Monthly Archives: September 2017

Mechanisms of action of cannabidiol in adoptively transferred experimental autoimmune encephalomyelitis.

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“Cannabidiol (CBD) is one of the most important compounds in Cannabis sativa, lacks psychotropic effects, and possesses a high number of therapeutic properties including the amelioration of experimental autoimmune encephalomyelitis (EAE).

The aim of this study was to analyse the relative efficacy of CBD in adoptively transferred EAE (at-EAE), a model that allows better delineation of the effector phase of EAE.

Preventive intraperitoneal treatment with CBD ameliorated the clinical signs of at-EAE. CBD markedly improved the clinical signs of at-EAE and reduced infiltration, demyelination and axonal damage. The CBD-mediated decrease in the viability of encephalitogenic cells involves ROS generation, apoptosis and a decrease in IL-6 production and may contribute to the therapeutic effect of this compound.”

https://www.ncbi.nlm.nih.gov/pubmed/28867485

http://www.sciencedirect.com/science/article/pii/S0014488617302212

Cannabis use among two national samples of Aboriginal and Torres Strait Islander tobacco smokers.

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Drug and Alcohol Review

“There is a concern that cannabis use is an important barrier to reducing Aboriginal and Torres Strait Islander smoking.

We investigate the associations of cannabis use and tobacco smoking and quitting in two large national samples.

We did not find consistent evidence in this setting that cannabis use is an obstacle to quitting tobacco smoking.”

https://www.ncbi.nlm.nih.gov/pubmed/28868760

http://onlinelibrary.wiley.com/doi/10.1111/dar.12609/abstract

Parent use of cannabis for intractable pediatric epilepsy: Everyday empiricism and the boundaries of scientific medicine.

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Social Science & Medicine

“Cannabis is an increasingly sought-after remedy for US children with intractable (biomedically uncontrollable) epilepsy. However, like other complementary-alternative medicine (CAM) modalities, and particularly as a federally illegal, stigmatized substance, it is unsanctioned by mainstream medicine. Parents are largely on their own when it comes to learning about, procuring, dispensing, and monitoring treatments. Exploring how they manage is crucial to better assist them. Moreover, it can illuminate how ‘research’ done on the ground by laypeople variously disrupts and reinforces lay-expert and science-non-science divides. To those ends, in 2016, 25 Southern California parents who used, had used, or sought to use cannabis pediatrically for epilepsy/seizures were interviewed regarding their evidentiary standards, research methods, and aims when trying the drug. Parents generally described their work as experimentation; they saw their efforts as adhering to authorized scientific practices and standards, and as contributing to the authorized medical cannabis knowledge base. Findings subverted assumptions, based on an outdated stereotype of CAM, that cannabis-using parents do not believe in biomedicine. Indeed, parents’ desire for their children’s biomedical demarginalization, combined with biomedical dependency and a high caregiver burden, fueled a collaborative stance. Implications for understanding the boundaries of science are explored, as are norms for parent agency as ill children’s care managers, radicalization among people affected by contested illnesses, and the future of ‘medical marijuana.'”

https://www.ncbi.nlm.nih.gov/pubmed/28865255

http://www.sciencedirect.com/science/article/pii/S0277953617304756?via%3Dihub

 

Systematic Review of the Costs and Benefits of Prescribed Cannabis-Based Medicines for the Management of Chronic Illness: Lessons from Multiple Sclerosis.

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PharmacoEconomics

“Cannabis-based medicines (CBMs) may offer relief from symptoms of disease; however, their additional cost needs to be considered alongside their effectiveness. We sought to review the economic costs and benefits of prescribed CBMs in any chronic illness, and the frameworks used for their economic evaluation.

CONCLUSIONS:

Prescribed CBMs are a potentially cost-effective add-on treatment for MS spasticity; however, this evidence is uncertain. Further investment in randomised trials with in-built economic evaluations is warranted for a wider range of clinical indications.”

https://www.ncbi.nlm.nih.gov/pubmed/28866778

https://link.springer.com/article/10.1007%2Fs40273-017-0565-6

CHANGES IN THE CANNABINOIDS RECEPTORS IN RATS FOLLOWING TREATMENT WITH ANTIDEPRESSANTS.

