Anhedonia, Apathy, Pleasure, and Effort-Based Decision-Making in Adult and Adolescent Cannabis Users and Controls.

BACKGROUND: Cannabis use may be linked with anhedonia and apathy. However, previous studies have shown mixed results, and few have examined the association between cannabis use and specific reward sub-processes. Adolescents may be more vulnerable than adults to harmful effects of cannabis. This study investigated (1) the association between non-acute cannabis use and apathy, anhedonia, pleasure, and effort-based decision-making for reward; and (2) whether these relationships were moderated by age group. METHODS: We used data from the "CannTeen" study. Participants were 274 adult (26-29 years) and adolescent (16-17 years) cannabis users (1-7 d/wk use in the past 3 months) and gender- and age-matched controls. Anhedonia was measured with the Snaith-Hamilton Pleasure Scale (n = 274), and apathy was measured with the Apathy Evaluation Scale (n = 215). Effort-based decision-making for reward was measured with the Physical Effort task (n = 139), and subjective wanting and liking of rewards was measured with the novel Real Reward Pleasure task (n = 137). RESULTS: Controls had higher levels of anhedonia than cannabis users (F1,258 = 5.35, P = .02, η p2 = .02). There were no other significant effects of user-group and no significant user-group*age-group interactions. Null findings were supported by post hoc Bayesian analyses. CONCLUSION: Our results suggest that cannabis use at a frequency of 3 to 4 d/wk is not associated with apathy, effort-based decision-making for reward, reward wanting, or reward liking in adults or adolescents. Cannabis users had lower anhedonia than controls, albeit at a small effect size. These findings are not consistent with the hypothesis that non-acute cannabis use is associated with amotivation.

Apathy and Anhedonia in Adult and Adolescent Cannabis Users and Controls Before and During the COVID-19 Pandemic Lockdown.

BACKGROUND: COVID-19 lockdown measures have caused severe disruptions to work and education and prevented people from engaging in many rewarding activities. Cannabis users may be especially vulnerable, having been previously shown to have higher levels of apathy and anhedonia than non-users. METHODS: In this survey study, we measured apathy and anhedonia, before and after lockdown measures were implemented, in n = 256 adult and n = 200 adolescent cannabis users and n = 170 adult and n = 172 adolescent controls. Scores on the Apathy Evaluation Scale (AES) and Snaith-Hamilton Pleasure Scale (SHAPS) were investigated with mixed-measures ANCOVA, with factors user group, age group, and time, controlling for depression, anxiety, and other drug use. RESULTS: Adolescent cannabis users had significantly higher SHAPS scores before lockdown, indicative of greater anhedonia, compared with adolescent controls (P = .03, η p2 = .013). Contrastingly, adult users had significantly lower scores on both the SHAPS (P < .001, η p2 = .030) and AES (P < .001, η p2 = .048) after lockdown compared with adult controls. Scores on both scales increased during lockdown across groups, and this increase was significantly smaller for cannabis users (AES: P = .001, η p2 = .014; SHAPS: P = .01, η p2 = .008). Exploratory analyses revealed that dependent cannabis users had significantly higher scores overall (AES: P < .001, η p2 = .037; SHAPS: P < .001, η p2 = .029) and a larger increase in scores (AES: P = .04, η p2 =.010; SHAPS: P = .04, η p2 = .010), compared with non-dependent users. CONCLUSIONS: Our results suggest that adolescents and adults have differential associations between cannabis use as well as apathy and anhedonia. Within users, dependence may be associated with higher levels of apathy and anhedonia regardless of age and a greater increase in levels during the COVID-19 lockdown.

Sex Differences in Early Cognitive Development After Prenatal Exposure to Opioids.

