Tag Archives: Cannabinoids

A systematic review of plant-derived natural compounds for anxiety disorders.

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“Anxiety disorders are the most common mental illnesses affecting human beings. They range from panic to generalized anxiety disorders upsetting the well-being and psychosocial performance of patients. Several conventional anxiolytic drugs are being used which in turn result in several adverse effects. Therefore, studies to find suitable safe medicines from natural sources are being conducted by researchers.

The aim of the present study is to comprehensively review phytochemical compounds with well-established anxiolytic activities and their structure-activity relationships as well as neuropsychopharmacological aspects. Results showed that phytochemicals like; alkaloids, flavonoids, phenolic acids, lignans, cinnamates, terpenes and saponins possess anxiolytic effects in a wide range of animal models of anxiety.

The involved mechanisms include interaction with γ-aminobutyric acid (GABA)A receptors at benzodiazepine (BZD) and non-BZD sites with various affinity to different subunits, serotonergic 5-hydrodytryptamine (5-HT)1A and 5-HT2A/C receptors, noradrenergic and dopaminergic systems, glycine and glutamate receptors, and κ-opioid receptor as well as cannabinoid (CB)1 and CB2 receptors.

Phytochemicals also modulate the hypothalamo-pituitary-adrenal (HPA) axis, the levels of pro-inflammatory cytokines like interleukin (IL)-2, IL-6, IL-1β and tumor necrosis factor (TNF)-α, and improve brain derived neurotrophic factor (BDNF) levels. Transient receptor potential cation channel subfamily V (TRPV)3, nitric oxide cyclic guanosine monophosphate (NO-cGMP) pathway and monoamine oxidase enzymes are other targets of phytochemicals with anxiolytic activity.

Taking together, these phytochemicals may be considered as supplements to conventional anxiolytic therapies in order to improve efficacy and reduce adverse effects.

Further preclinical and clinical studies are still needed in order to recognize the structure-activity relationships, metabolism, absorption, and neuropsychopharmacological mechanisms of plant-derived natural agents.”

http://www.ncbi.nlm.nih.gov/pubmed/26845556

Cannabinoids for the Treatment of Schizophrenia: An Overview.

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“Δ9-tetrahydrocannabinol and its analogues are found to have particular application in psychiatry because of their antipsychotic properties suggesting a therapeutic use as neuroleptic agents in limiting psychotic diseases.

These treatments should not only aim to alleviate specific symptoms but also attempt to delay/arrest disease progression.

In the present review, we reported recent studies supporting the view that the cannabinoid signalling system is a key modulatory element in the activity of the striatum and temporal cortex that has been traditionally associated with psychosis and schizophrenia.

This idea is supported by different anatomical, electrophysiological, pharmacological and biochemical data.

Furthermore, these studies indicate that the cannabinoid system is impaired in different psychotic disorders, supporting the idea of developing novel pharmacotherapies with compounds that selectively target specific elements of the cannabinoid system.”

http://www.ncbi.nlm.nih.gov/pubmed/26845552

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

The Cannabinoid CB1/CB2 Agonist WIN55212.2 Promotes Oligodendrocyte Differentiation In Vitro and Neuroprotection During the Cuprizone-Induced Central Nervous System Demyelination.

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“Different types of insults to the CNS lead to axon demyelination. Remyelination occurs when the CNS attempts to recover from myelin loss and requires the activation of oligodendrocyte precursor cells.

With the rationale that CB1 receptor is expressed in oligodendrocytes and marijuana consumption alters CNS myelination, we study the effects of the cannabinoid agonist WIN55212.2 in (1) an in vitro model of oligodendrocyte differentiation and (2) the cuprizone model for demyelination.

The cannabinoid agonist WIN55212.2 promotes oligodendrocyte differentiation in vitro.

Moreover, 0.5 mg/kg of the drug confers neuroprotection during cuprizone-induced demyelination, while 1 mg/kg aggravates the demyelination process.”

http://www.ncbi.nlm.nih.gov/pubmed/26842941

JWH-133, a Selective Cannabinoid CB2 Receptor Agonist, Exerts Toxic Effects on Neuroblastoma SH-SY5Y Cells.

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“Endocannabinoid system plays an important role in the regulation of diverse physiological functions.

Although cannabinoid type 2 receptors (CB2) are involved in the modulation of immune system in peripheral tissues, recent findings demonstrated that they are also expressed in the central nervous system and could constitute a new target for the treatment of neurodegenerative disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26842917

Simultaneous Activation of Induced Heterodimerization between CXCR4 Chemokine Receptor and Cannabinoid Receptor 2 (CB2) Reveal a Mechanism for Regulation of Tumor Progression.

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“The G-protein-coupled chemokine receptor, CXCR4, generates signals that lead to cell migration, cell proliferation, and other survival mechanisms which result in the metastatic spread of primary tumor cells to distal organs.

Numerous studies have demonstrated that CXCR4 can form homodimers, or can heterodimerize with other GPCRs to form receptor complexes that can amplify or decrease the signaling capacity of each individual receptor.

Using biophysical and biochemical approaches, we found that CXCR4 can form an induced heterodimer with cannabinoid receptor 2 (CB2) in human breast and prostate cancer cells.

Simultaneous, agonist-dependent activation of CXCR4 and CB2 resulted in reduced CXCR4-mediated expression of phosphorylated ERK1/2, and ultimately, reduced cancer cell functions such as calcium mobilization and cellular chemotaxis.

