Tag Archives: Cannabinoids

[The role of endocannabinoid system in physiological and pathological processes in the eye].

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“Plant of Cannabis sativa/ marihuana except for its psychotropic effects possesses a range of pharmacological properties, that has been utilized for medical purposes over a period of millenia.

Investigations concerning biochemical mechanism of action of the main and most active pharmacological compound of Cannabis sativa, cannabinoid 9-THC, contributed to the discovery of cannabinoid receptors both in the central nervous system (CNS) and peripheral tissues, that mediated actions of this substance.

The discovery made possible identification of a new, endogenous signaling system referred to as the endocannabinoid system.

Besides cannabinoid receptors CB1 and CB2, the system includes it’s endogenic ligands (endocannabinoids) and compounds that participate in their biosynthesis and inactivation. Structure and functioning of the endocannabinoid system is conservative in all vertebrates.

It’s activation with plant, synthetic and endogenous cannabinoids has an influence on multiple physiological and pathological processes within the eye.”

http://www.ncbi.nlm.nih.gov/pubmed/19195174

Effects of cannabinoids on lithium-induced conditioned rejection reactions in a rat model of nausea.

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“Marijuana has been reported to suppress nausea produced by chemotherapy treatment in human cancer patients.

… there is abundant evidence that cannabinoid agonists attenuate vomiting in emetic species…

The present experiments evaluated the potential of low doses of the cannabinoid agonists, delta-9-tetrahydrocannabinol (THC; 0.5 mg/kg, i.p.), and HU-210 (0.001 mg/kg and 0.01 mg/kg, i.p.), and the CB(1) antagonist SR-141716A in modulating the establishment and the expression of lithium-induced conditioned rejection reactions in rats.

These results indicate that the establishment and the expression of lithium-induced conditioned rejection reactions are suppressed by pretreatment with cannabinoid agents.”

http://www.ncbi.nlm.nih.gov/pubmed/12528012

http://www.thctotalhealthcare.com/category/nauseavomiting/

Cannabidiol, a non-psychoactive component of cannabis and its synthetic dimethylheptyl homolog suppress nausea in an experimental model with rats.

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“Rats display conditioned rejection reactions during an oral infusion of a flavor previously paired with an emetic drug; considerable evidence indicates that these rejection reactions reflect nausea.

Here we report that cannabidiol, a major non-psychoactive cannabinoid found in marijuana and its synthetic dimethylheptyl homolog interfere with nausea elicited by lithium chloride and with conditioned nausea elicited by a flavor paired with lithium chloride.

These results suggest that cannabinoids without psychoactive side-effects may have therapeutic value in the treatment of chemotherapy-induced nausea.”

http://www.ncbi.nlm.nih.gov/pubmed/11973447

http://www.thctotalhealthcare.com/category/nauseavomiting/

The endocannabinoid system as a target for the treatment of neurodegenerative disease.

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“The Cannabis sativa plant has been exploited for medicinal, agricultural and spiritual purposes in diverse cultures over thousands of years.

Cannabis has been used recreationally for its psychotropic properties, while effects such as stimulation of appetite, analgesia and anti-emesis have lead to the medicinal application of cannabis.

Indeed, reports of medicinal efficacy of cannabis can been traced back as far as 2700 BC, and even at that time reports also suggested a neuroprotective effect of the cultivar.

…alterations in the endocannabinoid system have been extensively investigated in a range of neurodegenerative disorders.

In this review we examine the evidence implicating the endocannabinoid system in the cause, symptomatology or treatment of neurodegenerative disease. We examine data from human patients and compare and contrast this with evidence from animal models of these diseases. On the basis of this evidence we discuss the likely efficacy of endocannabinoid-based therapies in each disease context.

There has been anecdotal and preliminary scientific evidence of cannabis affording symptomatic relief in diverse neurodegenerative disorders. These include multiple sclerosis, Huntington’s, Parkinson’s and Alzheimer’s diseases, and amyotrophic lateral sclerosis.

This evidence implied that hypofunction or dysregulation of the endocannabinoid system may be responsible for some of the symptomatology of these diseases.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931550/

Therapeutic potential of cannabis in pain medicine†

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BJA

“Cannabis has been of medicinal and social significance for millennia.

It is obtained from Cannabis sativa and the plant’s name reflects its ancient use—cannabis may represent a compound of Sanskrit and Hebrew words meaning ‘fragrant cane’, while sativa is Latin for cultivated.

Cannabis is also known as hemp.

Marijuana describes the dried cannabis flowers and leaves which are smoked, while hashish refers to blocks of cannabis resin which can be eaten.

