Cannabidiol treatment in an adolescent with multiple substance abuse, social anxiety and depression.

 “In this report, we present a case of a 16,9-year-old patient with multiple substance use disorder (cannabis, MDMA, cocaine, ecstacy), severe depression, social phobia and narcissistic personality disorder.We administered Cannabidiol (CBD) capsules in different dosages (starting dosage 100 mg up to 600 mg over 8 weeks) after unsuccessful treatment with antidepressants.

CBD was a safe and well tolerated medication for this patient. Upon treatment with CBD and cessation of the antidepressant medication, the patient improved regarding depressive as well as anxiety symptoms including simple phobias and symptoms of paranoia and dissociation.

Furthermore, the patient quit abusing illegal drugs including THC without showing withdrawal symptoms. This is the first report of CBD medication in a patient with multiple substance use disorder with a positive outcome.Until today it is not clear if CBD holds promise as a therapeutic option in substance use disorder as RCTs are lacking, but in this single case the substance seems to work in various domains.”

https://www.ncbi.nlm.nih.gov/pubmed/32052321

https://link.springer.com/article/10.1007%2Fs40211-020-00334-0

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Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation and epithelial-mesenchymal transition in vitro.

Image result for plos one “Patients with non-small cell lung cancer (NSCLC) develop resistance to antitumor agents by mechanisms that involve the epithelial-to-mesenchymal transition (EMT). This necessitates the development of new complementary drugs, e.g., cannabinoid receptors (CB1 and CB2) agonists including tetrahydrocannabinol (THC) and cannabidiol (CBD).

The combined use of THC and CBD confers greater benefits, as CBD enhances the effects of THC and reduces its psychotropic activity. We assessed the relationship between the expression levels of CB1 and CB2 to the clinical features of a cohort of patients with NSCLC, and the effect of THC and CBD (individually and in combination) on proliferation, EMT and migration in vitro in A549, H460 and H1792 lung cancer cell lines.

METHODS:

Expression levels of CB1, CB2, EGFR, CDH1, CDH2 and VIM were evaluated by quantitative reverse transcription-polymerase chain reaction. THC and CBD (10-100 μM), individually or in combination (1:1 ratio), were used for in vitro assays. Cell proliferation was determined by BrdU incorporation assay. Morphological changes in the cells were visualized by phase-contrast and fluorescence microscopy. Migration was studied by scratch recolonization induced by 20 ng/ml epidermal growth factor (EGF).

RESULTS:

The tumor samples were classified according to the level of expression of CB1, CB2, or both. Patients with high expression levels of CB1, CB2, and CB1/CB2 showed increased survival reaching significance for CB1 and CB1/CB2 (p = 0.035 and 0.025, respectively).

Both cannabinoid agonists inhibited the proliferation and expression of EGFR in lung cancer cells, and CBD potentiated the effect of THC. THC and CBD alone or in combination restored the epithelial phenotype, as evidenced by increased expression of CDH1 and reduced expression of CDH2 and VIM, as well as by fluorescence analysis of cellular cytoskeleton.

Finally, both cannabinoids reduced the in vitro migration of the three lung cancer cells lines used.

CONCLUSIONS:

The expression levels of CB1 and CB2 have a potential use as markers of survival in patients with NSCLC. THC and CBD inhibited the proliferation and expression of EGFR in the lung cancer cells studied. Finally, the THC/CBD combination restored the epithelial phenotype in vitro.”

https://www.ncbi.nlm.nih.gov/pubmed/32049991

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228909

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Targeting GPCRs Against Cardiotoxicity Induced by Anticancer Treatments.

Image result for frontiers in cardiovascular medicine“Novel anticancer medicines, including targeted therapies and immune checkpoint inhibitors, have greatly improved the management of cancers. However, both conventional and new anticancer treatments induce cardiac adverse effects, which remain a critical issue in clinic.

Cardiotoxicity induced by anti-cancer treatments compromise vasospastic and thromboembolic ischemia, dysrhythmia, hypertension, myocarditis, and cardiac dysfunction that can result in heart failure. Importantly, none of the strategies to prevent cardiotoxicity from anticancer therapies is completely safe and satisfactory.

Certain clinically used cardioprotective drugs can even contribute to cancer induction. Since G protein coupled receptors (GPCRs) are target of forty percent of clinically used drugs, here we discuss the newly identified cardioprotective agents that bind GPCRs of adrenalin, adenosine, melatonin, ghrelin, galanin, apelin, prokineticin and cannabidiol.

We hope to provoke further drug development studies considering these GPCRs as potential targets to be translated to treatment of human heart failure induced by anticancer drugs.”

https://www.ncbi.nlm.nih.gov/pubmed/32039239

https://www.frontiersin.org/articles/10.3389/fcvm.2019.00194/full

“Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating Mitochondrial Function and Biogenesis.”  https://www.ncbi.nlm.nih.gov/pubmed/25569804

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Dietary intake of polyunsaturated fatty acids alleviates cognition deficits and depression-like behaviour via cannabinoid system in sleep deprivation rats.

