Category Archives: Depression

Therapeutic potential of minor cannabinoids in psychiatric disorders: A systematic review

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“Interest in cannabinoids’ therapeutic potential in mental health is growing, supported by evidence of the involvement of the endocannabinoid system in psychiatric disorders such as anxiety, depression, and addiction.

While the major cannabinoids cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) have been more extensively researched, approximately 120 minor cannabinoids from the cannabis plant have been identified. Although some displayed promising pharmacological profiles, research on their application for psychiatric disorders is fragmented.

This systematic review evaluates, for the first time, both preclinical and clinical studies exploring minor cannabinoids’ therapeutic potential in psychiatric disorders. 22 preclinical studies and one clinical study were included, investigating various minor cannabinoids in substance use disorders, anxiety disorders, depressive disorders, trauma and stressor-related disorders, psychotic disorders, neurodevelopmental disorders, and eating disorders. Despite the heterogeneous results and the moderate to high risk of bias in several articles, certain compounds demonstrate promise for further investigation.

Δ8-tetrahydrocannabidivarin (Δ8-THCV) exhibited potential for nicotine addiction; Δ9-tetrahydrocannabidivarin (Δ9-THCV) for psychotic-like symptoms; cannabidiolic acid methyl ester (CBDA-ME) alleviated anxiety and depression-like symptoms, and cannabidivarin (CBDV) autism spectrum disorder-like symptoms.”

https://pubmed.ncbi.nlm.nih.gov/39541799/

https://www.sciencedirect.com/science/article/pii/S0924977X24007508?via%3Dihub

Antidepressant-like Effects of Cannabis sativa L. Extract in an Lipopolysaccharide Model: Modulation of Mast Cell Activation in Deep Cervical Lymph Nodes and Dura Mater

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“Background: Lipopolysaccharide (LPS)-induced neuroinflammation is a well-established model for studying depression-like behavior, driven by pro-inflammatory cytokines such as TNF-α and IL-1β. Mast cells (MCs) contribute to neuroinflammation by releasing mediators that exacerbate depressive-like symptoms. This study evaluates the antidepressant-like and anti-inflammatory effects of Cannabis sativa L. inflorescence extract (CSL) in an LPS-induced neuroinflammation model.

Methods: Male C57BL/6 mice were intraperitoneally injected with CSL at doses of 10, 20, and 30 mg/kg, 30 min prior to LPS (0.83 mg/kg) administration. Depressive behaviors were assessed using the sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST). The neutrophil-to-lymphocyte ratio (NLR) was measured to assess systemic inflammation. Cytokine levels in the prefrontal cortex (PFC) were measured, and mast cell degranulation in the lymph nodes and dura mater was analyzed histologically (approval number: WKU24-64).

Results: CSL significantly improved depressive-like behaviors and decreased the NLR, indicating reduced systemic inflammation. CSL also significantly reduced TNF-α and IL-1β levels in the PFC. Furthermore, CSL inhibited MC degranulation in the deep cervical lymph nodes and dura mater, with the strongest effects observed at 30 mg/kg.

Conclusions: CSL demonstrated antidepressant-like and anti-inflammatory effects in an LPS-induced neuroinflammation model, likely through the modulation of cytokine expression and mast cell activity. These results suggest the potential of CSL as a therapeutic option for treating inflammation-related depression.”

https://pubmed.ncbi.nlm.nih.gov/39459047/

“We demonstrated that CSL exhibits significant antidepressant-like and anti-inflammatory effects in an LPS-induced neuroinflammatory model. CSL administration effectively reduced depressive-like behaviors, as observed in the SPT, TST, and FST, and modulated the degranulation of MCs in LNs and the dura mater. Furthermore, CSL decreased the expression of pro-inflammatory cytokines TNF-α and IL-1β in the PFC in a dose-dependent manner. These findings suggest that CSL acts both through immune modulation and neuroinflammation suppression, possibly via the endocannabinoid system and pathways such as NF-κB, PPAR-γ, and VEGF-C. The synergistic interaction between cannabinoids and terpenes in CSL likely contributes to its therapeutic potential, supporting the notion of the “entourage effect”. While these results are promising, further studies are required to clarify the exact mechanisms involved and to assess the long-term safety and efficacy of CSL in chronic depression models.”

https://www.mdpi.com/1424-8247/17/10/1409

Effects of Cannabidiol (CBD) on Doxorubicin-Induced Anxiety and Depression-like Behaviors and mRNA Expression of Inflammatory Markers in Rats

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“Background: Post-treatment side effects of chemotherapy can include cognitive deficits commonly known as Chemo-brain. The treatment of patients with Doxorubicin (DOX), one of the most widely used chemotherapeutic drugs in the treatment of cancer, can induce depression, anxiety, and impaired cognitive function. Cannabidiol (CBD) is a non-psychoactive component of Cannabis sativa that has been identified as a possible therapeutic agent against many neurodegenerative disorders, including traumatic brain injury, spinal cord injury, Tau-protein-induced neurodegeneration, and neuropathic pain. Therefore, this study aimed to assess whether oral CBD administration could reduce DOX-induced anxiety and depression-like behaviors and alter the expression of mRNA associated with neuroinflammation. 

