The anti-inflammatory and analgesic effects of formulated full-spectrum cannabis extract in the treatment of neuropathic pain associated with multiple sclerosis.

 SpringerLink“Cannabis has been used for thousands of years in many cultures for the treatment of several ailments including pain.

The benefits of cannabis are mediated largely by cannabinoids, the most prominent of which are tetrahydrocannabinol (THC) and cannabidiol (CBD). As such, THC and/or CBD have been investigated in clinical studies for the treatment of many conditions including neuropathic pain and acute or chronic inflammation.

While a plethora of studies have examined the biochemical effects of purified THC and/or CBD, only a few have focused on the effects of full-spectrum cannabis plant extract. Accordingly, studies using purified THC or CBD may not accurately reflect the potential health benefits of full-spectrum cannabis extracts.

Indeed, the cannabis plant produces a wide range of cannabinoids, terpenes, flavonoids, and other bioactive molecules which are likely to contribute to the different biological effects. The presence of all these bioactive molecules in cannabis extracts has garnered much attention of late especially with regard to their potential role in the treatment of neuropathic pain associated with multiple sclerosis.:

Herein, the current knowledge about the potential beneficial effects of existing products of full-spectrum cannabis extract in clinical studies involving patients with multiple sclerosis is extensively reviewed. In addition, the possible adverse effects associated with cannabis use is discussed along with how the method of extraction and the delivery mechanisms of different cannabis extracts contribute to the pharmacokinetic and biological effects of full-spectrum cannabis extracts.”

https://www.ncbi.nlm.nih.gov/pubmed/32239248

https://link.springer.com/article/10.1007%2Fs00011-020-01341-1

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Treatment studies with cannabinoids in anorexia nervosa: a systematic review.

SpringerLink“Anorexia nervosa (AN) is a psychiatric disorder with a high mortality and unknown etiology, and effective treatment is lacking.

For decades, cannabis has been known to cause physical effects on the human body, including increasing appetite, which may be beneficial in the treatment of AN.

More research on cannabinoids in anorexia nervosa is warranted, especially its effects on psychopathology.”

https://www.ncbi.nlm.nih.gov/pubmed/32240516

https://link.springer.com/article/10.1007%2Fs40519-020-00891-x

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Dosage, Efficacy and Safety of Cannabidiol Administration in Adults: A Systematic Review of Human Trials.

“Considering data from in vitro and in vivo studies, cannabidiol (CBD) seems to be a promising candidate for the treatment of both somatic and psychiatric disorders.

The aim of this review was to collect dose(s), dosage schemes, efficacy and safety reports of CBD use in adults from clinical studies.

From the controlled trials, we identified anxiolytic effects with acute CBD administration, and therapeutic effects for social anxiety disorder, psychotic disorder and substance use disorders.

There was evidence to support single dose positive effect on social anxiety disorder, short medium-term effects on symptomatic improvement in schizophrenia and lack of effect in the short medium-term on cognitive functioning in psychotic disorders.

Overall, the administration was well tolerated with mild side effects.”

https://www.ncbi.nlm.nih.gov/pubmed/32231748

https://www.jocmr.org/index.php/JOCMR/article/view/4090

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n-3 Polyunsaturated Fatty Acid Amides: New Avenues in the Prevention and Treatment of Breast Cancer.

ijms-logo “Over the last decades a renewed interest in n-3 very long polyunsaturated fatty acids (PUFAs), derived mainly from fish oils in the human diet, has been observed because of their potential effects against cancer diseases, including breast carcinoma. These n-3 PUFAs mainly consist of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that, alone or in combination with anticancer agents, induce cell cycle arrest, autophagy, apoptosis, and tumor growth inhibition. A large number of molecular targets of n-3 PUFAs have been identified and multiple mechanisms appear to underlie their antineoplastic activities. Evidence exists that EPA and DHA also elicit anticancer effects by the conversion to their corresponding ethanolamide derivatives in cancer cells, by binding and activation of different receptors and distinct signaling pathways. Other conjugates with serotonin or dopamine have been found to exert anti-inflammatory activities in breast tumor microenvironment, indicating the importance of these compounds as modulators of tumor epithelial/stroma interplay. The objective of this review is to provide a general overview and an update of the current n-3 PUFA derivative research and to highlight intriguing aspects of the potential therapeutic benefits of these low-toxicity compounds in breast cancer treatment and care.”

https://www.ncbi.nlm.nih.gov/pubmed/32224850

https://www.mdpi.com/1422-0067/21/7/2279

“Anticancer effects of n-3 EPA and DHA and their endocannabinoid derivatives on breast cancer cell growth and invasion.”  https://www.ncbi.nlm.nih.gov/pubmed/31679810

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Adolescent treatment admissions for marijuana following recreational legalization in Colorado and Washington.