Behavioural Brain Research“Sleep deprivation (SD) is a common feature in modern society. Prolonged sleep deprivation causes cognition deficits and depression-like behavior in the model of animal experiments.

Endocannabinoid system are key modulators of synaptic function, which were related to memory and mood. Although the underlying mechanism remains unknown, several studies indicated the benefits of polyunsaturated fatty acids (PUFAs, linolenic acid, 39.7%; linoleic acid, 28%; and oleic acid, 22%) on brain function through the endocannabinoid system.

The present study aimed to evaluate the influence of dietary PUFAs on cognition deficits induced by sleep deprivation in Sprague Dawley rats.

The results revealed that SD led to the disorder of cognition and mood which was improved by the supplement of PUFAs.

SD significantly increased the mEPSC frequency, and decreased the protein level of cannabinoid type-1 receptors (CB1R). These changes were restored by supplement of PUFAs, which showed a similar level to the control group. Behaviour tests showed that the positive effects on repairing cognition and anxiety disorders were almost completely abolished when the CB1R receptor antagonist rimonabant was applied to the SD rats.

These findings indicated that PUFAs are a factor regulating cognition deficits and depression induced by SD via cannabinoid type-1 receptors.”

https://www.ncbi.nlm.nih.gov/pubmed/32035867

“PUFAs reduced cognition deficits and depression-like behaviours of sleep deprivation rats in the behaviour tests.”

https://www.sciencedirect.com/science/article/pii/S0166432819317218?via%3Dihub

“Hempseed oil is over 80% in polyunsaturated fatty acids (PUFAs), and is an exceptionally rich source of the two essential fatty acids (EFAs) linoleic acid (18:2 omega-6) and alpha-linolenic acid (18:3 omega-3). The omega-6 to omega-3 ratio (n6/n3) in #hempseed oil is normally between 2:1 and 3:1, which is considered to be optimal for human health.”

https://www.researchgate.net/publication/226272227_Hempseed_as_a_nutritional_resource_An_overview

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Cannabinoid Signaling in Glioma Cells.

 “Cannabinoids are a group of structurally heterogeneous but pharmacologically related compounds, including plant-derived cannabinoids, synthetic substances and endogenous cannabinoids, such as anandamide and 2-arachidonoylglycerol.

Cannabinoids elicit a wide range of central and peripheral effects mostly mediated through cannabinoid receptors. There are two types of specific Gi/o-protein-coupled receptors cloned so far, called CB1 and CB2, although an existence of additional cannabinoid-binding receptors has been suggested. CB1 and CB2 differ in their predicted amino acid sequence, tissue distribution, physiological role and signaling mechanisms.

Significant alterations of a balance in the cannabinoid system between the levels of endogenous ligands and their receptors occur during malignant transformation in various types of cancer, including gliomas.

Cannabinoids exert anti-proliferative action in tumor cells.

Induction of cell death by cannabinoid treatment relies on the generation of a pro-apoptotic sphingolipid ceramide and disruption of signaling pathways crucial for regulation of cellular proliferation, differentiation or apoptosis. Increased ceramide levels lead also to ER-stress and autophagy in drug-treated glioblastoma cells.

Beyond blocking of tumor cells proliferation cannabinoids inhibit invasiveness, angiogenesis and the stem cell-like properties of glioma cells, showing profound activity in the complex tumor microenvironment. Advances in translational research on cannabinoid signaling led to clinical investigations on the use of cannabinoids in treatments of glioblastomas.”

https://www.ncbi.nlm.nih.gov/pubmed/32034716

https://link.springer.com/chapter/10.1007%2F978-3-030-30651-9_11

“Cannabinoids exert anti-proliferative action in tumor cells.” https://www.ncbi.nlm.nih.gov/pubmed/22879071

“A glioma is a primary brain tumor that originates from the supportive cells of the brain, called glial cells.” http://neurosurgery.ucla.edu/body.cfm?id=159

“Remarkably, cannabinoids kill glioma cells selectively and can protect non-transformed glial cells from death.” http://www.ncbi.nlm.nih.gov/pubmed/15275820

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Abrupt withdrawal of cannabidiol (CBD): A randomized trial.

Cover image volume 103, Issue “The rationale of this study was to assess occurrence of withdrawal symptoms induced by abrupt cessation of cannabidiol (CBD) after prolonged administration in healthy volunteers.

CONCLUSION:

In healthy volunteers, no evidence of withdrawal syndrome was found with abrupt discontinuation of short-term treatment with CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/32036242

“There was no evidence of a physical withdrawal syndrome after abrupt cessation of CBD.”

https://www.epilepsybehavior.com/article/S1525-5050(19)31116-3/fulltext

Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa” https://www.ncbi.nlm.nih.gov/pubmed/19690824

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Neuroprotective effect of chronic administration of cannabidiol during the abstinence period on methamphetamine-induced impairment of recognition memory in the rats.

