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| ID | Type | Description | Link |
|---|---|---|---|
| F31DA040369 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Drug Abuse (NIDA) | NIH |
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In this study, 21 non-treatment-seeking cigarette smokers were recruited to investigate the effects of acute stress on brain function and nicotine seeking/self-administration behavior.
Non-treatment-seeking cigarette smoking individuals were recruited from the Detroit, MI area. Individuals were screened for cardiovascular, neurological, and psychiatric contraindications. 21 healthy smokers completed two oral pre-treatment experimental sessions (on separate non-consecutive days) in randomized order under double-blind conditions: placebo (lactose) and stress (54mg yohimbine and 10mg hydrocortisone). Yohimbine + hydrocortisone elicit a neurochemical and physiological response that mimics a 'natural' stressor. Placebo and stress sessions were identical and started at 11am. Upon arrival, subject sobriety was confirmed with expired breath alcohol measurement (<.02%). At 11:30am, each subject smoked 6 cigarette puffs (preferred brand; provided by study) over 5 minutes to control for recent nicotine exposure. Throughout each experimental session, subjects periodically completed self-reported measures of cigarette craving, nicotine withdrawal symptoms, affect, and anxiety, and vital signs were measured. Subjects self-administered (swallowed) oral doses of yohimbine (or placebo) at 11:45am and hydrocortisone (or placebo) at 12:15pm. At 1pm, subjects completed a 60-min neuroimaging scan which included: 1) T1-weighted structural scan, 2) proton functional magnetic resonance spectroscopy (fMRS) acquisition from the left prefrontal cortex during a letter 2-back working memory paradigm, and 3) functional magnetic resonance imaging (fMRI) acquisition during an N-back paradigm yoked with cigarette cues. At 2:30pm, subjects completed an 11-trial choice progressive ratio task in which they could earn cigarette puffs (preferred brand; provided by study) or money. At 3pm, subjects self-administered earned cigarette puffs (video monitored). Subjects remained on site until 4pm discharge.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | The placebo compound, Lactose Monohydrate Powder, was encapsulated in generic opaque capsules identical to the capsules used in the acute stress session. During the placebo session, two capsules were self-administered (swallowed) by each subject. At 11:45am, subjects self-administered a capsule containing 54mg of lactose. At 12:15pm, subjects self-administered a capsule containing 10mg of lactose. |
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| Acute Stress | Experimental | During the acute stress experimental session, subjects self-administered two generic opaque capsules. At 11:45am, subjects self-administered a capsule containing 54mg of Yohimbine Hydrochloride powder. At 12:15pm, subjects self-administered a capsule containing 10mg of Hydrocortisone. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Yohimbine Hydrochloride | Drug | 54mg of yohimbine powder was encapsulated in a generic opaque capsule and swallowed with water. |
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| Measure | Description | Time Frame |
|---|---|---|
| Cigarette puff vs. money choice task | Participants could earn (via computer mouse 'clicks') money or cigarette puffs (preferred brand; provided by the study) across 11 independent choice trials. At the start of each trial, subjects selected either money or cigarette puffs on a computer screen. After each selection, subjects could earn one unit of that selection by satisfying the computer 'mouse' click requirement. The click requirement increased with each successive unit earned separately for cigarette puffs and money following a progressive ratio schedule (5, 12, 33, 100, 180, 340, 540, 835, 1220, 1660, and 2275 'mouse' clicks; identical schedule for both options and experimental sessions). Units were $0.25 money and 1 cigarette puff. Earned cigarette puffs were smoked at the end of the task and earned money was applied to the subject's study payment. The task was completed between 2:30pm and 3pm for each session. | 30 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| Letter 2-back task | Participants completed 5 blocks of a letter 2-back working memory task during proton functional magnetic resonance spectroscopy data acquisition from the left dorsolateral prefrontal cortex. The 2-back task consisted of a neurochemistry normalization period (passive viewing of a 3Hz flashing checkerboard; 208s) and alternating periods of passive visual fixation (centered fixation cross; 32s) and letter 2-back (64s; 4s instructions ['2-back'], 20 letters [3s/letter; 500ms on screen; 2500ms blank screen], 6 target letters). Changes in neurochemistry as quantified using LCModel were the primary outcome variable. 2-back response accuracy (% correct) and response latency (ms) were secondary outcomes. |
| Measure | Description | Time Frame |
|---|---|---|
| Minnesota Nicotine Withdrawal Scale | Well-validated self-report measure of nicotine withdrawal symptoms was measured (MNWS; Hughes and Hatsukami, 1986). Subjects were asked to rate 15 adjectives describing common nicotine withdrawal symptoms on a 5-point Likert scale reflecting symptom severity during the past 10 minutes from 0='not present' to 4='severe'. Mean scores were calculated across items with higher values (maximum=4) reflecting greater withdrawal symptom severity and lower scores (minimum=0) reflecting less severe withdrawal symptoms. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Eric A Woodcock, PhD | Wayne State University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wayne State University | Detroit | Michigan | 48201 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11260806 | Background | Cox LS, Tiffany ST, Christen AG. Evaluation of the brief questionnaire of smoking urges (QSU-brief) in laboratory and clinical settings. Nicotine Tob Res. 2001 Feb;3(1):7-16. doi: 10.1080/14622200020032051. | |
| Background | Spielberger CD. Assessment of state and trait anxiety: Conceptual and methodological issues. Southern Psychologist 2(4): 6-16, 1985. | ||
| 3397865 |
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| ID | Term |
|---|---|
| D000073865 | Cigarette Smoking |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D000073869 | Tobacco Smoking |
| D012907 | Smoking |
| D001519 | Behavior |
| D064424 | Tobacco Use |
| D020969 |
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| ID | Term |
|---|---|
| D015016 | Yohimbine |
| D006854 | Hydrocortisone |
| ID | Term |
|---|---|
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
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Double-blind, placebo-controlled, and randomized cross-over study design. Each subject completed both the placebo and acute stress experimental sessions.
