Development and Initial Validation of a Momentary Cannabis Craving Scale Within a Homogeneous Sample of U.S. Emerging Adults.

Given the popularity and ease of single-item craving assessments, we developed a multi-item measure and compared it to common single-item assessments in an ecological momentary assessment (EMA) context. Two weeks of EMA data were collected from 48 emerging adults (56.25% female, 85.42% White) who frequently used cannabis. Eight craving items were administered, and multilevel factor analyses were used to identify the best fitting model. The resulting scale's factors represented purposefulness/general desire and emotionality/negative affect craving. Convergent validity was examined using measures of craving, cannabis use disorder symptoms, frequency of use, cannabis cue reactivity, cannabis use, negative affect, and impulsivity. The scale factors were associated with cue-reactivity craving, negative affect, impulsivity, and subfactors of existing craving measures. For researchers interested in using a single item to capture craving, one item performed particularly well. However, the new scale may provide a more nuanced assessment of mechanisms underlying craving.

Evidence for sex differences in the impact of cytochrome P450 genotypes on early subjective effects of cannabis.

Early positive subjective effects of cannabis predict the development of cannabis use disorder (CUD). Genetic factors, such as the presence of cytochrome P450 genetic variants that are associated with reduced Δ9-tetrahydrocannabinol (THC) metabolism, may contribute to individual differences in subjective effects of cannabis. Young adults (N = 54) with CUD or a non-CUD substance use disorder (control) provided a blood sample for DNA analysis and self-reported their early (i.e., effects upon initial uses) and past-year positive and negative subjective cannabis effects. Participants were classified as slow metabolizers if they had at least one CYP2C9 or CYP3A4 allele associated with reduced activity. Though the CUD group and control group did not differ in terms of metabolizer status, slow metabolizer status was more prevalent among females in the CUD group than females in the control group. Slow metabolizers reported greater past year negative THC effects compared to normal metabolizers; however, slow metabolizer status did not predict early subjective cannabis effects (positive or negative) or past year positive effects. Post-hoc analyses suggested males who were slow metabolizers reported more negative early subjective effects of cannabis than female slow metabolizers. Other sex-by-genotype interactions were not significant. These initial findings suggest that genetic variation in CYP2C9 and CYP3A4 may have sex-specific associations with cannabis-related outcomes. Slow metabolizer genes may serve as a risk factor for CUD for females independent of subjective effects. Male slow metabolizers may instead be particularly susceptible to the negative subjective effects of cannabis.

Exploration into Patterns of Cannabis Use across Pregnancy and Postpartum.

OBJECTIVES: Peripartum cannabis use can be harmful to pregnant individual's and children's health, yet it is the most used illicit substance during the peripartum period. Despite the ability of some people to reduce and abstain from cannabis use during pregnancy, the first year postpartum is a high-risk time for returning to cannabis. However, characterization of cannabis use patterns in the peripartum period and risk factors for return to use postpartum are not well established. The aims of this exploratory study were to describe patterns of peripartum cannabis use and identify factors associated with increased frequency of postpartum cannabis use among individuals who reported reduced use during pregnancy. METHODS: An online survey identified 47 individuals who used cannabis during the peripartum period. Descriptive statistics characterized the sample and among those who reduced use during pregnancy, χ2 determined the frequency of postpartum cannabis use per preconception reasons for use. RESULTS: During preconception, 95.7% of individuals used cannabis, and of those who were presently postpartum, 65% resumed use after delivery. Anxiety and stress were the most common motivations for cannabis use throughout the peripartum period, but social motivations (ie, fun, relaxation) were the only preconception factors that increased frequency of return to cannabis use postpartum. CONCLUSIONS: Our exploratory study describes the characteristics of individuals using cannabis in the peripartum period and provides insight into correlates of resumption of cannabis use postpartum. These findings may inform future work to further determine temporal associations, confounding risk factors, and intervention techniques to prevent the return to cannabis use postpartum.

