Unique treatment potential of cannabidiol for the prevention of relapse to drug use: preclinical proof of principle

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“Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa, has received attention for therapeutic potential in treating neurologic and psychiatric disorders.

Recently, CBD has also been explored for potential in treating drug addiction. Substance use disorders are chronically relapsing conditions and relapse risk persists for multiple reasons including craving induced by drug contexts, susceptibility to stress, elevated anxiety, and impaired impulse control. Here, we evaluated the “anti-relapse” potential of a transdermal CBD preparation in animal models of drug seeking, anxiety and impulsivity.

Rats with alcohol or cocaine self-administration histories received transdermal CBD at 24 h intervals for 7 days and were tested for context and stress-induced reinstatement, as well as experimental anxiety on the elevated plus maze. Effects on impulsive behavior were established using a delay-discounting task following recovery from a 7-day dependence-inducing alcohol intoxication regimen.

CBD attenuated context-induced and stress-induced drug seeking without tolerance, sedative effects, or interference with normal motivated behavior. Following treatment termination, reinstatement remained attenuated up to ≈5 months although plasma and brain CBD levels remained detectable only for 3 days. CBD also reduced experimental anxiety and prevented the development of high impulsivity in rats with an alcohol dependence history.

The results provide proof of principle supporting potential of CBD in relapse prevention along two dimensions CBD: beneficial actions across several vulnerability states, and long-lasting effects with only brief treatment. The findings also inform the ongoing medical marijuana debate concerning medical benefits of non-psychoactive cannabinoids and their promise for development and use as therapeutics.”


“Non-psychoactive cannabis ingredient could help addicts stay clean. Preclinical study using rats shows that Cannabidiol can reduce the risk of relapse”  https://www.sciencedaily.com/releases/2018/03/180323104821.htm

“Non-psychoactive cannabis ingredient could reduce risk of relapse among recovering addicts. A preclinical study in rats has shown that there might be value in using a non-psychoactive and non-addictive ingredient of the Cannabis sativa plant to reduce the risk of relapse among recovering drug and alcohol addicts.”  https://www.news-medical.net/news/20180323/Non-psychoactive-cannabis-ingredient-could-reduce-risk-of-relapse-among-recovering-addicts.aspx

“Non-psychoactive cannabis ingredient could help addicts stay clean”  https://www.springer.com/gp/about-springer/media/research-news/all-english-research-news/non-psychoactive-cannabis-ingredient-could-help-addicts-stay-clean/15548156

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Plasma anandamide concentrations are lower in children with autism spectrum disorder.

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“Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted, stereotyped behaviors and impairments in social communication.

Although the underlying biological mechanisms of ASD remain poorly understood, recent preclinical research has implicated the endogenous cannabinoid (or endocannabinoid), anandamide, as a significant neuromodulator in rodent models of ASD. Despite this promising preclinical evidence, no clinical studies to date have tested whether endocannabinoids are dysregulated in individuals with ASD.

Here, we addressed this critical gap in knowledge by optimizing liquid chromatography-tandem mass spectrometry methodology to quantitatively analyze anandamide concentrations in banked blood samples collected from a cohort of children with and without ASD (N = 112).


Anandamide concentrations significantly differentiated ASD cases (N = 59) from controls (N = 53), such that children with lower anandamide concentrations were more likely to have ASD (p = 0.041). In keeping with this notion, anandamide concentrations were also significantly lower in ASD compared to control children (p = 0.034).


These findings are the first empirical human data to translate preclinical rodent findings to confirm a link between plasma anandamide concentrations in children with ASD. Although preliminary, these data suggest that impaired anandamide signaling may be involved in the pathophysiology of ASD.”



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Cannabinoids for Treatment of Dystonia in Huntington’s Disease.

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“Motor symptoms in Huntington’s disease (HD) are heterogeneous with dystonia being described as a symptom with a very high prevalence not only in juvenile cases.


