Immune system dysfunction can alter the link between cannabis use and psychosis

trader32176
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Re: Immune system dysfunction can alter the link between cannabis use and psychosis

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Cannabinoids for the treatment of rheumatic diseases - where do we stand ?

8/14/18


https://pubmed.ncbi.nlm.nih.gov/29884803/


As medical use of cannabis is increasingly legalized worldwide, a better understanding of the medical and hazardous effects of this drug is imperative. The pain associated with rheumatic diseases is considered a prevalent indication for medicinal cannabis in various countries. Thus far, preliminary clinical trials have explored the effects of cannabis on rheumatoid arthritis, osteoarthritis and fibromyalgia; preliminary evidence has also found an association between the cannabinoid system and other rheumatic conditions, including systemic sclerosis and juvenile idiopathic arthritis. The potential medicinal effects of cannabis could be attributable to its influence on the immune system, as it exerts an immunomodulatory effect on various immune cells, including T cells, B cells and macrophages. However, the available evidence is not yet sufficient to support the recommendation of cannabinoid treatment for rheumatic diseases.
trader32176
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Re: Immune system dysfunction can alter the link between cannabis use and psychosis

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The Endogenous Cannabinoid System: A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain

https://pubmed.ncbi.nlm.nih.gov/28857069/


A great need exists for the development of new medications to treat pain resulting from various disease states and types of injury. Given that the endogenous cannabinoid (that is, endocannabinoid) system modulates neuronal and immune cell function, both of which play key roles in pain, therapeutics targeting this system hold promise as novel analgesics. Potential therapeutic targets include the cannabinoid receptors, type 1 and 2, as well as biosynthetic and catabolic enzymes of the endocannabinoids N-arachidonoylethanolamine and 2-arachidonoylglycerol. Notably, cannabinoid receptor agonists as well as inhibitors of endocannabinoid-regulating enzymes fatty acid amide hydrolase and monoacylglycerol lipase produce reliable antinociceptive effects, and offer opioid-sparing antinociceptive effects in myriad preclinical inflammatory and neuropathic pain models. Emerging clinical studies show that 'medicinal' cannabis or cannabinoid-based medications relieve pain in human diseases such as cancer, multiple sclerosis, and fibromyalgia. However, clinical data have yet to demonstrate the analgesic efficacy of inhibitors of endocannabinoid-regulating enzymes. Likewise, the question of whether pharmacotherapies aimed at the endocannabinoid system promote opioid-sparing effects in the treatment of pain reflects an important area of research. Here we examine the preclinical and clinical evidence of various endocannabinoid system targets as potential therapeutic strategies for inflammatory and neuropathic pain conditions.
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Re: Immune system dysfunction can alter the link between cannabis use and psychosis

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Immune system: a possible nexus between cannabinoids and psychosis

2/7/14


https://pubmed.ncbi.nlm.nih.gov/24509089/


Background:
Endocannabinoid system is involved in the regulation of the brain-immune axis. Cannabis consumption is related with the development, course, and severity of psychosis. The epidemiological evidence for increased occurrence of immunological alterations in patients with psychosis has not been sufficiently addressed. The aim of this review is to establish whether there is any scientific evidence of the influence of cannabinoids on aspects of immunity that affect susceptibility to psychotic disorder induction.

Methods: A comprehensive search of PubMed/MEDLINE, EMBASE and ISI Web of Knowledge was performed using combinations of key terms distributed into three blocks: "immune", "cannabinoid", and "endocannabinoid receptor". Studies were considered to be eligible for the review if they were original articles, they reported a quantitative or qualitative relation between cannabinoid ligands, their receptors, and immune system, and they were carried out in vitro or in mammals, included humans. All the information was systematically extracted and evaluated.

Results:
We identified 122 articles from 446 references. Overall, endocannabinoids enhanced immune response, whereas exogenous cannabinoids had immunosuppressant effects. A general change in the immune response from Th1 to Th2 was also demonstrated for cannabinoid action. Endogenous and synthetic cannabinoids also modulated microglia function and neurotransmitter secretion.