A preliminary randomized controlled trial of repetitive transcranial magnetic stimulation applied to the left dorsolateral prefrontal cortex in treatment seeking participants with cannabis use disorder.

BACKGROUND: Cannabis use disorder (CUD) is a common and consequential disorder. When applied to the dorsolateral prefrontal cortex (DLPFC), repetitive transcranial magnetic stimulation (rTMS) reduces craving across substance use disorders and may have therapeutic clinical effects when applied in serial-sessions. The present study sought to preliminarily determine whether serial-sessions of rTMS applied to the DLPFC had a therapeutic effect in CUD. METHODS: This study was a two-site, phase-2, double-blind, randomized-controlled-trial. Seventy-two treatment-seeking participants (37.5% Women, mean age 30.2±9.9SD) with ≥moderate-CUD were randomized to active or sham rTMS (Beam-F3, 10Hz, 20-total-sessions, two-sessions-per-visit, two-visits-per-week, with cannabis cues) while undergoing a three-session motivational enhancement therapy intervention. The primary outcome was the change in craving between pre- and post- treatment (Marijuana Craving Questionnaire Short-Form-MCQ-SF). Secondary outcomes included the number of weeks of abstinence and the number of days-per-week of cannabis use during 4-weeks of follow-up. RESULTS: There were no significant differences in craving between conditions. Participants who received active-rTMS reported numerically, but not significantly, more weeks of abstinence in the follow-up period than those who received sham-rTMS (15.5%-Active; 9.3%-Sham; rate ratio = 1.66 [95% CI: 0.84, 3.28]; p=0.14). Participants who received active-rTMS reported fewer days-per-week of cannabis use over the final two-weeks of the follow-up period than those receiving sham-rTMS (Active vs. Sham: -0.72; Z=-2.33, p=0.02). CONCLUSIONS: This trial suggests rTMS is safe and feasible in individuals with CUD and may have a therapeutic effect on frequency of cannabis use, though further study is needed with additional rTMS-sessions and a longer follow-up period.

Comparison of three magnetic resonance imaging measures of brain iron in healthy and cocaine use disorder participants.

Several magnetic resonance imaging (MRI) measures for quantifying endogenous nonheme brain iron have been proposed. These correspond to distinct physical properties with varying sensitivities and specificities to iron. Moreover, they may depend not only on tissue iron concentration, but also on the intravoxel spatial pattern of iron deposition, which is complex in many brain regions. Here, the three MRI brain iron measures of R 2 * , magnetic field correlation (MFC), and magnetic susceptibility are compared in several deep gray matter regions for both healthy participants (HPs) and individuals with cocaine use disorder (CUD). Their concordance is assessed from their correlations with each other and their relative dependencies on age. In addition, associations between the iron measures and microstructure in adjacent white matter regions are investigated by calculating their correlations with diffusion MRI measures from the internal capsule, and associations with cognition are determined by using results from a battery of standardized tests relevant to CUD. It is found that all three iron measures are strongly correlated with each other for the considered gray matter regions, but with correlation coefficients substantially less than one indicating important differences. The age dependencies of all three measures are qualitatively similar in most regions, except for the red nucleus, where the susceptibility has a significantly stronger correlation with age than R 2 * . Weak to moderate correlations are seen for the iron measures with several of the diffusion and cognitive measures, with the strongest correlations being obtained for R 2 * . The iron measures differ little between the HP and CUD groups, although susceptibility is significantly lower in the red nucleus for the CUD group. For the comparisons made, the iron measures behave similarly in most respects, but with notable quantitative differences. It is suggested that these differences may be, in part, attributable to a higher sensitivity to the spatial pattern of iron deposition for R 2 * and MFC than for susceptibility. This is supported most strongly by a sharp contrast between the values of the iron measures in the globus pallidus relative to those in the red nucleus. The observed correlations of the iron measures with diffusion and cognitive scores point to possible connections between gray matter iron, white matter microstructure, and cognition.

