IV Nicotine Induced Changes in Hormone Function, Mood States and Behavior

Clinical studies are proposed to analyze the interactions between nicotine, alterations in endocrine hormones, mood and cardiovascular measures. The studies are designed to examine the contribution of gender and menstrual cycle phase. It is hypothesized that analysis of nicotine's rapid hormonal, cardiovascular and subjective effects will be important for developing novel biologic approaches to treatment for nicotine abuse and dependence as well as advancing understanding of the neurobiology of nicotine reinforcement.

Study Overview

• Status: Withdrawn
• Conditions: Nicotine Dependence
• Intervention / Treatment: Drug: Intravenous Nicotine

Detailed Description

These clinical studies are designed to examine the acute effects of intravenous nicotine on anterior pituitary (ACTH, LH) and adrenal hormones (DHEA and cortisol). We also plan to study norepinephrine (NE) and epinephrine (E), because nicotine stimulates rapid release of NE and E in preclinical and clinical studies. The studies will examine the acute effects of intravenous nicotine on the gonadal steroid hormones and the reciprocal feedback regulation by LH. The temporal covariance of hormonal changes with serum nicotine levels and nicotine-induced changes in subjective states and cardiovascular measures will be measured. The covariance between nicotine-induced changes in endocrine, subjective and cardiovascular effects and the temporal concordance with increases in serum nicotine and cotinine levels will be determined. Gender and menstrual cycle phase influences on the effects of nicotine on HPA and HPG hormones and subjective effects will be assessed.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • Alcohol and Drug Abuse Research Center at McLean Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Men and women between the ages of 18 and 40 who currently smoke at least 15 cigarettes every day, and who fulfill DSM-IV diagnostic criteria for nicotine dependence (305.10) will be eligible for participation.
• No evidence of clinically significant disease based upon complete medical history and physical examination by Dr. Arthur Siegel (Chief of Internal Medicine, McLean Hospital).
• Absence of DSM-IV Axis I Disorders other than nicotine dependence (305.10) as measured by the Structured Clinical Interview (SCID).
• Routine laboratory blood tests including complete blood count, electrolytes, BUN and creatinine, liver function test, hepatitis panel and urinalysis will be performed. Laboratory parameters must be within the normal range. HBsAg must be negative but subjects who have hepatitis serology consistent with previous exposure to Hepatitis A, Hepatitis B, or Hepatitis C, but who do not have clinical and biochemical evidence of acute infection, will be acceptable.
• Hematocrit levels ≥ 39% for males and ≥ 35% for females.
• Serum pregnancy test (hCG beta subunit) results must be negative within 24 hrs of the study day.
• Normal ECG.
• Subjects must be able to read and understand instructions, as well as provide a valid informed consent.

Exclusion Criteria:

• Women and men with any lifetime DSM-IV Axis I disorder other than nicotine abuse or dependence will be excluded.
• Women who are pregnant will be excluded.
• Women who use hormonal contraceptive medications will not be accepted for participation because this would confound the hormonal measures.
• Men and women with clinically significant medical disorders will be excluded.
• Obese and underweight subjects will be excluded. A mean Body Mass Index (ratio of weight (W) to height (H) squared; W/H2=kg/m2) will be calculated. Women with a mean Body Mass Index (BMI) of between 18.0-27.0 and men with a BMI between 21.4-29.0 will be accepted.
• Treatment seeking subjects will not be selected but will be referred to local smoking cessation programs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Male Smokers	Drug: Intravenous Nicotine; Subjects will be given an intravenous challenge dose of nicotine or placebo in a constant volume of 1 ml on any study day. The nicotine solution (1.0 mg/70kg or 1.5 mg/70kg or 2.0 mg/70kg) will be administered over 1 min. This rate of drug delivery (1 ml over 1 min) has been safe in our IRB approved studies of nicotine. Most investigators have administered nicotine over 10 sec without any adverse reactions. We concur with the IRB recommendation that the lower doses (1.0 mg/70kg and 1.5 mg/70kg;) should be administered first and the higher dose (2.0 mg/70kg) will be administered last.; Other Names: IV Nicotine
Active Comparator: Female Smokers (Mid-Luteal Phase; cycle days 18-22)	Drug: Intravenous Nicotine; Subjects will be given an intravenous challenge dose of nicotine or placebo in a constant volume of 1 ml on any study day. The nicotine solution (1.0 mg/70kg or 1.5 mg/70kg or 2.0 mg/70kg) will be administered over 1 min. This rate of drug delivery (1 ml over 1 min) has been safe in our IRB approved studies of nicotine. Most investigators have administered nicotine over 10 sec without any adverse reactions. We concur with the IRB recommendation that the lower doses (1.0 mg/70kg and 1.5 mg/70kg;) should be administered first and the higher dose (2.0 mg/70kg) will be administered last.; Other Names: IV Nicotine
Active Comparator: Female Smokers (Early Follicular Phase; cycle days 4-8)	Drug: Intravenous Nicotine; Subjects will be given an intravenous challenge dose of nicotine or placebo in a constant volume of 1 ml on any study day. The nicotine solution (1.0 mg/70kg or 1.5 mg/70kg or 2.0 mg/70kg) will be administered over 1 min. This rate of drug delivery (1 ml over 1 min) has been safe in our IRB approved studies of nicotine. Most investigators have administered nicotine over 10 sec without any adverse reactions. We concur with the IRB recommendation that the lower doses (1.0 mg/70kg and 1.5 mg/70kg;) should be administered first and the higher dose (2.0 mg/70kg) will be administered last.; Other Names: IV Nicotine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of nicotine on hormones and mood states	We are examining the effects of IV nicotine on serum nicotine levels, serum/plasma hormone levels and nicotine-induced changes in subjective statues, as measured by a visual analog scale.	From baseline to study completion (approximately 4 months for males and 8 months for females)

Collaborators and Investigators

• Sponsor: Mclean Hospital
• Investigators: Principal Investigator: Nancy K M, PhD, McLean Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: April 27, 2012
• First Submitted That Met QC Criteria: April 27, 2012
• First Posted (Estimated): May 1, 2012

Study Record Updates

• Last Update Posted (Estimated): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 15, 2024
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: 2005-p-001057