Psychopharmacology最新文献

{"title":"Obtusin ameliorates diabetic retinopathy by inhibiting oxidative stress and inflammation.","authors":"Jingyi Xu, Rongjing Shen, Mengting Qian, Luying Ning, Xinyu Zhang, Bingqing Xie, Yong Jiang, Zhengjun Zhou, Wei Dong","doi":"10.1007/s00213-024-06689-4","DOIUrl":"10.1007/s00213-024-06689-4","url":null,"abstract":"<p><strong>Rationale: </strong>Diabetic retinopathy (DR) is linked to an increased risk of psychiatric and neurological conditions, largely due to chronic inflammation, oxidative stress, and microvascular damage associated with the disease. Emerging evidence suggests that Cassia seed extract has significant anti-inflammatory and antioxidant properties. However, the therapeutic potential of obtusin, a major compound in Cassia seed, and its underlying mechanisms remain unclear.</p><p><strong>Objective: </strong>This study aimed to evaluate the therapeutic efficacy of obtusin in the treatment of DR.</p><p><strong>Methods: </strong>Db/db mice were treated with obtusin (5 and 10 mg/kg/day) for 12 weeks. Throughout the study, body weight, blood glucose levels, and lipid profiles were monitored. Retinal histopathology and transmission electron microscopy were used to assess the pharmacological effects of obtusin in vivo. Additionally, in vitro assays were conducted on human retinal microvascular endothelial cells cultured under high glucose conditions to explore obtusin's potential role in mitigating DR.</p><p><strong>Results: </strong>Obtusin treatment in diabetic mice significantly reduced blood glucose levels, improved dyslipidemia, thickened retinal layers, reduced retinal oxidative stress, and inhibited the upregulation of inflammatory cytokines. It also lessened fundus microangiopathy and preserved the retina's normal barrier function. Mechanistic in vitro analysis suggested that obtusin targets the Poldip2-Nox4 oxidative stress axis and the NF-κB-MAPK-VEGFA inflammatory pathway, both of which are implicated in DR.</p><p><strong>Conclusions: </strong>Our findings suggest that the Poldip2-Nox4 oxidative stress axis and the NF-κB-MAPK-VEGFA inflammatory pathway could be therapeutic targets for obtusin in the treatment of DR and its associated psychiatric and neurological conditions.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2471-2484"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depression-like effects induced by chronic unpredictable mild stress in mice are rapidly reversed by a partial negative allosteric modulator of mGlu₅ receptor, M-5MPEP.","authors":"Agnieszka Pałucha-Poniewiera, Bartosz Bobula, Anna Rafało-Ulińska, Katarzyna Kaczorowska","doi":"10.1007/s00213-024-06724-4","DOIUrl":"https://doi.org/10.1007/s00213-024-06724-4","url":null,"abstract":"<p><strong>Rationale: </strong>Due to the numerous limitations of ketamine as a rapid-acting antidepressant drug (RAAD), research is still being conducted to find an effective and safe alternative to this drug. Recent studies indicate that the partial mGlu₅ receptor negative allosteric modulator (NAM), 2-(2-(3-methoxyphenyl)ethynyl)-5-methylpyridine (M-5MPEP), has therapeutic potential as an antidepressant.</p><p><strong>Objectives: </strong>The study aimed to investigate the potential rapid antidepressant-like effect of M-5MPEP in a mouse model of depression and to determine the mechanism of this action.</p><p><strong>Methods: </strong>Chronic unpredictable mild stress (CUMS) was used as an animal model of depression. The effects of single and four-day administration of M-5MPEP on CUMS-induced animal behaviors reflecting anhedonia, apathy, and helplessness were studied. Western blot was applied to measure the levels of proteins potentially involved in a rapid antidepressant effect, including mammalian target of rapamycin (mTOR), eukaryotic elongation factor 2 (eEF2), tropomyosin receptor kinase B (TrkB), and serotonin transporter (SERT), both in the hippocampus and the prefrontal cortex (PFC). Furthermore, excitatory synaptic transmission and long-term potentiation (LTP) were measured in the medial PFC (mPFC).</p><p><strong>Results: </strong>We showed that M-5MPEP administration for four consecutive days abolished CUMS-induced apathy- and anhedonia-like symptoms in a mouse model of depression. We also found that these effects were accompanied by changes in hippocampal TrkB levels and mTOR and eEF2 levels in the PFC. Using electrophysiological techniques, we showed that the four-day M-5MPEP treatment reversed chronic stress-induced increases in excitatory synaptic potential and CUMS-impaired LTP in the mPFC.