Tag Archives: endocannabinoid system

Safety and Toxicology of Cannabinoids.

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“There is extensive research on the safety, toxicology, potency, and therapeutic potential of cannabis.

However, uncertainty remains facilitating continued debate on medical and recreational cannabis policies at the state and federal levels.

This review will include a brief description ofcannabinoids and the endocannabinoid system; a summary of the acute and long-term effects of cannabis; and a discussion of the therapeutic potential of cannabis.

The conclusions about safety and efficacy will then be compared with the current social and political climate to suggest future policy directions and general guidelines.”

http://www.ncbi.nlm.nih.gov/pubmed/26269228

Dissecting the cannabinergic control of behavior: The where matters.

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“The endocannabinoid system is the target of the main psychoactive component of the plant Cannabis sativa, the Δ9 -tetrahydrocannabinol (THC).

This system is composed by the cannabinoid receptors, the endogenous ligands, and the enzymes involved in their metabolic processes, which works both centrally and peripherally to regulate a plethora of physiological functions.

This review aims at explaining how the site-specific actions of the endocannabinoid system impact on memory and feeding behavior through the cannabinoid receptors 1 (CB1 R).

Centrally, CB1 R is widely distributed in many brain regions, different cell types (e.g. neuronal or glial cells) and intracellular compartments (e.g. mitochondria).

Interestingly, cellular and molecular effects are differentially mediated by CB1 R according to their cell-type localization (e.g. glutamatergic or GABAergic neurons).

Thus, understanding the cellular and subcellular function of CB1 R will provide new insights and aid the design of new compounds in cannabinoid-based medicine.”

http://www.ncbi.nlm.nih.gov/pubmed/26260530

On the effects of CP 55-940 and other cannabinoid receptor agonists in C6 and U373 cell lines.

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“Cannabinoid receptor (CBs) agonists affect the growth of tumor cells via activation of deadly cascades. The spectrum of action of these agents and the precise role of the endocannabinoid system (ECS) on oncogenic processes remain elusive.

Herein we compared the effects of synthetic (CP 55-940 and WIN 55,212-2) and endogenous (anandamide or AEA) CBs agonists (10-20 μM) on morphological changes, cell viability, and induction of apoptosis in primary astrocytes and in two glioblastoma cell lines (C6 and U373 cells) in order to characterize their possible differential actions on brain tumor cells.

None of the CBs agonist tested induced changes in cell viability or morphology in primary astrocytes.

In contrast, CP 55-940 significantly decreased cell viability in C6 and U373 cells at 5 days of treatment, whereas AEA and WIN 55,212-2 moderately decreased cell viability in both cell lines. Treatment of U373 and C6 for 3 and 5 days with AEA or WIN 55,212-2 produced discrete morphological changes in cell bodies, whereas the exposure to CP 55-940 induced soma degradation. CP 55-940 also induced apoptosis in both C6 and U373 cell lines.

Our results support a more effective action of CP 55-940 to produce cell death of both cell lines through apoptotic mechanisms. Comparative aspects between cannabinoids with different profiles are necessary for the design of potential treatments against glial tumors.”

http://www.ncbi.nlm.nih.gov/pubmed/26255146

Microinjection of orexin-A into the rat locus coeruleus nucleus induces analgesia via cannabinoid type-1 receptors.

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“Locus coeruleus (LC) nucleus is involved in noradrenergic descending pain modulation.

LC receives dense orexinergic projections from the lateral hypothalamus. Orexin-A and -B are hypothalamic peptides which modulate a variety of brain functions via orexin type-1 (OX1) and orexin type-2 (OX2) receptors.

Previous studies have shown that activation of OX1 receptors induces endocannabinoid synthesis and alters synaptic neurotransmission by retrograde signaling via affecting cannabinoid type-1 (CB1) receptors.

In the present study the interaction of orexin-A and endocannabinoids was examined at the LC level in a rat model of inflammatory pain…

This data show that, activation of OX1 receptors in the LC can induce analgesia and also the blockade of OX1 or CB1 receptors is associated with hyperalgesia during formalin test.

Our findings also suggest that CB1 receptors may modulate the analgesic effect of orexin-A.

These results outline a new mechanism by which orexin-A modulates the nociceptive processing in the LC nucleus.”

http://www.ncbi.nlm.nih.gov/pubmed/26254729

Cannabis, Cannabinoids, and Cerebral Metabolism: Potential Applications in Stroke and Disorders of the Central Nervous System.

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“No compound has generated more attention in both the scientific and recently in the political arena as much as cannabinoids.

These diverse groups of compounds referred collectively as cannabinoids have both been vilified due to its dramatic and potentially harmful psychotropic effects and glorified due to its equally dramatic and potential application in a number of acute and chronic neurological conditions.