Drug and Alcohol Dependence“There is concern that recreational marijuana legalization (RML) may lead to increased cannabis use disorder (CUD) among youth due to increased marijuana use.

This study investigates whether adolescent substance use disorder treatment admissions for marijuana use increased in Colorado and Washington following RML.

RESULTS:

Over all states in the analysis, the rate of adolescent treatment admissions for marijuana use declined significantly over the study period (β=-3.375, 95 % CI=-4.842, -1.907), with the mean rate falling nearly in half. The decline in admissions rate was greater in Colorado and Washington compared to non-RML states following RML, though this difference was not significant (β=-7.671, 95 % CI=-38.798, 23.456).

CONCLUSION:

Adolescent treatment admissions for marijuana use did not increase in Colorado and Washington following RML. This may be because youth marijuana use did not increase, CUD did not increase (even if use did increase), or treatment seeking behaviors changed due to shifts in attitudes and perceptions of risk towards marijuana use.”

https://www.ncbi.nlm.nih.gov/pubmed/32222560

“Youth treatment admissions in Colorado and Washington did not increase after RML. Admissions for 2008–2017 declined in both Colorado/Washington and non-RML states.”

https://www.sciencedirect.com/science/article/abs/pii/S0376871620301253?via%3Dihub

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Δ9-Tetrahydrocannabinol (THC) Impairs CD8+ T Cell-Mediated Activation of Astrocytes.

“CD8+ T cells can contribute to neuroinflammation by secretion of inflammatory cytokines like interferon γ (IFNγ) and tumor necrosis factor α (TNFα). Astrocytes, a glial cell in the brain, can be stimulated by IFNγ and TNFα to secrete the inflammatory cytokines, monocyte chemotactic protein 1 (MCP-1), interleukin 6 (IL-6), and interferon-γ inducible protein 10 (IP-10).

Δ9-Tetrahydrocannabinol (THC), the primary psychoactive cannabinoid in Cannabis sativa, possesses potent anti-inflammatory activity.

The objective of this investigation was to assess the effects of THC treatment on CD8+ T cell-mediated activation of astrocytes.

The results suggest that cannabinoid treatment can selectively reduce certain CD8+ T cell responses that contribute to stimulation of astrocytes. Treatment with THC can abate CD8+ T cell-dependent neuroinflammatory processes by inhibiting CD8+ cell differentiation into effector cells, suppressing CD8+ effector cell function, and reducing activation of astrocytes by CD8+ T cell-derived inflammatory cytokines.”

https://www.ncbi.nlm.nih.gov/pubmed/32215844

https://link.springer.com/article/10.1007%2Fs11481-020-09912-z

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Cannabinoid receptor 2 agonist promotes parameters implicated in mucosal healing in patients with inflammatory bowel disease.

Issues“Cannabis benefits patients with inflammatory bowel disease (IBD).

Cannabinoid receptors are expressed in gut immune cells and in epithelial cells of inflamed guts.

Mucosal healing (MH) requires epithelial layer restoration.

CONCLUSION:

Using ex vivo and in vitro human models, we demonstrated that manipulating the cannabinoid system affects colon cells and secretome characteristics that facilitate MH in IBD.”

https://www.ncbi.nlm.nih.gov/pubmed/32213014

“Experimental studies and recent clinical trials suggest that treatment with cannabis benefits patients with IBD.”

https://journals.sagepub.com/doi/10.1177/2050640619889773

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From Cannabis sativa to Cannabidiol: Promising Therapeutic Candidate for the Treatment of Neurodegenerative Diseases.

frontiers in pharmacology – Retraction Watch“Cannabis sativa, commonly known as marijuana, contains a pool of secondary plant metabolites with therapeutic effects.

Besides Δ9-tetrahydrocannabinol that is the principal psychoactive constituent of Cannabiscannabidiol (CBD) is the most abundant nonpsychoactive phytocannabinoid and may represent a prototype for anti-inflammatory drug development for human pathologies where both the inflammation and oxidative stress (OS) play an important role to their etiology and progression.

To this regard, Alzheimer’s disease (AD), Parkinson’s disease (PD), the most common neurodegenerative disorders, are characterized by extensive oxidative damage to different biological substrates that can cause cell death by different pathways. Most cases of neurodegenerative diseases have a complex etiology with a variety of factors contributing to the progression of the neurodegenerative processes; therefore, promising treatment strategies should simultaneously target multiple substrates in order to stop and/or slow down the neurodegeneration.

