Combined Cognitive Training and Vortioxetine Mitigates Age-Related Declines in Functional Brain Network Integrity.

OBJECTIVE: Age-related cognitive decline is common and potentially modifiable with cognitive training. Combining cognitive training with pro-cognitive medication offers an opportunity to modify brain networks to mitigate age-related cognitive decline. We tested the hypothesis that the efficacy of cognitive training could be amplified by combining it with vortioxetine, a pro-cognitive and pro-neuroplastic multimodal antidepressant. METHODS: We evaluated the effects of 6 months of computerized cognitive training plus vortioxetine (versus placebo) on resting state functional connectivity in older adults (age 65+) with age-related cognitive decline. We first evaluated the association of functional connectivity with age and cognitive performance (N = 66). Then we compared the effects of vortioxetine plus cognitive training versus placebo plus cognitive training on connectivity changes over the training period (n = 20). RESULTS: At baseline, greater age was significantly associated with lower within-network strength and network segregation, and poorer cognitive function. Cognitive training plus vortioxetine over 6 months positively impacted the relationship between age to mean network segregation. These effects were not observed in the placebo group. In contrast, vortioxetine did not modify the relationship of age to change in mean within-network strength. Exploratory analyses identified the cingulo-opercular network as the network most affected by cognitive training plus vortioxetine. CONCLUSION: This preliminary study provides evidence that combining cognitive training with pro-cognitive medication may modulate the effects of aging on functional brain networks. Results indicate that for older adults experiencing age-related cognitive decline, vortioxetine has a potentially beneficial effect on the correspondence between aging and functional brain network segregation. These results await replication in a larger sample.

A free boundary problem-in time-for the spread of Covid-19.

In this paper we deal with two aspects of the Covid epidemic. The first is a phase change during the epidemic. The empirical observation is that once a certain threshold of active infections is reached, the rate of infection is increasing significantly. This threshold depends, among others, also on the season. We model this phenomenon as a jump in the coefficient of the virus exposition, giving the force of infection. In a chemical mass action law this coefficient corresponds to the reaction rate. We get a free boundary problem in time, which exhibits deterministic 'metastability'. In a population which is in a state of herd immunity, still, if the number of imported infections is large enough, an epidemic wave can start. The second aspect is the two scale nature of the infection network. On one hand side, there is always a finite number of reoccuring-deterministic-contacts, and on the other hand there is a large number of possible random contacts. We present a simple example, where the group size of deterministic contacts is two, and the graph of random contacts is complete.

Cannabis use and posttraumatic stress disorder: prospective evidence from a longitudinal study of veterans.

BACKGROUND: Posttraumatic stress disorder (PTSD) is the most highly co-occurring psychiatric disorder among veterans with cannabis use disorder (CUD). Despite some evidence that cannabis use prospectively exacerbates the course of PTSD, which in turn increases the risk for CUD, the causal nature of the relationship between cannabis and psychiatric comorbidity is debated. The longitudinal relationship between PTSD diagnosis and traumatic intrusion symptoms with cannabis use and CUD was examined using cross-lagged panel model (CLPM) analysis. METHODS: Prospective data from a longitudinal observational study of 361 veterans deployed post-9/11/2001 included PTSD and CUD diagnoses, cannabis use, and PTSD-related traumatic intrusion symptoms from the Inventory of Depression and Anxiety Symptoms. RESULTS: A random intercept CLPM analysis that leveraged three waves (baseline, 6 months and 12 months) of cannabis use and PTSD-related intrusion symptoms to account for between-person differences found that baseline cannabis use was significantly positively associated with 6-month intrusion symptoms; the converse association was significant but reduced in magnitude (baseline use to 6-month intrusions: ß = 0.46, 95% CI 0.155-0.765; baseline intrusions to 6-month use: ß = 0.22, 95% CI -0.003 to 0.444). Results from the two-wave CLPM reveal a significant effect from baseline PTSD to 12-month CUD (ß = 0.15, 95% CI 0.028-0.272) but not from baseline CUD to 12-month PTSD (ß = 0.12, 95% CI -0.022 to 0.262). CONCLUSIONS: Strong prospective associations capturing within-person changes suggest that cannabis use is linked with greater severity of trauma-related intrusion symptoms over time. A strong person-level directional association between PTSD and CUD was evident. Findings have significant clinical implications for the long-term effects of cannabis use among individuals with PTSD.

