Category Archives: Uncategorized

No smoke, no fire: What the initial literature suggests regarding vapourized cannabis and respiratory risk

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“Given current limitations in developing an inhalant alternative for delivering cannabis medication, smoked marijuana remains the most readily accessible form of cannabis among medicinal users…

Cannabis actually served as an asthma treatment in the 1800s and, perhaps, in ancient times…

Informed health care professionals may consider making recommendations to their medicinal cannabis patients for vapourization of the plant, particularly for those who want the rapid relief that oral administration fails to provide.

It is not our intention to encourage inappropriate use of the plant, but to increase safety for those who choose to use it.

Vapourization of cannabis is likely less harmful than smoking.

Preliminary findings do support the idea that vapourization is an improvement over smoking.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456813/

Endocannabinoids drive the acquisition of an alternative phenotype in microglia.

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“The ability of microglia to acquire diverse states of activation, or phenotypes, reflects different features that are determinant for their contribution to homeostasis in the adult CNS, and their activity in neuroinflammation, repair or immunomodulation.

Despite the widely reported immunomodulatory effects of cannabinoids in both the peripheral immune system and the CNS, less is known about how the endocannabinoid signaling system (eCBSS) influence the microglial phenotype.

The general aim of the present study was to investigate the role of endocannabinoids in microglia polarization by using microglia cell cultures.

We show that alternative microglia (M2a) and acquired deactivated microglia (M2c) exhibit changes in the eCB machinery that favor the selective synthesis of 2-AG and AEA, respectively.

Once released, these eCBs might be able to act through CB1 and/or CB2 receptors in order to influence the acquisition of an M2 phenotype.

We present three lines of evidence that the eCBSS is critical for the acquisition of the M2 phenotype: (i) M2 polarization occurs on exposure to the two main endocannabinoids 2-AG and AEA in microglia cultures; (ii)cannabinoid receptor antagonists block M2 polarization; and, (iii) M2 polarization is dampened in microglia from CB2 receptor knockout mice.

Taken together, these results indicate the interest of eCBSS for the regulation of microglial activation in normal and pathological conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/26086345

Medical use of cannabis: an addiction medicine perspective.

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“The use of cannabis for medical purposes, evident throughout history, has become a topic of increasing interest. Yet on the present medical evidence, cannabis-based treatments will only be appropriate for a small number of people in specific circumstances. Experience with cannabis as a recreational drug, and with use of psychoactive drugs that are prescribed and abused, should inform harm reduction in the context of medical cannabis.”  http://www.ncbi.nlm.nih.gov/pubmed/26059881

“A safer alternative: Cannabis substitution as harm reduction.”  http://www.ncbi.nlm.nih.gov/pubmed/25919477

Pharmacologic effects of cannabidiol on acute reperfused myocardial infarction in rabbits: evaluated with 3.0T cardiac magnetic resonance imaging and histopathology.

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“Cannabidiol (CBD) has anti-inflammatory effects.

We explored its therapeutic effects on cardiac ischemia-reperfusion injury with an experimental imaging platform…

Compared to controls, CBD treatment improved systolic wall thickening, significantly increased blood flow in the AAR, significantly decreased microvascular obstruction, increased the PDR by 1.7-fold, lowered the AMI-core/AAR ratio, and increased the MSI.

These improvements were associated with reductions in serum cTnI, cardiac leukocyte infiltration, and myocellular apoptosis.

Thus, CBD therapy reduced AMI size and facilitated restoration of LV function.

We demonstrated that this experimental platform has potential theragnostic utility.”

http://www.ncbi.nlm.nih.gov/pubmed/26065843

Neurobiological Interactions Between Stress and the Endocannabinoid System.

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“Stress affects a constellation of physiological systems in the body and evokes a rapid shift in many neurobehavioral processes.

A growing body of work indicates that the endocannabinoid (eCB) system is an integral regulator of the stress response.

In the current review, we discuss the evidence to date that demonstrates stress-induced regulation of eCB signaling and the consequential role changes in eCB signaling play with respect to many of the effects of stress.

Across a wide array of stress paradigms, studies have generally shown that stress evokes bidirectional changes in the two eCB molecules, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), with stress exposure reducing AEA levels and increasing 2-AG levels.

Additionally, in almost every brain region examined, exposure to chronic stress reliably causes a down-regulation or loss of cannabinoid type 1 (CB1) receptors.

With respect to the functional role of changes in eCB signaling during stress, studies have demonstrated that the decline in AEA appears to contribute to the manifestation of the stress response, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and increases in anxiety behavior, while the increased 2-AG signaling contributes to termination and adaptation of the HPA axis, as well as potentially contributing to changes in pain perception and synaptic plasticity.

More so, translational studies have shown that eCB signaling in humans regulates many of the same domains and appears to be a critical component of stress regulation, and impairments in this system may be involved in the vulnerability to stress-related psychiatric conditions, such as depression and post-traumatic stress disorder.