OBJECTIVE: Prenatal opioid exposure has been linked with impaired cognitive development, with boys potentially at elevated risk. In the present study, we examined cognitive and language development of children prenatally exposed to opioids, with an additional focus on sex differences. METHODS: A sample of 378 children (n = 194 girls and n = 184 boys) aged 1.2-42.8 months was drawn from the Danish Family Outpatient Clinic database. Developmental outcomes were assessed using the Bayley-III cognitive and language scales, and substance exposure was determined with urine screening and/or verbal report. Children exposed to opioids (n = 94) were compared to children with no prenatal substance exposure (n = 38), and children exposed to alcohol (n = 131) or tobacco (n = 115). Group and sex differences were investigated with separate linear mixed models for each Bayley scale, controlling for concurrent cannabis exposure. RESULTS: There were significantly reduced scores in opioid-exposed boys compared to boys with no prenatal substance exposure, but no difference between opioid-exposed and nonexposed girls. Additionally, alcohol-exposed boys had lower cognitive scores than nonexposed boys, and alcohol-exposed girls had lower scores on both scales compared to opioid-exposed girls. There were otherwise no significant differences according to group, sex, or scale. CONCLUSIONS: The present findings indicate poorer cognitive and language development in boys after prenatal opioid exposure. As academic performance is rooted in cognitive functioning, long-term follow-up might be necessary for exposed children.

The Effects of Acute Cannabis With and Without Cannabidiol on Neural Reward Anticipation in Adults and Adolescents.

BACKGROUND: Adolescents may respond differently to cannabis than adults, yet no previous functional magnetic resonance imaging study has examined acute cannabis effects in this age group. In this study, we investigated the neural correlates of reward anticipation after acute exposure to cannabis in adolescents and adults. METHODS: This was a double-blind, placebo-controlled, randomized, crossover experiment. Forty-seven adolescents (n = 24, 12 females, ages 16-17 years) and adults (n = 23, 11 females, ages 26-29 years) matched on cannabis use frequency (0.5-3 days/week) completed the Monetary Incentive Delay task during functional magnetic resonance imaging after inhaling cannabis with 0.107 mg/kg Δ9-tetrahydrocannabinol ("THC") (8 mg THC for a 75-kg person) or with THC plus 0.320 mg/kg cannabidiol ("THC+CBD") (24 mg CBD for a 75-kg person), or placebo cannabis. We investigated reward anticipation activity with whole-brain analyses and region of interest analyses in the right and left ventral striatum, right and left anterior cingulate cortex, and right insula. RESULTS: THC reduced anticipation activity compared with placebo in the right (p = .005, d= 0.49) and left (p = .003, d = 0.50) ventral striatum and the right insula (p = .01, d = 0.42). THC+CBD reduced activity compared with placebo in the right ventral striatum (p = .01, d = 0.41) and right insula (p = .002, d = 0.49). There were no differences between "THC" and "THC+CBD" conditions and no significant drug by age group interaction effect, supported by Bayesian analyses. There were no significant effects in the whole-brain analyses. CONCLUSIONS: In weekly cannabis users, cannabis suppresses the brain's anticipatory reward response to money, and CBD does not modulate this effect. Furthermore, the adolescent reward circuitry is not differentially sensitive to acute effects of cannabis on reward anticipation.

The CannTeen Study: Cannabis use disorder, depression, anxiety, and psychotic-like symptoms in adolescent and adult cannabis users and age-matched controls.

BACKGROUND: Adolescence is characterised by psychological and neural development. Cannabis harms may be accentuated during adolescence. We hypothesised that adolescents would be more vulnerable to the associations between cannabis use and mental health and addiction problems than adults. METHOD: As part of the 'CannTeen' study, we conducted a cross-sectional analysis. There were 274 participants: split into groups of adolescent users (n = 76; 16-17 years old) and controls (n = 63), and adult users (n = 71; 26-29 years old) and controls (n = 64). Among users, cannabis use frequency ranged from 1 to 7 days/week, while controls had 0-10 lifetime exposures to cannabis. Adolescent and adult cannabis users were matched on cannabis use frequency (mean=4 days/week). We measured Diagnostic and Statistical Manual (DSM-5) Cannabis Use Disorder (CUD), Beck Depression Inventory, Beck Anxiety Inventory and Psychotomimetic States Inventory-adapted. RESULTS: After adjustment for covariates, adolescent users were more likely to have severe CUD than adult users (odd ratio = 3.474, 95% confidence interval (CI) = 1.501-8.036). Users reported greater psychotic-like symptoms than controls (b = 6.004, 95% CI = 1.211-10.796) and adolescents reported greater psychotic-like symptoms than adults (b = 5.509, 95% CI = 1.070-9.947). User-group was not associated with depression or anxiety. No significant interactions between age-group and user-group were identified. Exploratory analyses suggested that cannabis users with severe CUD had greater depression and anxiety levels than cannabis users without severe CUD. CONCLUSION: Adolescent cannabis users are more likely than adult cannabis users to have severe CUD. Adolescent cannabis users have greater psychotic-like symptoms than adult cannabis users and adolescent controls, through an additive effect. There was no evidence of an amplified vulnerability to cannabis-related increases in subclinical depression, anxiety or psychotic-like symptoms in adolescence. However, poorer mental health was associated with the presence of severe CUD.