The role of alcohol and cannabis co-use in drinking rate and its impact on consequences.

BACKGROUND: The impact of alcohol and cannabis co-use on college student drinking and related outcomes is complex. Specific characteristics or patterns of co-use events beyond drinking quantity may be important to the experience of consequences. The present study used repeated daily surveys to examine the association between co-use (versus use of alcohol only) and drinking rate on negative consequences. METHODS: The sample included 318 college students (Mage  = 19.8, 47% female, 76% non-Hispanic White) who were co-users of alcohol and cannabis, recruited from three U.S. college campuses. Participants completed 56 days of data collection (number of drinking days ranged from 1 to 38). Two measures of drinking rate were examined: (1) daily rate (number of drinks divided by number of hours spent drinking per day); and (2) peak hour rate (maximum number of drinks consumed in a single hour) to account for anomalous drinking days of long duration. Generalized linear mixed models examined: (1) associations of co-use with peak hour rate (model 1a) and daily rate (model 1b); (2) associations of peak hour rate (model 2a) and daily rate (model 2b) with experiencing any negative consequence; and (3) interactions of co-use with peak hour rate (model 3a) and daily rate (model 3b) on experiencing a consequence. RESULTS: Co-use was positively associated with peak hour rate but not daily rate. Both peak hour and daily rate positively predicted likelihood of experiencing a negative consequence. The interaction of both peak hour and daily rate by co-use was significant such that the association of rate with experiencing a consequence was stronger on alcohol-only days compared to co-use days. CONCLUSIONS: Daily drinking rate and peak hour drinking rate are unique and should be considered when discussing drinking patterns. Both predict negative consequences and may be important aspects of interventions for negative drinking-related outcomes among college students.

Discussion of alcohol consequences during a brief motivational intervention session: Comparing those who do and do not increase readiness to change.

The present study was designed to take an inductive, qualitative approach to understanding how discussion of alcohol-related consequences during brief motivational interventions (BMI) relate to readiness to change (RTC) prior to versus at the end of a session. Participants were thirty-four adults (35% female) recruited from the emergency room and enrolled in a randomized clinical trial of a BMI for risky alcohol use and risky sex. Seventeen participants both began and remained low on RTC over the course of the session. We selected 17 additional participants, matched on demographics, but who increased RTC over the session. Transcripts were qualitatively coded and analyzed separately within groups. Among participants who increased their RTC relative to participants who remained low on RTC by BMI end, evaluation of alcohol consequences as negative was more typical. In both groups, several consequences were neutrally evaluated. Many who remained low on RTC attributed consequences to something other than alcohol and/or minimized consequence severity. Study findings highlight the value for clinicians in eliciting and maximizing the importance of subjectively negative recent consequences to perhaps increase heavy drinkers' readiness to decrease heavy alcohol use.

Changes in Alcohol Use and Drinking Context due to the COVID-19 Pandemic: A Multimethod Study of College Student Drinkers.

BACKGROUND: In spring 2020, U.S. universities closed campuses to limit the transmission of COVID-19, resulting in an abrupt change in residence, reductions in social interaction, and in many cases, movement away from a heavy drinking culture. The present mixed-methods study explores COVID-19-related changes in college student drinking. We characterize concomitant changes in social and location drinking contexts and describe reasons attributed to changes in drinking. METHODS: We conducted two studies of the impact of the COVID-19 pandemic on drinking behavior, drinking context, and reasons for both increases and decreases in consumption among college students. Study 1 (qualitative) included 18 heavy-drinking college students (Mage  = 20.2; 56% female) who completed semi-structured interviews. Study 2 (quantitative) included 312 current and former college students who reported use of alcohol and cannabis (Mage  = 21.3; 62% female) and who completed an online survey. RESULTS: In both studies, COVID-19-related increases in drinking frequency were accompanied by decreases in quantity, heavy drinking, and drunkenness. Yet, in Study 2, although heavier drinkers reduced their drinking, among non-heavy drinkers several indices of consumption increased or remained stable . Both studies also provided evidence of reductions in social drinking with friends and roommates and at parties and increased drinking with family. Participants confirmed that their drinking decreased due to reduced social opportunities and/or settings, limited access to alcohol, and reasons related to health and self-discipline. Increases were attributed to greater opportunity (more time) and boredom and to a lesser extent, lower perceived risk of harm and to cope with distress. CONCLUSION: This study documents COVID-19-related changes in drinking among college student drinkers that were attributable to changes in context, particularly a shift away from heavy drinking with peers to lighter drinking with family. Given the continued threat of COVID-19, it is imperative for researchers, administrators, and parents to understand these trends as they may have lasting effects on college student drinking behaviors.