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Double-blinded study. Subjects, the experimenter, research assistants, and MRI technician did not know if the oral doses were active (acute stress condition) or inert (placebo session).
| Hydrocortisone | Drug | 10mg hydrocortisone was encapsulated in a generic opaque capsule and swallowed with water. |
|
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| Lactose Monohydrate Powder | Drug | Lactose powder was encapsulated in generic opaque capsules identical to those used during the acute stress session. Lactose doses weighed the same as the acute stress session doses (54mg and 10mg, respectively). |
|
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| 12 minutes |
| Cigarette-cued letter N-back task | Participants completed a neutral image vs. cigarette smoking-related image cued letter N-back task during functional magnetic resonance imaging acquisition. The task consisted of pseudo-randomly ordered blocks of 0-, 1-, and 2-back with either cigarette cues or matched neutral images behind each letter. Two 32s blocks of each task permutation were collected separated by 16s of blank screen (to minimize carry-over effects). Patterns of brain activation throughout the task was the primary outcome measure while N-back response accuracy (% correct) and response latency (ms) were secondary outcomes. | 15 minutes |
| 1 minute; collected five times throughout each experimental session |
| Brief Questionnaire of Smoking Urges | Well-validated self-report measure of subjective cigarette craving was measured (QSU; Cox et al., 2001). The self-report measure consists of 10-items with first-person statements describing one's desire to smoke a cigarette. Items are rated on a 7-point Likert scale: 1='strongly disagree' to 7='strongly agree'. Two sub-scales were considered separately; appetitive vs. relief-motivated craving. Sub-scales were quantified as a sum of items: higher scores reflected greater cigarette craving (both sub-scale scores range=5-35). | 1 minute; collected five times throughout each experimental session |
| State-Trait Anxiety Inventory | Well-validated self-report measure of state anxiety symptoms was measured (STAI; Spielberger, 1985). Subjects were asked to rate 20 first-person statements describing one's anxiety at this moment from 1='not at all' to 4='very much so'. State anxiety was quantified as a sum across items with higher scores reflecting more anxiety (range=20-80). | 1 minute; collected five times throughout each experimental session |
| Positive-Negative Affect Scale | Well-validated measure of self-reported positive and negative affect was measured (PANAS; Watson et al., 1988). Subjects were asked to rate 20 adjectives on a 5-point Likert scale from 1='not at all or very slightly' to 5='extremely'. Two sub-scales were analyzed separately: positive vs. negative affect. Mean scores for each sub-scale were calculated and ranged from 1 to 5 with higher scores reflecting more positive or more negative affect. | 1 minute; collected five times throughout each experimental session |
| Blood pressure | Seated and resting systolic and diastolic blood pressure (BP; mmHg) was measured. | 1 minute; collected six times throughout each experimental session |
| Heart Rate | Seated and resting heart rate (HR; bpm) was measured. | 1 minute; collected six times throughout each experimental session |
| Background |
| Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 1988 Jun;54(6):1063-70. doi: 10.1037//0022-3514.54.6.1063. |
| 3954551 | Background | Hughes JR, Hatsukami D. Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry. 1986 Mar;43(3):289-94. doi: 10.1001/archpsyc.1986.01800030107013. |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007211 |
| Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D015062 | 11-Hydroxycorticosteroids |
| D006889 | Hydroxycorticosteroids |
| D000305 | Adrenal Cortex Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D015065 | 17-Hydroxycorticosteroids |