Endogenous cannabinoid levels and suicidality in combat veterans.

Psychiatry Research“Combat veterans are at elevated suicide risk. The goal of this study was to test the hypothesis that combat veterans who have made a suicide attempt post-deployment can be distinguished from combat veterans who have never made a suicide attempt based on differences in psychological and biological variables. For the latter, we focused on endogenous cannabinoids, neuroendocrine markers that are associated with stress. Demographic and clinical parameters of suicide attempters and non-attempters were assessed. Blood samples were assayed for anandamide (AEA), 2-arachidonoylglycerol (2-AG), and cortisol. Suicide attempters had higher Scale for Suicidal Ideation (SSI) scores in comparison to non-attempters. Controlling for gender, 2-AG levels were higher among suicide attempters in comparison to non-attempters. Cortisol levels positively correlated with 2-AG levels and negatively correlated with SSI scores among non-attempters but not among attempters. AEA levels negatively correlated with SSI scores among attempters but not among non-attempters. Our results indicate that there are psychological and biological differences between combat veterans with or without a history of suicidal attempt. Our findings also suggest that clinically observed differences between the groups may have a neurobiological basis.”

https://www.ncbi.nlm.nih.gov/pubmed/31375282

https://www.sciencedirect.com/science/article/abs/pii/S0165178119315173?via%3Dihub

“Role of the Endocannabinoid System in the Neurobiology of Suicide”  https://www.ncbi.nlm.nih.gov/books/NBK107200/

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Medical Marijuana Laws and Suicide

Publication Cover“In the current study we use a synthetic control group design to estimate the causal effect of a medical marijuana initiative on suicide risk.

In 1996, California legalized marijuana use for medical purposes. Implementation was abrupt and uniform, presenting a “natural experiment.” Utilizing a panel dataset containing annual frequencies of Total, gun, and non-gun suicides aggregated by state for the years 1970–2004, we construct a control time series for California as a weighted combination of the 41 states that did not legalize marijuana during the analysis period. Post-intervention differences for California and its constructed control time series can be interpreted as the effects of the medical marijuana law on suicide. Significance of the effects were assessed with permutation tests.

Our findings suggest that California’s 1996 legalization resulted in statistically significant (p<.05) reductions in suicides and gun suicides, but only a non-significant reduction in non-gun suicides (p≥.488). Since the effect for non-gun suicides was indistinguishable from chance, we infer that the overall causal effect was realized through gun suicides. The mechanism could not be determined, however. Participation in the medical marijuana program legally disqualifies participants from purchasing guns. But since most suicides involve guns, it is possible that the effect on total suicide is driven by gun suicide alone.”

https://www.tandfonline.com/doi/full/10.1080/13811118.2019.1612803

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Cannabis use disorder and suicide attempts in bipolar disorder: A meta-analysis.

Neuroscience & Biobehavioral Reviews

“We aimed at clarifying the strength and consistency of the association between cannabis use disorder and suicide attempts in bipolar disorder.

We could not perform a meta-analysis exploring the longitudinal association between cannabis use disorder and suicide attempts, due to the lack of suitable data.

The current evidence highlights a weak association between cannabis use disorder and suicidal attempts in bipolar disorder.

Due to the cross-sectional design of included studies, causal inferences could not be explored.”

https://www.ncbi.nlm.nih.gov/pubmed/31121199

https://www.sciencedirect.com/science/article/pii/S014976341830993X?via%3Dihub

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Social isolation as a promising animal model of PTSD comorbid suicide: neurosteroids and cannabinoids as possible treatment options.

Progress in Neuro-Psychopharmacology and Biological Psychiatry

“Post-traumatic stress disorder (PTSD) is a psychiatric condition characterized by drastic alterations in mood, emotions, social abilities and cognition. Notably, one aspect of PTSD, particularly in veterans, is its comorbidity with suicide.

Elevated aggressiveness predicts high-risk to suicide in humans and despite the difficulty in reproducing a complex human suicidal behavior in rodents, aggressive behavior is a well reproducible behavioral trait of suicide. PTSD animal models are based on a peculiar phenotype, including exaggerated fear memory, anxiety- and depressive-like behaviors associated with neurochemical dysregulations in emotional brain circuitry.