Methods: Female Long Evans Hooded rats received intraperitoneal injections of DOX (6 mg/kg) or the vehicle (0.9% saline) once a week for four weeks, followed by oral administration of CBD (10 mg/kg) three times a week for the same period. 

Results: CBD was significantly protective against DOX-induced anxiety and depression-like behaviors, as measured by several behavioral tests. Furthermore, CBD improved DOX-induced alterations in the gene expression of biomarkers of neuroinflammation in the hippocampus and prefrontal cortex. 

Conclusions: This provides insights into future studies on possible mechanisms by which DOX-induced cognitive dysfunction could be alleviated by CBD.”

https://pubmed.ncbi.nlm.nih.gov/39452013/

“In conclusion, this study demonstrated that the chronic, systemic administration of DOX impairs cognitive abilities in rats, increases anxiety and depression-like behaviors, and regulates the expression of genes involved in neuroinflammation. We found that CBD-treated rats had fewer anxiety and depression-like behaviors than rats treated with DOX alone.”

https://www.mdpi.com/2076-3425/14/10/999

Cannabidiol partially rescues behavioral, neuroinflammatory and endocannabinoid dysfunctions stemming from maternal obesity in the adult offspring

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“Maternal obesity is known to increase the risk of psychiatric disorders, such as anxiety, depression, schizophrenia and autism spectrum disorder in the offspring. While preventive measures are well-documented, practical approaches for addressing the damages once they are already established are limited.

We have recently demonstrated the interplay between maternal obesity and treatment with cannabidiol (CBD) on neuroinflammation and peripheral metabolic disturbances during adolescence, however, it is known that both factors tend to vary throughout life. Therefore, here we investigated the potential of CBD to mitigate these alterations in the adult offspring of obese dams.

Female Wistar rats were fed a cafeteria diet for 12 weeks prior to mating, and during gestation and lactation. Offspring received CBD (50 mg/kg) for 3 weeks from the 70th day of life. Behavioral tests assessed anxiety-like manifestations and social behavior, while neuroinflammatory and endocannabinoid markers were evaluated in the hypothalamus, prefrontal cortex (PFC) and hippocampus, as well as the biochemical profile in the plasma.

CBD treatment attenuated maternal obesity-induced anxiety-like and social behavioral alterations, restoring exacerbated astrocytic and microglial markers in the hypothalamus, PFC and hippocampus of the offspring, as well as endocannabinoid levels in the PFC, with notable sex differences. Additionally, CBD attenuated plasma glucose and lipopolysaccharides (LPS) concentrations in females.

These findings underscore the persistent influence of maternal obesity on the offspring’s health, encompassing metabolic irregularities and behavioral impairments, as well as the role of the endocannabinoid system in mediating these outcomes across the lifespan.”

https://pubmed.ncbi.nlm.nih.gov/39447736/

“Treatment with cannabidiol rescues anxiety and social disturbances in the offspring.”

https://www.sciencedirect.com/science/article/abs/pii/S0028390824003654?via%3Dihub


Psychiatric comorbidities before and after cannabidiol treatment in adult patients with drug resistant focal epilepsy

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“Cannabidiol oil (CBD) has been approved as an antiseizure medication for the treatment of drug -resistant epilepsy in pediatric patients in 2018 for some special types of epilepsy.

Since this time its use was extended to other forms of epilepsy. However, to date, there are few publications on the use of CBD in adult patients with drug-resistant focal epilepsy and psychiatric comorbidities. We conducted a prospective, observational, open cohort study, with a before-after design, in adult patients, we assessed the effectiveness, dosage, and tolerance of adjunctive CBD treatment.

Our study concluded that CBD was effective and safe.

Our study in line with others examining CBD use in adult patients with drug-resistant epilepsy, omits consideration of psychiatric aspects. The aim of this study was to evaluate, in the same patient population that was part of a previous observational study, depression, quality of life, anxious symptoms and daytime sleepiness before and after CBD treatment.

