Blunted Opiate Modulation of Hypothalamic-Pituitary-Adrenocortical Activity in Men and Women Who Smoke

Abstract

Objective To examine the extent to which nicotine dependence alters endogenous opioid regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis functions. Endogenous opiates play an important role in regulating mood, pain, and drug reward. They also regulate the HPA functions. Previous work has demonstrated an abnormal HPA response to psychological stress among dependent smokers. Methods Smokers and nonsmokers (total n = 48 participants) completed two sessions during which a placebo or 50 mg of naltrexone was administered, using a double-blind design. Blood and saliva samples, cardiovascular and mood measures were obtained during a resting absorption period, after exposure to two noxious stimuli, and during an extended recovery period. Thermal pain threshold and tolerance were assessed in both sessions. Participants also rated pain during a 90-second cold pressor test. Results Opioid blockade increased adrenocorticotropin, plasma cortisol, and salivary cortisol levels; these increases were enhanced by exposure to the noxious stimuli. These responses were blunted in smokers relative to nonsmokers. Smokers tended to report less pain than nonsmokers, and women reported more pain during both pain procedures, although sex differences in pain were significant only among nonsmokers. Conclusions We conclude that nicotine dependence is associated with attenuated opioid modulation of the HPA. This dysregulation may play a role in the previously observed blunted responses to stress among dependent smokers.

A new biomarker of hedonic eating? A preliminary investigation of cortisol and nausea responses to acute opioid blockade

“…Cortisol concentrations increased 103% on average in response to naltrexone over a 3-hour period, whereas they decreased 48% on average across three control days without naltrexone during the same time period. These findings replicate those of prior studies showing reliable naltrexone-induced increases in HPA activity (al'Absi et al, 2008; King et al, 2002a; Roche et al, 2010). We also found a wide range of individual variation in nausea severity in response to naltrexone, with a subgroup of 40% showing a meaningful (moderate to severe) level of nausea.…”

“…There are no validated functional markers of central opioidergic activity in humans, short of positron-emission tomography (PET) scans to assess opioid receptor binding potential. However, as an indirect functional measure, the effects of opioid antagonists on the hypothalamic-pituitary-adrenal axis (HPA) have been studied to assess the role of endogenous opioidergic activity in alcohol and nicotine addictions (e.g., al'Absi, Wittmers, Hatsukami, & Westra, 2008; Ouwens, van Strien, van Leeuwe, & van der Staak, 2009; Wand, Mangold, El Deiry, McCaul, & Hoover, 1998; Wand et al, 2012). Endogenous opioids inhibit the HPA axis through two pathways.…”

Acute analgesic effects of nicotine and tobacco in humans: a meta-analysis

“…Nicotine has been shown to increase cardiovascular activity [5; 74; 76], which in turn has been associated with reduced pain sensitivity [2; 3; 12; 49]. Other promising mechanisms of interest include the pain-modulating role of serotonin [18; 70], nicotine effects on executive functioning and self-control processes [36; 37], smoking-related blunting of the stress response [4; 17; 32], and nicotine-induced anti-inflammatory actions [54; 81]. …”

Sex differences in acute hormonal and subjective response to naltrexone: The impact of menstrual cycle phase

“…The laboratory screening consisted of a general physical examination by the study nurse, administration of a diagnostic psychiatric interview, and completion of several questionnaires, which included the Beck Depression Inventory, State–Trait Anxiety Inventory, Childhood Trauma Questionnaire (Bernstein et al, 2003), and health and substance use history questionnaires. These questionnaires were chosen because depression, anxiety, and history of trauma and substance abuse disorders may affect hormonal function and response pharmacological challenge (al’Absi et al, 2008; Burnett et al, 1999; Hubert and de Jong-Meyer, 1992; Lovallo et al, 2012a; Mangold and Wand, 2006). Individuals were excluded from participation if they had a current or past major medical condition (e.g., cardiovascular, hepatic, neurological, endocrine, etc.)…”