Given that treatment with cannabinoids has been shown to reduce invasiveness of cancer cells, as well as CXCR4-mediated migration of immune cells, it is therefore plausible that CXCR4 signaling can be silenced through a physical heterodimeric association with CB2, thereby inhibiting subsequent functions of CXCR4.

Taken together, the data illustrates a mechanism by which the cannabinoid system can negatively modulate CXCR4 receptor function, and perhaps, tumor progression.”

http://www.ncbi.nlm.nih.gov/pubmed/26841863

Cannabinoids for treatment of glaucoma.

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“The purpose of this article is to review the current status of cannabis in the treatment of glaucoma, including the greater availability of marijuana in the USA.

The pharmacology of marijuana and its effect on intraocular pressure has not changed since the research in the 1970s and 1980s.

Marijuana is an effective ocular hypotensive agent.

However, cardiovascular and neurological effects are observed at the same dose, and may theoretically reduce the beneficial effect of lowering intraocular pressure by reducing ocular blood flow. The clinician must be cognizant of this potential in diagnosis, prognosis, and therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/26840343

Cannabinoids for pediatric epilepsy? Up in smoke or real science?

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“Public interest in the use of “medical marijuana” for the treatment of childhood epilepsy has burgeoned in the last few years. This has occurred in parallel with a growing interest in “medical marijuana” in general. Physicians and pediatricians must balance their patients’ desire for immediate access to these products with the tenets of evidence-based medicine. This review discusses the biochemistry of cannabis products (the phytocannabinoids) setting this in the context of the endogenous endocannabinoid system. The differing and potentially modulating effects of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are reviewed. The evidence-base supporting or not the use of cannabis products for the treatment of neurological disease and specifically epilepsy is explored. The potential for adverse effects and particularly of neurotoxicity is addressed. Finally, public health and sociocultural implications are touched upon. Specific recommendations for interested physicians are provided including advocacy for patients and for a change in the “scheduling” of cannabis in order to better foster much-needed high-quality scientific research in this important area.”

http://www.ncbi.nlm.nih.gov/pubmed/26835389

[Efficacy, tolerability and safety of cannabinoids for chronic neuropathic pain : A systematic review of randomized controlled studies].

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“Recently published systematic reviews came to different conclusions with respect to the efficacy, tolerability and safety of cannabinoids for treatment of chronic neuropathic pain.

Cannabinoids were marginally superior to placebo in terms of efficacy and inferior in terms of tolerability.

Cannabinoids and placebo did not differ in terms of safety during the study period.

Short-term and intermediate-term therapy with cannabinoids can be considered in selected patients with chronic neuropathic pain after failure of first-line and second-line therapies.”

http://www.ncbi.nlm.nih.gov/pubmed/26830780

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

Regulation of Stem Cells by the Endocannabinoid System

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“The endocannabinoids, endogenous lipid mediators of related chemical structure to the prototype exogenous cannabinoid Δ9-THC found in marijuana, have emerged as important mediators that regulate central and peripheral neural functions as well as immune responses.

Endogenous and exogenous cannabinoid ligands bind to cannabinoid receptors: the predominant central cannabinoid receptor type 1 (CB1) and the peripheral cannabinoid receptor type 2 (CB2). CB1 and CB2 are members of the G-protein coupled receptor family.

Cannabinoids were shown to modulate the immune system and to affect the migration of blood cells, such as T-cells, monocytes and myeloid leukemia cells, through CB receptors.

Recent data indicate the potential role of cannabinoid ligands and receptors in the regulation of hematopoiesis and hematopoietic stem cell (HSC) migration and trafficking.

These studies may lead to clinical applications of cannabinoid-based compounds as new HSC-mobilizer agents for therapeutic intervention in bone marrow failure.”

http://link.springer.com/chapter/10.1007/978-94-007-2993-3_30

Cannabinoid receptor signaling in progenitor/stem cell proliferation and differentiation.

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“Cannabinoids, the active components of cannabis (Cannabis sativa) extracts, have attracted the attention of human civilizations for centuries, much earlier than the discovery and characterization of their substrate of action, the endocannabinoid system (ECS).

The latter is an ensemble of endogenous lipids, their receptors [in particular type-1 (CB1) and type-2 (CB2) cannabinoid receptors] and metabolic enzymes.

Cannabinoid signaling regulates cell proliferation, differentiation and survival, with different outcomes depending on the molecular targets and cellular context involved.

Cannabinoid receptors are expressed and functional from the very early developmental stages, when they regulate embryonic and trophoblast stem cell survival and differentiation, and thus may affect the formation of manifold adult specialized tissues derived from the three different germ layers (ectoderm, mesoderm and endoderm).

In the ectoderm-derived nervous system, both CB1 and CB2 receptors are present in neural progenitor/stem cells and control their self-renewal, proliferation and differentiation. CB1 and CB2 show opposite patterns of expression, the former increasing and the latter decreasing along neuronal differentiation.

Recently, endocannabinoid (eCB) signaling has also been shown to regulate proliferation and differentiation of mesoderm-derived hematopoietic and mesenchymal stem cells, with a key role in determining the formation of several cell types in peripheral tissues, including blood cells, adipocytes, osteoblasts/osteoclasts and epithelial cells.

Here, we will review these new findings, which unveil the involvement of eCB signaling in the regulation of progenitor/stem cell fate in the nervous system and in the periphery.

The developmental regulation of cannabinoid receptor expression and cellular/subcellular localization, together with their role in progenitor/stem cell biology, may have important implications in human health and disease.”

http://www.ncbi.nlm.nih.gov/pubmed/24076098