</p><p><strong>Conclusions: </strong>Partial mGlu₅ receptor NAM, M-5MPEP, appears to be a potentially effective new RAAD and deserves further study.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketamine differentially affects implicit and explicit memory processes in rats.","authors":"Bahar Yuksel, Zeynep Sen, Gunes Unal","doi":"10.1007/s00213-024-06720-8","DOIUrl":"https://doi.org/10.1007/s00213-024-06720-8","url":null,"abstract":"<p><strong>Rationale: </strong>Ketamine, a non-competitive NMDA receptor antagonist, produces antidepressant effects at subanesthetic doses. The therapeutic effect, however, is often accompanied by cognitive side effects, including memory impairments. Yet, the specific effects of ketamine on different processes of implicit and explicit memory remain to be elucidated.</p><p><strong>Objectives: </strong>We examined the effect of an antidepressant dose of ketamine (10 mg/kg, IP) on the encoding, retrieval, and modulation processes of fear memory and spatial memory in adult Wistar rats.</p><p><strong>Methods: </strong>Ketamine was administered before the fear acquisition, retrieval, or extinction procedures in a Pavlovian fear conditioning task. In another set of experiments, it was administered before the training, probe trial, or reversal training phases of the Morris Water Maze (MWM).</p><p><strong>Results: </strong>The antidepressant dose of ketamine partially impaired fear extinction when administered before the acquisition or retrieval. In contrast, it facilitated memory modulation and decreased the escape latency in the first day of reversal training in the MWM when administered before the training or reversal training sessions. Encoding or retrieval performance in either type of memory was not affected.</p><p><strong>Conclusions: </strong>These findings show that ketamine does not impair the acquisition or retrieval processes of cued fear or spatial memory; but exerts differential effects on memory modulation of these implicit and explicit memory paradigms, by disrupting fear extinction and facilitating reversal spatial learning.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the nicotine uptake and safety of Nordic spirit tobacco-free oral nicotine pouches: A randomized cross-over study.","authors":"Karine Renard, Daisuke Nishihara, Johan Nilsson, Sylvain Larroque, Javier Martinez, Lesley Giles","doi":"10.1007/s00213-024-06721-7","DOIUrl":"https://doi.org/10.1007/s00213-024-06721-7","url":null,"abstract":"<p><strong>Rationale: </strong>Given the nascency of tobacco-free oral nicotine pouches (NPs) and the heterogeneity of commercially available NP brands, there is a need for scientific evaluation of different NP formulations. Nordic Spirit, novel NPs are distinguished by their unique composition.</p><p><strong>Objectives: </strong>To characterize blood nicotine delivery, pharmacokinetics (PK), subjective and physiological effects and to monitor safety of three Nordic Spirit NPs (6 mg, 9 mg and 11.2 mg/pouch) compared with LD tobacco snus (11.2 mg/pouch) and Nicorette® gum (4 mg/unit) following single 30 min use.</p><p><strong>Methods: </strong>This was a randomized, open-label, ten-sequence, single-use, cross-over clinical study with 30 healthy adult Swedish snus users.</p><p><strong>Results: </strong>Peak nicotine concentrations (C_max) ranged from 10.92 to 17.32 ng/mL for the three Nordic Spirit NPs, with a trend toward dose proportionality, and 8.18 ng/mL and 9.23 ng/mL for the LD snus and Nicorette® gum comparators, respectively. Peak concentration for Nordic Spirit NPs was reached (T_max) after 30 to 38 min, and after 45 min for LD snus and Nicorette® gum. No notable safety concerns were observed after single use for any of the study products.</p><p><strong>Conclusions: </strong>Delivery of nicotine from the three Nordic Spirit NPs appeared to be nicotine content-dependent, based on C_max and AUC. The amount of nicotine extracted showed positive correlation with the reported C_max and AUC. For Nordic Spirit NPs, T_max was immediately after end of use. The characteristics of Nordic Spirit NPs were found to be favourable for profiling NP nicotine delivery and safety in human use, and for further product development. ISRCTN registry study no. ISRCTN75583947.