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Varenicline Improves Mood and Cognition During Smoking Abstinence
Open accessAbstract
Background Neuronal nicotinic acetylcholine receptors (nAChRs) are a key target in medication development efforts for a range of neuropsychiatric disorders, including nicotine dependence. Varenicline, a partial agonist at the α4β2 nAChRs, is a new efficacious medication for nicotine dependence. Its effects on the affective and cognitive dimensions of nicotine withdrawal have yet to be well characterized. Methods Sixty-seven treatment-seeking smokers were administered varenicline (× 21 days) and placebo (× 21 days) in a double-blind within-subject cross-over design. Following the medication run-up phase (days 1–10), there was a 3-day mandatory smoking abstinence phase (days 11–13) during which subjective symptoms and cognitive performance were assessed. Participants were re-exposed to a scheduled smoking lapse (day 14) and followed for days to lapse (days 15–21) in each medication period. Results In the varenicline period, compared to placebo, withdrawal symptoms (p=.04), smoking urges (p<.001), and negative affect (p=.01) were significantly reduced, and levels of positive affect (p=.046), sustained attention (p=.018) and working memory (p=.001) were significantly greater during mandatory abstinence. Varenicline also significantly reduced the subjective rewarding effects of the scheduled smoking lapse (e.g., satisfaction, relief, liking) (p=.003). Medication effects on days to lapse following the scheduled smoking lapse were dependent on treatment order (p=.001); among participants who received placebo in the first period, varenicline increased days of abstinence in the follow-up period. Conclusions These data identify novel affective and cognitive effects of varenicline, and may have implications for medication development for other neuropsychiatric conditions.
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TL;DR
In a double-blind within-subject crossover study of 67 treatment-seeking smokers, varenicline reduced withdrawal, urges, negative affect, and smoking reward while improving positive affect, sustained attention, and working memory during 3-day mandatory abstinence. Varenicline increased days to lapse only among participants who received placebo first, revealing an order-dependent effect.
Key findings
- During mandatory abstinence (days 11–13), varenicline vs placebo significantly reduced withdrawal symptoms (p=.04), smoking urges (p<.001), and negative affect (p=.013), and increased positive affect (p=.046); effects were small to moderate (Cohen’s d = 0.26–0.42).
- Varenicline improved cognitive performance: Letter-N-back correct reaction time (F=11.08, p=.001; d=0.21), Penn Continuous Performance Task true positives (F=7.28, p=.009; d=0.33), and CPT correct reaction time (F=5.86, p=.018); no medication effect was found for N-back true positives (p=.98) or the Conditional Exclusion Test.
- Varenicline attenuated the subjective rewarding value of the scheduled lapse cigarette (F=9.25, p=.003; d=0.36), including satisfaction (p=.002; d=0.43), relief (p=.006; d=0.34), and liking (p=.001; d=0.41).
- Days to lapse showed a significant treatment-by-order interaction (F=11.99, p=.001): among placebo-first participants, mean days to lapse were 4.63 (SD=2.86) with varenicline vs 2.57 (SD=2.94) with placebo (Z=3.16, p=.002; d=0.71); among varenicline-first participants, means were 4.19 (SD=3.04) vs 4.94 (SD=2.87) (Z=1.34, p=.18; d=−0.25). Side effects reported as moderate or severe by over 5% occurred in 55.2% (37/67) on varenicline vs 28.4% (19/67) on placebo at day 10.
Methods
- Double-blind, placebo-controlled, within-subject crossover study of 67 treatment-seeking smokers (≥18 years, ≥10 cigarettes/day for previous 12 months; mean age 44.6 years, SD=11.6; 56.7% female; baseline mean 21.5 cigarettes/day, SD=10.0). Participants completed two 21-day medication periods (varenicline and placebo in counterbalanced order) with a 5–7 day washout; varenicline was titrated per standard guidelines, followed by a 10-day run-up, 3-day mandatory abstinence (days 11–13), scheduled smoking lapse (day 14), and follow-up days 15–21.
