Cannabinoid Receptor Type 1 Agonist ACEA Improves Cognitive Deficit on STZ-Induced Neurotoxicity Through Apoptosis Pathway and NO Modulation.

“The cannabinoid system has the ability to modulate cellular and molecular mechanisms, including excitotoxicity, oxidative stress, apoptosis, and inflammation, acting as a neuroprotective agent, by its relationship with signaling pathways associated to the control of cell proliferation, differentiation, and survival. Recent reports have raised new perspectives on the possible role of cannabinoid system in neurodegenerative diseases like Alzheimer disease’s (AD).

Our study has demonstrated a participation of the cannabinoid system in cellular survival, involving the CB1 receptor, which occurs by positive regulation of the anti-apoptotic proteins, suggesting the participation of this system in neurodegenerative processes. Our data suggest that the cannabinoid system is an interesting therapeutic target for the treatment of neurodegenerative diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/30607903

https://link.springer.com/article/10.1007%2Fs12640-018-9991-2

Tempering aversive/traumatic memories with cannabinoids: a review of evidence from animal and human studies.

“Aversive learning and memory are essential to cope with dangerous and stressful stimuli present in an ever-changing environment. When this process is dysfunctional, however, it is associated with posttraumatic stress disorder (PTSD). The endocannabinoid (eCB) system has been implicated in synaptic plasticity associated with physiological and pathological aversive learning and memory.

OBJECTIVE AND METHODS:

The objective of this study was to review and discuss evidence on how and where in the brain genetic or pharmacological interventions targeting the eCB system would attenuate aversive/traumatic memories through extinction facilitation in laboratory animals and humans. The effect size of the experimental intervention under investigation was also calculated.

RESULTS:

Currently available data indicate that direct or indirect activation of cannabinoid type-1 (CB1) receptor facilitates the extinction of aversive/traumatic memories. Activating CB1 receptors around the formation of aversive/traumatic memories or their reminders can potentiate their subsequent extinction. In most cases, the effect size has been large (Cohen’s d ≥ 1.0). The brain areas responsible for the above mentioned effects include the medial prefrontal cortex, amygdala, and/or hippocampus. The potential role of cannabinoid type-2 (CB2) receptors in extinction learning is now under investigation.

CONCLUSION:

Drugs augmenting the brain eCB activity can temper the impact of aversive/traumatic experiences by diverse mechanisms depending on the moment of their administration. Considering the pivotal role the extinction process plays in PTSD, the therapeutic potential of these drugs is evident. The sparse number of clinical trials testing these compounds in stress-related disorders is a gap in the literature that needs to be addressed.”

https://www.ncbi.nlm.nih.gov/pubmed/30604182

https://link.springer.com/article/10.1007%2Fs00213-018-5127-x

Knowledge, Attitudes, and Perceptions of Cannabinoids in the Dermatology Community

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“Recent research has identified potential uses of cannabinoids in dermatology, including psoriasis, atopic dermatitis, and wound healing.

This study examined dermatology providers’ knowledge, attitudes, and perceptions on therapeutic cannabinoids using a 20-question online survey.

The response rate was 21% (n=531). Most responders thought cannabinoids should be legal for medical treatment (86%). Nearly all (94%) believed it is worthwhile to research dermatologic uses of cannabinoids. 55% reported at least one patient-initiated discussion about cannabinoids in the last year. Yet, 48% were concerned about a negative stigma when proposing cannabinoid therapies to patients. While most responders (86%) were willing to prescribe an FDA-approved cannabinoid as a topical treatment, fewer (71%) were willing to prescribe an oral form. 64% of respondents did not know that cannabidiol is not psychoactive and 29% did not know that tetrahydrocannabinol is psychoactive.

 

CONCLUSIONS:

Dermatology providers are interested in prescribing cannabinoids and patients are speaking about cannabinoids with their dermatologists. However, providers’ fund of knowledge on this subject is lacking. These results highlight the need for further education and research to detangle the dermatologic benefits and risks of cannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/30586258

“Cannabinoid system in the skin – a possible target for future therapies in dermatology.” https://www.ncbi.nlm.nih.gov/pubmed/19664006

Medical Cannabis in the Skilled Nursing Facility: A Novel Approach to Improving Symptom Management and Quality of Life.

Journal of the American Medical Directors Association Home

“Throughout the millennia, the cannabis plant has been utilized as a recognized therapy for pain relief and symptom management.

Following the Prohibition-era stigmatization and criminalization of all forms of cannabis of the early 20th century, there has been a recent nationwide and worldwide resurgence in interest and use of the cannabinoid compounds extracted from the cannabis plant, that is, medical cannabis.