Conclusion:
The actions of cannabinoids through the immune system are quite regular and predictable in the peripheral but remain fuzzy in the central nervous system. Despite this uncertainty, it may be hypothesized that exposure to exocannabinoids, in particular during adolescence might prompt immunological dysfunctions that potentially cause a latent vulnerability to psychosis. Further investigations are warranted to clarify the relationship between the immunological effects of cannabis and psychosis.
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Re: Immune system dysfunction can alter the link between cannabis use and psychosis

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Cannabinoids in Medicine: Cancer, Immunity, and Microbial Diseases

12/29/20


https://pubmed.ncbi.nlm.nih.gov/33383838/


Recently, there has been a growing interest in the medical applications of Cannabis plants. They owe their unique properties to a group of secondary metabolites known as phytocannabinoids, which are specific for this genus. Phytocannabinoids, and cannabinoids generally, can interact with cannabinoid receptors being part of the endocannabinoid system present in animals. Over the years a growing body of scientific evidence has been gathered, suggesting that these compounds have therapeutic potential. In this article, we review the classification of cannabinoids, the molecular mechanisms of their interaction with animal cells as well as their potential application in the treatment of human diseases. Specifically, we focus on the research concerning the anticancer potential of cannabinoids in preclinical studies, their possible use in cancer treatment and palliative medicine, as well as their influence on the immune system. We also discuss their potential as therapeutic agents in infectious, autoimmune, and gastrointestinal inflammatory diseases. We postulate that the currently ongoing and future clinical trials should be accompanied by research focused on the cellular and molecular response to cannabinoids and Cannabis extracts, which will ultimately allow us to fully understand the mechanism, potency, and safety profile of cannabinoids as single agents and as complementary drugs.
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Re: Immune system dysfunction can alter the link between cannabis use and psychosis

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Cannabidiol Modulates Cytokine Storm in Acute Respiratory Distress Syndrome Induced by Simulated Viral Infection Using Synthetic RNA

9/2/20


https://pubmed.ncbi.nlm.nih.gov/32923657/


Introduction: In the absence of effective antivirals and vaccination, the pandemic of COVID-19 remains the most significant challenge to our health care system in decades. There is an urgent need for definitive therapeutic intervention. Clinical reports indicate that the cytokine storm associated with acute respiratory distress syndrome (ARDS) is the leading cause of mortality in severe cases of some respiratory viral infections, including COVID-19. In recent years, cannabinoids have been investigated extensively due to their potential effects on the human body. Among all cannabinoids, cannabidiol (CBD) has demonstrated potent anti-inflammatory effects in a variety of pathological conditions. Therefore, it is logical to explore whether CBD can reduce the cytokine storm and treat ARDS. Materials and Methods: In this study, we show that intranasal application of Poly(I:C), a synthetic analogue of viral double-stranded RNA, simulated symptoms of severe viral infections inducing signs of ARDS and cytokine storm. Discussion: The administration of CBD downregulated the level of proinflammatory cytokines and ameliorated the clinical symptoms of Poly I:C-induced ARDS. Conclusion: Our results suggest a potential protective role for CBD during ARDS that may extend CBD as part of the treatment of COVID-19 by reducing the cytokine storm, protecting pulmonary tissues, and re-establishing inflammatory homeostasis.
trader32176
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Re: Immune system dysfunction can alter the link between cannabis use and psychosis

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Fighting the storm: could novel anti-TNFα and anti-IL-6 C. sativa cultivars tame cytokine storm in COVID-19 ?

1/19/21


https://pubmed.ncbi.nlm.nih.gov/33465050/


The main aspects of severe COVID-19 disease pathogenesis include hyper-induction of proinflammatory cytokines, also known as 'cytokine storm', that precedes acute respiratory distress syndrome (ARDS) and often leads to death. COVID-19 patients often suffer from lung fibrosis, a serious and untreatable condition. There remains no effective treatment for these complications. Out of all cytokines, TNFα and IL-6 play crucial roles in cytokine storm pathogenesis and are likely responsible for the escalation in disease severity. These cytokines also partake in the molecular pathogenesis of fibrosis. Therefore, new approaches are urgently needed, that can efficiently and swiftly downregulate TNFα, IL-6, and the inflammatory cytokine cascade, in order to curb inflammation and prevent fibrosis, and lead to disease remission. Cannabis sativa has been proposed to modulate gene expression and inflammation and is under investigation for several potential therapeutic applications against autoinflammatory diseases and cancer. Here, we hypothesized that the extracts of novel C. sativa cultivars may be used to downregulate the expression of pro-inflammatory cytokines and pathways involved in inflammation and fibrosis. Initially, to analyze the anti-inflammatory effects of novel C. sativa cultivars, we used a well-established full thickness human 3D skin artificial EpiDermFTTM tissue model, whereby tissues were exposed to UV to induce inflammation and then treated with extracts of seven new cannabis cultivars. We noted that out of seven studied extracts of novel C. sativa cultivars, three (#4, #8 and #14) were the most effective, causing profound and concerted down-regulation of COX2, TNFα, IL-6, CCL2, and other cytokines and pathways related to inflammation and fibrosis. These data were further confirmed in the WI-38 lung fibroblast cell line model. Most importantly, one of the tested extracts had no effect at all, and one exerted effect that may be deleterious, signifying that careful cannabis cultivar selection must be based on thorough pre-clinical studies. The observed pronounced inhibition of TNFα and IL-6 is the most important finding, because these molecules are currently considered to be the main targets in COVID-19 cytokine storm and ARDS pathogenesis. Novel anti-TNFα and anti-IL-6 cannabis extracts can be useful additions to the current anti-inflammatory regimens to treat COVID-19, as well as various rheumatological diseases and conditions, and 'inflammaging' - the inflammatory underpinning of aging and frailty.
trader32176
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Re: Immune system dysfunction can alter the link between cannabis use and psychosis

