Allopregnanolone association with psychophysiological and cognitive functions during acute smoking abstinence in premenopausal women.

Abstract

Nicotine response may predict susceptibility to smoking relapse. Allopregnanolone, a neuroactive steroid metabolized from progesterone, has been shown to be associated with several symptoms of nicotine response. We sought to explore the association between allopregnanolone and response to nicotine during acute smoking abstinence in premenopausal women. Participants completed 2 nicotine response laboratory sessions, 1 in their follicular (low allopregnanolone) and 1 in their luteal (high allopregnanolone) menstrual phase, on the fourth day of biochemically confirmed smoking abstinence. During the laboratory sessions, participants self-administered a nicotine nasal spray and completed a timed series of cardiovascular, cognitive, and subjective assessments of response to nicotine. The relationships of allopregnanolone with baseline values and change scores of outcome measures were assessed via covariance pattern modeling. Study participants (n = 77) had a mean age of 29.9 (SD = 6.8) years and smoked 12.2 (4.9) cigarettes per day. Allopregnanolone concentration measured before nicotine administration was positively associated with systolic (β = 0.85, p = .04) and diastolic blood pressure (β = 1.19, p < .001); and self-report of physical symptoms (β = 0.58, p < .001), dizziness (β = 0.88, p < .01), jitteriness (β = 0.90, p = .04), and pleasantness (β = 2.05, p = .04). Allopregnanolone also had significant positive associations with change in cognition following nicotine nasal spray administration, specifically discriminability as a measure of attention (β = 1.15, p = .05) and response bias as a measure of impulsivity (β = 0.13, p = .02). These data suggest that allopregnanolone may be related to cardiovascular and subjective physical state during acute smoking abstinence, as well as cognitive response to nicotine.

Exogenous progesterone for smoking cessation in men and women: a pilot double‐blind, placebo‐controlled randomized clinical trial

“…Further, the physiological, subjective and cognitive effects of nicotine vary by allopregnanolone levels. This suggests that the reinforcing effects of nicotine, and perhaps cigarette smoking, may vary by allopregnanolone levels . Thus, future research could examine metabolism levels of progesterone to allopregnanolone, as well as absolute levels of allopregnanolone, as possible effect modifiers in the relationship between exogenous progesterone administration and cessation outcomes in women.…”

Clinical Potential of Neurosteroids for CNS Disorders

“…A growing body of preclinical and clinical evidence reveals the complex interplay between drug abuse behaviors and neurosteroids such as AP. In particular, smoking cessation outcomes in adult women may be substantially influenced by serum AP levels, which have been shown to vary across the menstrual cycle: for example, decreases in AP during smoking cessation attempts in the follicular phase are associated with increased risk of relapse [116]. A randomized, open-label clinical trial is currently enrolling participants to evaluate several aspects of the relationship between smoking symptomatology and AP and its precursors (NCT01811225).…”

Ovarian Hormones, Menstrual Cycle Phase, and Smoking: a Review with Recommendations for Future Studies

“…We highlight research methodology of the S. Allen et al [45]•• study because the controlled cross-over design has several strengths, including limiting confounds, multimodal assessments, between- and within-subject data, and information on both follicular and luteal phases within the same participant. As such, several publications have resulted from using this strong research approach [46–49, 26, 45, 50, 51]. …”

“…In addition to examining how depressive symptoms and menstrual phase influence nicotine response during acute smoking abstinence, two additional articles describe how allopregnanolone, a neuroactive steroid metabolized from progesterone, may also fluctuate by menstrual phase and influence response to nicotine [46, 47]. Findings revealed that change in allopregnanolone levels during acute smoking abstinence varied by menstrual phase such that allopregnanolone decreased by 10% in the follicular phase and increased by 31% in the luteal phase [47].…”

“…Findings revealed that change in allopregnanolone levels during acute smoking abstinence varied by menstrual phase such that allopregnanolone decreased by 10% in the follicular phase and increased by 31% in the luteal phase [47]. The second study [46] found that during acute smoking abstinence before nicotine administration, allopregnanolone was positively associated with cardiovascular and subjective physical state; however, after nicotine nasal spray administration, allopregnanolone levels were associated with changes in cognition. Together, these findings suggest that allopregnanolone may also play a role in smoking-related symptomatology, and this role might vary by menstrual phase.…”