Neural responses to reward anticipation and feedback in adult and adolescent cannabis users and controls.

Chronic use of drugs may alter the brain's reward system, though the extant literature concerning long-term cannabis use and neural correlates of reward processing has shown mixed results. Adolescents may be more vulnerable to the adverse effects of cannabis than adults; however, this has not been investigated for reward processing. As part of the 'CannTeen' study, in the largest functional magnetic resonance imaging study of reward processing and cannabis use to date, we investigated reward anticipation and feedback in 125 adult (26-29 years) and adolescent (16-17 years) cannabis users (1-7 days/week cannabis use) and gender- and age-matched controls, using the Monetary Incentive Delay task. Blood-oxygen-level-dependent responses were examined using region of interest (ROI) analyses in the bilateral ventral striatum for reward anticipation and right ventral striatum and left ventromedial prefrontal cortex for feedback, and exploratory whole-brain analyses. Results showed no User-Group or User-Group × Age-Group effects during reward anticipation or feedback in pre-defined ROIs. These null findings were supported by post hoc Bayesian analyses. However, in the whole-brain analysis, cannabis users had greater feedback activity in the prefrontal and inferior parietal cortex compared to controls. In conclusion, cannabis users and controls had similar neural responses during reward anticipation and in hypothesised reward-related regions during reward feedback. The whole-brain analysis revealed tentative evidence of greater fronto-parietal activity in cannabis users during feedback. Adolescents showed no increased vulnerability compared with adults. Overall, reward anticipation and feedback processing appear spared in adolescent and adult cannabis users, but future longitudinal studies are needed to corroborate this.

Investigating the frequency of intrusive memories after 24 hours using a visuospatial interference intervention: a follow-up and extension.

Background: There is a need for effective, low-cost, readily available measures for reducing trauma symptoms so that people exposed to potentially traumatic events can receive help more quickly. A previous study reported that performing an intervention including a visuospatial task shortly after a reminder of a series of unpleasant film clips seen 24 hours earlier reduced the number of intrusive memories over the following week. Objective: This study reports a follow-up and extension of the earlier promising finding. The prediction was that participants performing the visuospatial task immediately after the reminder would report fewer intrusions compared to three other groups who 1) performed no task, and novel conditions who 2) performed the task before the reminder, and 3) performed the task 90 minutes after the reminder. Method: A trauma-analogue method was used, where students (N = 200) watched a series of short films with unpleasant material. Over the following week, they were asked to write down any intrusive memories they experienced in a diary. On the second day they returned to the lab and saw static reminders of the films. They were then randomly allocated to condition, recorded intrusive memories over the following days and returned to the lab for final testing on Day 8. Results: A total of 49 participants did not report any intrusions and were excluded from the analyses. Two more participants were excluded as outliers, leaving a final sample of n = 149. Despite using largely the same materials as the original study there were no significant differences in the number of intrusive memories between the four groups post intervention. Conclusions: Possible explanations include the effect not being as robust as expected, a low number of intrusions across groups, baseline differences in attention, and minor but potentially important differences in procedure between this and the original study.

