: part I, basic principles, shift work and jet lag disorders. An American Academy of Sleep Medicine review.
No top-level findings curated for this source.
PMID:20530317
A phase 3, double-blind, randomized, placebo-controlled study of armodafinil for excessive sleepiness associated with jet lag disorder.
No top-level findings curated for this source.