Tag Archives: treatment

Endocannabinoid System Alterations in Posttraumatic Stress Disorder: A Review of Developmental and Accumulative Effects of Trauma.

Posted on by

 Image result for sage journals chronic stress“The role of the endocannabinoid system in stress-related psychiatric symptoms has been investigated in many animal and human studies.

Although most of these studies consistently report long-lasting effects of prolonged stress and trauma on the endocannabinoid system, the nature and direction of these changes are controversial.

We reviewed the available preclinical and clinical studies investigating the endocannabinoid system alterations long after chronic stress and trauma.

We propose that the effects of prolonged stress or trauma on the endocannabinoid system are different based on the developmental age of subjects at the time of experiencing the trauma and its repetitiveness and accumulative effects.

The current literature consistently demonstrates decreased levels of endocannabinoid ligands and receptors if the trauma occurs in childhood, whereas decreased levels of endocannabinoid ligands and increased levels of cannabinoid receptors are reported when trauma has happened in adulthood.

It is important to note that these changes are region-specific in the brain and also there are important sex differences, which are beyond the scope of this review.”

https://www.ncbi.nlm.nih.gov/pubmed/31660473

“More studies are needed to compare the effects of childhood and adulthood trauma, with or without PTSD presentations, on the eCB system. These studies would have important clinical implications, not only for individuals with trauma and PTSD who commonly have comorbid recreational cannabis use, and medical marijuana users with PTSD being one of its main indicators but also for studies investigating the potential therapeutic use of cannabinoids and eCB enhancers in PTSD treatment.”

https://journals.sagepub.com/doi/10.1177/2470547019864096

WIN55,212-2-Induced Expression of Mir-29b1 Favours the Suppression of Osteosarcoma Cell Migration in a SPARC-Independent Manner.

Posted on by

ijms-logo“WIN55,212-2 (WIN) is a synthetic agonist of cannabinoid receptors that displays promising antitumour properties.

The aim of this study is to demonstrate that WIN is able to block the migratory ability of osteosarcoma cells and characterize the mechanisms involved.

Overall, these findings suggest that WIN markedly affects cell migration, dependently on miR-29b1 and independently of SPARC, and can thus be considered as a potential innovative therapeutic agent in the treatment of osteosarcoma.”

https://www.ncbi.nlm.nih.gov/pubmed/31652569

https://www.mdpi.com/1422-0067/20/20/5235

A role for cannabinoids in the treatment of myotonia? Report of compassionate use in a small cohort of patients.

Posted on by

“The symptomatic treatment of myotonia and myalgia in patients with dystrophic and non-dystrophic myotonias is often not satisfactory.

Some patients anecdotally report symptoms’ relief through consumption of cannabis.

METHODS:

A combination of cannabidiol and tetrahydrocannabinol (CBD/THC) was prescribed as compassionate use to six patients (four patients with myotonic dystrophy types 1 and 2, and 2 patients with CLCN1-myotonia) with therapy-resistant myotonia and myalgia. CBD/THC oil was administered on a low dose in the first 2 weeks and adjusted to a higher dose in the following 2 weeks. Myotonia behaviour scale (MBS), hand-opening time, visual analogue scales (VAS) for myalgia and myotonia, and fatigue and daytime sleepiness severity scale (FSS, ESS) were performed weekly to monitor treatment response.

RESULTS:

All patients reported an improvement of myotonia especially in weeks 3 and 4 of treatment: MBS improved of at least 2 points in all patients, the hand-opening time variously improved in 5 out of 6 patients. Chronic myalgia was reported by both DM2 patients at baseline, one of them experienced a significant improvement of myalgia under treatment. Some gastrointestinal complaints, as abdominal pain and diarrhoea, improved in 3 patients; however, 4 out of 6 patients reported new-onset constipation. No other relevant side effect was noticed.

CONCLUSIONS:

These first empirical results suggest a potentially beneficial role of CBD/THC in alleviating myotonia and should encourage further research in this field including a randomized-controlled trial on larger cohorts.”

https://www.ncbi.nlm.nih.gov/pubmed/31655890

https://link.springer.com/article/10.1007%2Fs00415-019-09593-6

“Myotonia is a medical term that refers to a neuromuscular condition in which the relaxation of a muscle is impaired.” https://www.ninds.nih.gov/Disorders/All-Disorders/Myotonia-Information-Page

Cannabinoids in the treatment of rheumatic diseases: Pros and cons.

Posted on by

Autoimmunity Reviews“Medical cannabis is being increasingly used in the treatment of rheumatic diseases because, despite the paucity of evidence regarding its safety and efficacy, a growing number of countries are legalising its use for medical purposes in response to social pressure.

Cannabinoids may be useful in the management of rheumatic disorders for two broad reasons: their anti-inflammatory and immunomodulatory activity, and their effects on pain and associated symptoms.

It is interesting to note that, although a wide range of medications are available for the treatment of inflammation, including an ever-lengthening list of biological medications, the same is not true of the treatment of chronic pain, a cardinal symptom of many rheumatological disorders.