Forgoing plans for alcohol and cannabis use in daily life: Examining reasons for nonuse when use was planned in a predominantly white college student sample.

BACKGROUND: The reasons for college students to abstain from alcohol and cannabis use on a given day can inform efforts to prevent or intervene in those behaviors. Research on reasons for alcohol nonuse remains in its nascent stages and no study to date has examined reasons for cannabis nonuse on a given day. Here we examine reasons for nonuse among college students after they planned to use alcohol and/or cannabis. METHODS: College students (N = 341; Mage  = 19.79; 53% women; 74% White) from 3 universities completed 54 days of data collection across which approximately 50% were nonuse days. Each morning, participants indicated whether they planned to use that day; nonuse reasons were assessed the next morning, if applicable. Generalized linear mixed-effects models were used to disentangle within- and between-person effects. RESULTS: On a given nonuse day (at the within-person level), "work" and "school" were reasons associated with having no plan to use alcohol and "to feel in control" was linked to having no plan to use cannabis. "Did not want to get high" was related to forgoing plans (did not use when originally planned) for alcohol use at the within-person level. At the between-person level, "no desire" was associated with no plans for alcohol or cannabis use and "did not want to get high" was related to no plans for cannabis use. "School" and "could not get" were related to forgoing plans for alcohol and cannabis use, respectively, at the between-person level. CONCLUSION: An examination of earlier intentions for alcohol and/or cannabis use on nonuse days yielded novel findings on the intention-behavior gap. Reasons for nonuse can inform intervention and prevention strategies (e.g., those involving social norms or just-in-time adaptive efforts) for alcohol and cannabis use on college campuses.

Does the Combination Matter? Examining the Influence of Alcohol and Cannabis Product Combinations on Simultaneous Use and Consequences in Daily Life.

BACKGROUND: Alcohol and marijuana/cannabis are frequently used simultaneously (i.e., SAM use). SAM use is complex, and the ways in which alcohol and cannabis are simultaneously used may reveal differential effects. The purpose of this study was to examine day-level effects of distinct alcohol and cannabis product combinations on simultaneous use and consequences on that day. METHODS: College student SAM users (N = 274; 50% women; Mage  = 19.82 years) were recruited to complete 54 days of data collection, including 5 repeated daily surveys each day. We identified 12 distinct product combinations reported during SAM-use days. We tested 4 reference groups, with one reflecting the most common use pattern and 3 potentially risky use patterns. We considered 3 outcomes (negative consequences, number of drinks, and number of cannabis uses) and used generalized linear mixed-effects models disentangling within- from between-person effects in all analyses. RESULTS: Using multiple products (≥2) of alcohol was consistently linked to higher odds of experiencing a negative consequence. Combining beer with only one cannabis product (leaf or concentrate) was consistently associated with lower odds of a consequence. Combining cannabis with multiple alcohol products was associated with heavier alcohol consumption. Using dual cannabis products also was associated with heavier cannabis consumption, but this pattern was not significantly different than using concentrate only on a given day. CONCLUSION: This is the first study to examine day-level influences of distinct alcohol and cannabis product combinations on consumption and consequences among young adult SAM users. Findings suggest that mixing alcohol products confers greater risk for negative consequences and heavier consumption, whereas there is little difference in cannabis consumption when using concentrate only vs. 2 cannabis products on a given day, except for concentrate + beer. Our findings support existing protective strategies of not mixing alcohol products and avoiding use of cannabis concentrate for SAM use as well.

Signaling gradients in surface dynamics as basis for planarian regeneration.

Based on experimental data, we introduce and analyze a system of reaction-diffusion equations for the regeneration of planarian flatworms. We model dynamics of head and tail cells expressing positional control genes that translate into localized signals which in turn guide stem cell differentiation. Tissue orientation and positional information are encoded in a long range wnt-related signaling gradient. Our system correctly reproduces typical cut and graft experiments, and improves on previous models by preserving polarity in regeneration over orders of magnitude in body size during growth phases. Key to polarity preservation in our model flatworm is the sensitivity of cell differentiation to gradients of wnt-related signals relative to the tissue surface. This process is particularly relevant in small tissue layers close to cuts during their healing, and modeled in a robust fashion through dynamic boundary conditions.

