The purposes of this study are 1) to determine the pharmacokinetics of nicotine after multiple dose administration by electronic cigarette and 2) to compare the acute effects of multiple dose of nicotine administrated by electronic cigarette compared with those obteined by cigarette.

Electronic cigarettes (e-cigarettes) are battery-operated devices that deliver nicotine via inhaled vapour or "vaping". At present, e-cigarettes are becoming increasingly popular among smokers worldwide. However, knowledge about e-cigarette nicotine pharmacology remains limited.

The aims of this study are 1) to determine the pharmacokinetics of nicotine after multiple dose administration by electronic cigarette and 2) to compare the acute effects of multiple dose of nicotine administrated by electronic cigarette compared with those obteined by cigarette.

Inclusion Criteria:

• Understanding and accepting the study procedures and signing the informed consent.
• Male adults volunteers (18-45 years old).
• Clinical history and physical examination demonstrating no organic or psychiatric disorders.
• The ECG and general blood and urine laboratory tests performed before the study should be within normal ranges. Minor or occasional changes from normal ranges are accepted if, in the investigator's opinion, considering the current state of the art, they are not clinically significant, are not life-threatening for the subjects and do not interfere with the product assessment. These changes and their non-relevance will be justified in writing specifically.
• Present use of nicotine without serious adverse reactions.
• Smokers ≥ 3 cigarettes/day.

Exclusion Criteria:

• Having suffered any cardiovascular and/or respiratory disease in the three months prior to the study start.
• History of drug dependence (except for nicotine dependence).
• Daily consumption >4 standard units of ethanol.
• Regular use of any drug in the month prior to the study sessions. The treatment with single or limited doses of symptomatic medicinal products in the week prior to the study sessions will not be a reason for exclusion if it is calculated that it has been cleared completely the day of the experimental session.
• Having suffered any organic disease or major surgery in the three months prior to the study start.
• Blood donation 12 weeks before or participation in other clinical trials with drugs in the previous 12 weeks.
• History or clinical evidence of gastrointestinal, liver, renal or other disorders which may lead to suspecting a disorder in drug absorption, distribution, metabolism or excretion, or that suggest gastrointestinal irritation due to drugs.
• Subjects unable to understand the nature, consequences of the study and the procedures requested to be followed.
• Use of any drug or substance inhibitor of cytochrome P-450-1A6 (CYP1A6) (p.e. raloxifene, coumarins, etc)