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“The endocannabinoid (eCB) system plays a significant role in the pathophysiology of depression. The potential participation of this system in the mechanism of action of antidepressants has been highlighted in recent years.

The aim of this study was to investigate the expression of cannabinoid (CB) receptors using Western blot and CB1 receptor density using autoradiography after acute or chronic administration of antidepressant drugs [imipramine (IMI, 15mg/kg), escitalopram (ESC, 10mg/kg) and tianeptine (TIA, 10mg/kg)].

Antidepressants given chronically elevated CB1 receptor density in the cortical structures and hippocampal areas, while a decrease of CB1 receptor density was observed in the striatum after IMI and ESC treatment. The CB1 receptor expression decreases in the dorsal striatum after chronic administration of IMI and ESC or the receptor rise in the hippocampus after chronic ESC and TIA treatment were confirmed using Western blot analyses. An increase in the CB2 receptor expression was observed in the cortical structures and hippocampus after chronic administration of ESC and TIA, while a decrease in this expression was noted in the striatum and cerebellum after chronic IMI treatment.

Our results provide clear evidence that the antidepressant exposures provoke some modulations within the eCB system through CB receptors.”

https://www.ncbi.nlm.nih.gov/pubmed/28866072

http://www.sciencedirect.com/science/article/pii/S0161813X17301717

Can You Pass the Acid Test? Critical Review and Novel Therapeutic Perspectives of Δ9-Tetrahydrocannabinolic Acid A.

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Mary Ann Liebert, Inc. publishers

“Δ9-tetrahydrocannabinolic acid A (THCA-A) is the acidic precursor of Δ9-tetrahydrocannabinol (THC), the main psychoactive compound found in Cannabis sativa. THCA-A is biosynthesized and accumulated in glandular trichomes present on flowers and leaves, where it serves protective functions and can represent up to 90% of the total THC contained in the plant. THCA-A slowly decarboxylates to form THC during storage and fermentation and can further degrade to cannabinol. Decarboxylation also occurs rapidly during baking of edibles, smoking, or vaporizing, the most common ways in which the general population consumes Cannabis. Contrary to THC, THCA-A does not elicit psychoactive effects in humans and, perhaps for this reason, its pharmacological value is often neglected. In fact, many studies use the term “THCA” to refer indistinctly to several acid derivatives of THC. Despite this perception, many in vitro studies seem to indicate that THCA-A interacts with a number of molecular targets and displays a robust pharmacological profile that includes potential anti-inflammatory, immunomodulatory, neuroprotective, and antineoplastic properties. Moreover, the few in vivo studies performed with THCA-A indicate that this compound exerts pharmacological actions in rodents, likely by engaging type-1 cannabinoid (CB1) receptors. Although these findings may seem counterintuitive due to the lack of cannabinoid-related psychoactivity, a careful perusal of the available literature yields a plausible explanation to this conundrum and points toward novel therapeutic perspectives for raw, unheated Cannabis preparations in humans.”

https://www.ncbi.nlm.nih.gov/pubmed/28861488

http://online.liebertpub.com/doi/10.1089/can.2016.0008

Therapeutical strategies for anxiety and anxiety-like disorders using plant-derived natural compounds and plant extracts.

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“Anxiety and anxiety-like disorders describe many mental disorders, yet fear is a common overwhelming symptom often leading to depression. Currently two basic strategies are discussed to treat anxiety: pharmacotherapy or psychotherapy. In the pharmacotherapeutical clinical approach, several conventional synthetic anxiolytic drugs are being used with several adverse effects. Therefore, studies to find suitable safe medicines from natural sources are being sought by researchers. The results of a plethora experimental studies demonstrated that dietary phytochemicals like alkaloids, terpenes, flavonoids, phenolic acids, lignans, cinnamates, and saponins or various plant extracts with the mixture of different phytochemicals possess anxiolytic effects in a wide range of animal models of anxiety. The involved mechanisms of anxiolytics action include interaction with γ-aminobutyric acid A receptors at benzodiazepine (BZD) and non-BZD sites with various affinity to different subunits, serotonergic 5-hydrodytryptamine receptors, noradrenergic and dopaminergic systems, glutamate receptors, and cannabinoid receptors. This review focuses on the use of both plant-derived natural compounds and plant extracts with anxiolytic effects, describing their biological effects and clinical application.”

https://www.ncbi.nlm.nih.gov/pubmed/28863384

 

CB1 Receptors Signaling in the Brain: Extracting Specificity from Ubiquity.

