Prediction of suicidal thoughts and behaviors based on the diurnal cortisol pattern and THC dosage in continued cannabis users, a 5 year population-based matched cohort study.

It appears that the THC dosage is the link between dysregulation of the hypothalamic pituitary adrenal (HPA) axis and suicidal thoughts and behaviors (STB). We proposed a new model to understand the underlying pathophysiological mechanism of STB based on the interaction of cortisol and THC dosage. From September 1, 2019, to January 1, 2024, we conducted a population-based, matched-pair, nested case-control study resulting from a three-wave complete longitudinal, multicenter cohort study on a sample of congress 60 clients. A total of 368 male continued cannabis users (CCu) were allocated to four categories, including low, moderate and high THC dosages and relapse, using optimal matching. Several HPA axis measures were analyzed in the saliva using liquid chromatography with tandem mass spectrometry (LC-MS-MS), and carboxylic acids levels in the urine were assessed via gas chromatography/mass spectrometry (GC-MS). We used structural equation modeling (SEM) to examine the relationship between the variables of interest and the model fit test, and used the Akaike information criterion (AIC) to compare the model fit and select the best-fitting model. Population attributable fractions (PAFs) and cumulative risk score were also calculated for the best-fitting pattern. The analysis showed that the likelihood of STB in individuals with a cortisol awakening response (CAR) and a blunted diurnal cortisol slope (DCS) and higher area under the curve (AUC) who reported heavy cannabis use was more than three times higher than the control group (OR 3.2, 95 % CI 2.4-4.1). These findings indicate the importance of the specific cortisol secretion pattern in the increased clinical expression of STB and may be an important factor for guiding preventive efforts in this area.

The contribution of childhood maltreatment to the incidence of heavy cannabis use in Iran (IRNS-CCI): A multicenter, matched-pairs, nested, case-control study.

BACKGROUND: Previous studies have shown the role of the interaction between the endocannabinoid system (ECS) and life's adversities in the formation of addiction, including alcohol abuse. OBJECTIVE: Our objective was to identify childhood maltreatment (CM) patterns with the strongest impact on the probability of heavy cannabis use (THCCOOH concentrations ≥150 ng/mL) in Iran. PARTICIPANTS AND SETTING: Using survivor sampling, 350 adult participants were selected, and they were then allocated to three categories based on an optimal algorithm: 1) Sexual abuse, 2) Physical abuse, and 3) Physical neglect. METHODS: From 1 September 2019 to 1 May 2023, we implemented a multicenter, matched-pairs, nested, case-control study based on the wave 3-wave 6 data of a longitudinal, multicenter, cohort study. The cases and controls (n = 350 men) were defined according to the severity of CM. The THC potency was evaluated with the delta-9 carboxy tetrahydrocannabinol (THC-COOH) levels in urine using gas chromatography/mass spectrometry (GC/MS). We calculated the population attributable fractions (PAFs) to identify the patterns of maltreatment associated with the highest odds of high-potency cannabis use. RESULTS: Accumulating CM, including sexual abuse, physical abuse, and physical neglect, carried more than three times the risk of heavy cannabis use (OR 3.4 95 % CI 2.9-4.1), and the combination of the three indicators of maltreatment and a high BMI (25-29.9) carried more than four times the risk of heavy cannabis use (OR 4.7 95 % CI 2.7-4.1) compared to the controls. We estimated that in the case of zero CM for each of the three indicators, over 20 % of new cases of heavy cannabis use can be prevented. CONCLUSIONS: The findings show the significance of CM as a predicator of heavy cannabis use in adulthood and in the abstinence phase.

Mediating Role of Social Problem-Solving on the Relationship between Autistic Traits and Depression in a Non-Clinical Iranian Sample.

Background: Research on the role of social problem-solving in the relationship between autistic traits and depression is still in its nascent stage and more detailed research is required. Methods: We aimed to investigate the mediating role of problem-solving in the relationship between autistic traits and depression. A sample of 376 university students were assessed on depression, problem-solving and autism-spectrum quotient in 2019 at Shahed University, Tehran, Iran. Results: Social problem-solving played the role of a partial mediator in the relationship between autistic traits and depression. Positive problem orientation and negative problem-solving style fully mediated the effects of autistic traits on depression. Conclusion: Since people with autistic traits have deficits in problem-solving strategies, they may be vulnerable to symptoms of depression. Increasing the ability of positive problem-solving and decreasing negative problem orientation may serve as a buffer against depression in people with autistic traits.