Antecedentes: Existe la necesidad de medidas efectivas de bajo costo y fácilmente disponibles para reducir los síntomas del trauma, de modo que las personas expuestas a eventos potencialmente traumáticos puedan recibir ayuda más rápidamente. James y cols. (2015) reportaron que realizar una intervención que incluye una tarea viso-espacial poco después de un recordatorio consistente en una serie de clips de películas desagradables vistos 24 horas antes, redujo el número de recuerdos intrusivos durante la semana siguiente.Objetivo: Este estudio reporta un seguimiento y extensión del prometedor hallazgo de James y cols. La predicción fue que los participantes que realizaran la tarea viso-espacial inmediatamente después del recordatorio reportarían menos intrusiones en comparación con otros tres grupos que: 1) no realizaron ninguna tarea, y en condiciones novedosas que 2) realizaron la tarea antes del recordatorio y 3) realizaron la tarea 90 minutos después del recordatorio.Método: Se utilizó un método analógico de trauma, donde los estudiantes (N = 200) vieron una serie de cortometrajes con material desagradable. Durante la semana siguiente, se les pidió que escribieran cualquier recuerdo intrusivo que experimentaran en un diario. El segundo día regresaron al laboratorio y vieron recordatorios estáticos de las películas. Luego fueron asignados aleatoriamente a la condición, registraron recuerdos intrusivos durante los días siguientes y regresaron al laboratorio para la prueba final el día 8.Resultados: Un total de 49 participantes no reportó ninguna intrusión y fueron excluidos de los análisis. Se excluyeron dos participantes adicionales como valores atípicos, dejando una muestra final de n = 149. A pesar de utilizar en gran parte los mismos materiales que el estudio original, no hubo diferencias significativas en el número de recuerdos intrusivos entre los cuatro grupos después de la intervención.Conclusiones: Las posibles explicaciones incluyen que el efecto no es tan robusto como se esperaba, un número bajo de intrusiones entre los grupos, diferencias basales de atención y diferencias menores pero potencialmente importantes en el procedimiento entre éste y el estudio original.

The acute and non-acute effects of cannabis on reward processing: A systematic review.

Cannabis use has historically been thought to cause amotivation, but the relationship between cannabis and apathy, anhedonia, and reward processing remains poorly characterised. In this systematic review, we evaluated whether cannabis exposure acutely and/or non-acutely was associated with altered reward processing using questionnaire, behavioural, or functional neuroimaging measures. Questionnaire studies demonstrated greater anhedonia in adolescent cannabis users, and some indication of greater apathy in young adult cannabis users. Behavioural studies yielded some evidence of reduced reward learning in adolescent cannabis users, though there were too few studies in this category for reliable conclusions. Finally, longitudinal and acute functional neuroimaging studies showed an association between cannabis and blunted neural responses to reward, which did not emerge consistently in cross-sectional studies. The current results suggest that cannabis use is associated with specific impairments in reward and motivation. Future large-scale, longitudinal studies which use multiple behavioural and neuroimaging measures of reward processing may further clarify the impact of cannabis use on motivational and reward processes, and neural networks.

Parallel but independent reduction of emotional awareness and corpus callosum connectivity in older age.

Differential functional specialization of the left and right hemispheres for linguistic and emotional functions, respectively, suggest that interhemispheric communication via the corpus callosum is critical for emotional awareness. Accordingly, it has been hypothesized that the age-related decline in callosal connectivity mediates the frequently demonstrated reduction in emotional awareness in older age. The present study tests this hypothesis in a sample of 307 healthy individuals between 20-89 years using combined structural and diffusion-tensor magnetic resonance imaging (MRI) of the corpus callosum. As assumed, inter-hemispheric connectivity (midsagittal callosal area and thickness, as well as fractional anisotropy, FA) and emotional awareness (i.e., increase in externally-oriented thinking, EOT; assessed with the Toronto Alexithymia Scale, TAS-20) were found to be reduced in older (> 60 years) compared to younger participants. Furthermore, relating callosal measures to emotional awareness, FA in the genu of the corpus callosum was found to be negatively correlated with EOT in male participants. Thus, "stronger" structural connectivity (higher FA) was related with higher emotional awareness (lower EOT). However, a formal mediation analysis did not support the notion that age-related decline in emotional awareness is mediated by the corpus callosum. Thus, the observed reduction of emotional awareness and callosal connectivity in older age likely reflects parallel but not inter-dependent processes.