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The Immunopathology of COVID-19 and the Cannabis Paradigm

2/12/21


https://pubmed.ncbi.nlm.nih.gov/33643316/


Coronavirus disease-19 caused by the novel RNA betacoronavirus SARS-CoV2 has first emerged in Wuhan, China in December 2019, and since then developed into a worldwide pandemic with >99 million people afflicted and >2.1 million fatal outcomes as of 24th January 2021. SARS-CoV2 targets the lower respiratory tract system leading to pneumonia with fever, cough, and dyspnea. Most patients develop only mild symptoms. However, a certain percentage develop severe symptoms with dyspnea, hypoxia, and lung involvement which can further progress to a critical stage where respiratory support due to respiratory failure is required. Most of the COVID-19 symptoms are related to hyperinflammation as seen in cytokine release syndrome and it is believed that fatalities are due to a COVID-19 related cytokine storm. Treatments with anti-inflammatory or anti-viral drugs are still in clinical trials or could not reduce mortality. This makes it necessary to develop novel anti-inflammatory therapies. Recently, the therapeutic potential of phytocannabinoids, the unique active compounds of the cannabis plant, has been discovered in the area of immunology. Phytocannabinoids are a group of terpenophenolic compounds which biological functions are conveyed by their interactions with the endocannabinoid system in humans. Here, we explore the anti-inflammatory function of cannabinoids in relation to inflammatory events that happen during severe COVID-19 disease, and how cannabinoids might help to prevent the progression from mild to severe disease.
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Re: Immune system dysfunction can alter the link between cannabis use and psychosis

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Characterization of peripheral cannabinoid receptor expression and clinical correlates in schizophrenia

11/30/16


https://pubmed.ncbi.nlm.nih.gov/27591408/


The relationship between cannabinoid receptor signaling and psychosis vulnerability requires further exploration. The endocannabinoid signaling system is extensive, with receptors exerting regulatory functions in both immune and central nervous systems. In the brain, cannabinoid receptors (CBR) directly modulate neurotransmitter systems. In the peripheral lymphocyte, CBRs mediate cytokine release, with dysregulated cytokine levels demonstrated in schizophrenia. mRNA levels of CBRs were measured in human peripheral blood mononuclear cells (PBMCs) obtained from 70 participants (35 non-clinical controls, 35 participants with schizophrenia), who were recruited for the absence of marijuana use/abuse by self-report. Changes in mRNA expression were measured using qRT-PCR. Clinical measurements collected included the MATRICS Cognitive Battery and the Positive and Negative Syndrome Scale. Levels of CB1R and CB2R mRNA in PBMCs were significantly higher in participants with schizophrenia compared to the non-clinical controls. Additionally, CB1R and CB2R mRNA levels correlated with impairments in cognitive processing and clinical symptom severity in multiple domains. These results continue to support dysregulation of particular aspects of the endocannabinoid signaling system in participants with schizophrenia selected for the self-reported absence of marijuana abuse/dependence.
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The neuropsychiatric manifestations of COVID-19: Interactions with psychiatric illness and pharmacological treatment

3/21


https://www.sciencedirect.com/science/a ... 2220313937


Abstract

The recent outbreak of the corona virus disease (COVID-19) has had major global impact. The relationship between severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection and psychiatric diseases is of great concern, with an evident link between corona virus infections and various central and peripheral nervous system manifestations. Unmitigated neuro-inflammation has been noted to underlie not only the severe respiratory complications of the disease but is also present in a range of neuro-psychiatric illnesses. Several neurological and psychiatric disorders are characterized by immune-inflammatory states, while treatments for these disorders have distinct anti-inflammatory properties and effects. With inflammation being a common contributing factor in SARS-CoV-2, as well as psychiatric disorders, treatment of either condition may affect disease progression of the other or alter response to pharmacological treatment. In this review, we elucidate how viral infections could affect pre-existing psychiatric conditions and how pharmacological treatments of these conditions may affect overall progress and outcome in the treatment of SARS-CoV-2. We address whether any treatment-induced benefits and potential adverse effects may ultimately affect the overall treatment approach, considering the underlying dysregulated neuro-inflammatory processes and potential drug interactions. Finally, we suggest adjunctive treatment options for SARS-CoV-2-associated neuro-psychiatric symptoms.
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Do we need to change our treatment approach to schizophrenia during the COVID-19 pandemic ?