The role of childhood maltreatment in cortisol in the hypothalamic-pituitary-adrenal (HPA) axis in methamphetamine-dependent individuals with and without depression comorbidity and suicide attempts.

BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis dysregulation which was found to have an important role in the pathophysiology of depression, suicide, and substance dependence, may be influenced by childhood maltreatment (CM). The present study aimed to investigate the relationship between CM and cortisol changes in methamphetamine-dependent individuals. METHODS: In a cross-sectional study, methamphetamine-dependent individuals (n = =195) with or without both comorbid major depressive disorder (MDD) and a history of suicide attempts were selected and completed the Childhood Trauma Questionnaire-Short Form (CTQ-SF), the Beck Scale for Suicide Ideation (BSSI), and the Beck Depression Inventory-II (BDI-II). To assess cortisol levels, saliva samples were collected at six time intervals for two consecutive days. RESULTS: A history of CM significantly predicted wake-up cortisol level, cortisol awakening response (CAR), and diurnal cortisol slope. Methamphetamine-dependent individuals with both MDD and lifetime suicide attempts had higher CM and higher cortisol levels with a blunted diurnal cortisol slope than individuals who were merely methamphetamine-dependent. Individuals with high CM showed higher cortisol levels with a blunted diurnal slope than those with low or without CM. LIMITATIONS: Cross-sectional data and use of self-report scales, especially retrospective measurements (e.g., the CTQ-SF), were important limitations of this study. CONCLUSION: Findings suggest that methamphetamine-dependent individuals with adverse psychological factors such as CM, MDD, and suicide attempts may show dysregulation in biological factors including cortisol level. In addition, CM and its effects on cortisol in the HPA axis may emerge as important factors regarding psychopathological use of methamphetamine.

The Effectiveness of Intranasal Oxytocin on Addiction Severity Index and Anhedonia Symptoms in an Alcoholic Case with Oropharyngeal Cancer, a Protocol for a Single-case Experimental Design Pilot Study.

One of the goals of all pharmacological interventions aimed to increase the survival rate of patients with alcohol-dependent oropharyngeal cancers is to decrease alcohol use. Oxytocin is an alternative therapy for craving and alcohol management. However, the effectiveness of oxytocin on the severity of alcohol dependence has not been evaluated. In an ABABC study with a 6-month follow-up, during February 2015 to June 2016, a 67-year-old man with oropharyngeal squamous cell carcinoma with comorbidity of alcohol dependence syndrome and anhedonia was selected by Respondent-Driven sampling (RDS). The patient was treated with intranasal oxytocin in two six-week stages (B1 and B2) and received placebo only in the other two stages (A1 and A2), and the follow-up results were evaluated at stage C. The data were analyzed by Generalized Estimation Equation (GEE) and Repeated Measures Correlation (rmcorr). Primary outcomes showed that addiction severity Index (ASI) was significantly reduced in five domains of medical status, occupational status, alcohol consumption, family status, and mental status (all p's < 0.05). There was no significant effect of treatment on legal status (all p's > 0.05). Also, social (p < 0.05) and physical (p < 0.01) anhedonia syndrome decreased in the treatment stages. However, these changes did not persist until the 6-month follow-up (all p's > 0.05). Secondary outcomes showed that there was a significant direct relationship between the severity of addiction and anhedonia (rmcorr = 0.01). The findings of this study showed that the reduction of oxytocin-induced neurotoxic symptoms led to a decrease in the severity of addiction and an improvement in the anhedonia syndrome.