In this context, CBD, which interacts with the eCB system, but has also cannabinoid receptor-independent mechanism, might be a good candidate as a prototype for anti-oxidant drug development for the major neurodegenerative disorders, such as PD and AD. This review summarizes the multiple molecular pathways that underlie the positive effects of CBD, which may have a considerable impact on the progression of the major neurodegenerative disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/32210795

“The present review provided evidence that the nonpsychoactive phytocannabinoids CBD could be a potential pharmacological tool for the treatment of neurodegenerative disorders; its excellent safety and tolerability profile in clinical studies renders it a promising therapeutic agent.

The molecular mechanisms associated with CBD’s improvement in PD and AD are likely multifaceted, and although CBD may act on different molecular targets all the beneficial effects are in some extent linked to its antioxidant and anti-inflammatory profile, as observed in in vitro and in vivo studies. Therefore, this review describes evidence to prove the therapeutical efficacy of CBD in patients affected by neurodegenerative disorders and promotes further research in order to better elucidate the molecular pathways involved in the therapeutic potential of CBD.”

https://www.frontiersin.org/articles/10.3389/fphar.2020.00124/full

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Cannabidiol alleviates hemorrhagic shock-induced neural apoptosis in rats by inducing autophagy through activation of the PI3K/AKT pathway.

Publication cover image“Recently, several studies have reported that the pharmacological effects exerted by cannabidiol (CBD) are partially related to the regulation of autophagy. Increasing evidence indicates that autophagy provides protection against ischemia-induced brain injury. However, the protective effect of CBD against mitochondrial-dependent apoptosis in hemorrhagic shock (HS)-induced brain injury has not been studied.

In the present study, we observed the protective effects of CBD against neural mitochondrial-dependent apoptosis in a rat model of HS. In addition, CBD increased Beclin-1 and LC3II expression and reduced P62 expression, which were indicative of autophagy. CBD treatment attenuated the neural apoptosis induced by HS, as reflected by restoring mitochondrial dysfunction, downregulation of BAX, neuro-apoptosis ratio and NF-κB signaling activation, and upregulation of BCL2 in the cerebral cortex.

Such protective effects were reversed by 3-Methyladenine, a specific autophagy inhibitor, indicating that the protective effects of CBD treatment involved autophagy. LY294002, a PI3K inhibitor, significantly inhibited CBD-induced autophagy, demonstrating that PI3K/AKT signaling is involved in the CBD’s regulation of autophagy. Furthermore, we found that CBD treatment upregulated PI3K/AKT signaling via cannabinoid receptor 1.

Therefore, these findings suggested that CBD treatment protects against cerebral injury induced by HS-mediated mitochondrial-dependent apoptosis by activating the PI3K/AKT signaling pathway to reinforce autophagy.”

https://www.ncbi.nlm.nih.gov/pubmed/32215966

https://onlinelibrary.wiley.com/doi/abs/10.1111/fcp.12557

“Hemorrhagic shock occurs when the body begins to shut down due to large amounts of blood loss.” https://www.healthline.com/health/hemorrhagic-shock

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The molecular mechanisms that underpin the biological benefit of full spectrum cannabis extract in the treatment of neuropathic pain and inflammation.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease“Cannabis has been shown to be beneficial in the treatment of pain and inflammatory diseases.

The biological effect of cannabis is mainly attributed to two major cannabinoids, tetrahydrocannabinol and cannabidiol. In the majority of studies to-date, a purified tetrahydrocannabinol and cannabidiol alone or in combination have been extensively examined in many studies for the treatment of numerous disorders including pain and inflammation. However, few studies have investigated the biological benefits of full-spectrum cannabis plant extract.

Given that cannabis is known to generate a large number of cannabinoids along with numerous other biologically relevant products including terpenes, studies involving purified tetrahydrocannabinol and/or cannabidiol may not precisely consider the potential biological benefits of the full-spectrum cannabis extracts. This may be especially true in the role of cannabis as a treatment of pain and inflammation. Herein, we review the pre-clinical physiological and molecular mechanisms in biological systems that are affected by cannabis.”

https://www.ncbi.nlm.nih.gov/pubmed/32201189

“Full-spectrum cannabis extract demonstrates several convincing beneficial anti-inflammatory and analgesic effects in preclinical studies. Full-spectrum cannabis extract may represent a promising therapeutic agent that seems to benefit a variety of conditions associated with pain and inflammation.”

https://www.sciencedirect.com/science/article/abs/pii/S0925443920301162?via%3Dihub

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