Understanding Oral Nicotine Pouch Use in Healthy Volunteers

Inclusion criteria

• Healthy based on medical history and limited physical examination.

• Heart rate < 105 BPM*
• Systolic Blood Pressure < 160 and > 90*
• Diastolic Blood Pressure < 100 and > 50*

*Considered out of range if both machine and manual readings are above/below these thresholds.

• Body Mass Index ≤ 38.0
• Willingness to abstain from illicit drug use for the duration of the study and cannabis for 48 hours prior to each hospital visit
• Group 1 (n=12) Smoke cigarettes regularly (smoked 20 of past 30 days, 5 or more cigarettes per day)
• Group 2 (n=12) use nicotine-containing e-cigarettes regularly (use on 20 of past 30 days)
• Participants may be dual users of cigarettes and e-cigarettes, but during the study will use their predominant product (i.e., the product they use on more days in the past 30 and more frequently on days that they use it).
• Saliva Cotinine >50 ng/ml
• Age: ≥ 21 years old and ≤ 65 years old
• Willingness to abstain from smoking all combustible products (tobacco and cannabis) for 12 hours before admission
• Willingness to abstain from nicotine products (vaping/oral use) 12 hours before each admission

Exclusion criteria

• • Unstable medical conditions:

• Heart disease
• Seizures
• Cancer
• Thyroid disease (okay if controlled with medication)
• Diabetes
• Hepatitis B or C or Liver disease
• Glaucoma
• Kidney disease or urinary retention
• An ulcer in the past year
• Diagnosis of asthma or COPD

• Drug/Alcohol Dependence
• Alcohol or illicit drug dependence within the past 12 months (currently in treatment) with the exception of those who recently completed an alcohol/drug treatment program
• Positive toxicology test at the screening visit (THC & prescribed medications okay)
• Opioid replacement therapy (including methadone, buprenorphine, or other)

• Psychiatric conditions
• Current or past schizophrenia, and/or current or past bipolar disorder
• Major depression, current or within the past year
• Major personality disorder
• Participants with current or past minor or moderate depression and/or anxiety disorders will be reviewed by the PI [study physician] and considered for inclusion
• History of psychiatric hospitalizations are not exclusionary, but study participation will be determined as per PI's [study physician's] approval
• Suicidal ideation within the past month

• Current regular use of any psychiatric medications with the exception of SSRIs and SNRIs and current evaluation by the PI that the participant is otherwise healthy, stable, and able to participate
• Congenital or acquired immunodeficiency disorders (i.e. HIV, congenital immune deficiency syndrome, chronic diseases)
• Other disorders (i.e. ICU, malnutrition, immunosuppressive therapy)
• Traumatic brain injury
• Recent onset or change (worsening) in cough, fever and/or abdominal symptoms (vomiting or pain) in the past two weeks
• Medications
• Concurrent use of nicotine-containing medications
• Any stimulant medications (ex. Adderall) generally given for ADHD treatment
• Hypertension medications

• Other/Misc. Chronic Health Problems
• Oral thrush
• Fainting
• Other "life threatening illnesses" as per study physician's discretion

• Pregnancy
• Pregnancy (self-reported and urine pregnancy test)
• Breastfeeding (determined by self-report)

• Concurrent participation in another clinical trial
• Inability to communicate in English
• Current regular user of ONPs
• Planning to quit smoking or vaping within the next 60 days
• Uncomfortable with getting blood drawn