RESULTS: Forty-four patients were enrolled in the study. Prior to CBD treatment, 50 % of participants exhibited symptoms of depression. Following CBD treatment, 95.4 % of these individuals demonstrated a marked improvement (p = 0.001). Among this cohort, 71.5 % of patients reported minimal or no depressive symptoms post-treatment. Moreover, 68 % of patients experienced an enhancement in their overall quality of life. Comparative analysis of BDI-II and QOLIE-10 scores before and after CBD treatment revealed a statistically significant positive correlation (p < 0.036 and < 0.001, respectively). Improvements in depressive symptoms were found to correspond with enhancements in quality of life. In terms of anxiety symptoms, 54.5 % of patients exhibited such symptoms prior to CBD treatment, with 71 % showing improvement post-treatment.

Adjunctive CBD treatment in adult patients with drug-resistant focal epilepsy was effective, safe, well tolerated and associated with significant improvement in depressive symptoms, anxiety and quality of life.”

https://pubmed.ncbi.nlm.nih.gov/39433001/

https://www.epilepsybehavior.com/article/S1525-5050(24)00414-1/abstract

Changes in Pain and Mental Health Symptoms Associated with Prescribed Medicinal Cannabis Use: A One-Year Longitudinal Study

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“Chronic pain and mental health issues like depression and anxiety significantly contribute to disease burden in Western countries.

While cannabinoids are suggested to have analgesic, anxiolytic and antidepressant properties, evidence, especially for long-term use, is inconclusive. This 12-month observational study evaluated the effects of prescribed medicinal cannabis for 96 patients suffering from pain, as well as sleep disturbances, depression and anxiety. Treatment outcomes for pain, depression, anxiety and sleep problems were assessed at 3, 6, and 12 months using validated instruments.

Significant reductions were observed in pain scores and the interference of pain on daily functions, alongside improvements in mental health and sleep. Many patients reported notable improvements in pain severity and reduced use of pain medications in the first 6 months, with a decline at 12 months. Additionally, sustained improvements in depression, anxiety, stress and sleep were observed, with about half reporting substantial improvement. Adverse effects were common but mostly mild or moderate, most commonly dry mouth and sleepiness.

These results show that prescribed medicinal cannabis treatment is associated with improvements in chronic pain and mental health symptoms, such as depression, anxiety and stress. However, findings also suggest reduced effectiveness with longer-term use, emphasizing the need for additional research.”

https://pubmed.ncbi.nlm.nih.gov/39432717/

“Cannabis is a plant that has been used for thousands of years as a traditional medicine to treat various medical ailments, including pain.

Overall, we found that the use of medicinal cannabis was associated with reduced pain during the first 6 months and improved mental well-being over 12 months. Patients reported not only less pain but also experienced reduced interference from pain in their daily functions. Furthermore, they reported decreased use of pain medications and a large proportion felt that their pain symptoms had significantly improved, as reflected in their reported changes in the severity of pain.”

https://www.tandfonline.com/doi/full/10.1080/15360288.2024.2414898

An overview of major depression disorder: The endocannabinoid system as a potential target for therapy

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“Major depressive disorder is the psychiatric disease with the highest global prevalence, impacting social functioning and decreasing the quality of life. The partial pathophysiological knowledge of the disease, the economic burden and the low remission rates are sufficient justification to carry out an update on the subject in the search for new therapeutic approaches and targets.

The endocannabinoid system has been linked to the development of depression, and its stimulation or antagonism is a promising approach in the treatment of major depressive disorder.

Cannabidiol (CBD) and its properties have been widely studied recently; its analgesic, anti-inflammatory, antineoplastic and neuroprotective roles have even been reported in animal models and clinical trials, achieving its approved use for certain neurodegenerative pathologies. The use of CBD in depression biomodels and clinical trials has not been the exception, and here we contrast the current evidence of its administration and pharmacology against the pathological mechanisms of major depressive disorder.”

https://pubmed.ncbi.nlm.nih.gov/39370369/

“This focused review discusses the prevalence of major depressive disorder (MDD) globally, its impact on social functioning and quality of life, and the need for new therapeutic approaches. It highlights the role of the endocannabinoid system in MDD and the potential of cannabidiol (CBD) in treating depression due to its various beneficial properties. CBD’s effectiveness is supported by research in animal models and clinical trials, offering promise as a treatment for MDD by targeting its pathological mechanisms.”