Exploring the Utility of a Functional Magnetic Resonance Imaging (fMRI) Cannabis Cue-Reactivity Paradigm in Treatment Seeking Adults with Cannabis Use Disorder.

Introduction: Functional magnetic resonance imaging (fMRI) studies examining cue-reactivity in cannabis use disorder (CUD) to date have either involved non-treatment seeking participants or been small. We addressed this gap by administering an fMRI cue-reactivity task to CUD participants entering two separate clinical trials. Methods: Treatment-seeking participants with moderate or severe CUD had behavioral craving measured at baseline via the Marijuana Craving Questionnaire (MCQ-SF). They additionally completed a visual cannabis cue-reactivity paradigm during fMRI following 24-hours of abstinence from cannabis. During fMRI, the Blood Oxygen Level Dependent (BOLD) signal was acquired while participants viewed cannabis-images or matched-neutral-images. BOLD responses were correlated with the MCQ-SF using a General Linear Model. Results: N=65 participants (32% female; mean age 30.4±9.9SD) averaged 46.3±15.5SD on the MCQ-SF. When contrasting cannabis-images vs. matched-neutral-images, participants showed greater BOLD response in bilateral ventromedial prefrontal, dorsolateral prefrontal, anterior cingulate, and visual cortices, as well as the striatum. Similarly, there was stronger task-based functional-connectivity (tbFC) between the medial prefrontal cortex and both the amygdala and the visual cortex. There were no significant differences in either activation or tbFC between studies or between sexes. Craving negatively correlated with BOLD response in the left ventral striatum (R 2 =-0.25; p =0.01). Conclusions: We found that, among two separate treatment-seeking CUD groups, cannabis cue-reactivity was evidenced by greater activation and tbFC in regions related to executive function and reward processing, and craving was negatively associated with cue-reactivity in the ventral striatum. Future directions include examining if pharmacological, neuromodulatory, or psychosocial interventions can alter corticostriatal cue-reactivity.

Sex differences in endocannabinoid tone in a pilot study of cannabis use disorder and acute cannabis abstinence.

Cannabis use disorder (CUD) presents differently in men and women, particularly in symptoms of cannabis withdrawal. Novel pharmacotherapeutic interventions for CUD, such as those that target the endocannabinoid (eCB) system, must be developed in a manner consistent with these sex differences. The present pilot study sought to prospectively assess sex differences in cannabis withdrawal in a small sample of adults with moderate-to-severe CUD and to determine if withdrawal was associated with peripheral eCB and eCB congener tone. Men and women (n = 5/sex) completed 2 weeks of study participation separated by 1 month; in the latter week, participants abstained from cannabis use. Each week, participants attended in-person laboratory visits during which blood was drawn repeatedly to assess plasma eCB and eCB congener tone. Participants also completed multiple daily ambulatory assessments to assess cannabis use and withdrawal symptoms. As anticipated, women reported a greater increase in withdrawal symptoms during the abstinent week [Δ = 9.4 (SE = 1.1); p < 0.001] than men [Δ = 1.2 (SE = 1.2); p = 0.35]. Sex differences in levels of the eCB N-arachidonoylethanolamide (AEA), as well as the eCB congeners stearoylethanolamide (SEA) and linoleylethanolamide (LEA), were evident during abstinence at the morning time point only (p's < 0.05). LEA was associated with withdrawal symptom expression in both sexes [ß = 0.16 (SE = 0.09)] and palmitoylethanolamide (PEA) [ß = 0.22 (SE = 0.13)] and 2-arachidonoylglycerol (2-AG) [ß = 0.32 (SE = 0.15)] were associated with withdrawal symptoms in women only. Pharmacotherapeutic development for CUD should consider evident sex differences in eCB and eCB congener tone during abstinence and their associations with cannabis withdrawal, as eCB-based interventions may produce differential effects by sex.

Novel Collaborations Across Training Programs to Support Mentoring in Sex Differences Research.