The endocannabinoid and the neurosteroid systems regulate emotions and stress responses, and recent evidence shows these two systems are interrelated and critically compromised in neuropsychiatric disorders. For instance, levels of the neurosteroid, allopregnanolone, as well as those of the endocannabinoids, anandamide and its congener, palmitoylethanolamide are decreased in PTSD.

Similarly, the endocannabinoid system and neurosteroid biosynthesis are altered in suicidal individuals.

Selective serotonin reuptake inhibitors (SSRIs), the only FDA-approved treatments for PTSD and depression, fail to help half of the treatment-seeking patients. This highlights the need for developing biomarker-based efficient therapies. One promising hypothesis points to stimulation of allopregnanolone biosynthesis as a valid end-point to predict treatment response in PTSD patients.

This review highlights running findings on the role of the endocannabinoid and neurosteroid systems in PTSD and suicidal behavior both in a preclinical and clinical perspective. A specific focus is given to predictive PTSD/suicide animal models. Ultimately, we discuss the idea that disruption of neurosteroid and endocannabinoid biosynthesis may offer novel promising biomarker candidates to develop new treatments for PTSD and, perhaps, suicidal behavior.”

https://www.ncbi.nlm.nih.gov/pubmed/30586627

https://www.sciencedirect.com/science/article/pii/S0278584618305839?via%3Dihub

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The association between cannabis use and suicidal behavior in patients with psychiatric disorders: an analysis of sex differences.

Image result for bmc part of springer nature

“Cannabis is the most commonly used illicit drug. In the general population, its use has been linked to a heightened propensity for suicidal behavior (SB).

We hypothesize that this association varies in patients with psychiatric disorders. SB is known to vary by sex and therefore an investigation of cannabis‘ association with SB must consider sex differences.

The purpose of this study is to investigate the association between cannabis use and suicide attempts in men and women with psychiatric disorders.

We found no significant association between suicide attempts and cannabis use in men or women.

Our findings indicate that there is no association between cannabis use and suicidal behavior in men or women with psychiatric disorders unlike what was reported for the general population, though the heaviness of cannabis use may have an effect in men.

The impact of cannabis use in psychiatric disorders needs ongoing examination in light of its common use, impending legalization with expected increased access and the uncertainty about cannabis‘ effects on prognosis of psychiatric disorders.

In addition, research should continue to investigate modifiable risk factors of SB in this population of which cannabis is not a significant factor based on this study.”

https://www.ncbi.nlm.nih.gov/pubmed/29891008

https://bsd.biomedcentral.com/articles/10.1186/s13293-018-0182-x

“Cannabis Does Not Increase Suicidal Behavior in Psychiatric Patients” https://neurosciencenews.com/psychiatry-cannabis-suicide-9330/
“Researchers Find That Cannabis Does Not Increase Suicidal Behavior in Psychiatric Patients” https://www.laboratoryequipment.com/news/2018/06/researchers-find-cannabis-does-not-increase-suicidal-behavior-psychiatric-patients
“Cannabis does not increase suicidal behavior in psychiatric patients: McMaster” https://eurekalert.org/pub_releases/2018-06/mu-cdn061318.php

“Cannabis does not increase suicidal behavior in psychiatric patients”  https://www.sciencedaily.com/releases/2018/06/180613162658.htm

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Cannabinoid Receptors, Mental Pain and Suicidal Behavior: a Systematic Review.

Current Psychiatry Reports

“The current serotonin-based biological model of suicidal behavior (SB) may be too simplistic. There is emerging evidence that other biomarkers and biological systems may be involved in SB pathophysiology. The literature on the endocannabinoid (EC) systems and SB is limited. The objective of the present article is to review all available information on the relationship between cannabinoid receptors (CB1 and CB2 receptors), and SB and/or psychological pain.