Joint Attention in the Context of Hearing Loss: A Meta-Analysis and Narrative Synthesis.

Joint attention is important for children's language development. We report two meta-analyses that demonstrate that the congruency in hearing status between parent and child affects the establishment and maintenance of joint attention. Dyads consisting of hearing parents and children with hearing loss, achieve fewer and briefer moments of joint attention in comparison to dyads of hearing parents and hearing children and dyads of deaf parents and deaf children. The theoretical and practical implications of these differences are discussed and placed in the context of two narrative syntheses. The first one focusing on parental strategies used to achieve and maintain moments of joint attention and the second one on the relation between joint attention and spoken language proficiency. We also expect that this review may serve as the start of quest towards a more detailed description (taxonomy) and operationalization of joint attention in the context of hearing loss.

Heaviness of Alcohol Use, Alcohol Problems, and Subjective Intoxication Predict Discrepant Drinking Reports in Daily Life.

BACKGROUND: Self-reported consumption is pervasive in alcohol research, though retrospective recall bias is a concern. Fine-grained methods are designed to limit retrospection; yet, discrepancies can arise when comparing responses on fine-grained surveys with responses to retrospective surveys across weeks or months. Many fine-grained studies use both repeated daily surveys (RDS) and end-of-day (EOD) summaries, but little research has examined whether these survey types are consistent. The purpose of this study was to quantify the magnitude and directionality of discrepancy between EOD summaries and RDS and identify alcohol-related predictors of discrepancy. METHODS: As a part of a larger study, college student alcohol and cannabis users (N = 341; 53% women; Mage  = 19.79 years) were recruited to complete 56 days of data collection, including 5 daily assessments of their substance use and related constructs, one of which included an EOD summary of the previous day. Generalized linear mixed-effects models were used to examine between- and within-person predictors of a 5-category, discrepancy outcome: no discrepancy, low discrepancy where RDS < EOD, low discrepancy where EOD < RDS, high discrepancy where RDS < EOD, and high discrepancy where EOD < RDS. RESULTS: Discrepancies between EOD and RDS were observed in both directions. Alcohol problems predicted more alcohol consumption reported on the EOD survey than across RDS. Within-person alcohol quantity and hourly rate of consumption were most strongly related to less alcohol consumption reported on the EOD survey. Between- and within-person peak subjective intoxication and within-person liquor consumption were associated with discrepancies in both directions. CONCLUSIONS: Surveys requiring more retrospection may overestimate alcohol consumption in problematic drinkers and underestimate consumption on days where more alcohol is consumed than typical. Evidence also suggests that greater day-to-day instability in alcohol behavior is linked to less consistent reporting overall. More research is needed to discern factors contributing to inconsistent reporting on fine-grained surveys to maximize the validity of reports.

Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial.

Importance: Coronavirus disease 2019 (COVID-19) may lead to serious illness as a result of an excessive immune response. Fluvoxamine may prevent clinical deterioration by stimulating the σ-1 receptor, which regulates cytokine production. Objective: To determine whether fluvoxamine, given during mild COVID-19 illness, prevents clinical deterioration and decreases the severity of disease. Design, Setting, and Participants: Double-blind, randomized, fully remote (contactless) clinical trial of fluvoxamine vs placebo. Participants were community-living, nonhospitalized adults with confirmed severe acute respiratory syndrome coronavirus 2 infection, with COVID-19 symptom onset within 7 days and oxygen saturation of 92% or greater. One hundred fifty-two participants were enrolled from the St Louis metropolitan area (Missouri and Illinois) from April 10, 2020, to August 5, 2020. The final date of follow-up was September 19, 2020. Interventions: Participants were randomly assigned to receive 100 mg of fluvoxamine (n = 80) or placebo (n = 72) 3 times daily for 15 days. Main Outcomes and Measures: The primary outcome was clinical deterioration within 15 days of randomization defined by meeting both criteria of (1) shortness of breath or hospitalization for shortness of breath or pneumonia and (2) oxygen saturation less than 92% on room air or need for supplemental oxygen to achieve oxygen saturation of 92% or greater. Results: Of 152 patients who were randomized (mean [SD] age, 46 [13] years; 109 [72%] women), 115 (76%) completed the trial. Clinical deterioration occurred in 0 of 80 patients in the fluvoxamine group and in 6 of 72 patients in the placebo group (absolute difference, 8.7% [95% CI, 1.8%-16.4%] from survival analysis; log-rank P = .009). The fluvoxamine group had 1 serious adverse event and 11 other adverse events, whereas the placebo group had 6 serious adverse events and 12 other adverse events. Conclusions and Relevance: In this preliminary study of adult outpatients with symptomatic COVID-19, patients treated with fluvoxamine, compared with placebo, had a lower likelihood of clinical deterioration over 15 days. However, the study is limited by a small sample size and short follow-up duration, and determination of clinical efficacy would require larger randomized trials with more definitive outcome measures. Trial Registration: ClinicalTrials.gov Identifier: NCT04342663.

