Tag Archives: therapeutic

Promising cannabinoid-based therapies for Parkinson’s disease: motor symptoms to neuroprotection.

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“Parkinson’s disease (PD) is a slow insidious neurological disorder characterized by a loss of dopaminergic neurons in the midbrain. Although several recent preclinical advances have proposed to treat PD, there is hardly any clinically proved new therapeutic for its cure.

Increasing evidence suggests a prominent modulatory function of the cannabinoid signaling system in the basal ganglia. Hence, use of cannabinoids as a new therapeutic target has been recommended as a promising therapy for PD.

The elements of the endocannabinoid system are highly expressed in the neural circuit of basal ganglia wherein they bidirectionally interact with dopaminergic, glutamatergic, and GABAergic signaling systems.

As the cannabinoid signaling system undergoes a biphasic pattern of change during progression of PD, it explains the motor inhibition typically observed in patients with PD.

Cannabinoid agonists such as WIN-55,212-2 have been demonstrated experimentally as neuroprotective agents in PD, with respect to their ability to suppress excitotoxicity, glial activation, and oxidative injury that causes degeneration of dopaminergic neurons.

Additional benefits provided by cannabinoid related compounds including CE-178253, oleoylethanolamide, nabilone and HU-210 have been reported to possess efficacy against bradykinesia and levodopa-induced dyskinesia in PD.

Despite promising preclinical studies for PD, use of cannabinoids has not been studied extensively at the clinical level. In this review, we reassess the existing evidence suggesting involvement of the endocannabinoid system in the cause, symptomatology, and treatment of PD. We will try to identify future threads of research that will help in the understanding of the potential therapeutic benefits of the cannabinoid system for treating PD.”

http://www.ncbi.nlm.nih.gov/pubmed/25888232

“To conclude, development of safe, effective cannabis-based medicines targeting different mechanisms may have a significant impact in PD therapy.”

Full-text: http://www.molecularneurodegeneration.com/content/10/1/17

http://www.thctotalhealthcare.com/category/parkinsons-disease/

The biology that underpins the therapeutic potential of cannabis-based medicines for the control of spasticity in multiple sclerosis.

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“Cannabis-based medicines have recently been approved for the treatment of pain and spasticity in multiple sclerosis (MS).

This supports the original perceptions of people with MS, who were using illegal street cannabis for symptom control and pre-clinical testing in animal models of MS.

This activity is supported both by the biology of the disease and the biology of the cannabis plant and the endocannabinoid system.

MS results from disease that impairs neurotransmission and this is controlled by cannabinoid receptors and endogenous cannabinoid ligands. This can limit spasticity and may also influence the processes that drive the accumulation of progressive disability.”

http://www.ncbi.nlm.nih.gov/pubmed/25876933

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

The role of cannabinoids and leptin in neurological diseases.

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“Cannabinoids exert a neuroprotective influence on some neurological diseases, including Alzheimer’s, Parkinson’s, Huntington’s, multiple sclerosis and epilepsy.

Synthetic cannabinoid receptor agonists/antagonists or compounds can provide symptom relief or control the progression of neurological diseases. However, the molecular mechanism and the effectiveness of these agents in controlling the progression of most of these diseases remain unclear.

Cannabinoids may exert effects via a number of mechanisms and interactions with neurotransmitters, neurotropic factors and neuropeptides.

Leptin is a peptide hormone involved in the regulation of food intake and energy balance via its actions on specific hypothalamic nuclei. Leptin receptors are widely expressed throughout the brain, especially in the hippocampus, basal ganglia, cortex and cerebellum. Leptin has also shown neuroprotective properties in a number of neurological disorders, such as Parkinson’s and Alzheimer’s.

Therefore, cannabinoid and leptin hold therapeutic potential for neurological diseases.

Further elucidation of the molecular mechanisms underlying the effects on these agents may lead to the development of new therapeutic strategies for the treatment of neurological disorders.”

Minireview: From the Bench, Toward the Clinic: Therapeutic Opportunities for Cannabinoid Receptor Modulation.

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The effects of cannabinoids have been known for centuries and over the past several decades two G-protein coupled receptors, CB1 and CB2, have been identified that are responsible for their activity.

Endogenous lipid-derived cannabinergic agents have been found, biosynthetic and catabolic machinery characterized, and synthetic agents have been designed to modulate these receptors.

Selective agents including agonists, antagonists, inverse agonists and novel allosteric modulators targeting either CB1 or CB2 have been developed to inhibit or augment their basal tone.

As a result, the role these receptors play in human physiology and their potential therapeutic applications in disease states are being elucidated.

The CB1 receptor while ubiquitous is densely expressed in the brain and CB2 is largely found on cells of immune origin.

This minireview highlights the role of CB1 in excitotoxic assaults in the brain and its potential to limit addiction liability.

In addition, it will examine the relationship between receptor activity and stimulation of insulin release from pancreatic β-cells, insulin resistance and feeding behavior leading toward obesity.

