Electronic cigarettes (ECs) represent a promising harm reduction strategy among people with opioid use disorder who smoke. Prior research has shown that reducing cigarettes per day by at least 50% is associated with reduced morbidity. We tested whether the number of EC puffs per day is associated with achieving a >= 50% reduction in cigarettes per day among adults with opioid use disorder who smoke attempting to switch to ECs. A secondary data analysis of a 4-week trial testing ECs as a harm reduction tool among adults with opioid use disorder who smoke (N = 30). Daily EC puff counts were recorded using the study EC. Participants were categorized as reducers (n = 16) or nonreducers (n = 14) based on achieving a >= 50% reduction in cigarettes per day from baseline to Week 4. Longitudinal patterns of daily EC puff counts over the 4-week study were then compared between the two groups. A spline mixed-effect model (Bayesian information criterion = 1,527; Akaike information criterion = 1,469) identified changes in EC puffing during three phases: early (Days 1-9), middle (Days 10-18), and late (Days 19-28). Reducers showed an increase in EC puffs on early treatment days and maintained the number of EC puffs in the following two phases. Nonreducers showed a stable number of EC puff counts, followed by a decrease in the final treatment phase, b = -0.914; t(456.3) = -1.97. Distinct patterns of EC use were observed among reducers and nonreducers. These findings suggest that switching trials should consider incorporating increases in the daily number of EC puffs as a therapeutic target.
Alcohol tolerance is a core diagnostic feature of alcohol use disorder, yet little research has investigated its role in risky drinking during late adolescence. Low sensitivity to alcohol sedation is also linked to alcohol use disorder risk, but few studies have examined how acquired tolerance and alcohol sensitivity concurrently relate to heavy drinking. This study examined the concurrent and prospective associations of acquired tolerance and alcohol sensitivity with heavy drinking among late adolescent heavy drinkers (N = 308, ages 18-21, 52.6% female). At baseline, participants completed self-report measures of acquired tolerance, early and current alcohol sensitivity, and alcohol-consumption outcomes. Analyses tested for differences in alcohol tolerance and sensitivity by family history (FH) of alcohol use disorder and path analyses examined associations and indirect effects from a positive FH and age at first/regular drinking to alcohol sensitivity, acquired tolerance, and heavy drinking. Positive FH and early regular drinking were associated with greater acquired tolerance, lower sensitivity to alcohol sedation, and greater heavy drinking. In supplemental prospective analyses involving a subset of partcipants who completed a 1-year follow-up, acquired tolerance predicted 1-year follow-up heavy drinking, whereas alcohol sensitivity did not. Concurrent indirect effects from positive FH and early regular drinking to heavy drinking episodes, through acquired tolerance and low sedation sensitivity, were found; however, prospective indirect effects were only found through acquired tolerance. Findings suggest that acquired tolerance may represent a key mechanism linking a positive FH and early regular drinking to heavy drinking in late adolescence.
Delay discounting describes the devaluation of consequences as the delay to their occurrence increases, which can yield a preference for smaller, sooner over larger, later rewards. Conceptual models and preliminary data suggest that delay discounting is exacerbated in deprivation states, including opioid withdrawal, which can shift choice allocation to more immediate rewards. Although withdrawal is hypothesized to affect decision making in opioid use disorder, research that experimentally manipulates withdrawal in people with opioid use disorder is limited by feasibility considerations. Simulated withdrawal manipulations could address this gap, but their validity is not well established. The current analysis compared the effects of real and simulated opioid withdrawal on delay discounting in people with moderate-to-severe opioid use disorder and daily fentanyl use by combining data from two previous studies. Study 1 (n = 12) elicited opioid withdrawal via double-blind, placebo substitution of oxycodone maintenance medication during inpatient admission. Study 2 (n = 17) simulated opioid withdrawal via verbal instructions to outpatient participants. All participants completed five-trial, adjusting delay discounting tasks for money and opioid pills. Linear mixed models revealed steeper rates of discounting of delayed opioid pills during opioid withdrawal, regardless of withdrawal manipulation modality (real or simulated). Delay discounting for money was steeper in the simulated withdrawal group only, potentially reflecting pre-existing group differences in the sensitivity of money discounting during withdrawal. These results are consistent with prior research and support the use of simulated withdrawal as an effective experimental proxy in decision-making studies when real withdrawal manipulations are not feasible or warranted.