Although at the Federal level, cannabis remains a Schedule I substance, 31 states have already decriminalized possession and use of medical cannabis for specific diagnoses.

It is noteworthy that many of these indicated diagnoses are prevalent in the skilled nursing facility (SNF). This creates regulatory concerns as SNFs and other healthcare facilities must maintain compliance with Federal laws, while balancing the individual resident’s rights to utilize medical cannabis where indicated.

The authors developed an innovative program that affords their residents the ability to participate in a state-approved medical cannabis program while remaining compliant with Federal law. As medical cannabis use becomes more widespread and accepted, clinicians providing medical care in healthcare facilities will encounter residents who may benefit from and request this alternative therapy.

Studies examining older adults that are utilizing medical cannabis legally have demonstrated significant decreases in prescription medication use, most notably a reduction in opioid analgesic usage. As such, medical cannabis should be viewed as an additional option in the clinician’s toolbox of therapeutic interventions for symptom relief.”

https://www.ncbi.nlm.nih.gov/pubmed/30580820

https://www.jamda.com/article/S1525-8610(18)30662-5/fulltext

Attenuation Effect of Cannabinoid Type 1 Receptor Activation on Methamphetamine-Induced Neurodegeneration and Locomotion Impairments among Male Rats.

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“A number of neuroimaging studies on human addicts have revealed that abuse of Methamphetamine (METH) can induce neurodegenerative changes in various brain regions like the cerebral cortex and cerebellum. Although the underlying mechanisms of METH-induced neurotoxicity have been studied, the cellular and molecular mechanisms of METH-induced neurotoxicity remain to be clarified.

Previous studies implicated that cannabinoid type 1 receptors (CB1Rs) exert neuroprotective effects on several models of cerebral toxicity, but their role in METH-induced neurotoxicity has been rarely investigated. Moreover, the cerebellum was considered as a potential target to evaluate the effects of cannabinoids on locomotion activity as the CB1Rs are most widely distributed in the molecular layer of cerebellum. Therefore, the present study was carried out to evaluate whether neurodegeneration induced in the cerebellum tissue implicated in locomotion deficit induced by METH.

FINDINGS:

The results of the present study demonstrated that repeated exposure to METH increased cerebellar degeneration level as compared to the saline and dimethyl sulfoxide (DMSO) groups. In addition, METH-treated rats showed hyperactivity as compared to the saline and DMSO groups. Pretreatment with WIN significantly attenuated neurodegeneration and hyperactivity induced by METH.

CONCLUSION:

The findings of this study provided evidence that CB1Rs may serve as a therapeutic strategy for attenuation of METH-induced locomotor deficits.”

https://www.ncbi.nlm.nih.gov/pubmed/30574283

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294485/

Cannabis for cancer – illusion or the tip of an iceberg: a review of the evidence for the use of Cannabis and synthetic cannabinoids in oncology.

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“A flowering plant of variegated ingredients and psychoactive qualities, Cannabis has long been used for medicinal and recreational purposes.

Regulatory approvals have been gained across a broad range of palliative and therapeutic indications, and in some cases, included in standard treatment guidelines.

Areas covered: The use of Cannabis and cannabinoid-based-medicines in oncology is summarized in this article. Cannabinoids were classified according to natural and synthetic subtypes and their mechanisms of action expounded. The variability of available products is discussed in the clinical context and data regarding chemotherapy-induced nausea and vomiting, cancer-related pain, anorexia, insomnia and anxiety are presented.

Moreover, immunological and antineoplastic effects in preclinical and clinical trials are addressed. Concepts such as synergism or opposition with conventional treatment modalities, sequence of administration and dosage, molecular cross-talk and malignancy-cannabinoid congruence, are explored. Finally, side-effects, limitations in trial design and legislation barriers are related.

Expert opinion: Sufficient evidence supports use of Cannabis for palliative indications in oncology, however, patients should be carefully selected, guided and followed. Promising research suggests potent antineoplastic activity, but more data must be accrued before conclusions can be drawn.”

https://www.ncbi.nlm.nih.gov/pubmed/30572744

https://www.tandfonline.com/doi/abs/10.1080/13543784.2019.1561859?journalCode=ieid20

Cannabinoid receptor expression in estrogen-dependent and estrogen-independent endometrial cancer.

Publication Cover

“The lack of good diagnostic/prognostic biomarkers and the often late presentation of endometrial cancer (EC) hinders the amelioration of the morbidity and mortality rates associated with this primarily estrogen-driven disease, a disease that is becoming more prevalent in the population.

Previous studies on the expression of the classical cannabinoid receptors, CB1 and CB2, suggest these could provide good diagnostic/prognostic biomarkers for EC but those observations have been contradictory. In this study, we sought to resolve the inconsistency of CB1 and CB2 expression levels in different EC studies.