Advances in cannabis research have paralleled developments in opioid pharmacology whereby a psychoactive plant extract has elucidated novel endogenous signalling systems with therapeutic significance.

Cannabinoids (CBs) are chemical compounds derived from cannabis.

This review discusses the basic science and clinical aspects of CB pharmacology with a focus on pain medicine.

Advances in cannabis research have ensured a future for these analgesic molecules which have been used since antiquity.”

http://bja.oxfordjournals.org/content/101/1/59.long

http://www.thctotalhealthcare.com/category/pain-2/

Evaluation of prevalent phytocannabinoids in the acetic acid model of visceral nociception.

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“Cannabis has been used for thousands of years as a therapeutic agent for pain relief, as well as for recreational purposes.

Delta-9-Tetrahydrocannabinol (Δ9-THC)… produces antinociceptive effects in a wide range of preclinical assays of pain.

Considerable preclinical research has demonstrated the efficacy of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the primary psychoactive constituent of Cannabis sativa, in a wide variety of animal models of pain, but few studies have examined other phytocannabinoids.

Indeed, other plant-derived cannabinoids, including cannabidiol (CBD), cannabinol (CBN), and cannabichromene (CBC) elicit antinociceptive effects in some assays. In contrast, tetrahydrocannabivarin (THCV), another component of cannabis, antagonizes the pharmacological effects of Delta(9)-THC.

These results suggest that various constituents of this plant may interact in a complex manner to modulate pain.

The primary purpose of the present study was to assess the antinociceptive effects of these other prevalent phytocannabinoids in the acetic acid stretching test, a rodent visceral pain model…

Importantly, the antinociceptive effects of Delta(9)-THC and CBN occurred at lower doses than those necessary to produce locomotor suppression, suggesting motor dysfunction did not account for the decreases in acetic acid-induced abdominal stretching.

These data raise the intriguing possibility that other constituents of cannabis can be used to modify the pharmacological effects of Delta(9)-THC by either eliciting antinociceptive effects (i.e., CBN) or antagonizing (i.e., THCV) the actions of Delta(9)-THC.

The results obtained in the present study are consistent with the view that Δ9-THC is the major phytocannabinoid present in marijuana that produces antinociception in the acetic acid abdominal stretching test.

…these results suggest that there is potential to develop medications containing various concentrations of specific phytocannabinoids to optimize therapeutic effects (e.g., antinociception) and minimize psychomimetic effects.

In sum, the results of the present study further support the notion that Δ9-THC is the predominant constituent of marijuana that is responsible for eliciting antinociceptive effects and indicate that CB1 receptors play a predominant role in mediating these effects.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765124/

http://www.thctotalhealthcare.com/category/pain-2/

The complex modulation of lysosomal degradation pathways by cannabinoid receptor 1 and 2.

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“The two main receptors of the endocannabinoid system, cannabinoid receptor 1 (CB1R) and 2 (CB2R) were described in the early 1990s. Since then, different physiological functions have been revealed that are linked to the activity of these two G-protein-coupled receptors.

CB1R and CB2R activity influences signal Cascades, which are known to play a role in the regulation of the cellular “self-digestion” process called autophagy. A variety of these signaling pathways are integrated by the mammalian target of rapamycin complex 1 (mTORC1) that acts as an inhibitor of autophagy. Others, like AMP-activated protein kinase dependent signaling pathway, are able to bypass mTORC1 to modulate the autophagic activity directly.

In the recent years, several scientific reports demonstrate an involvement of CB1R and CB2R signaling in the control of the autophagic activity in different paradigms.

In this review, we summarize the recent literature on this topic, which is in part contradictory and therefore, it is of great importance to illuminate the results of the single reports in the physiological context of the model systems used in these studies.

Utilizing CB1R and CB2R as pharmacological targets to modulate the autophagic activity is a promising treatment strategy for the treatment of different patho-physiological conditions and disease.”

http://www.ncbi.nlm.nih.gov/pubmed/25908257

CB1 Knockout Mice Unveil Sustained CB2-Mediated Anti-Allodynic Effects of the Mixed CB1/CB2 Agonist CP55,940 in a Mouse Model of Paclitaxel-Induced Neuropathic Pain.

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“Cannabinoids suppress neuropathic pain through activation of cannabinoid CB1 and/or CB2 receptors. However, unwanted CB1-mediated cannabimimetic effects limit clinical use…

Our results using the mixed CB1/CB2 agonist document that CB1 and CB2 receptor activations produce mechanistically distinct suppression of neuropathic pain.