There is a critical need to develop a capable and well-trained workforce dedicated to the systematic study of sex differences and examination of sex as a biological variable. Through the support of the Office of Research on Women's Health and partner National Institute of Health centers, the Specialized Centers of Research Excellence (SCORE) on Sex Differences Career Enhancement Cores (CECs) were established to help address this need. We describe the integration of the Medical University of South Carolina SCORE CEC with other National Institutes of Health (NIH)-funded and institutional training programs to promote training synergies, share resources, and enhance mentorship opportunities. Benefits of developing an intrainstitutional training platform have included facilitating cross-disciplinary interactions, encouragement of peer mentorship, and reduced burden on training program leadership.

A Preliminary Investigation Of Repetitive Transcranial Magnetic Stimulation Applied To The Left Dorsolateral Prefrontal Cortex In Treatment Seeking Participants With Cannabis Use Disorder.

Background: Cannabis use disorder (CUD) is a common and consequential disorder. When applied to the dorsolateral prefrontal cortex (DLPFC), repetitive transcranial magnetic stimulation (rTMS) reduces craving across substance use disorders and may have a therapeutic clinical effect when applied in serial sessions. The present study sought to preliminarily determine whether serial sessions of rTMS applied to the DLPFC had a therapeutic effect in CUD. Methods: This study was a two-site, phase-2, double-blind, randomized-controlled-trial. Seventy-two treatment-seeking participants (37.5% Women, mean age 30.2±9.9SD) with ≥moderate-CUD were randomized to active or sham rTMS (Beam-F3, 10Hz, 20-total-sessions, with cannabis cues) while undergoing a three-session motivational enhancement therapy intervention. The primary outcome was the change in craving between pre- and post-treatment (Marijuana Craving Questionnaire Short-Form-MCQ-SF). Secondary outcomes included the number of weeks of abstinence and the number of days-per-week of cannabis use during 4-weeks of follow-up. Results: There were no significant differences in craving between conditions. Participants who received active rTMS reported numerically, but not significantly, more weeks of abstinence in the follow-up period than those who received sham rTMS (15.5%-Active; 9.3%-Sham; rate ratio = 1.66 [95% CI: 0.84, 3.28]; p=0.14). Participants who received active rTMS reported fewer days-per-week of cannabis use over the final two-weeks of the follow-up period (Active vs. Sham: -0.72; Z=-2.33, p=0.02). Conclusions: This trial suggests rTMS is safe and feasible in individuals with CUD and may have a therapeutic effect on frequency of cannabis use, though further study is needed with additional rTMS-sessions and a longer follow-up period.

Sex differences in the relationship between cannabis use motives and cannabis craving in daily life in emerging adults.

OBJECTIVE: Cannabis use motives and craving are associated with increased risk for cannabis-related problems and are ideal targets for prevention and early intervention. Patterns of motives and craving reactivity to cannabis cues differ by sex; however, few studies closely examine the relationship between motives and craving and how it may differ by valence (±) across men and women. METHOD: The present study used Cue Reactivity Ecological Momentary Assessment to assess reward (+) and relief (-) craving four semirandom times per day for 2 weeks in a sample of 63 emerging adults (age 18-21; 54% cisgender women; 85.7% White) who frequently use cannabis (≥ 3 times per week). We assessed craving before and after exposure to brief neutral or cannabis image cues and examined within- and between-participant effects of cue type, motives, sex/gender, and their interactions, on postcue cannabis craving. RESULTS: Regardless of cue type, women with high coping motives (-) reported less postcue relief (-) craving, and men with high enhancement motives (+) reported more postcue reward (+) craving. High enhancement motives (+), regardless of sex/gender, were associated with elevated relief (-) craving reactivity to cannabis cues, and women with high coping motives (-) reported elevated reward (+) craving reactivity to cannabis cues. CONCLUSIONS: Sex/gender differences in the relationships between cannabis motives and craving reactivity indicate the value of a more targeted examination of valence (±) of craving experiences in addition to motives for use. Higher levels of precision may better inform interventions for emerging adults at risk for experiencing cannabis-related problems. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Restructuring reward: A pilot study to enhance natural reward response in adults with cannabis use disorder.