Effect of Magnesium Sulfate Added to Tincture of Opium and Buprenorphine on Pain and Quality of Life in Women with Dysmenorrhea: A Prospective, Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: Adding magnesium sulfate (MgSO4) to opioid receptor agonists increases the opioid analgesic effects via blocking this receptor. The current study aimed to evaluate the effectiveness of adding MgSO4 to tincture of opium (TOP) and buprenorphine (BUP) on pain and quality of life (QOL). METHODS: In prospective, randomized, double-blind, placebo-controlled clinical trial, one hundred and sixty-three women with secondary dysmenorrhea caused by endometriosis were selected using a respondent-driven sampling (RDS) and assigned into six groups using block randomization. Patients received 50 mg/kg MgSO4 in 100 ml saline by micro set in six monthly menstrual periods and completed the visual analogue scale (VAS) and QOL Questionnaire (QOLQ). Data were analyzed by repeated measures analysis of variance (ANOVA) and hierarchical regression. FINDINGS: The primary outcomes showed that pain scores in magnesium (MAG) + opium tincture (OT) [F = 5.7(1,162), P = 0.004] and MAG+ BUP [F = 4.5(1,162), P = 0.006] groups showed a significant decrease compared with control group. Also, QOL scores in MAG + OT [F = 4.8(1,162), P = 0.005] and MAG + BUP [F = 5.9(1,162), P = 0.003] showed a significant increase. However, there was no significant difference between the two groups (P = 0.140) and the changes did not persist until follow-up (P = 0.810). Secondary outcomes indicated that the low scores of the two components of QOL including physical and psychological components were predictors of pain (P = 0.011, Beta > 3.09). CONCLUSION: Simultaneous use of MAG with opioids is associated with pain reduction and the improvement of QOL. However, this hypothesis requires careful handling in a randomized controlled trial.

Challenges of Differential Diagnosis, Symptoms of Coronavirus Disease 2019 (COVID-19) or Cannabinoid Hyperemesis Syndrome (CHS)? A Rare Case Report.

Coronavirus Disease 2019 (COVID-19) has become a pandemic since Mar 2020. Iran has been one of the first countries dealing with the outbreak of COVID-19 and severe measures have been adopted to limit viral transmission. Cannabinoid hyperemesis syndrome (CHS) is a syndrome of cyclic vomiting associated with cannabis use. Many of the clinical symptoms of COVID-19 are similar to CHS. Here, we report a 26-year-old man with CHS, that the presented symptoms are similar to COVID-19 in many cases, and in our knowledge, it is the first in this type. Paying attention to the symptoms can help to differential diagnosis of the two diseases and reduce the burden of treatment during this critical period.

Topiramate for the Treatment of Dually Dependent on Opiates and Cocaine: A Single-center Placebo-controlled Trial.

BACKGROUND: Topiramate facilitates gamma aminobutyric acid (GABA) transference and an ideal candidate for reducing cocaine use in methadone patients. The present study evaluated topiramate in Dual dependence on opiate and cocaine. METHODS: This placebo-controlled study (Clinical Trial Registration Code: TCTR20170201001) conducted during the period 2013-2014, Cocaine-dependent individuals maintained on methadone (n=50) were randomized to receive topiramate or identical placebo capsules. Participants' dosage ranged between 25-300 mg/day (12 wk) in escalating doses. Methadone Doses started at 30 mg/day (median 100 mg/day; range 20 -140 mg/day). In addition, all subjects received brief behavioral compliance enhancement treatment (BBCET). The data were analyzed by Chi-square Test, generalized estimating equations (GEE) models, linear mixed effects (LME) model and Analysis of covariance (ANCOVA). Primary outcome measures included twelve weekly urine drug screens (cocaine abstinence, detection of benzoylecgonine) and treatment retention. Secondary outcome measures included correlation between cocaine craving with cocaine urine samples and Side effects of depression. RESULTS: Topiramate was not better than placebo in reducing cocaine use. The secondary outcome showed that Topiramate was better than placebo in reducing cocaine craving. The mean [99% confidence interval (CI)] scores of cocaine craving were 24.31 (18.61-30.01) in experimental group and 21.84 (16.86-26.81) in control group (all P > 0.01). Retention and correlation between cocaine craving and cocaine urine samples were not significantly different between the groups. Topiramate usage was not associated with increase in depression symptoms as a side effect (P>0.05). CONCLUSION: The efficacy of topiramate in cocaine treatment is limited and needs the similar controlled clinical trials and can be used as a complementary intervention.