4/21/21


https://onlinelibrary.wiley.com/doi/ful ... ijcp.14013


According to the World Health Organization, coronavirus disease (COVID-19) has affected over 55 000 000 people worldwide and has resulted in approximately 1 300 000 deaths. It is still in progress at the time of writing this letter. Schizophrenia is a chronic mental disorder that affects 20 million people worldwide.1, 2 Patients with schizophrenia have high rates of comorbidities, including important predisposing factors for COVID-19, such as hypertension, diabetes mellitus and chronic obstructive pulmonary disease.3 Therefore, more attention should be paid to the treatment of these patients during this pandemic.

The first step of viral infection is viral entry into host cells, which begins and maintains infection and triggers the host's immune response. Activation of the endocytic pathway and autophagy are critical processes for viral entry and replication. Therefore, these processes can be expected to play important roles in determining the efficacy of drugs developed to combat COVID-19.4 Many drugs previously approved to treat various human diseases have been suggested as options for the treatment of COVID because of the rapid and global spread of this disease. Existing drugs with established antiviral efficacy can be directly and immediately used to treat COVID-19 because we have a significant understanding of their safety profiles.5

Chlorpromazine has a well-established lysosomotropic property that modulates autophagy and inhibits clathrin-mediated endocytosis. Clathrin-mediated endocytosis is an important potential mechanism of SARS-CoV cell invasion. Chlorpromazine blocks the assembly of clathrin adaptor protein 2 (AP2) at the cell surface and has been shown to significantly inhibit SARS-CoV entry into HepG2 cells.6, 7 Furthermore, previous studies have reported that chlorpromazine exerts immunomodulatory effects by increasing the levels of anti-inflammatory cytokines while decreasing those of inflammatory cytokines.8 Additionally, chlorpromazine has been suggested to have antiviral properties for HCV, alphavirus and various coronaviruses, including human coronavirus 229E, SARS-CoV and MERS-CoV.9

Haloperidol has been reported to decrease the mortality rate of patients on mechanical ventilation, a finding attributed to the lowering of cytokine levels by the drug and the subsequent prevention of the cytokine storm.10 Therefore, haloperidol may have a therapeutic effect on the progression and severity of COVID-19, which have been suggested to be related to the cytokine storm.11 Furthermore, haloperidol can cause alkalinisation and inhibit autophagy; therefore, it may prevent SARS-CoV-2 entry into host cells because this process requires autophagy modulation and a low pH in intracytoplasmic vesicles.12, 13

In the treatment of psychiatric patients during this global pandemic, it can be more appropriate to choose psychotropic drugs that have antiviral properties and possible therapeutic effects against the pathogenic mechanisms of the virus. The use of such drugs may contribute to the treatment of COVID-19 among infected patients and play a protective role against the transmission of SARS-CoV-2.14 Haloperidol and chlorpromazine have been used for more than half a century for the treatment of schizophrenia. These two drugs, classified as first-generation antipsychotics (FGAs), are used less frequently now than in the past, although they are known to be effective and safe for the treatment of schizophrenia.15

Haloperidol may produce significant extrapyramidal side effects (EPS) which were often associated with its high doses.16 However, PET studies have suggested that its low doses are preferable. Clinical response was associated with at least 65% occupancy of D2 receptors, while greater than 78% associated with EPS. Doses of haloperidol greater than 5 mg increased the risk of side effects without improving efficacy.17 Therefore, we recommend that clinicians should use it in the lowest dose needed to avoid dose-related side effects including EPS during the current pandemic. Chlorpromazine has more anticholinergic side effects, and lower rates of EPS in contrast to haloperidol. However, there is a well-known risk of hepatotoxicity induced by chlorpromazine. Moreover, chlorpromazine was discontinued in chronic treatments because of its hepatotoxic effec 18, 19 Nonetheless, clinicians may prescribe it in low doses and as a short-term treatment in patients with schizophrenia during COVID-19 pandemic.

The current pandemic has changed our views of and treatment approaches to many clinical conditions.20 We must consider the side and therapeutic effects of drugs related to the immune system and infectious conditions when choosing treatment options for our patients.21 In light of the possible antiviral and anticytokine properties of FGAs, including haloperidol and chlorpromazine, we recommend that clinicians reconsider these drugs for the treatment of patients with schizophrenia during the COVID-19 pandemic, weighing the potential benefits against the risk of adverse effects and drug interactions. At this time, however, the idea remains rather theoretical because there is no clinical data from COVID-19 patients with schizophrenia that have received SGAs or FGAs. Therefore, the effects of different antipsychotics on the prognosis and course of COVID-19 need to be studied in patients with schizophrenia.
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