BACKGROUND: Hedonic dysregulation is a core mechanism of addiction. There is a dearth of research on hedonic dysregulation in cannabis use disorder (CUD). The current study tested whether personalized scripted imagery may be an efficacious approach to remediate reward functioning in adults with CUD. METHODS: Adults with CUD (n=10) and non-CUD controls (n=12) completed a single session personalized scripted imagery procedure. Non-drug (i.e. natural) reward and neutral scripts were transcribed and participants listened to the scripts in counterbalanced order. Primary outcomes included positive affect (PA), galvanic skin response (GSR), and cortisol and were assessed at four timepoints. Mixed effects models were used to compare between and within subject effects. RESULTS: Mixed effects models revealed a Condition (reward vs. neutral) X Group (CUD vs. control) interaction (p=0.01) on PA response, indicating blunted PA response to the neutral script relative to the reward script in CUD participants. Likewise, GSR response in CUD participants was decreased in response to the neutral script relative to the reward script (p=0.034; interaction n.s.). An interaction effect of Group X PA on cortisol response was found (p=.036) indicating that cortisol was positively correlated with PA in healthy control participants, but not CUD participants. CONCLUSIONS: Adults with CUD may demonstrate acute deficits in hedonic tone under neutral conditions relative to healthy controls. Personalized scripted imagery may be an efficacious tool to remediate hedonic dysregulation in CUD. Cortisol may play a role in healthy positive affect regulation warranting further investigation.

Cannabis use prevalence, patterns, and reasons for use among patients with cancer and survivors in a state without legal cannabis access.

PURPOSE: Cannabis use among patients with cancer is common, yet data are limited regarding use patterns, reasons for use, and degree of benefit, which represents an unmet need in cancer care delivery. This need is salient in states without legal cannabis programs, where perceptions and behavior among providers and patients may be affected. METHODS: A cross-sectional survey of patients with cancer and survivors at the Hollings Cancer Center at the Medical University of South Carolina (no legal cannabis marketplace in SC) was completed as part of the NCI Cannabis Supplement. Patients (ages 18 +) were recruited using probability sampling from patient lists (N = 7749 sampled; N = 1036 completers). Weight-adjusted Chi-square tests compared demographics and cancer details among patients using cannabis since diagnosis versus those not using cannabis, while weighted descriptives are presented for cannabis use prevalence, consumption, symptom management, and legalization beliefs. RESULTS: Weighted prevalence of cannabis use since diagnosis was 26%, while current cannabis use was 15%. The most common reasons for cannabis use after diagnosis were difficulty sleeping (50%), pain (46%), and mood changes and stress, anxiety, or depression (45%). Symptom improvement was endorsed for pain (57%), stress/anxiety/depression (64%), difficulty sleeping (64%), and loss of appetite (40%). CONCLUSIONS: Among patients with cancer and survivors at a NCI-designated cancer center within SC, a state without legal access to medical cannabis, prevalence rates, and reasons for cannabis use are consistent with emerging literature in oncology populations. These findings have implications for care delivery, and work is needed to inform recommendations for providers and patients.

Developmental trajectories of alcohol and cannabis concurrent use in a nationally representative sample of United States youths.