Collectively, these data create a compelling argument that eCB signaling is an important regulatory system in the brain that largely functions to buffer against many of the effects of stress and that dynamic changes in this system contribute to different aspects of the stress response.”

http://www.ncbi.nlm.nih.gov/pubmed/26068727

In vivo inflammation imaging using a CB2R-targeted near infrared fluorescent probe.

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“Chronic inflammation is considered as a critical cause of a host of disorders, such as cancer, rheumatoid arthritis, atherosclerosis, and neurodegenerative diseases…

Imaging tools that can specifically target inflammation are therefore important to help reveal the role of inflammation in disease progression, and allows for developing new therapeutic strategies to ultimately improve patient care.

The purpose of this study was to develop a new in vivo inflammation imaging approach by targeting the cannabinoid receptor type 2 (CB2R), an emerging inflammation biomarker, using a unique near infrared (NIR) fluorescent probe…

The combined evidence indicates that NIR760-mbc94 is a promising inflammation imaging probe. Moreover, in vivo CB2R-targeted fluorescence imaging may have potential in the study of inflammation-related diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/26069858

Does cannabis affect dopaminergic signaling in the human brain? A systematic review of evidence to date.

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“While abnormalities in multiple pathways may lead to schizophrenia, an abnormality in dopamine neurotransmission is considered to be the final common abnormality.

One would thus expect cannabis use to be associated with dopamine signaling alterations.

This is the first systematic review of all studies, both observational as well as experimental, examining the acute as well as chronic effect of cannabis or its main psychoactive ingredient, THC, on the dopamine system in man…

In man, there is as yet little direct evidence to suggest that cannabis use affects acute striatal dopamine release or affects chronic dopamine receptor status in healthy human volunteers. ”

http://www.ncbi.nlm.nih.gov/pubmed/26068702

Medical Marijuana in Pediatric Neurological Disorders.

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“Marijuana and marijuana-based products have been used to treat medical disease.

Recently, derivatives of the plant have been separated or synthesized to treat various neurological disorders, many of them affecting children.

Unfortunately, data are sparse in regard to treating children with neurologic illness. Therefore, formal conclusions about the potential efficacy, benefit, and adverse effects for these products cannot be made at this time.

Further robust research using strong scientific methodology is desperately needed to formally evaluate the role of these products in children.”

http://www.ncbi.nlm.nih.gov/pubmed/26060306

“The endocannabinoid-CB receptor system: Importance for development and in pediatric disease.”  http://www.ncbi.nlm.nih.gov/pubmed/15159678

Localization of an endocannabinoid system in the hypophysial pars tuberalis and pars distalis of man.

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“The hypophysial pars tuberalis (PT) acts as an important interface between neuroendocrine brain centers (hypothalamus, pineal organ) and the pars distalis (PD) of the hypophysis.

Recently, we have identified an endocannabinoid system in the PT of hamsters and provided evidence that 2-arachidonoylglycerol is a messenger molecule that appears to play an essential role in seasonal reproduction and prolactin release by acting on the cannabinoid receptors in the PD.”

“An endocannabinoid system is localized to the hypophysial pars tuberalis of Syrian hamsters and responds to photoperiodic changes.”  http://www.ncbi.nlm.nih.gov/pubmed/20165884

“We now demonstrate the enzymes involved in endocannabinoid synthesis and degradation, namely sn-1-selective diacylglycerol lipase α, N-acylphosphatidylethanolamine-specific phospholipase D, and monoacylglycerol lipase, in the PT of man by means of immunohistochemistry.

High-performance liquid chromatography coupled with tandem mass spectrometry revealed 2-arachidonoylglycerol and other endocannabinoids in the human PT.

Furthermore, we detected the expression of the cannabinoid receptor 1 (CB1), a primary receptor for endocannabinoids, in the PD.

Our data thus indicate that the human PT comprises an endocannabinoid system, and that corticotrophs and FS-cells are the main target cells for endocannabinoids.

The functional significance of this newly discovered pathway remains to be elucidated in man; it might be related to the control of stress responses and/or reflect a remnant seasonal control of hypophysial hormonal secretion.”

http://www.ncbi.nlm.nih.gov/pubmed/20957495

The rat pineal gland comprises an endocannabinoid system.

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“In the mammalian pineal gland, the rhythm in melatonin biosynthesis depends on the norepinephrine (NE)-driven regulation of arylalkylamine N-acetyltransferase (AANAT), the penultimate enzyme of melatonin biosynthesis.

A recent study showed that phytocannabinoids like tetrahydrocannabinol reduce AANAT activity and attenuate NE-induced melatonin biosynthesis in rat pineal glands, raising the possibility that an endocannabinoid system is present in the pineal gland…

In summary, the pineal gland comprises indispensable compounds of the endocannabinoid system indicating that endocannabinoids may be involved in the control of pineal physiology.”

http://www.ncbi.nlm.nih.gov/pubmed/18554250