The publication of systematic reviews (SR) concerning the use of cannabis-based medicines for chronic pain (with and without meta-analyses) is outpacing that of randomised controlled trials. Furthermore, narrative reviews of public institution are largely based on these SRs, which often reach different conclusions regarding the efficacy and safety of cannabis-based medicines because of the lack of high-quality evidence of efficacy and the presence of indications that they may be harmful for patients.

Societal safety concerns about medical cannabis (e.g. driving risks, workplace safety and pediatric intoxication) must always be borne in mind, and will probably not be addressed by clinical studies. Medical cannabis and cannabis-based medicines have often been legalised as therapeutic products by legislative bodies without going through the usual process of regulatory approval founded on the results of traditional evidence-based studies. This review discusses the advantages and limitations of using cannabis to treat rheumatic conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/31648042

https://www.sciencedirect.com/science/article/abs/pii/S1568997219302162?via%3Dihub

Utilization of medicinal cannabis for pain by individuals with spinal cord injury.

Posted on by

Image result for spinal cord series and cases“A cross-sectional multi-center study using an on-line survey addressing utilization, knowledge, and perceptions of medicinal cannabis (MC) by people with spinal cord injury (SCI).

OBJECTIVE:

To characterize differences between current (CU), past (PU), and never users (NU) of MC with SCI; to determine why people with SCI use MC; to examine reports of MCs’ efficacy and tolerability by individuals with SCI.

SETTING:

Three academic medical centers in the United States.

METHODS:

Comparison of demographic and attitudinal differences between CU, PU, and NU and differences in the groups’ reports of pain, health, and quality of life (QOL). Evaluation of utilization patterns and perceived efficacy of MC among CU and PU and reports of side effects of MC versus prescription medications. Data were analyzed using either Chi Square, distribution-free exact statistics, or t-tests for continuous data.

RESULTS:

Among a nationwide sample (n = 353) of individuals with SCI, NU were less likely than CU and PU to believe that cannabis ought to be legalized and more likely to endorse risks of use. Current users and PU reported greater pain interference in daily life than did NU, but there were no between group differences in QOL or physical or emotional health. Current users and PU took MC to address pain (65.30%), spasms (63.30%), sleeplessness (32.70%), and anxiety (24.00%), and 63.30% reported it offered “great relief” from symptoms. Participants reported that MC is more effective and carries fewer side effects than prescription medications.

CONCLUSIONS:

Medicinal cannabis is an effective and well-tolerated treatment for a number of SCI-related symptoms.”

https://www.ncbi.nlm.nih.gov/pubmed/31632724

https://www.nature.com/articles/s41394-019-0208-6

Cannabidiol As A Novel Therapeutic Strategy For Oral Inflammatory Diseases: A Review Of Current Knowledge And Future Perspectives.

Posted on by

Image result for altern ther health med “The high frequency and painful profile of inflammatory oral lesions and the lack of an effective drug protocol for their management stimulate the search for pharmacological alternatives for the treatment of these conditions. Cannabidiol is the major non-psychotropic constituent of Cannabis sativa, receiving lately scientific interest because of its potential in the treatment of inflammatory disorders such as asthma, colitis and arthritis. There is little published in the current literature about the use of cannabidiol in oral health. Among its many protective functions, the ability to attenuate inflammation through the modulation of cytokines and its antiedema and analgesic effects may be important features in the treatment of oral lesions. In this review, we suggest that cannabidiol can be useful in the management of oral inflammatory disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31634872

Kinetics of acetylcholinesterase inhibition by hemp seed protein-derived peptides.

Posted on by

Journal of Food Biochemistry banner“The aim of this work was to enhance the acetylcholinesterase (AChE)-inhibitory activity of a pepsin-produced hemp seed protein hydrolysates (HPH) through reverse-phase HPLC separation followed by identification of peptide sequences present in the most active fraction. The HPH was separated into eight fractions (F1-F8) with F7 exhibiting significantly (p < 0.05) the strongest (97.5%) in vitro inhibition of electric eel AChE (eeAChE) activity in comparison to 53.8% for HPH. The HPH consisted mostly of low molecular weight peptides of < 11 amino acid residues and most contained at least one hydrophobic amino acid. Kinetics of enzyme inhibition revealed a mixed-type inhibition of eeAChE activity by HPH whereas F7 acted through an uncompetitive mode; in contrast inhibition of human AChE by HPH and F7 was uncompetitive. The stronger inhibitory potency of the F7 peptides fraction against both enzymes was confirmed through reduced maximal velocity, catalytic efficiency, and inhibition constant values when compared to the HPH.