Talk with me! Parental linguistic input to toddlers with moderate hearing loss.

This study examined the quantity and quality of parental linguistic input to toddlers with moderate hearing loss (MHL) compared with toddlers with normal hearing (NH). The linguistic input to eighteen toddlers with MHL and twenty-four toddlers with NH was examined during a 10-minute free-play activity in their home environment. Results showed that toddlers with MHL were exposed to an equivalent amount of parental linguistic input compared to toddlers with NH. However, parents of toddlers with MHL used less high-level facilitative language techniques, used less mental state language, and used shorter utterances than parents of toddlers with NH. Quantity and quality measures of parental linguistic input were positively related to the expressive language abilities of toddlers with MHL.

Wavenumber selection in coupled transport equations.

We study mechanisms for wavenumber selection in a minimal model for run-and-tumble dynamics. We show that nonlinearity in tumbling rates induces the existence of a plethora of traveling- and standing-wave patterns, as well as a subtle selection mechanism for the wavenumbers of spatio-temporally periodic waves. We comment on possible implications for rippling patterns observed in colonies of myxobacteria.

Changes in negative urgency, positive urgency, and sensation seeking across adolescence.

The development and potential co-development of traits related to impulsivity and sensation seeking across adolescence has garnered substantial attention within the extant literature. Some prior research suggests that facets show distinct patterns of change across adolescence and that intraindividual changes in these traits may be unrelated. However, the extant literature is somewhat hampered by measurement issues and inconsistent findings. Using an accelerated longitudinal design in a sample of adolescents (n = 1018; ages 11-16), changes in negative urgency, positive urgency, and sensation seeking were examined. The three facets showed similar trajectories across time (i.e., increasing during early adolescence before leveling off). Across all facets, there was strong evidence of correlated change, suggesting these traits are, developmentally, strongly related phenomena.

Attempting to successfully straddle the cultural divide: Hopelessness model of bicultural stress, mental health, and caregiver connection for Mexican descent adolescents.

The present study extends the Hopelessness Model of Depression through: (a) investigating the applicability of bicultural stress as precipitant in this model, (b) expanding mental health outcomes in addition to depression (i.e., life satisfaction), and (c) examining the protective role that male and female caregiver connection may play in disrupting this model for Mexican descent adolescents. With a sample of 524 Mexican descent adolescents (46.9% male; 53.1% female; age range: 14-20; M = 16.23 years; SD = 1.10 years), 2 structural equation models were tested, The first model (Theoretical Model) sought to determine the relationship between bicultural stress, life satisfaction, and depressive symptoms with hopelessness as a mediator. The second model (Protective Factor Model) investigated both male and female caregiver connectedness as potential protective factors in the bicultural stress-mental health relationships. Both models were supported. In the Theoretical Model, hopelessness mediated the relationship between bicultural stress and the mental health variables (i.e., depression and life satisfaction). Additionally, in the Protective Factor Model, female caregiver connection moderated the relationships between bicultural stress and life satisfaction, highlighting that female caregiver connection is a protective factor in the bicultural stress-life satisfaction relationship. Findings will be discussed from a resilience perspective with recommendations of how practitioners can use these findings for mental health prevention and intervention purposes.

Piezo1-induced durotaxis of pancreatic stellate cells depends on TRPC1 and TRPV4 channels.