Treatment options for dystonia are limited. Cannabinoids have been described as a potential treatment for patients with dystonia of a different origin. Here, we present early onset HD patients with a marked improvement of motor symptoms mainly due to alleviation of dystonia due to treatment with cannabinoids. In addition we review the current literature concerning the use of cannabinoids in HD.


Improvement of motor symptoms, mainly dystonia, led to several relevant improvements from a global clinical perspective such as improvement of care, gait and fine motor skills and weight gain. Moreover, we observed changes in behavior with less irritability and apathy, as well as less hypersalivation in some cases.”



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Medical cannabis in the treatment of cancer pain and spastic conditions and options of drug delivery in clinical practice.

“The use of cannabis for medical purposes has been recently legalised in many countries including the Czech Republic. As a result, there is increased interest on the part of physicians and patients in many aspects of its application. This mini review briefly covers the main active substances of the cannabis plant and mechanisms of action. It focuses on two conditions, cancer pain and spasticity in multiple sclerosis, where its effects are well-documented. A comprehensive overview of a few cannabis-based products and the basic pharmacokinetics of marijuana’s constituents follows. The review concludes with an outline for preparing cannabis (dried inflorescence) containing drug dosage forms that can be produced in a hospital pharmacy.”

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Maternal administration of cannabidiol promotes an anti-inflammatory effect on the intestinal wall in a gastroschisis rat model.

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“Gastroschisis (GS) is an abdominal wall defect that results in histological and morphological changes leading to intestinal motility perturbation and impaired absorption of nutrients.

Due to its anti-inflammatory, antioxidant, and neuroprotective effects, cannabidiol(CBD) has been used as a therapeutic agent in many diseases.

Our aim was to test the effect of maternal CBD in the intestine of an experimental model of GS.

Maternal use of CBD had a beneficial effect on the intestinal loops of GS with decreased nitrite/nitrate and iNOS expression.”



“Is CBD Oil Safe To Use During Pregnancy? It’s Said To Relieve Pain & Your Body Is Hurting” https://www.romper.com/p/is-cbd-oil-safe-to-use-during-pregnancy-its-said-to-relieve-pain-your-body-is-hurting-8280324

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The Use of Cannabinoids in Colitis: A Systematic Review and Meta-Analysis.

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“Clinical trials investigating the use of cannabinoid drugs for the treatment of intestinal inflammation are anticipated secondary to preclinical literature demonstrating efficacy in reducing inflammation.

We systematically reviewed publications on the benefit of drugs targeting the endo-cannabinoid system in intestinal inflammation.



There is abundant preclinical literature demonstrating the anti-inflammatory effects of cannabinoid drugs in inflammation of the gut.”



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Medical marijuana laws and adolescent marijuana use in the United States: A systematic review and meta‐analysis

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“Synthesis of the current evidence does not support the hypothesis that US medical marijuana laws (MMLs) until 2014 have led to increases in adolescent marijuana use prevalence. None of the 11 studies found significant estimates of pre–post MML changes compared with contemporaneous changes in non‐MML states for marijuana use prevalence among adolescents. In summary, current evidence does not support the hypothesis that MML passage is associated with increased marijuana use prevalence among adolescents in states that have passed such laws up until 2014.”  https://onlinelibrary.wiley.com/doi/full/10.1111/add.14136

“Medical Marijuana Hasn’t Affected Teen Pot Use: Meta-Analysis. Medical marijuana laws have had little impact on recreational pot use among U.S. teens, according to a meta-analysis of 11 studies dating back to 1991. The findings appear to debunk claims by opponents of medical marijuana that the laws have led to greater cannabis use among adolescents, wrote researcher Deborah Hasin, PhD, of Columbia University’s Mailman School of Public Health, New York City, and colleagues in the journal Addiction.”  https://www.medpagetoday.com/psychiatry/addictions/71342

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Glial expression of cannabinoid CB(2) receptors and fatty acid amide hydrolase are beta amyloid-linked events in Down’s syndrome.