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“Endocannabinoids (eCBs) are amongst the most ubiquitous signaling molecules in the nervous system. Over the past few decades, observations based on a large volume of work, first examining the pharmacological effects of exogenous cannabinoids, and then the physiological functions of eCBs, have directly challenged long-held and dogmatic views about communication, plasticity and behavior in the Central Nervous System (CNS). The eCBs and their cognate cannabinoid receptors exhibit a number of unique properties that distinguish them from the widely studied classical amino acid transmitters, neuropeptides and catecholamines. Although we now have a loose set of mechanistic rules based on experimental findings, new studies continue to reveal that our understanding of the endocannabinoid system (ECS) is continuously evolving and challenging long-held conventions. Here, we will briefly summarize findings on the current canonical view of the ‘endocannabinoid system’ and will address novel aspects that reveal how a nearly ubiquitous system can determine highly specific functions in the brain. In particular, we will focus on findings that push for an expansion of our ideas around long-held beliefs about eCB signaling that, whilst clearly true, may be contributing to an oversimplified perspective on how cannabinoid signaling at the microscopic level impacts behavior at the macroscopic level.”

https://www.ncbi.nlm.nih.gov/pubmed/28862250

https://www.nature.com/npp/journal/vaop/naam/abs/npp2017206a.html

Explorative Placebo-Controlled Double-Blind Intervention Study with Low Doses of Inhaled Δ9-Tetrahydrocannabinol and Cannabidiol Reveals No Effect on Sweet Taste Intensity Perception and Liking in Humans.

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“Introduction: The endocannabinoid system (ECS) plays an important role in food reward. For example, in humans, liking of palatable foods is assumed to be modulated by endocannabinoid activity. Studies in rodents suggest that the ECS also plays a role in sweet taste intensity perception, but it is unknown to what extent this can be extrapolated to humans. Therefore, this study aimed at elucidating whether Δ9-tetrahydrocannabinol (THC) or cannabidiol (CBD) affects sweet taste intensity perception and liking in humans, potentially resulting in alterations in food preferences.

Results: Inhalation of the Cannabis preparations did not affect sweet taste intensity perception and liking, ranking order, or ad libitum consumption of the favorite drink. In addition, food preferences were not influenced by the interventions. Reported fullness was lower, whereas desire to eat was higher throughout the THC compared to the CBD condition.

Conclusions: These results suggest that administration of Cannabis preparations at the low doses tested does not affect sweet taste intensity perception and liking, nor does it influence food preferences in humans.”

https://www.ncbi.nlm.nih.gov/pubmed/28861511

http://online.liebertpub.com/doi/10.1089/can.2017.0018

Cannabidiol Does Not Dampen Responses to Emotional Stimuli in Healthy Adults.

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“Introduction: Cannabidiol (CBD) is a nonpsychoactive constituent of whole plant cannabis that has been reported to reduce anxiety-like behaviors in both pre-clinical and human laboratory studies. Yet, no controlled clinical studies have demonstrated its ability to reduce negative mood or dampen responses to negative emotional stimuli in humans. The objective of this study was to investigate the effects of CBD on responses to negative emotional stimuli, as a model for its potential anxiety-reducing effects.

Discussion: CBD did not dampen responses to negative emotional stimuli and did not affect feelings of social rejection. The high dose of CBD (900 mg) marginally reduced attentional bias toward happy and sad facial expressions, and produced a slight increase in late-session heart rate. CBD did not produce detectable subjective effects or alterations in mood or anxiety.

Conclusion: These findings indicate that CBD has minimal behavioral and subjective effects in healthy volunteers, even when they are presented with emotional stimuli. Further research into the behavioral and neural mechanisms of CBD and other phytocannabinoids is needed to ascertain the clinical function of this drug.”

https://www.ncbi.nlm.nih.gov/pubmed/28861510

 http://online.liebertpub.com/doi/10.1089/can.2017.0014