Cannabinoid hyperemesis syndrome co-occurring with superior mesenteric artery syndrome in adolescents.

OBJECTIVES: Both superior mesenteric artery syndrome (SMAS) and cannabinoid hyperemesis syndrome (CHS) may present with abdominal pain, nausea, and emesis - making them difficult to differentiate or determine when they co-occur in adolescents who regularly use cannabis. Here, we present nine cases of CHS co-occurring with SMAS and characterize their clinical courses. METHODS: Patients admitted at Children's Hospital of Colorado between January 1, 2015, and March 23, 2023, who had both cannabis use (F12.1-F12.99) and chronic vascular disorders of the intestine (K55.1) on their problem lists were identified from the electronic medical record using ICD 10 codes. Nine met criteria for SMAS and chronic cannabis use. RESULTS: Six of nine patients were female. The most common presenting symptoms were nausea (9), vomiting (9), and weight loss (9). Four patients received cannabis cessation support. Patients lost a mean of 6.0 kg, had an average body mass index (BMI) of 15.61 percentile (17.7 kg/m2) and BMI Z-scores of -1.5. Symptoms were present for a mean of 19.6 weeks before diagnosis. CONCLUSIONS: Adolescents who experience nausea, vomiting, abdominal pain, and weight loss in association with chronic cannabis use and/or SMAS can present with confusing and overlapping symptoms. Our cohort was described as having CHS with co-occurring SMAS on imaging. Although the etiology of weight loss cannot be definitively ascertained, we postulate that the recurring emetic attacks from CHS led to weight loss resulting in SMAS. Improvement in diagnostic criteria for this population as well as cannabis cessation programming may aid in deceasing morbidity from these co-occurring conditions.

DNA methylation and gene expression of immune cell markers in adolescents with chronic cannabis use: an exploratory study.

BACKGROUND: Experimental studies indicate that phytocannabinoids have immune-modulatory properties. However, the effects of chronic cannabis use (CCU) in adolescents on their immune cells have been scarcely investigated to date, although CCU is increasingly observed in this age group. METHODS: In this study, we analyzed DNA methylation and gene expression of immune cell markers in whole-blood samples of adolescent CCU-outpatients and non-cannabis-using (NCU) controls (n = 14 vs. n = 15, mean age = 16.1 ± 1.3 years). Site-specific DNA methylation values were used to calculate A) proportion estimates of circulating white blood cell (WBC) types and B) mean DNA methylation values of common immune cell markers (CD4, CD8A, CD19, FCGR3A, CD14, FUT4, MPO), whose gene expression levels were additionally determined. RESULTS: CCU adolescents had a lower estimated proportion of B cells compared to NCU subjects. An originally observed higher proportion of granulocytes in CCU subjects, however, was attenuated when controlling for past-year tobacco use. The observed differences in mean DNA methylation and gene expression of immune cell markers were not statistically significant. CONCLUSION: The results of our explorative study indicate that CCU in adolescents is associated with altered levels of circulating WBCs. Further studies with larger cohorts are warranted to confirm our findings and to provide insights regarding their functional consequences.

Adolescent cannabis exposure interacts with mutant DISC1 to produce impaired adult emotional memory.

Cannabis is an increasingly popular and controversial drug used worldwide. Cannabis use often begins during adolescence, a highly susceptible period for environmental stimuli to alter functional and structural organization of the developing brain. Given that adolescence is a critical time for the emergence of mental illnesses before full-onset in early adulthood, it is particularly important to investigate how genetic insults and adolescent cannabis exposure interact to affect brain development and function. Here we show for the first time that a perturbation in disrupted in schizophrenia 1 (DISC1) exacerbates the response to adolescent exposure to delta-9-tetrahydrocannabinol (Δ(9)-THC), a major psychoactive ingredient of cannabis, consistent with the concept that gene-environment interaction may contribute to the pathophysiology of psychiatric conditions. We found that chronic adolescent treatment with Δ(9)-THC exacerbates deficits in fear-associated memory in adult mice that express a putative dominant-negative mutant of DISC1 (DN-DISC1). Synaptic expression of cannabinoid receptor 1 (CB1R) is down-regulated in the prefrontal cortex, hippocampus, and amygdala, critical brain regions for fear-associated memory, by either expression of DN-DISC1 or adolescent Δ(9)-THC treatment. Notably, elevation of c-Fos expression evoked by context-dependent fear memory retrieval is impaired in these brain regions in DN-DISC1 mice. We also found a synergistic reduction of c-Fos expression induced by cue-dependent fear memory retrieval in DN-DISC1 with adolescent Δ(9)-THC exposure. These results suggest that alteration of CB1R-mediated signaling in DN-DISC1 mice may underlie susceptibility to detrimental effects of adolescent cannabis exposure on adult behaviors.