- Outcomes included subjective withdrawal symptoms, smoking urges, PANAS positive/negative affect, computerized neurocognitive tasks (Letter-N-back, Penn Continuous Performance Task, Conditional Exclusion Test) at baseline and day 13, Cigarette Evaluation Scale and Sensory Questionnaire after the lapse cigarette, CO-verified abstinence, medication adherence, and side-effect severity.
- Mixed effects models tested medication effects, controlling for sex, baseline cigarettes per day, and medication order; subjective models also included day 10 (smoking as usual) levels as a time-varying covariate, and neurocognitive models included baseline scores as a time-invariant covariate. Cohen’s d was calculated for raw varenicline–placebo differences.
Limitations
- The authors state that order effects were observed for the smoking abstinence outcome: varenicline increased days to lapse only among participants who received placebo first, not among those who received varenicline first. They suggest this may reflect greater self-efficacy after varenicline-induced abstinence success or longer-lasting nAChR modulation.
- The authors note recent reports of adverse psychiatric events with varenicline but state it is not possible to determine whether these events are partly attributable to nicotine withdrawal.
- Evident from the text: the abstinence phase was only 3 days and lapse follow-up only 7 days; several medication effects were small; the positive affect effect became nonsignificant when side-effect severity was included as a covariate (F=1.62, p=.21); side effects were more common on varenicline, which could affect blinding; and the sample excluded current or historical DSM-IV Axis I psychiatric disorders or substance abuse other than nicotine, limiting generalizability.
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Claims the paper makes
19 Not checked yet · 11 Own result · 9 Own method · 4 Own interpretation
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During the varenicline period, compared to placebo, participants reported lower levels of withdrawal symptoms (p=.04), smoking urges (p<.001), and negative affect (p=.013).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Results > Subjective Outcomes
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The 5–7 day washout period between the two medication periods was sufficient to eliminate carryover effects of varenicline.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During the varenicline period, compared to placebo, participants reported lower levels of withdrawal symptoms (p=.04), smoking urges (p<.001), and negative affect (p=.013).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Results > Subjective Outcomes
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The 5–7 day washout period between the two medication periods was sufficient to eliminate carryover effects of varenicline.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Significant effects were observed for satisfaction (F = 10.05, p = .002; d = 0.43), relief (F = 8.12, p = .006; d = 0.34), and liking (F = 11.09, p = .001; d = 0.41).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Results > Smoking Reward and Days to Lapse
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The 5–7 day washout period between the two medication periods was sufficient to eliminate carryover effects of varenicline.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For days to lapse in the observation phase (days 15–21), there was a significant treatment by order interaction (F = 11.99, p = .001).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Results > Smoking Reward and Days to Lapse
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The 5–7 day washout period between the two medication periods was sufficient to eliminate carryover effects of varenicline.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Significant effects were observed for satisfaction (F = 10.05, p = .002; d = 0.43), relief (F = 8.12, p = .006; d = 0.34), and liking (F = 11.09, p = .001; d = 0.41).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Results > Smoking Reward and Days to Lapse
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The 5–7 day washout period between the two medication periods was sufficient to eliminate carryover effects of varenicline.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“compared to placebo, varenicline attenuated the subjective rewarding value of the scheduled lapse cigarette (day 14) (F = 9.25, p = .003; Cohen’s d = 0.36).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Results > Smoking Reward and Days to Lapse
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The 5–7 day washout period between the two medication periods was sufficient to eliminate carryover effects of varenicline.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Significant effects were observed for satisfaction (F = 10.05, p = .002; d = 0.43), relief (F = 8.12, p = .006; d = 0.34), and liking (F = 11.09, p = .001; d = 0.41).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Results > Smoking Reward and Days to Lapse
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The 5–7 day washout period between the two medication periods was sufficient to eliminate carryover effects of varenicline.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All significant effects of treatment on outcomes remained significant, with the exception of the treatment effect in the model of positive affect, which became nonsignificant when the side effect measure was included (F=1.62, p=.21).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Results > Medication Adherence and Side Effects
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Levels of positive affect were also greater during the varenicline period compared to placebo (p=.046).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Results > Subjective Outcomes
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The 5–7 day washout period between the two medication periods was sufficient to eliminate carryover effects of varenicline.
