The aim of this randomized, double-blind, placebo-controlled crossover trial is to determine the effects of caffeine vs. placebo on psychomotor vigilance and carbon dioxide tolerance during graded hypercapnia.

Healthy and fit young adults (men and women) will participate in this study. Participants will perform two primary experimental trials on separate days, one after consuming 400 mg caffeine, and the other after consuming a non-caffeinated placebo. During each trial, participants will breathe increasing levels of inspired CO2 in a stepwise manner (0%, 2%, 4%, 6%, 8% CO2; all with 21% oxygen) during successive 12-minute stages. The endpoints of the graded hypercapnia protocol will be completion of the 8% CO2 stage, voluntary subject termination due to discomfort, or end-tidal CO2 greater than 70 mmHg. The investigators hypothesize that, compared to placebo, caffeine will lower end tidal and arterialized PCO2 and mitigate CO2-mediated decrements in psychomotor vigilance.

Inclusion Criteria:

• Male or female, age 18-45
• Body mass index 18.5-30.0 kg m-2
• Body mass 50-100 kg
• In good health as determined by the Office of Medical Support & Oversight (OMSO) General Medical Clearance
• Perform exercise at least 2 times per week
• Willing to abstain from exercise and alcoholic beverages for 24 hours before each study visit.
• Willing to abstain from caffeine for 12 hours prior to all study visits
• Willing to abstain from caffeine for 12 hours after visits 3 and 4
• Willing to remain fasted (no food or fluid other than water) from lights out until after arrival at the laboratory the following morning on each study day (~10 hours)
• Have supervisor approval if permanent party military or a federal employee at U.S. Army Natick Soldier System Center

Exclusion Criteria:

• Females who are pregnant or planning to become pregnant during the study
• Females who are surgically sterile
• History of severe adverse reaction to caffeine (e.g., headache, dizziness, diarrhea, insomnia)
• Taking dietary supplements, prescriptions, or over the counter medication, other than a contraceptive (unless approved by OMSO & PI)
• Abnormal blood count (For example: hemoglobin (Hb) outside of the typical normal values reported by LabCorp in accordance with OMSO (Normal [Hb] Males = 12.6-17.7 g/dL; Females = 11.1-15.9 g/dL) or hematocrit (Hct) outside of the normal ranges (Normal Hct Males = 37.5-51.0%; Females = 34.0-46.6%) levels, presence of abnormal blood chemicals (hemoglobin S or sickle cell traits)
• Any history of pulmonary or cardiovascular disease
• Current diagnosis of asthma (childhood asthma with no recurrence in the last 5 years ok)
• Smokers or nicotine users (unless have quit >1 month prior)
• Current or recent respiratory tract or sinus infections (< 1 month prior)
• Current diagnosis of migraine or recurrent headaches (previous diagnosis with no recurrence in the last 5 years ok)
• Any history of seizures
• Any history of panic disorder
• Blood donation in the previous 8 weeks
• Positive Covid-19 test within the last month (based on self-report)