“Neuropsychiatric disorders, such as addiction, are associated with cognitive impairment, including learning and memory deficits.

Previous research has demonstrated that the chronic use of methamphetamine (METH) induces long-term cognitive impairment and cannabidiol (CBD), as a neuroprotectant, can reverse spatial memory deficits induced by drug abuse.

The study aimed to evaluate the effect of CBD on METH-induced memory impairment in rats chronically exposed to METH (CEM).

For the induction of CEM, animals received METH (2 mg/kg, twice/day) for 10 days. Thereafter, the effect of intracerebroventricular (ICV) administration of CBD (32 and 160 nmol) during the (10 days) abstinence period on spatial memory was evaluated using the Y-Maze test, while recognition memory was examined using the novel object recognition (NOR) test.

The results revealed a significant increase in the motor activity of METH-treated animals compared with the control group and, after the 10-day abstinence period, motor activity returned to baseline. Notably, the chronic administration of METH had impairing effects on spontaneous alternation performance and recognition memory, which was clearly observed in the NOR test.

Additionally, although the ICV administration of CBD (160 nmol) could reverse long-term memory, a lower dose (32 nmol) did not result in any significant increase in exploring the novel object during short-term memory testing.

These novel findings suggest that the chronic administration of METH induces memory impairment and presents interesting implications for the potential use of CBD in treating impairment deficits after chronic exposure to psychostimulant drugs such as METH.”

https://www.ncbi.nlm.nih.gov/pubmed/32032100

https://journals.lww.com/behaviouralpharm/Abstract/publishahead/Neuroprotective_effect_of_chronic_administration.99194.aspx

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Cannabinoid receptor 2 activation alleviates septic lung injury by promoting autophagy via inhibition of inflammatory mediator release.

Cellular Signalling“Septic lung injury is one of main causes of high mortality in severe patients. Inhibition of excessive inflammatory response is considered as an effective strategy for septic lung injury.

Previous studies have shown that cannabinoid receptor 2 (CB2), a G protein-coupled receptor, play an important role in immunosuppression.

Whether CB2 can be used as a therapeutic target for septic lung injury is unclear. The aim of this study is to explore the role of CB2 in sepsis and its potential mechanism.

These results suggest that CB2 serves as a protective target for septic lung injury by decreasing inflammatory factors, which is associated with the enhancement of autophagy.”

https://www.ncbi.nlm.nih.gov/pubmed/32027949

“Activation of cannabinoid receptor 2 can alleviate sepsis-induced lung injury.”

https://www.sciencedirect.com/science/article/abs/pii/S0898656820300334?via%3Dihub

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Endocannabinoids as Therapeutic Targets.

Archives of Medical Research“Most of the drugs of abuse affect the brain by interacting with naturally expressed molecular receptors. Marihuana affects a series of receptors including cannabinoid receptor 1 (CB1R) and CB2R, among others. Endogenous molecules with cannabinoid activity interact with these receptors naturally. Receptors, ligands, synthesizing and degrading enzymes, as well as transporters, have been described.

This endocannabinoid system modulates behaviors and physiological processes, i.e. food intake, the sleep-waking cycle, learning and memory, motivation, and pain perception, among others. The rather broad distribution of endocannabinoids in the brain explains the different effects marihuana induces in its users. However, this very same anatomical and physiological distribution makes this system a useful target for therapeutic endeavors.

In this review, we briefly discuss the potential of small molecules that target the endocannabinoids as therapeutic tools to improve behaviors and treat illnesses. We believe that under medical supervision, endocannabinoid targets offer new advantages for patients for controlling multiple medical disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/32028095

https://www.sciencedirect.com/science/article/abs/pii/S0188440919304746?via%3Dihub

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Medical Cannabis in Children.

 Logo of rmmj“The use of medical cannabis in children is rapidly growing.

While robust evidence currently exists only for pure cannabidiol (CBD) to treat specific types of refractory epilepsy, in most cases, artisanal strains of CBD-rich medical cannabis are being used to treat children with various types of refractory epilepsy or irritability associated with autism spectrum disorder (ASD).

Other common pediatric disorders that are being considered for cannabis treatment are Tourette syndrome and spasticity.

As recreational cannabis use during youth is associated with serious adverse events and medical cannabis use is believed to have a relatively high placebo effect, decisions to use medical cannabis during childhood and adolescence should be made with caution and based on evidence.

This review summarizes the current evidence for safety, tolerability, and efficacy of medical cannabis in children with epilepsy and in children with ASD. The main risks associated with use of Δ9-tetrahydrocannabinol (THC) and CBD in the pediatric population are described, as well as the debate regarding the use of whole-plant extract to retain a possible “entourage effect” as opposed to pure cannabinoids that are more standardized and reproducible.”

https://www.ncbi.nlm.nih.gov/pubmed/32017680

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