“Recent data suggest that the endocannabinoid system (ECS) may be involved in the glial response in different types of brain injury. Both acute and chronic insults seem to trigger a shift in the pattern of expression of some elements of this system from neuronal to glial. Specifically, data obtained in human brain tissue sections from Alzheimer’s disease patients showed that the expression of cannabinoid receptors of the CB(2) type is induced in activated microglial cells while fatty acid amide hydrolase (FAAH) expression is increased in reactive astrocytes. The present study was designed to determine the time-course of the shift from neuronal to glial induction in the expression of these proteins in Down‘s syndrome, sometimes referred to as a human model of Alzheimer-like beta-amyloid (Abeta) deposition. Here we present immunohistochemical evidence that both CB(2) receptors and FAAH enzyme are induced in Abeta plaque-associated microglia and astroglia, respectively, in Down‘s syndrome. These results suggest that the induction of these elements of the ECS contributes to, or is a result of, amyloid deposition and subsequent plaque formation. In addition, they confirm a striking differential pattern of distribution of FAAH and CB(2) receptors.”



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Marijuana use and mortality following orthopedic surgical procedures.

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“The association between marijuana use and surgical procedures is a matter of increasing societal relevance that has not been well studied in the literature.

The primary aim of this study is to evaluate the relationship between marijuana use and in-hospital mortality, as well as to assess associated comorbidities in patients undergoing commonly billed orthopedic surgeries.


The National Inpatient Sample (NIS) database from 2010 to 2014 was used to determine the odds ratios for the associations between marijuana use and in-hospital mortality, heart failure (HF), stroke, and cardiac disease (CD) in patients undergoing five common orthopedic procedures: hip (THA), knee (TKA), and shoulder arthroplasty (TSA), spinal fusion, and traumatic femur fracture fixation.


Of 9,561,963 patients who underwent one of the five selected procedures in the four-year period, 26,416 (0.28%) were identified with a diagnosis of marijuana use disorder. In hip and knee arthroplasty patients, marijuana use was associated with decreased odds of mortality compared to no marijuana use (p<0.0001), and increased odds of HF (p = 0.018), stroke (p = 0.0068), and CD (p = 0.0123). Traumatic femur fixation patients had the highest prevalence of marijuana use (0.70%), which was associated with decreased odds of mortality (p = 0.0483), HF (p = 0.0076), and CD (p = 0.0003). For spinal fusions, marijuana use was associated with increased odds of stroke (p<0.0001) and CD (p<0.0001). Marijuana use in patients undergoing shoulder arthroplasty was associated with decreased odds of mortality (p<0.001) and stroke (p<0.001).


In this study, marijuana use was associated with decreased mortality in patients undergoing THA, TKA, TSA and traumatic femur fixation, although the significance of these findings remains unclear. More research is needed to provide insight into these associations in a growing surgical population.”



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Anti-invasion Effects of Cannabinoids Agonist and Antagonist on Human Breast Cancer Stem Cells.

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“Studies show that cancer cell invasion or metastasis is the primary cause of death in malignancies including breast cancer.

The existence of cancer stem cells (CSCs) in breast cancer may account for tumor initiation, progression, and metastasis.

Recent studies have reported different effects of cannabinoids on cancer cells via CB1 and CB2 cannabinoid receptors.

In the present study, the effects of ACEA (a selective CB1 receptor agonist) and AM251 (a selective CB1 antagonist) on CSCs and their parental cells were investigated.

It was observed that ACEA decreased CD44+/CD24-/low/ESA+ cancer stem cell invasiveness.

Since one of the main cancer recurrence factors is anti-cancer drugs fail to inhibit CSC population, this observation would be useful for cancer treatment.”


“Our results indicate that cannabinoids may interfere with invasive cancer stem cells in benefit of cancer eradication. In summary, our results clarified that cannabinoid receptor agonist possesses anti-invasion potential in both main population and breast cancer stem cells. Considering that most anti-cancer drugs do not eradicate stem cells and only target main population cells, the results disclosed here can be used for prevention of cancer recurrence.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843309/

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