https://onlinelibrary.wiley.com/doi/10.1111/bcpt.14089

“Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866040/

Nanocarriers for Cannabinoid Delivery: Enhancing Therapeutic Potential

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“Medical cannabis has potential therapeutic benefits in managing pain, anxiety, depression, and neurological and movement disorders. Phytocannabinoids derived from the cannabis plant are responsible for their pharmacological and therapeutic properties. However, the complexity of cannabis components, especially cannabinoids, poses a challenge to effective medicinal administration. Even with the increasing acceptance of cannabis-based medicines, achieving consistent bioavailability and targeted distribution remains difficult. Conventional administration methods are plagued by solubility and absorption problems requiring innovative solutions. After conducting a thorough review of research papers and patents, it has become evident that nanotechnology holds great promise as a solution. The comprehensive review of 36 research papers has yielded valuable insights, with 7 papers reporting enhanced bioavailability, while others have focused on improvements in release, solubility, and stability. Additionally, 19 patents have been analyzed, of which 7 specifically claim enhanced bioavailability, while the remaining patents describe various formulation methods. These patents outline effective techniques for encapsulating cannabis using nanocarriers, effectively addressing solubility and controlled release. Studies on the delivery of cannabis using nanocarriers focus on improving bioavailability, prolonging release, and targeting specific areas. This synthesis highlights the potential of nanotechnology to enhance cannabis therapies and pave the way for innovative interventions and precision medicine.”

https://pubmed.ncbi.nlm.nih.gov/39356097/

https://www.eurekaselect.com/article/141807

Repeated Administration of a Full-Spectrum Cannabidiol Product, Not a Cannabidiol Isolate, Reverses the Lipopolysaccharide-Induced Depressive-Like Behavior and Hypolocomotion in a Rat Model of Low-Grade Subchronic Inflammation

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“Background: Mounting evidence suggests that the phytocannabinoid cannabidiol (CBD) holds promise as an antidepressant agent in conditions underlined by inflammation. Full-spectrum CBD extracts might provide greater behavioral efficacy than CBD-only isolates and might require lower doses to achieve the same outcomes due to the presence of other cannabinoids, terpenes, and flavonoids. However, investigations in this area remain limited. 

Methods: We evaluated the behavioral response to the administration for 7 days of 15 and 30 mg/kg of a CBD isolate and a full-spectrum CBD product in a rat model of subchronic lipopolysaccharide (LPS, 0.5 mg/kg/day/7 days, intraperitoneal)-induced depressive-like and sickness behavior. The forced swim test was used to assess depressive-like behavior, the open field test (OFT) to assess locomotion, and the elevated plus maze to assess anxiety-like behavior. 

Results: The full-spectrum CBD extract at both doses, but not the CBD isolate, reversed the LPS-induced depressive-like behavior in the forced swim test. Moreover, the full-spectrum CBD extract at the higher dose but not the CBD isolate restored the subchronic LPS-induced hypolocomotion in the OFT. Repeated administration of both formulations elicited an anxiogenic-like trend in the elevated plus maze. 

Conclusion: Full-spectrum CBD products might have greater therapeutic efficacy in resolving inflammation-induced depressive and sickness behavior compared to a CBD-only isolate.”

https://pubmed.ncbi.nlm.nih.gov/39347620/

https://www.liebertpub.com/doi/10.1089/can.2024.0086

P2X7 receptors from the perspective of NLRP3 inflammasome pathway in depression: Potential role of cannabidiol

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“Many patients with depressive disorder do not respond to conventional antidepressant treatment. There is an ongoing interest in investigating potential mechanisms of treatment resistance in depression to provide alternative treatment options involving inflammatory mechanisms.

Increasing evidence implicates the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome as a critical factor in neuroinflammation. ATP-induced P2X7 receptor (P2X7R) activation is a major trigger for inflammation, activating the canonical NLRP3 inflammatory cascade.

Psychosocial stress, the primary environmental risk factor for depression, is associated with changes in ATP-mediated P2X7R signaling.

Depression and stress response can be alleviated by Cannabidiol (CBD).

CBD has an anti-inflammatory activity related to the regulation of NLRP3 inflammasome activation. However, CBD’s effects on the inflammasome pathway are poorly understood in central nervous system (CNS) cells, including microglia, astrocytes, and neurons.

This review will emphasize some findings for neuroinflammation and NLRP3 inflammasome pathway involvement in depression, particularly addressing the ATP-induced P2X7R activation. Moreover, we will underline evidence for the effect of CBD on depression and address its potential impacts on neuroinflammation through the NLRP3 inflammasome cascade.”

https://pubmed.ncbi.nlm.nih.gov/39296605/

“Highlights

  • •Neuroinflammation plays an important role in the development of depressive disorder.
  • •The NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome contributes to the pathogenesis of depression.
  • •ATP-induced P2X7 receptor (P2X7R) activation triggers the canonical NLRP3 inflammatory cascade.
  • •P2X7R antagonists have potential antidepressant effects.
  • •CBD has anti-inflammatory properties related to the regulation of NLRP3 inflammasome activation.”

https://www.sciencedirect.com/science/article/pii/S2666354624001315?via%3Dihub