Assessment of frontal lobe functions in a sample of male cannabis users currently in abstinence: correlations with duration of use and their functional outcomes.

BACKGROUND: Previous research literature reported different results regarding the long-term effects that cannabis use can exert on the frontal lobe neurocognitive functions of its users. Another body of research suggested that cannabis use negatively affects the person's general level of occupational and psychosocial functioning consequently to these alterations. Some other research results did not support these findings. To date, it is still debatable whether chronic cannabis use triggers negative neurocognitive effects in chronic users even after a period of abstinence. Research data exploring consequent adverse outcomes on the general individual occupational and psychosocial functioning is not yet conclusive. RESULTS: We conducted this study to examine the residual neurocognitive effects of cannabis use, whether it is affected by duration of cannabis use before abstinence, and its relation to individual's global assessment of functioning exhibited in the person's occupational and social life whether it's family or friends. Our sample comprised 80 male participants (18-45 years old) who were grouped into 4 groups (3 groups with different durations of use and a control group), with no significant difference between the four studied groups regarding age, education, and socioeconomic level. The Kruskal Wallis test was used to test the significance of differences in the distribution of total frontal lobe battery results and the general assessment of function scores using GAF scores between study groups. Post hoc testing was performed to adjust for multiple comparisons using Bonferroni method. CONCLUSION: Data analysis showed that cannabis users experienced general functional disturbances that encompass impairments in social and occupational life aspects. These impairments in function are correlated with the presence of neurocognitive deficits even after a period of abstinence. Both having significant positive correlation with longer duration of cannabis use.

Cannabinoid hyperemesis syndrome.

BACKGROUND: The purpose of this review is to describe cannabinoid hyperemesis syndrome (CHS), which is thought to be induced by long-term cannabis use, and provide clinical pharmacists with information to manage the hyperemetic phase of CHS. METHOD: Published literature was searched and reviewed using PubMed. RESULTS: CHS is characterized by intractable nausea and vomiting without an obvious organic cause and associated learned compulsive hot water bathing behavior. Patients often seek care in the emergency department (ED) for symptomatic relief. CONCLUSION: CHS is potentially underrecognized and underdiagnosed in the ED, and it should be considered in the differential diagnosis in long-term cannabis use patients with CHS symptoms to avoid unnecessary extensive diagnostic workup including invasive radiologic imaging. Pharmacists have an important role in CHS recognition, education, and symptom management.

Cannabinoid-Associated Hyperemesis Syndrome Treated With Dronabinol: Killing a Poison With the Poison.

Cannabinoid hyperemesis syndrome (CHS) is a medical condition characterized by recurrent nausea, vomiting, and abdominal pain in individuals who frequently use cannabis. This case report highlights the successful treatment of CHS using dronabinol, a synthetic cannabinoid compound. A 21-year-old female presented with severe abdominal symptoms, including vomiting and pain, alongside a history of chronic cannabis use. Despite initial symptomatic treatment, her symptoms persisted. After being diagnosed with CHS, the patient was administered one dose of haloperidol, which led to agitation and worsening of her symptoms. Eventually, she was given one dose of dronabinol resulting in significant symptom improvement. Subsequent doses of dronabinol led to the complete resolution of her CHS symptoms. This case underscores the importance of thorough history-taking, especially for complex patients. Also, with cannabis legalization, cases of CHS are on the rise, and widespread awareness is vital for healthcare practitioners to recognize and appropriately manage nausea and vomiting induced by long-term cannabis intake. Although this case provides valuable insights, its limitations emphasize the need for further research to establish evidence-based guidelines for CHS management.

Chronic use of cannabis might impair sensory error processing in the cerebellum through endocannabinoid dysregulation.

Chronic use of cannabis leads to both motor deficits and the downregulation of CB1 receptors (CB1R) in the cerebellum. In turn, cerebellar damage is often related to impairments in motor learning and control. Further, a recent motor learning task that measures cerebellar-dependent adaptation has been shown to distinguish well between healthy subjects and chronic cannabis users. Thus, the deteriorating effects of chronic cannabis use in motor performance point to cerebellar adaptation as a key process to explain such deficits. We review the literature relating chronic cannabis use, the endocannabinoid system in the cerebellum, and different forms of cerebellar-dependent motor learning, to suggest that CB1R downregulation leads to a generalized underestimation and misprocessing of the sensory errors driving synaptic updates in the cerebellar cortex. Further, we test our hypothesis with a computational model performing a motor adaptation task and reproduce the behavioral effect of decreased implicit adaptation that appears to be a sign of chronic cannabis use. Finally, we discuss the potential of our hypothesis to explain similar phenomena related to motor impairments following chronic alcohol dependency.