Our study highlights the therapeutic potential of targeting cannabinoid CB2 receptors to bypass unwanted central effects associated with CB1receptor activation.”

http://www.ncbi.nlm.nih.gov/pubmed/25904556

http://www.thctotalhealthcare.com/category/neuropathic-pain/

Cannabidiol stimulates Aml-1a-dependent glial differentiation and inhibits glioma stem-like cells proliferation by inducing autophagy in a TRPV2-dependent manner.

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“Glioma stem-like cells (GSCs) correspond to a tumor cell subpopulation, involved in glioblastoma multiforme (GBM) tumor initiation and acquired chemoresistance. Currently, drug-induced differentiation is considered as a promising approach to eradicate this tumor-driving cell population.

Recently, the effect of cannabinoids (CBs) in promoting glial differentiation and inhibiting gliomagenesis has been evidenced. Herein, we demonstrated that cannabidiol (CBD) by activating Transient Receptor Potential Vanilloid-2 (TRPV2) triggers GSCs differentiation activating the autophagic process and inhibits GSCs proliferation and clonogenic capability.

Above all, CBD and carmustine (BCNU) in combination overcome the high resistance of GSCs to BCNU treatment, by inducing apoptotic cell death…

Altogether, these results support a novel mechanism by which CBD inducing TRPV2-dependent autophagic process stimulates Aml-1a-dependent GSCs differentiation, abrogating the BCNU chemoresistance in GSCs.”

http://www.ncbi.nlm.nih.gov/pubmed/25903924

http://www.thctotalhealthcare.com/category/gllomas/

The endocannabinoid system and plant-derived cannabinoids in diabetes and diabetic complications.

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“Oxidative stress and inflammation play critical roles in the development of diabetes and its complications.

Recent studies provided compelling evidence that the newly discovered lipid signaling system (ie, the endocannabinoid system) may significantly influence reactive oxygen species production, inflammation, and subsequent tissue injury, in addition to its well-known metabolic effects and functions.

The modulation of the activity of this system holds tremendous therapeutic potential in a wide range of diseases, ranging from cancer, pain, neurodegenerative, and cardiovascular diseases to obesity and metabolic syndrome, diabetes, and diabetic complications.

This review focuses on the role of the endocannabinoid system in primary diabetes and its effects on various diabetic complications, such as diabetic cardiovascular dysfunction, nephropathy, retinopathy, and neuropathy, particularly highlighting the mechanisms beyond the metabolic consequences of the activation of the endocannabinoid system.

The therapeutic potential of targeting the endocannabinoid system and certain plant-derived cannabinoids, such as cannabidiol and Δ9-tetrahydrocannabivarin, which are devoid of psychotropic effects and possess potent anti-inflammatory and/or antioxidant properties, in diabetes and diabetic complications is also discussed.

Although there is much controversy in the field of EC research, experimental evidence and clinical trials have clearly shown that ECS plays a key role in the development of primary diabetes and various diabetic complications. Although inhibition of CB1 receptors has proven to be effective in clinical trials of obesity and metabolic syndrome, this approach has ultimately failed because of increasing patient anxiety. However, recent preclinical studies clearly showed that peripherally restricted CB1 antagonists may represent a viable therapeutic strategy to avoid the previously mentioned adverse effects.

Importantly, CB1 inhibition, as discussed in this review, may also directly attenuate inflammatory responses and ROS and reactive nitrogen species generation in endothelial, immune, and other cell types, as well as in target tissues of diabetic complications, far beyond its known beneficial metabolic consequences. The main effects of CB1 receptor activation on the development of diabetes and diabetic complications are summarized in Figure 1. CB2 agonists may exert beneficial effects on diabetes and diabetic complications by attenuating inflammatory response and ensuing oxidative stress (Figure 2).

Natural cannabinoids, such as CBD and THCV, also have tremendous therapeutic potential.

CBD is a potent antioxidant and anti-inflammatory agent that does not appear to exert its beneficial effects through conventional CB receptors and is already approved for human use.

THCV and its derivatives, which may combine the beneficial effects of simultaneous CB1 inhibition and CB2 stimulation, are still under intense preclinical investigation. It will be interesting to see how newly developed, peripherally restricted CB1 receptor antagonists and/or CB2 receptor agonists and certain natural cannabinoids, such as CBD and THCV, will influence the clinical outcomes of diabetic patients.

We hope that some of these new approaches will be useful in clinical practice in the near future to aid patients with diabetes.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349875/

http://www.thctotalhealthcare.com/category/diabetes/