None of the sources cited for this claim have been checked yet.
In the paper
“Varenicline, a partial agonist at the α4β2 nAChRs, and a full agonist at the α7 nAChRs, is a new, efficacious treatment for nicotine dependence (4–6).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Introduction
What the sources say
- Not checked yetcites [4] Gonzales, 2006, Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: A randomized controlled trial, JAMA source
- Not checked yetcites [5] Jorenby, 2006, Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: A randomized controlled trial, JAMA source
- Not checked yetcites [6] Mihalak, 2006, Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors, Mol Pharmacol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 14
- The quote only partly states this claim. 1
- Probably not a substantial claim. 15
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Only baseline performance was significant in the models of CET true positives (p = .02) and correct reaction time (p < .001).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Results > Neurocognitive Outcomes
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The 5–7 day washout period between the two medication periods was sufficient to eliminate carryover effects of varenicline.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“in the model of CPT correct reaction time, there were effects of medication (F = 5.86, p = .018) and baseline performance (F = 117.1, p < .001).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Results > Neurocognitive Outcomes
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
- Rests on an assumption: The 5–7 day washout period between the two medication periods was sufficient to eliminate carryover effects of varenicline.
In the paper
“Varenicline, a partial agonist at the α4β2 nAChRs, and a full agonist at the α7 nAChRs, is a new, efficacious treatment for nicotine dependence (4–6).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Introduction
What the sources say
- Not checked yetcites [6] Mihalak, 2006, Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors, Mol Pharmacol source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Neuronal nicotinic acetylcholine receptors (nAChRs) are a key target of drug discovery efforts for nicotine dependence, as well as for neuropsychiatric conditions (3).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Introduction
What the sources say
- Not checked yetcites [3] Arneric, 2007, Neuronal nicotinic receptors: A perspective on two decades of drug discovery research, Biochem Pharmacol source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Cronbach’s alphas for all scales ranged from .79 to .96.”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Methods and Materials > Subjective Outcomes
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The MINI International Neuropsychiatric Interview (MINI) was administered by trained research technicians to screen for psychiatric and substance abuse disorders (21). Ten percent of MINI interviews were recorded and reviewed by a licensed clinician.”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Methods and Materials > Procedures
What the sources say
- Not checked yetcites [21] Sheehan, 1998, The Mini-International Neuropsychiatric Interview (MINI): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10, J Clin Psychiatry
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The models of neurocognitive outcomes included baseline scores as a time-invariant covariate.”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Methods and Materials > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Varenicline produces a moderate level of nAChR stimulation and lower sustained levels of dopamine release, thereby replacing some of nicotine’s effects (7).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Introduction
What the sources say
- Not checked yetcites [7] Coe, 2005, Varenicline: An alpha4beta2 nicotinic receptor partial agonist for smoking cessation, J Med Chem source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Aside from urges to smoke, the most common symptoms involve emotional dysregulation and cognitive deficits (13, 14).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Discussion
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Further, competitive nAChR binding should, theoretically, reduce nicotine reward (7, 8).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Introduction
What the sources say
- Not checked yetcites [7] Coe, 2005, Varenicline: An alpha4beta2 nicotinic receptor partial agonist for smoking cessation, J Med Chem source
- Not checked yetcites [8] Rollema, 2007, Rationale, pharmacology and clinical efficacy of partial agonists of alpha4beta2 nACh receptors for smoking cessation, Trends Pharmacol Sci source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“These trials document treatment-related reductions in smoking urges and withdrawal-related negative affect (4, 5, 9), as well as reduced smoking reward during a lapse (10).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Introduction
What the sources say
- Not checked yetcites [4] Gonzales, 2006, Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: A randomized controlled trial, JAMA source
- Not checked yetcites [5] Jorenby, 2006, Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: A randomized controlled trial, JAMA source