PRACTICAL APPLICATIONS: The use of natural products for the prevention or treatment of human diseases continues to be an area of intense research activities. Food protein-derived peptides obtained through enzymatic hydrolysis of hemp seed proteins were shown in vitro to be strong inhibitors of activities of both the eel and human forms of acetylcholinesterase (AChE). AChE is an important therapeutic target because excessive activity of this enzyme is a causative factor of neurodegenerative diseases such as dementia and Alzheimer’s. This work showed that peptides in the most active fraction are small in sizes, which may favor their absorption into blood circulation and possible permeation of the blood-brain barrier. Therefore, the hemp seed peptides are potential agents that can be used to formulate functional foods and nutraceuticals against neurodegenerative diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/31353736

https://onlinelibrary.wiley.com/doi/abs/10.1111/jfbc.12897

Hemp seed/evening primrose oil affects expression of STAT3, IL-17, and FOXP3+ in experimental autoimmune encephalomyelitis.

Posted on by

Research in Pharmaceutical Sciences“T helper (Th)-17 mediate inflammation in both peripheral tissues and the central nervous system. Signal transducer and activator of transcription factor3 (STAT3) is required for Th-cell pathogenicity and its activation in the brain has been demonstrated during the acute phase of experimental autoimmune encephalomyelitis (EAE) through the mammalian target of rapamycin (mTOR) signaling. Rapamycin (RAPA), an inhibitor of mTOR, can drive Forkhead box P3 (FOXP3+) induction as a regulatory factor.

The aim of this study was to determine the effects of hemp seed/evening primrose oils (HSO/EPO) supplement on the expression of FOXP3+, STAT3, and interleukin (IL)-17 genes in EAE lymph nodes.

EAE was induced by myelin oligodendrocyte glycoprotein peptide in mice, and then the mice were assigned to three treatment groups compared to two control groups (EAE and naive). The histological findings of the spinal cord were evaluated. To determine the expression of FOXP3+, STAT3, and IL-17 genes in the lymphocytes, qRT-PCR was used.

Our results showed that EAE severity was reduced in HSO/EPO mice by reducing the expression of STAT3 and IL-17 genes and increasing the expression of FOXP3+ gene, which was confirmed by slight inflammation in the spinal cord. Histological findings showed a significant improvement in the HSO/EPO group.

Our findings suggest that the HSO/EPO treatment can be used to ameliorate the demyelination of spinal cord, which was confirmed by immunological and histological findings.”

https://www.ncbi.nlm.nih.gov/pubmed/31620191

http://www.rpsjournal.net/article.asp?issn=1735-5362;year=2019;volume=14;issue=2;spage=146;epage=154;aulast=Rezapour%2DFirouzi

The endocannabinoid system: Novel targets for treating cancer induced bone pain.

Posted on by

Biomedicine & Pharmacotherapy“Treating Cancer-induced bone pain (CIBP) continues to be a major clinical challenge and underlying mechanisms of CIBP remain unclear.

Recently, emerging body of evidence suggested the endocannabinoid system (ECS) may play essential roles in CIBP. Here, we summarized the current understanding of the antinociceptive mechanisms of endocannabinoids in CIBP and discussed the beneficial effects of endocannabinoid for CIBP treatment.

Targeting non-selective cannabinoid 1 receptors or selective cannabinoid 2 receptors, and modulation of peripheral AEA and 2-AG, as well as the inhibition the function of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have produced analgesic effects in animal models of CIBP.

Management of ECS therefore appears to be a promising way for the treatment of CIBP in terms of efficacy and safety. Further clinical studies are encouraged to confirm the possible translation to humans of the very promising results already obtained in the preclinical studies.”

https://www.ncbi.nlm.nih.gov/pubmed/31627091

“Thus, cannabinoids may be clinically useful for treating chronic pain and CIBP.”

https://www.sciencedirect.com/science/article/pii/S075333221933731X?via%3Dihub

The Endocannabinoid System as a Window Into Microglial Biology and Its Relationship to Autism.

Posted on by

Image result for frontiers in cellular neuroscience“Microglia are the resident, innate immune cells of the central nervous system (CNS) and are critical in managing CNS injuries and infections. Microglia also maintain CNS homeostasis by influencing neuronal development, viability, and function. However, aberrant microglial activity and phenotypes are associated with CNS pathology, including autism spectrum disorder (ASD). Thus, improving our knowledge of microglial regulation could provide insights into the maintenance of CNS homeostasis as well as the prevention and treatment of ASD.

Control of microglial activity is in part overseen by small, lipid-derived molecules known as endogenous cannabinoids (endocannabinoids). Endocannabinoids are one component of the endocannabinoid system (ECS), which also includes the enzymes that metabolize these ligands, in addition to cannabinoid receptor 1 (CB1) and 2 (CB2).

Interestingly, increased ECS signaling leads to an anti-inflammatory, neuroprotective phenotype in microglia. Here, we review the literature and propose that ECS signaling represents a largely untapped area for understanding microglial biology and its relationship to ASD, with special attention paid to issues surrounding the use of recreational cannabis (marijuana). We also discuss major questions within the field and suggest directions for future research.”

https://www.ncbi.nlm.nih.gov/pubmed/31619967

“Microglial activity can be modulated by eCB signaling, which makes the ECS a potentially forceful tool in the prevention and management of CNS dysfunction.”

https://www.frontiersin.org/articles/10.3389/fncel.2019.00424/full