Pancreatic stellate cells (PSCs) are primarily responsible for producing the stiff tumor tissue in pancreatic ductal adenocarcinoma (PDAC). Thereby, PSCs generate a stiffness gradient between the healthy pancreas and the tumor. This gradient induces durotaxis, a form of directional cell migration driven by differential stiffness. The molecular sensors behind durotaxis are still unclear. To investigate the role of mechanosensitive ion channels in PSC durotaxis, we established a two-dimensional stiffness gradient mimicking PDAC. Using pharmacological and genetic methods, we investigated the role of the ion channels Piezo1, TRPC1, and TRPV4 in PSC durotaxis. We found that PSC migration towards a stiffer substrate is diminished by altering Piezo1 activity. Moreover, disrupting TRPC1 along with TRPV4 abolishes PSC durotaxis even when Piezo1 is functional. Hence, PSC durotaxis is optimal with an intermediary level of mechanosensitive channel activity, which we simulated using a numerically discretized mathematical model. Our findings suggest that mechanosensitive ion channels, particularly Piezo1, detect the mechanical microenvironment to guide PSC migration.

Prospective Associations Between Anxiety Sensitivity, Distress Intolerance, Depressive Symptoms, and Indices of Alcohol and Cannabis Use Among Veterans.

OBJECTIVE: There is substantial evidence linking anxiety sensitivity and distress intolerance to depressive symptoms, and further evidence linking depressive symptoms to alcohol and cannabis use. However, the prospective indirect associations of anxiety sensitivity and distress intolerance with alcohol and cannabis use through depressive symptoms remain uncertain. Thus, the current study examined whether depressive symptoms mediated the associations between anxiety sensitivity and distress intolerance with alcohol and cannabis use frequency, quantity, and problems in a longitudinal sample of veterans. METHOD: Participants (N = 361; 93% male; 80% White) were military veterans with lifetime cannabis use recruited from a Veterans Health Administration in the Northeastern United States. Eligible veterans completed three semi-annual assessments. Prospective mediation models were used to test for the effects of baseline anxiety sensitivity and distress intolerance on alcohol and cannabis use quantity, frequency and problems at 12 months via depressive symptoms at 6 months. RESULTS: Baseline anxiety sensitivity was positively associated with 12-month alcohol problems. Baseline distress intolerance was positively associated with 12-month cannabis use frequency and quantity. Baseline anxiety sensitivity and distress intolerance significantly predicted increased alcohol problems and cannabis use frequency at 12 months through depressive symptoms at 6 months. There were no significant indirect effects of anxiety sensitivity and distress intolerance on alcohol use frequency or quantity, cannabis use quantity, or cannabis problems. CONCLUSIONS: Anxiety sensitivity and distress intolerance share a common pathway to alcohol problems and cannabis use frequency through depressive symptoms. Interventions focused on modulating negative affectivity may reduce cannabis use frequency and alcohol problems.

Cannabis demand and use among veterans: A prospective examination.

OBJECTIVE: Cannabis demand (i.e., relative value), assessed cross-sectionally via a hypothetical marijuana purchase task (MPT), has been associated with use, problems, and dependence symptoms, among others. However, limited work exists on the prospective stability of the MPT. Furthermore, cannabis demand among veterans endorsing cannabis use, and the prospective cyclical relationship between demand and use over time, have yet to be investigated. METHOD: Two waves of data from a veteran sample (N = 133) reporting current (past 6-month) cannabis use were analyzed to assess stability in cannabis demand over 6 months. Autoregressive cross-lagged panel models (CLPMs) assessed the longitudinal associations between demand indices (i.e., intensity, Omax, Pmax, breakpoint) and cannabis use. RESULTS: Baseline cannabis use predicted greater intensity (ß = .32, p < .001), Omax (ß = .37, p < .001), breakpoint (ß = .28, p < .001), and Pmax (ß = .21, p = .017) at 6 months. Conversely, baseline intensity (ß = .14, p = .028), breakpoint (ß = .12, p = .038), and Pmax (ß = .12, p = .043), but not Omax, predicted greater use at 6 months. Only intensity demonstrated acceptable prospective reliability. CONCLUSIONS: Cannabis demand demonstrated stability over 6 months in CLPM models, varying along with natural changes in cannabis use. Importantly, intensity, Pmax, and breakpoint displayed bidirectional predictive associations with cannabis use, and the prospective pathway from use to demand was consistently stronger. Test-retest reliability ranged from good to poor across indices. Findings highlight the value of assessing cannabis demand longitudinally, particularly among clinical samples, to determine how demand fluctuates in response to experimental manipulation, intervention, and treatment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).