- Not checked yetcites [9] West, 2008, Effect of varenicline and bupropion SR on craving, nicotine withdrawal symptoms, and rewarding effects of smoking during a quit attempt, Psychopharmacology (Berl) source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Depression symptoms are common among smokers and motivate smoking to reduce negative affect (44).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Discussion
What the sources say
- Not checked yetcites [44] Lerman, 1996, Investigation of mechanisms linking depressed mood to nicotine dependence, Addict Behav source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“There were no significant differences in these variables by medication order, nor were there any differences in smoking rate during the two run up periods (all Ps>.20).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Results
plainn = 7- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“CO ≤ 10 ppm needed to confirm abstinence on days 11–13”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Methods and Materials > Procedures
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All models controlled for sex, cigarettes per day at baseline, and order of medication phases.”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Methods and Materials > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The models of subjective outcomes also included day 10 (smoking as usual) levels of the measure as a time-varying covariate; thus, these models tested the effect of medication on changes in outcomes from pre-abstinence (day 10) to abstinence (mean of days 11–13).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Methods and Materials > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“using validated computerized tasks: the Letter-N-back task of working memory (28), the Penn Continuous Performance Task (P-CPT) of sustained attention (29), and the Conditional Exclusion Test (CET) of abstraction in executive function (30, 31).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Methods and Materials > Neurocognitive Outcomes
What the sources say
- Not checked yetcites [28] Ragland, 2002, Working memory for complex figures: An fMRI comparison of letter and fractal n-back tasks, Neuropsychology source
- Not checked yetcites [29] Kurtz, 2001, Comparison of the continuous performance test with and without working memory demands in healthy controls and patients with schizophrenia, Schizophr Res source
- Not checked yetcites [30] Kurtz, 2004, The Penn Conditional Exclusion Test: A new measure of executive-function with alternate forms of repeat administration, Arch Clin Neuropsychol source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In this placebo-controlled double-blind crossover study, participants completed two 21-day medication periods (varenicline and placebo in counterbalanced order) and a 5–7 day washout period (four participants had longer washout periods due to scheduling issues) (see Figure 1).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Methods and Materials > Procedures
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“In chronic smokers, abstinence from nicotine increases the availability of unbound α4β2 nAChRs, which in turn contributes to abstinence symptoms (35).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Discussion
What the sources say
- Not checked yetcites [35] Staley, 2006, Human tobacco smokers in early abstinence have higher levels of beta2* nicotinic acetylcholine receptors than nonsmokers, J Neurosci source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Mean adherence levels were 99.27% for the placebo period and 98.70% for the varenicline period (Z = 1.89, p = .06 by Wilcoxon test).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Results > Medication Adherence and Side Effects
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Participants who did not remain abstinent (n=3) were excluded.”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Methods and Materials > Procedures
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Data from the present study indicate that varenicline, a partial agonist at the α4β2 nAChRs, enhances mood and cognitive function during early abstinence from nicotine.”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The 5–7 day washout period between the two medication periods was sufficient to eliminate carryover effects of varenicline.
In the paper
“Prior evidence for the cognitive enhancing effects of selective nAChR agonists suggests further that varenicline might have additional potential benefits in this area beyond those specific to nicotine withdrawal (52).”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Discussion
What the sources say
- Not checked yetcites [52] Mineur, 2007, Cytisine, a partial agonist of high-affinity nicotinic acetylcholine receptors, has antidepressant-like properties in male C57BL/6J mice, Neuropharmacology source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, the data suggest two novel and potentially important clinical effects of varenicline, namely enhancement of positive affect and cognitive function.”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
The 5–7 day washout period between the two medication periods was sufficient to eliminate carryover effects of varenicline.
