Special Considerations and Assessment in Patients with Multiple Sclerosis.

Physical Medicine and Rehabilitation Clinics of North America

“Multiple sclerosis is a progressive autoimmune neurologic disorder that may affect any region of the central nervous system. Spasticity in patients with multiple sclerosis can be debilitating and detrimental to the function and quality of life of patients. Treatment options include oral medications, chemodenervation, physical therapy, and modalities.

Cannabinoids in the form of a delta-9-tetrahydrocannabinol/cannabidiol oro-mucosal spray has been shown to be effective in addressing spasticity in multiple sclerosis.

Successful treatment of spasticity will be integrated, multimodal, and individualized.”

https://www.ncbi.nlm.nih.gov/pubmed/30626509

https://www.sciencedirect.com/science/article/pii/S1047965118307617?via%3Dihub

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Expression and Preparation of a G-Protein-Coupled Cannabinoid Receptor CB2 for NMR Structural Studies.

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“Cannabinoid receptor type II, or CB2 , is an integral membrane protein that belongs to a large class of G-protein-coupled receptors (GPCR)s. CB2 is a part of the endocannabinoid system, which plays an important role in the regulation of immune response, inflammation, and pain.

Information about the structure and function of CB2 is essential for the development of specific ligands targeting this receptor.

We present here a methodology for recombinant expression of CB2 and its stable isotope labeling, purification, and reconstitution into liposomes, in preparation for its characterization by nuclear magnetic resonance (NMR).

Correctly folded, functional CB2 labeled with [13 C,15 N]tryptophan or uniformly labeled with 13 C and 15 N is expressed in a medium of defined composition, under controlled aeration, pH, and temperature conditions.

The receptor is purified by affinity chromatography and reconstituted into lipid bilayers in the form of proteoliposomes suitable for analysis by NMR spectroscopy.”

https://www.ncbi.nlm.nih.gov/pubmed/30624864

https://currentprotocols.onlinelibrary.wiley.com/doi/abs/10.1002/cpps.83

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Medical Cannabis Users’ Comparisons between Medical Cannabis and Mainstream Medicine.

 Publication Cover“An evidence-based approach is needed to shape policies and practices regarding medical cannabis, thereby reducing harm and maximizing benefits to individuals and society.

This project assesses attitudes towards and utilization of medical cannabis and the mainstream healthcare system among medical cannabis users. The research team administered brief hard copy surveys to 450 adults attending an annual public event advocating for cannabis law reform.

Among usable responses (N = 392), the majority (78%) reported using cannabis to help treat a medical or health condition.

Medical cannabis users reported a greater degree of use of medical cannabis and a greater degree of trust in medical cannabis compared to mainstream healthcare.

In comparison to pharmaceutical drugs, medical cannabis users rated cannabis better on effectiveness, side effects, safety, addictiveness, availability, and cost.

Due to the medical use of cannabis, 42% stopped taking a pharmaceutical drug and 38% used less of a pharmaceutical drug.

A substantial proportion (30%) reported that their mainstream healthcare provider did not know that they used medical cannabis.

Other issues identified included lack of access to mainstream healthcare, self-initiated treatment of health issues, little knowledge of psychoactive content, and heavy cannabis use.”

https://www.ncbi.nlm.nih.gov/pubmed/30616501

https://www.tandfonline.com/doi/abs/10.1080/02791072.2018.1563314?journalCode=ujpd20

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The effects of cannabinoids on the endocrine system.

“Cannabinoids are the derivatives of the cannabis plant, the most potent bioactive component of which is tetrahydrocannabinol (THC). The most commonly used drugs containing cannabinoids are marijuana, hashish, and hashish oil.

These compounds exert their effects via interaction with the cannabinoid receptors CB1 and CB2. Type 1 receptors (CB1) are localised mostly in the central nervous system and in the adipose tissue and many visceral organs, including most endocrine organs. Type 2 cannabinoid receptors (CB2) are positioned in the peripheral nervous system (peripheral nerve endings) and on the surface of the immune system cells.

Recently, more and more attention has been paid to the role that endogenous ligands play for these receptors, as well as to the role of the receptors themselves. So far, endogenous cannabinoids have been confirmed to participate in the regulation of food intake and energy homeostasis of the body, and have a significant impact on the endocrine system, including the activity of the pituitary gland, adrenal cortex, thyroid gland, pancreas, and gonads.

Interrelations between the endocannabinoid system and the activity of the endocrine system may be a therapeutic target for a number of drugs that have been proved effective in the treatment of infertility, obesity, diabetes, and even prevention of diseases associated with the cardiovascular system.”