BACKGROUND: Previous studies have identified common trajectories of single type substance use over the course of adolescence; however, no study to date has examined joint trajectories of cannabis and alcohol concurrent use. Given that expansion of legal cannabis has increased availability, it is important to understand patterns of concurrent use in adolescents and factors that place male and female youth at risk for harmful trajectories of concurrent use. The current study sought to identify joint trajectories of cannabis and alcohol use - and predictors of harmful use trajectories - among male and female adolescents. METHOD: We used 4 waves of data from 6997 early adolescent participants (age 12-14 years at Wave 1) in the Population Assessment of Tobacco and Health, a nationally representative longitudinal study in the United States. Participants reported their cannabis and alcohol use reassessed yearly for 5 years (2013-2018). We used joint trajectory growth mixture modeling to identify trajectory groups as defined by changes in alcohol and cannabis use over time. RESULTS: Five classes of alcohol and cannabis concurrent use trajectories were identified. Both internalizing and externalizing symptoms at Wave 1 increased the odds of membership in trajectory groups characterized by more harmful use trajectories. Internalizing symptomatology was a stronger predictor of membership in escalating use trajectories among girls, whereas externalizing symptomatology stronger predictor among boys. CONCLUSIONS: These findings underscore the utility of jointly considering alcohol and cannabis use when describing common developmental trajectories of use and identifying risk factors for trajectories characterized by harmful use.

Differential prevalence of Adverse Childhood Experiences (ACEs) by gender and substance used in individuals with cannabis, cocaine, opioid, and tobacco use disorders.

Background: Adverse childhood experiences (ACEs) show a graded association with the development of substance use disorders (SUDs) and engagement in risky substance use behaviors. Women are overrepresented among individuals with more severe childhood adversity (≥4 types of ACEs) and may be at particular risk for aberrant substance use.Objectives: To assess the prevalence of ACEs among men and women with cannabis, opioid, cocaine, and tobacco use disorders.Methods: Non-treatment-seeking individuals participating in clinical addiction research at a single site completed the ACE questionnaire and provided a detailed substance use history. Data were analyzed using proportional odds models and logistic regression.Results: Most participants (424/565; 75%) reported at least one ACE, and more than one-quarter (156/565; 27%) reported severe childhood adversity. Relative to men (n = 283), women (n = 282) reported more ACEs (OR = 1.49; p = .01) and more experiences of emotional/physical abuse (OR = 1.52; p = .02), sexual abuse (OR = 4.08; p = .04), and neglect (OR = 2.30; p < .01). Participants in the cocaine (OR = 1.87; n = .01) and opioid (OR = 2.21; p = .01) use disorder, but not cannabis use disorder (OR = 1.46; p = .08), studies reported more severe adversity relative to the tobacco group. Relative to tobacco users, emotional/physical abuse (OR = 1.92; p = .02) and neglect (OR = 2.46; p = .01) scores were higher in cocaine users and household dysfunction scores were higher in opioid users (OR = 2.67; p = .01).Conclusion: The prevalence of ACEs differs with respect to both participant gender and primary substance used. Novel SUD treatment strategies that incorporate ACEs may be uniquely beneficial in specific subpopulations of people with SUDs.

Sex and Gender Differences in Simultaneous Alcohol and Cannabis Use: a Narrative Review.

Purpose of Review: The aim is to review recent literature on sex and gender differences in patterns of use, motives, pharmacological effects, and consequences of simultaneous alcohol and cannabis use (SAC). Recent Findings: Men engage in SAC more frequently than women. Women may have more substance-specific motives for use, while men tend to consistently endorse social/enhancement motives for both alcohol and cannabis. Regarding pharmacological effects, women experience the same subjective effects as men do at lower levels of use, with some evidence that women modulate cannabis use during simultaneous use episodes to avoid greater subjective intoxication. Finally, women appear more vulnerable to experiencing a range of positive and negative consequences from SAC relative to men. Summary: Research has identified several important sex/gender differences in SAC and its correlates and consequences. However, research has primarily focused on white and cisgender populations, with a need for more research among racial/ethnic and gender minorities.

Distress tolerance and reactivity to negative affective cues in naturalistic environments of cannabis-using emerging adults.