“a 5–7 day washout period (four participants had longer washout periods due to scheduling issues)”
The paper relies on this without support.
The sample of treatment-seeking smokers is representative enough to generalize the study's findings to clinical populations of smokers attempting to quit.
“To increase the generalizability of results to the clinical setting, we enrolled treatment-seeking smokers (those planning to quit in the next 3 months) (19, 20).”
The paper relies on this without support.
The placebo capsule was indistinguishable from the active medication, so blinding was maintained.
“The placebo was a sucrose capsule that resembled the active medication (active medication was encapsulated also).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Clinically, varenicline has demonstrated enhancement of both positive affect and cognitive function during smoking cessation (Patterson et al., 2009), and it was recently shown to augment the effects of antidepressants in depressed smokers (Philip et al., 2009).”
From Nicotinic Partial Agonists Varenicline and Sazetidine-A Have Differential Effects on Affective Behavior (2010) · cites this paper as Patterson et al., 2009
In the citing paper
“In clinical studies, administration of varenicline during smoking cessation results in the improvement of both positive affect and cognitive function (Patterson et al., 2009).”
From Nicotinic Partial Agonists Varenicline and Sazetidine-A Have Differential Effects on Affective Behavior (2010) · cites this paper as Patterson et al., 2009
Statistics recomputed
Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.
- Consistentz = 3.16reported p = .002 · recomputed p = .002
“(Z=3.16, p = .002”
- Consistentz = 1.34reported p = .18 · recomputed p = .180
“(Z=1.34, p = .18”
- Consistentz = 1.89reported p = .06 · recomputed p = .059
“(Z = 1.89, p = .06”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > References
“2007 December, 2007”
§ Varenicline Improves Mood and Cognition during Smoking Abstinence > References
“[cited 2007 November 16, 2007]”
Citations
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“Finally, evidence-based behavioral approaches that improve various cognitive functions, such as working memory, attention, and attentional bias to smoking cues, have also shown some promise, but negative findings indicate that this area of research needs further development to optimize these approaches that have such…”
Background
Metadata
- Authors
- Patterson, F., Jepson, C., Strasser, A. A., Loughead, J., Perkins, K. A., Gur, R. C., Frey, J. M., Siegel, S., & Lerman, C.
- Affiliations
- University of Pittsburgh Medical Center (US)
- University of Pennsylvania (US)
- Abramson Cancer Center (US)
- University of Pittsburgh (US)
- AstraZeneca (United States) (US)
- Corresponding author
- Lerman, Caryn
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 65
- Issue
- 2
- Pages
- 144-149
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2615779
- OpenAlex
- W2070192651
- Semantic Scholar
- da3580cf90b2994b54327bb9684de9ef3730a592
- Cited by
- 222
- References
- 60
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 5 · 2023: 11 · 2022: 8 · 2021: 1 · 2020: 6 · 2019: 8 · 2018: 9 · 2017: 16 · 2016: 22 · 2015: 9 · 2014: 24 · 2013: 23 · 2012: 19
- FWCI
- 11.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Public Health Service (P5084718)
- National Cancer Institute (P50CA084718)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- varenicline, nicotine dependence, smoking abstinence, nicotine withdrawal symptoms, smoking urges, mood, cognition, sustained attention, working memory, α4β2 nicotinic acetylcholine receptor, smoking lapse
- MeSH terms
- Varenicline, Adult, Affect, Attention, Benzazepines, Cognition, Double-Blind Method, Female, Humans, Male, Memory, Short-Term, Middle Aged, Quinoxalines, Reaction Time, Substance Withdrawal Syndrome, Smoking Cessation, Cross-Over Studies, Nicotinic Agonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-08, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-08 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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