To that end, we used qRT-PCR and immunohistochemistry (IHC) for CB1 and CB2 in endometrial biopsies from women with or without EC and found that transcript levels for both CB1 and CB2 were significantly decreased by 90 and 80%, respectively in EC. These observations were supported by histomorphometric studies where CB1 and CB2 staining intensity was decreased in all types of EC.

These data suggest that the loss of both types of CB receptors is potentially involved in the development of or progression of EC and that CB1 and CB2 receptor expression could serve as useful histological markers and therapeutic targets in the treatment of or prevention of EC.”

https://www.ncbi.nlm.nih.gov/pubmed/30569804

https://www.tandfonline.com/doi/abs/10.1080/10799893.2018.1531890?journalCode=irst20

Effects of cannabidiol in males and females in two different rat models of depression.

Physiology & Behavior

“The current study explores the therapeutic potential of Cannabidiol (CBD), a compound in the Cannabis plant, using both sexes of 2 “depressive-like” genetic models, Wistar Kyoto (WKY) and Flinders Sensitive Line (FSL) rats. Rats ingested CBD (30 mg/kg) orally. In the saccharin preference test, following a previous report of a pro-hedonic effect of CBD in male WKY, we now found similar results in female WKY. CBD also decreased immobility in the forced swim test in males (both strains) and in female WKY. These findings suggest a role for CBD in treating mental disorders with prominent symptoms of helplessness and anhedonia.”

https://www.ncbi.nlm.nih.gov/pubmed/30571957

https://www.sciencedirect.com/science/article/abs/pii/S0031938418307509?via%3Dihub

[Neonatal hypoxia-ischemia: cellular and molecular brain damage and therapeutic modulation of neurogenesis].

 

 

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“Perinatal asphyxia remains a major cause of both mortality and neurological morbidity. Neonatal encephalopathy affects to 1-3/1,000 newborns, leading to significant brain damage and childhood disability.

The only standard therapy is moderate hypothermia, whose efficacy, despite proved, is limited, being partially effective.

The use of therapeutic agents such as erythropoietin and cannabinoids and mesenchymal stem cells have shown promising results in experimental models of perinatal asphyxia, being able of modulate neurogenesis, neuronal plasticity and neuroreparation processes after hypoxic-ischemic brain injury.”

https://www.ncbi.nlm.nih.gov/pubmed/30560986

Antimicrobial potential of endocannabinoid and endocannabinoid-like compounds against methicillin-resistant Staphylococcus aureus.

 Scientific Reports

“Infections caused by antibiotic-resistant strains of Staphylococcus aureus have reached epidemic proportions globally. Staphylococcal biofilms are associated with increased antimicrobial resistance and are generally less affected by host immune factors. Therefore, there is an urgent need for novel agents that not only aim at multidrug-resistant pathogens, but also ones that will act as anti biofilms. In the present study, we investigated the antimicrobial activity of the endocannabinoid (EC) anandamide (AEA) and the endocannabinoid-like (EC-like), arachidonoyl serine (AraS) against methicillin resistant S. aureus strains (MRSA). We observed a strong inhibition of biofilm formation of all tested MRSA strains as well as a notable reduction of metabolic activity of pre-formed MRSA biofilms by both agents. Moreover, staphylococcal biofilm-associated virulence determinants such as hydrophobicity, cell aggregation and spreading ability were altered by AEA and AraS. In addition, the agents were able to modify bacterial membrane potential. Importantly, both compounds prevent biofilm formation by altering the surface of the cell without killing the bacteria. Therefore, we propose that EC and EC-like compounds may act as a natural line of defence against MRSA or other antibiotic resistant bacteria. Due to their anti biofilm action these agents could also be a promising alternative to antibiotic therapeutics against biofilm-associated MRSA infections.”

https://www.ncbi.nlm.nih.gov/pubmed/30523307

https://www.nature.com/articles/s41598-018-35793-7

“Antimicrobial activity of Cannabis sativa, Thuja orientalis and Psidium guajava leaf extracts against methicillin-resistant Staphylococcus aureus.”  https://www.ncbi.nlm.nih.gov/pubmed/30120078

“Antimicrobial Activity of Cannabis sativa L.”  https://www.scirp.org/journal/PaperInformation.aspx?PaperID=18123

“Characterization and antimicrobial activity of essential oils of industrial hemp varieties (Cannabis sativa L.).” https://www.ncbi.nlm.nih.gov/pubmed/19969046

“Antimicrobial studies of the leaf of cannabis sativa L.”   https://www.ncbi.nlm.nih.gov/pubmed/16414764