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of mixed tobacco monoamine oxidase inhibitors in animal models relevant to tobacco dependence.","authors":"Penelope Truman, Diana Vivian Atigari, Meyrick Kidwell, Joyce Colussi-Mas, Bart Ellenbroek","doi":"10.1007/s00213-024-06712-8","DOIUrl":"https://doi.org/10.1007/s00213-024-06712-8","url":null,"abstract":"<p><strong>Rationale: </strong>Tobacco monoamine oxidase (MAO) inhibitors have long been suspected of influencing tobacco dependence, but direct evidence of their effects has been difficult to obtain. Recently we have identified two new groups of monoamine oxidase inhibitors, hydroquinones and polyunsaturated fatty acids (linoleic and linolenic acid), abundant in tobacco smoke.</p><p><strong>Objectives: </strong>To test, in relevant animal models, whether the combined effect of these inhibitors is sufficient to affect addictive responses to nicotine.</p><p><strong>Methods: </strong>Here we report the first tests of the effects of mixed tobacco MAO inhibitors in three animal behavioural tests relevant to nicotine addiction, conditioned place preference, locomotor sensitisation and nicotine self-administration. Inhibitors used were the aforementioned linoleic and linolenic acid, and catechol, 4-ethylcatechol, 4-methyl catechol and hydroquinone, together with the already known inhibitors harman and norharman. They were administered together in the ratios found in tobacco smoke.</p><p><strong>Results: </strong>In conditioned place preference and in self-administration tests the addition of these tobacco MAO inhibitors significantly increased responding to nicotine and motivation to self-administer nicotine, supporting the hypothesis that inhibition of MAO enzymes in the brain enhances addictive responses such as that for nicotine. The combined MAO inhibitors without nicotine did not cause increased locomotor activity and did not induce a place conditioned response.</p><p><strong>Conclusions: </strong>Our results show that the combined effect of three groups of major MAO inhibitors present in tobacco smoke can enhance the addictive responses to nicotine in rats. There is no evidence from this study that these MAO inhibitors are addictive in themselves.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of prophylactic use of benzhexol after risperidone treatment in MK-801-induced mouse model of schizophrenia.","authors":"Yongjie Zhong, Wenhui Wang, Miaomiao Zhang, Yitan Yao, Huanzhong Liu, Kai Zhang","doi":"10.1007/s00213-024-06716-4","DOIUrl":"https://doi.org/10.1007/s00213-024-06716-4","url":null,"abstract":"<p><strong>Rationale: </strong>There is a debate about whether doctors should prophylactically use benzhexol in schizophrenic patients to reduce the occurrence of extrapyramidal side effects (EPS) after risperidone treatment.</p><p><strong>Objectives: </strong>We conducted a prospective animal model to explore the efficacy and safety of the prophylactic use of benzhexol after risperidone treatment and the mechanism of the process.</p><p><strong>Methods: </strong>C57/BL mice were injected with MK-801 (0.5 mg/kg, i.p.) once a day for two weeks. The open field test (OFT) and the novel object recognition test (NORT) assessed the schizophrenia-like behavior of mice. After four weeks of treatment with benzhexol (10 mg/kg, i.g.) and risperidone (3 mg/kg, i.g.), the inclined screen test (IST), rotarod test (RT), open field test (OFT), novel object recognition test (NORT) and the Morris water maze test (MWM) were conducted successively. The expression of BDNF, p-Tau, and Tau in the hippocampus was detected by Western blot assay.</p><p><strong>Results: </strong>We showed that benzhexol can significantly attenuate risperidone-induced motor coordination impairments and catalepsy and did not affect the efficacy of risperidone in reducing spontaneous activity. Notably, the prophylactic use of benzhexol reduced the recognition memory and spatial memory in MK-801-induced model mice after risperidone. In addition, benzhexol increased the ratio of p-Tau/Tau and decreased BDNF expression levels in the hippocampus.</p><p><strong>Conclusions: </strong>We found that the prophylactic use of benzhexol can reduce the occurrence of EPS and does not affect the efficacy of risperidone in the treatment of positive symptoms. Benzhexol may impair cognitive function but did not cause further deterioration of cognitive function in MK-801 mice.