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Blood-brain barrier disturbances in diabetes-associated dementia: Therapeutic potential for cannabinoids.

Pharmacological Research

“Type-2 diabetes (T2D) increases the risk of dementia by ˜5-fold, however the mechanisms by which T2D increases dementia risk remain unclear. Evidence suggests that the heightened inflammation and oxidative stress in T2D may lead to disruption of the blood-brain barrier (BBB), which precedes premature cognitive decline. Studies show that vascular-targeted anti-inflammatory treatments protect the BBB by attenuating neuroinflammation, and in some studies attenuate cognitive decline. Yet, this potential pathway is understudied in T2D-associated cognitive impairment.

In recent years, therapeutic potential of cannabinoids has gained much interest. The two major cannabinoids, cannabidiol and tetrahydrocannabinol, exert anti-inflammatory and vascular protective effects, however few studies report their potential for reversing BBB dysfunction, particularly in T2D. Therefore, in this review, we summarize the current findings on the role of BBB dysfunction in T2D-associated dementia and consider the potential therapeutic use of cannabinoids as a protectant of cerebrovascular BBB protection.”

https://www.ncbi.nlm.nih.gov/pubmed/30616019

https://www.sciencedirect.com/science/article/abs/pii/S1043661818314634?via%3Dihub

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Successful cannabis derivatives oromucosal spray therapy for a seronegative stiff-person syndrome: a case report.

 

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“Stiff-person syndrome (SPS) is an uncommon and disabling disorder characterised by progressive rigidity and episodic painful spasms involving axial and limb musculature.

The authors report a patient with seronegative SPS successfully treated with THC-CBD oromucosal spray.

In conclusion cannabinoids can be a therapeutic option to treat spasticity associated with neurological diseases such as stiff-person syndrome.

Our patient’s quality of life has improved remarkably although more information is needed about this particular use.”

https://ejhp.bmj.com/content/19/2/219.2?fbclid=IwAR0PVg0GRQDmu_tXu_vYJmmKHo2MGnJ_EsnkdsR4HE7deFVUtqhAxziHQBc

http://dx.doi.org/10.1136/ejhpharm-2012-000074.352

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Adenosine A2A-Cannabinoid CB1 Receptor Heteromers in the Hippocampus: Cannabidiol Blunts Δ9-Tetrahydrocannabinol-Induced Cognitive Impairment

“At present, clinical interest in the plant-derived cannabinoid compound cannabidiol (CBD) is rising exponentially, since it displays multiple therapeutic properties. In addition, CBD can counteract the undesirable effects of the psychoactive cannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) that hinder clinical development of cannabis-based therapies. Here, by combining in vivo and complementary molecular techniques, we demonstrate for the first time that CBD blunts the Δ9-THC-induced cognitive impairment in an adenosine A2A receptor (A2AR)-dependent manner. Overall, these data provide new evidence regarding the mechanisms of action of CBD and the nature of A2AR-CB1R interactions in the brain.”

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The Cerebellum, THC, and Cannabis Addiction: Findings from Animal and Human Studies.

“Despite being legally scheduled as a drug with high harm potential and no therapeutic utility in countries like the USA, evidence shows otherwise and legislative changes and reinterpretations of existing ambiguous laws make this drug increasingly available by legal means.”

https://www.ncbi.nlm.nih.gov/pubmed/30610540

https://link.springer.com/article/10.1007%2Fs12311-018-0993-7

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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

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Gender and the Politics of Marijuana

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“The objectives of this study were to understand why, even though women are more liberal than men on a broad range of issues, when it comes to the increasingly prominent issue of marijuana legalization, the direction of the gender gap is reversed, with women more conservative than men.

We find that women’s role as mothers cannot explain this gap, and that mothers are in fact no different from those without children in terms of their support for marijuana policy, as well as their reported use of marijuana. The greater religiosity of women does play a prominent role in the gender gap on marijuana policy, but does not account for the full difference of opinion between women and men. Our findings suggest that men’s greater propensity relative to women to use marijuana is a major driver behind the gender gap.

Conclusions

Not only are attitudes on marijuana legalization likely to continue to liberalize, but as marijuana legalization and marijuana use become normalized, rather than viewed as immoral and dangerous behavior, the existing gender gap should shrink.”

https://onlinelibrary.wiley.com/doi/abs/10.1111/ssqu.12558

“Drug use, religion explain ‘reverse gender gap’ on marijuana”  https://www.sciencedaily.com/releases/2018/11/181126134251.htm?fbclid=IwAR072Y-SGz0PElUfNtQCTe56kzRC5ZBDoBMmlW2oTagAOy-IOcT_8UxVCEI

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