RECENT FINDINGS:

Our review is limited by the small number and heterogeneity of studies identified: (1) an autopsy study describing elevated levels of CB1 receptor activity in the prefrontal cortex and suicide in both depression and alcoholism and (2) studies supporting the involvement of both CB1 and CB2 receptors in the regulation of neuropathic pain and stress-induced analgesia. We conclude that cannabinoid receptors, particularly CB1 receptors, may become promising targets for the development of novel therapeutic tools for the treatment of SB.”

https://www.ncbi.nlm.nih.gov/pubmed/29546501

https://link.springer.com/article/10.1007%2Fs11920-018-0880-4

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Role of the Endocannabinoid System in the Neurobiology of Suicide

Cover of The Neurobiological Basis of Suicide

“In the past decade, remarkable advances have been made in cannabinoid (CB) research. The brain endocannabinoid (eCB) system modulates several neurobiological processes and its dysfunction is suggested to be involved in the pathophysiology of mood and drug use disorders.

The CB1 receptor–mediated signaling, in particular, has been shown to play a critical role in the neural circuitry that mediates mood, motivation, and emotional behaviors. This chapter presents the data pertaining to the involvement of the eCB system in depression, suicide, and alcohol addiction.

It appears that the eCB system might have a critical role in the regulation of mood and emotional responses that are impaired in patients with depression and suicidal behavior.

The data provided in this chapter support the notion that the eCB system might be an additional target for the development of a drug against alcohol use, depression, and suicidal behavior.

Among therapeutic agents, antidepressants are the most widely used drugs for the treatment of depression-related disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/23035286

https://www.ncbi.nlm.nih.gov/books/NBK107200/

“Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from cannabis sativa L. The antidepressant action of cannabis as well as the interaction between antidepressants and the endocannabinoid system has been reported. Results of this study show that Δ9-THC and other cannabinoids exert anti-depressant-like actions, and thus may contribute to the overall mood-elevating properties of cannabis.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866040/

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High on Life? Medical Marijuana Laws and Suicide

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“Our research examines the relationship between medical marijuana laws (hereafter MMLs) and suicides.

Our results suggest that the passage of a MML is associated with an almost 5 percent reduction in the total suicide rate.

We conclude that the legalization of medical marijuana leads to fewer suicides among young adult males.”

https://www.cato.org/publications/research-briefs-economic-policy/high-life-medical-marijuana-laws-suicide

Study: Medical Marijuana Legalization leads to decrease in suicide rates”   https://www.dailykos.com/stories/2012/2/26/1068413/-Study-Medical-Marijuana-Legalization-leads-to-decrease-in-suicide-rates

“Legal Weed Appears to Cause a Sharp Reduction in Suicides”  https://www.eastbayexpress.com/LegalizationNation/archives/2012/02/07/legal-weed-appears-to-cause-a-sharp-reduction-in-suicides-discuss

“Marijuana Can Help Prevent Suicide, Study Suggests”  http://www.laweekly.com/news/marijuana-can-help-prevent-suicide-study-suggests-2389148

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ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

Image result for Curr Clin Pharmacol.

“Cannabis sativa is also popularly known as marijuana. It is being cultivated and used by man for recreational and medicinal purposes from many centuries.

Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries.

The research of drugs acting on endocannabinoid system has seen many ups and down in recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve “protective role” in many medical conditions.

Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and Tourette’s syndrome could possibly be treated by drugs modulating endocannabinoid system.

Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008.

Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite of some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists.

One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that acts selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted.

Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids.

In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as “protective” and “disease inducing substance”, time-dependent changes in the expression of cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27086601

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Medical Marijuana Laws and Suicides by Gender and Age.

:American Journal of Public Health Logo

 

“We estimated the association between legalizing medical marijuana and suicides.

Legalization was associated with a 10.8%  and 9.4% reduction in the suicide rate of men aged 20 through 29 years and 30 through 39 years, respectively.

Suicides among men aged 20 through 39 years fell after medical marijuana legalization compared with those in states that did not legalize.

The negative relationship between legalization and suicides among young men is consistent with the hypothesis that marijuana can be used to cope with stressful life events.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232164/

http://www.ncbi.nlm.nih.gov/pubmed/24432945

http://ajph.aphapublications.org/doi/10.2105/AJPH.2013.301612

“Legalizing Medical Marijuana May Lead To Fewer Suicides”  https://www.huffingtonpost.com/2014/02/04/marijuana-legalization-suicide_n_4726390.html

“Medical Marijuana Cuts Suicide Rates By 10% In Years Following Legalization”  http://www.medicaldaily.com/medical-marijuana-cuts-suicide-rates-10-years-following-legalization-268472

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