Neurocognitive consequences of chronic cannabis use: a systematic review and meta-analysis.

Cannabis is currently the most used illicit substance in the world with a global widespread distribution. Although its acute neurocognitive effects on human behaviour have been reported, there is a lack of robust analysis investigating the link, if any, between chronic cannabis use and neurocognitive function. A systematic review of the literature was conducted in order to identify relevant studies published from 2010 to 2019. A meta-analysis was performed on 13 selected studies testing performance of chronic cannabis users compared with non-users in six different neurocognitive domains. There was a low cross-sectional association between neurocognitive impairments and chronic cannabis use in cognitive impulsivity, cognitive flexibility, attention, short-term memory and long-term memory. No association was found between chronic cannabis use and motor impulsivity. By analysing a specific target population with strict inclusion criteria, these findings provide inconclusive evidence that there are cognitive impairments associated with chronic cannabis use. Future research is needed to determine if the findings of this meta-analysis are biased by the methodological limitations encountered.

Chronic cannabis use and attentional bias: Extended attentional capture to cannabis cues.

INTRODUCTION: A significant proportion of chronic cannabis users experience occupational, social, and psychological problems thought to reflect, in part, cannabis-related cognitive and emotional attentional biases. The emotional attentional blink (EAB) is a unique test of attentional bias that assesses automatic responses, cue-detection failures, and rapid and temporally extended biases. Using the EAB, we tested users' and non-users' attentional biases and how cannabis exposure correlates with these attentional biases. METHODS: Forty-eight regular cannabis users and 51 non-users completed demographic, psychological, and cannabis-use reports and two EAB target-detection experiments. Each experiment comprised 160 trials. Each trial included a rapid serial visual presentation of images with one of four types of distractor images (cannabis, generically positive, neutral, or scrambled) preceding the target image. Distractor images were presented 200ms (Lag 2) or 800ms (Lag 8) before the target in Experiment 1 and 200ms (Lag 2) or 500ms (Lag 5) before the target in Experiment 2. RESULTS: Chronic cannabis users exhibited exaggerated, immediate attentional bias (Lag 2) and exaggerated, extended attentional bias (Lag 5) compared to non-users. The intensity of cannabis-use (grams per week) correlated with more errors at the extended attentional bias durations (Lags 5 and 8). CONCLUSIONS: Our results represent novel evidence of automatic attentional capture consistent with an exaggerated "wanting" motive in models of addiction. Our unique evidence of temporally extended attentional biases is consistent with attentional disengagement deficits associated with chronic cannabis use.

Abstinence phenomena of chronic cannabis-addicts prospectively monitored during controlled inpatient detoxification (Part II): Psychiatric complaints and their relation to delta-9-tetrahydrocannabinol and its metabolites in serum.

OBJECTIVE: To investigate the impact of inpatient detoxification treatment on psychiatric symptoms of chronic cannabis addicts and to analyze the influence of serum cannabinoid levels on the severity of these symptoms. METHODS: Thirty five treatment-seeking, not active co-morbid chronic cannabis dependents (ICD-10) were studied on admission and on abstinence days 8 and 16, using several observational and self-report scales, such as Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Young Mania Rating Scale (YMRS) and Brief Psychiatric Rating Scale (BPRS), and the Symptom Checklist-90-Revised (SCL-90-R). Simultaneously obtained serum was analyzed with regard to levels of delta-9-tetrahydrocannabinol (THC) and its main metabolites 11-hydroxy-delta-9-tetrahydrocannabinol (THC-OH) and 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). RESULTS: At admission, nearly 90% of the patients were not, or only mildly, affected by depression, anxiety or manic symptoms. In contrast, patients' self-description indicated a strong psychiatric burden in approximately 60% of the cases. All patients improved significantly within 16 days of the treatment. Effect sizes ranged from 0.7 to 1.4. (Cohen's d) for the respective scales. Serum THC-levels were positively associated with impairment of cognition in HAMA and motor retardation in BPRS. All other test results were not significantly related to the serum levels of the measured cannabinoids. DISCUSSION: Effects of the cannabis withdrawal syndrome and executive dysfunctions might explain the discrepancy between the observer ratings and self-reported psychiatric burden. CONCLUSION: Inpatient cannabis detoxification treatment significantly improved psychiatric symptoms. Serum THC-levels were not associated with affective symptoms and anxiety but predicted cognitive impairment and motor retardation.