BACKGROUND: Distress tolerance (DT) has been implicated as an important factor in the experience of negative affect (NA) and cannabis craving. However, previous research is limited by its use of laboratory paradigms that may not replicate in naturalistic settings. The current study examined how DT influenced reactivity to NA cues in daily life in a sample of frequent (≥3 times per week) cannabis-using emerging adults (age 18-21). METHODS: Using cue-reactivity ecological momentary assessment (CREMA), 63 (54 % female; 85.7 % white; Mage = 19.62) participants reported on their cannabis craving and affect (sadness, relaxation) four semi-random times per day for two weeks (56 possible CREMA sessions/participant). We assessed affect and cannabis craving before and after exposure to neutral and NA cues. Multilevel modeling was used to examine within- and between-participant effects of cues, DT, and sex, as well as within- and between-participant average pre-cue affect and craving, on post-cue affect and craving. RESULTS: NA cues consistently predicted higher-than-normal post-cue sadness and lower relaxation, but not greater-than-normal post-cue craving. Cue type interacted with sex and DT to predict post-cue sadness, but not craving. Female participants and those reporting low DT reported higher sadness following NA cues compared to males and those with high DT, respectively. CONCLUSIONS: Frequent cannabis-using emerging adults differed in affect, but not cannabis craving, reactivity to NA cues as a function of sex and DT. Our results were partially consistent with prior human laboratory and CREMA research finding greater reactivity to NA cues among females and individuals with low DT.

Consideration of sex and gender differences in addiction medication response.

Substance use continues to contribute to significant morbidity and mortality in the United States, for both women and men, more so than another other preventable health condition. To reduce the public health burden attributable to substances, the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism have identified that medication development for substance use disorder is a high priority research area. Furthermore, both Institutes have stated that research on sex and gender differences in substance use medication development is a critical area. The purpose of the current narrative review is to highlight how sex and gender have been considered (or not) in medication trials for substance use disorders to clarify and summarize what is known regarding sex and gender differences in efficacy and to provide direction to the field to advance medication development that is consistent with current NIH 'sex as a biological variable' (SABV) policy. To that end, we reviewed major classes of abused substances (nicotine, alcohol, cocaine, cannabis, opioids) demonstrating that, sex and gender have not been well-considered in addiction medication development research. However, when adequate data on sex and gender differences have been evaluated (i.e., in tobacco cessation), clinically significant differences in response have been identified between women and men. Across the other drugs of abuse reviewed, data also suggest sex and gender may be predictive of outcome for some agents, although the relatively low representation of women in clinical research samples limits making definitive conclusions. We recommend the incorporation of sex and gender into clinical care guidelines and improved access to publicly available sex-stratified data from medication development investigations.

Sex and drug differences in stress, craving and cortisol response to the trier social stress task.

RATIONALE: The hypothalamic-pituitary-adrenal (HPA) axis is a critical hormonal system involved in stress response. A number of studies have investigated the HPA axis response of drug-dependent individuals to stressors. Stress-induced vulnerabilities in the HPA axis may differ in response to chronic use of different substances, possibly leading to different target therapies. There has not been a direct comparison of HPA axis and subjective response between individuals with different types of substance use disorders following a laboratory stress intervention. OBJECTIVES: The primary goal of the current study was to compare subjective and neuroendocrine response to the Trier Social Stress Task (TSST) across multiple primary types of substance use disorders and investigate differential response between males and females. METHODS: Four hundred participants were drawn from seven studies completed at the Medical University of South Carolina between 2011 and 2021. The TSST was utilized across studies and subjective and neuroendocrine responses measured following completion. Generalized linear mixed effects models and area under the response curve analysis were used to compare both substance type and sex differences. RESULTS: The study groups involving individuals with cocaine use disorder had blunted stress, craving and cortisol response following the TSST as compared to other substance use groups. Females in the cocaine groups reported higher subjective stress but lower cortisol than males. CONCLUSIONS: The study results indicate that there may be differential effects of substances on the HPA axis, with cocaine using individuals exhibiting more blunting of the HPA axis response as compared to users of other substances.