Previously illegal to possess, cannabis, the plant where natural form of cannabinoids are derived, is now accepted in a growing number of states for medicinal purpose, and some even for recreational use, increasing opportunities for more scientific experimentation.

The purpose of this review is to summarize the growing body of literature on cannabinoids and to present an overview of our current state of knowledge of the human endocannabinoid system in the hope of defining the future of cannabinoids and its potential applications in disorders of the central nervous system, focusing on stroke.”

http://www.ncbi.nlm.nih.gov/pubmed/26238742

Cannabinoids: is there a potential treatment role in epilepsy?

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“Cannabinoids have been used medicinally for centuries, and in the last decade, attention has focused on their broad therapeutic potential particularly in seizure management.

While some cannabinoids have demonstrated anticonvulsant activity in experimental studies, their efficacy for managing clinical seizures has not been fully established.

This commentary will touch on our understanding of the brain endocannabinoid system’s regulation of synaptic transmission in both physiological and pathophysiological conditions, and review the findings from both experimental and clinical studies on the effectiveness of cannabinoids to suppress epileptic seizures.

At present, there is preliminary evidence that non-psychoactive cannabinoids may be useful as anticonvulsants, but additional clinical trials are needed to fully evaluate the efficacy and safety of these compounds for the treatment of epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/26234319

The levels of the endocannabinoid receptor CB2 and its ligand 2-arachidonoylglycerol are elevated in endometrial carcinoma.

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“The endocannabinoid system plays protective roles against the growth and the spreading of several types of carcinomas.

Because estrogens regulate this system both in physiological states and cancer, in this paper we evaluated its involvement in endometrial carcinoma, a well-known estrogen-dependent tumor.

In conclusion, the endocannabinoid system seems to play an important role in human endometrial carcinoma, and modulation of CB(2) activity/expression may account for a tumor-suppressive effect.”

http://www.ncbi.nlm.nih.gov/pubmed/20133454

https://academic.oup.com/endo/article/151/3/921/2456492

Endocannabinoid Signaling in Autism.

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“Autism spectrum disorder (ASD) is a complex behavioral condition with onset during early childhood and a lifelong course in the vast majority of cases. To date, no behavioral, genetic, brain imaging, or electrophysiological test can specifically validate a clinical diagnosis of ASD. However, these medical procedures are often implemented in order to screen for syndromic forms of the disorder (i.e., autism comorbid with known medical conditions).

In the last 25 years a good deal of information has been accumulated on the main components of the “endocannabinoid (eCB) system”, a rather complex ensemble of lipid signals (“endocannabinoids”), their target receptors, purported transporters, and metabolic enzymes.

It has been clearly documented that eCB signaling plays a key role in many human health and disease conditions of the central nervous system, thus opening the avenue to the therapeutic exploitation of eCB-oriented drugs for the treatment of psychiatric, neurodegenerative, and neuroinflammatory disorders.

Here we present a modern view of the eCB system, and alterations of its main components in human patients and animal models relevant to ASD. This review will thus provide a critical perspective necessary to explore the potential exploitation of distinct elements of eCB system as targets of innovative therapeutics against ASD.”

http://www.ncbi.nlm.nih.gov/pubmed/26216231#

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

COMPARATIVE EFFECTS OF PARATHION AND CHLORPYRIFOS ON ENDOCANNABINOID AND ENDOCANNABINOID-LIKE LIPID METABOLITES IN RAT STRIATUM.

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“Parathion and chlorpyrifos are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE).

The endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) are endogenous neuromodulators that regulate presynaptic neurotransmitter release in neurons throughout the central and peripheral nervous systems.

Differential changes in extracellular and/or tissue levels of eCBs and eCBLs could potentially influence a number of signaling pathways and contribute to selective neurological changes following acute OP intoxications.”

http://www.ncbi.nlm.nih.gov/pubmed/26215119

Cannabinoids for the Treatment of Movement Disorders.

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“Use of cannabinoids as medications has a long history.

Unfortunately, the prohibition of cannabis and its classification in 1970 as a schedule 1 drug has been a major obstacle in studying these agents in a systematic, controlled manner.

The number of class 1 studies (randomized, double-blind, placebo-controlled) in patients with movement disorders is limited. Hence, it is not possible to make recommendations on the use of these cannabinoids as primary treatments for any of the movement disorders at this time.

Fortunately, there is an expanding body of research in animal models of age-dependent and disease-related changes in the endocannabinoid system that is providing new targets for drug development.

Moreover, there is growing evidence of a “cannabinoid entourage effect” in which a combination of cannabinoids derived from the plant are more effective than any single cannabinoid for a number of conditions.

Cannabis preparations may presently offer an option for compassionate use in severe neurologic diseases, but at this point, only when standard-of-care therapy is ineffective.

As more high-quality clinical data are gathered, the therapeutic application of cannabinoids will expand.”

http://www.ncbi.nlm.nih.gov/pubmed/26206230