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocannabinoid dysregulation and PTSD in urban adolescents: Associations with anandamide concentrations and FAAH genotype.","authors":"Hilary A Marusak, Samantha L Ely, Clara G Zundel, Leah C Gowatch, MacKenna Shampine, Carmen Carpenter, Reem Tamimi, Alaina M Jaster, Tehmina Shakir, Len May, Terri A deRoon-Cassini, Cecilia J Hillard","doi":"10.1007/s00213-024-06717-3","DOIUrl":"https://doi.org/10.1007/s00213-024-06717-3","url":null,"abstract":"<p><strong>Background: </strong>The endocannabinoid system, which regulates fear- and anxiety-related behaviors, is dysregulated in adults with posttraumatic stress disorder (PTSD), as indicated by higher circulating anandamide (AEA) concentrations. The C385A (rs324420) polymorphism in the fatty acid amide hydrolase (FAAH) gene, which catabolizes AEA, is linked to higher AEA concentrations and greater PTSD symptoms in adults. Given that adolescence is a critical period during which trauma and psychiatric disorders emerge, understanding this relationship in youth is essential. This study examines PTSD symptoms, AEA concentrations, and FAAH genotype in a diverse adolescent sample.</p><p><strong>Methods: </strong>This study included 102 Detroit-area adolescents (M ± SD = 13.33 ± 2.21 years, 54.9% female) and their parents/guardians. The sample consisted of 40.2% White Non-Hispanic, 34.3% Black Non-Hispanic, 6.9% White Hispanic, 4.9% Asian/Pacific Islander, and 12.7% Biracial adolescents. Trauma exposure and PTSD symptoms were assessed using the UCLA PTSD Reaction Index for DSM-5. Plasma concentrations of AEA were measured by liquid chromatography-tandem mass spectrometry, and FAAH genotype was determined from saliva samples and high-throughput screening.</p><p><strong>Results: </strong>The majority (90%) of adolescents reported trauma exposure, and 20% met PTSD criteria. Higher AEA concentrations were associated with more severe PTSD symptoms (p = 0.009), especially hyperarousal. The FAAH A-allele (present in 52.5% of participants) was associated with higher AEA concentrations (2.11 ± 0.69 pmol/ml, p = 0.013) and greater PTSD severity (22.65 ± 15.931, p = 0.027), particularly those with the reexperiencing cluster, compared to the CC genotype (1.79 ± 0.66 pmol/ml and 15.87 ±+ 13.043, respectively).</p><p><strong>Conclusion: </strong>Elevated AEA concentrations and the FAAH A-allele were associated with greater PTSD symptom severity in urban adolescents. These findings suggest endocannabinoid dysregulation may play a role in adolescent PTSD, highlighting the need for further research and targeted interventions.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behavioral studies of the abuse potential and anesthetic and sedative effects of etomidate in male rodents.","authors":"Lixin Kuai, Xiangyu Li, Deli Xu, Linggao Zeng, Peng Xu, Bin Di, Fang Yan, Dan Wang","doi":"10.1007/s00213-024-06715-5","DOIUrl":"https://doi.org/10.1007/s00213-024-06715-5","url":null,"abstract":"<p><strong>Rationale: </strong>Etomidate is a short-acting general anesthetic for clinical use and has been used as alternative to propofol or added to the powdered drug and e-cigarette cartridges recently, leading to an increase in abuse. But there have been no studies conducted on the abuse potential of etomidate.</p><p><strong>Objectives and methods: </strong>This study aimed to evaluate the abuse potential of etomidate via conditioned place preference (CPP) and self-administration tests, reflecting its rewarding and reinforcing effects. In addition, righting reflex and open-field tests were conducted to evaluate the anesthetic and sedative effects of etomidate.</p><p><strong>Results: </strong>In male mice, the ED₅₀ after intraperitoneal (i.p.) injection of anesthetic effect for etomidate was 9.156 mg/kg and the ED₅₀ of the sedative effect 5 min after intraperitoneal injection was 2.389 mg/kg. Etomidate induced CPP in male mice at the minimum dose of 3 mg/kg i.p. and supported stable self-administration in male rats at the dose of 0.075 mg/kg/intravenous infusion. The dose-response curve of etomidate was an inverted U-shape, which showed significant self-administrations compared with the vehicle group at doses of 0.05-0.1 mg/kg/infusion etomidate and the highest intake of 21.1 ± 0.64 infusions per 4 h-session.</p><p><strong>Conclusions: </strong>These results clearly demonstrate that etomidate has rewarding and reinforcing effects in male rodents, as well as effects on anesthesia and motor inhibition. These findings indicate the possibility of abuse potential in humans using etomidate.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delineating anticipatory arousal from reward consumption: evaluating fixed-intervals in cocaine seeking-taking response chains.","authors":"Michael Z Leonard, Klaus A Miczek, Herbert E Covington","doi":"10.1007/s00213-024-06711-9","DOIUrl":"10.1007/s00213-024-06711-9","url":null,"abstract":"<p><strong>Rationale: </strong>Anticipation is a critical antecedent to drug use, in which the prospect of imminent drug availability can potently motivate instrumental actions directed to procure it. Models that capture the behavioral dynamics that precede drug access may allow for the dissociation of key neural mechanisms underlying appetitive or consummatory processes in drug self-administration.</p><p><strong>Objectives: </strong>We aimed to isolate measurements attributed to the procurement and consumption of a reward by defining distinct actions for each using a chain-schedule of reinforcement.</p><p><strong>Methods: </strong>Male Long-Evans rats were trained to self-administer cocaine or saccharin under a chained schedule of reinforcement (FI-FR) in order to dissociate appetitive ('seeking') from consummatory ('taking') behaviors. Completion of a fixed-interval (5 min) was followed by 5 min of continuously reinforced responding (FR1) on another lever.</p><p><strong>Results: </strong>The FI-FR chain procedure appears to provide sensitive and dissociable dimensions of cocaine self-administration within a single experimental session. Importantly, we demonstrate that responding during the FI (i.e., seeking) link tracks with the incentive value of anticipated reward access - whereby response rates corresponded to expected reward magnitude, degree of reward-specific satiety, and general motivational state.</p><p><strong>Conclusions: </strong>The FI component is a sensitive and reliable index of motivational changes induced by either the extrinsic incentive value of reinforcement (i.e., anticipated dose) or intrinsic motive states (i.e., satiety or deprivation). This procedure provides a valuable tool for interrogating the neural dynamics of drug-seeking and -taking behavior, in isolation.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal examination of daily stress rhythms in chronic Cannabis users.","authors":"Nicholas C Glodosky, Michael J Cleveland, Reza Rahimi Azghan, Hassan Ghasemzadeh, Ryan J McLaughlin, Carrie Cuttler","doi":"10.1007/s00213-024-06709-3","DOIUrl":"https://doi.org/10.1007/s00213-024-06709-3","url":null,"abstract":"<p><strong>Rationale: </strong>Chronic cannabis users frequently report stress relief as their primary reason for use. The endocannabinoid system is involved in the neuroendocrine stress response, and diurnal cortisol rhythms may be disrupted in chronic cannabis users.</p><p><strong>Objectives: </strong>The objectives were to determine whether cannabis users demonstrate disruptions in diurnal stress rhythms and examine the acute effects of cannabis on stress-related outcomes in cannabis users' natural environments.</p><p><strong>Methods: </strong>Eighty-two participants (39 cannabis users, 43 non-users) collected saliva samples to quantify cortisol concentrations and provided subjective stress ratings at 8 time points throughout the day. They wore a medical-grade wearable device for 24 h that recorded physiological indicators of stress (heart rate variability, electrodermal activity). Cannabis users collected additional saliva samples before and after cannabis use to examine acute effects of cannabis use.</p><p><strong>Results: </strong>Cannabis users exhibited significant dysregulations in diurnal cortisol rhythms, including a blunted cortisol awakening response, flattened diurnal cortisol slope, and elevated afternoon cortisol concentrations. There were no differences in diurnal heart rate variability or electrodermal activity except for elevated evening heart rate in cannabis users. Finally, there were significant decreases in cortisol, subjective stress, and electrodermal activity following acute cannabis use in cannabis users' natural environment.</p><p><strong>Conclusions: </strong>These results provide evidence of dysregulated diurnal cortisol rhythms in cannabis users that were related to later waking times and acute stress-relieving properties of cannabis use in naturalistic environments. Future research should examine the direction of the relationship between cannabis use and diurnal cortisol rhythms and potential implications for other psychological disorders.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}