The role of CB2 in the neuropathology of amyotrophic lateral sclerosis and in the central manifestations of chronic HIV infection potentially converges at inflammatory cell activation thereby providing an opportunity for intervention.

Lastly, CB2 modulation is discussed in the context of an experimental model of post-menopausal osteoporosis.

Achieving exquisite receptor selectivity and elucidating the mechanisms underlying receptor inhibition and activation will be essential for the development of the next generation of cannabinergic-based therapeutic agents.”

The multidrug transporter ABCG2 (BCRP) is inhibited by plant-derived cannabinoids.

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“Multiple drug resistance (MDR) is one of the principal causes of chemotherapeutic treatment failure in malignant disease…

Cannabinoids are used therapeutically for the palliation of the adverse side effects associated with cancer chemotherapy. However, cannabinoids also inhibit both the activity and expression of the multidrug transporter…

Cannabinoids are novel Abcg2/ABCG2 inhibitors, reversing the Abcg2-mediated multidrug-resistant phenotype in vitro. This finding may have implications for the co-administration of cannabinoids with pharmaceuticals that are ABCG2 substrates…

Cannabis and cannabinoid preparations are used as therapeutic agents.

One of the many applications of cannabinoids is in the palliation of cancer chemotherapy-induced nausea, vomiting and anorexia. Indeed, the commercial preparations, Marinol and Cesamet, containing the synthetic Δ9-tetrahydrocannabinol (THC) analogue, dronabinol (or nabilone), are approved in some countries for this use.

Interestingly, in the future, cannabinoids might be co-administered with conventional cancer chemotherapies not only in a palliative capacity but also as primary anticancer medications. Accordingly, cannabinoids have demonstrated antiproliferative actions on cancer cells in vitro and in vivo…

To conclude, this is the first study to address the interaction of cannabinoids with the multidrug transporter ABCG2/Abcg2. The results presented here indicate that plant-derived cannabinoids are a novel class of ABCG2/Abcg2 inhibitors. Our results may have important implications for the use of cannabinoid compounds with therapeutic drugs that are substrates for ABCG2.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190019/

A sativex-like combination of phytocannabinoids as a disease-modifying therapy in a viral model of multiple sclerosis.

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“Sativex® is an oromucosal spray, containing equivalent amounts of Δ9 -tetrahydrocannabinol (Δ9 -THC) and cannabidiol (CBD)-botanical drug substance (BDS), and which has been approved for the treatment of spasticity and pain associated to multiple sclerosis (MS).

In this study, we investigated whether Sativex® may also serve as a disease-modifying agent in the Theiler’s murine encephalomyelitis virus induced demyelinating disease model of MS…

The data support the therapeutic potential of Sativex® to slow MS progression and its relevance in CNS repair.”

http://www.ncbi.nlm.nih.gov/pubmed/25857324

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

 

Clearing the Smokescreen: The Current Evidence on Cannabis Use

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“The therapeutic potential of cannabis is one of the factors driving the push for legalization of cannabis use…

Decisions regarding the legal status of cannabis have long been framed (for the public at least) with reference to the perceived health risks and harms associated with use. Yet, drug policy and legislation relating to the use of cannabis are rarely based on the scientific evidence of the known risks and harms.

There are many reasons for this discrepancy, with the politicization of cannabis use, where ideology and moralizing are given precedence over the science, being one.

Thus, we begin this research topic with Aggarwal discussion of how such politicization has contributed to the current smokescreen that is obscuring our understanding of cannabis, including the impact it has on the ability of researchers to collect and disseminate accurate information about the effects of cannabis use.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358058/

Chronic administration with AM251 improves albuminuria and renal tubular structure in obese rats.

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“Modulation of the endocannabinoid system as an anti-obesity therapeutic is well established, however the direct effects of CB1 antagonism on renal function and structure in a model of diet-induced obesity (DIO) are unknown. The aim of this study was to characterise the renal effects of the CB1 antagonist AM251 in a model of DIO.

Antagonism of CB1 with AM251 significantly reduced weight gain, systolic blood pressure, plasma leptin, and reduced albuminuria and plasma creatinine levels in obese rats.

Importantly, there was a significant reduction in tubular cross-section diameter in the obese rats treated with AM251. An improvement in albuminuria was likely due to the reduction in tubular size, reduced leptinemia and maintenance of megalin expression levels. In obese rats, AM251 did not alter diastolic blood pressure, sodium excretion, creatinine clearance or expression of the fibrotic proteins VEGF, TGFb1 and collagen IV in the kidney.

This study demonstrates that treatment with CB1 antagonist AM251 improves renal outcomes in obese rats.”

http://www.ncbi.nlm.nih.gov/pubmed/25804605

“Alexandros Makriyannis is a professor in the Department of Medicinal Chemistry at Northeastern University, where his research group has synthesized many new compounds with cannabinoid activity… AM-251 — an inverse agonist at the CB1 cannabinoid receptor that is structurally related to SR141716A (rimonabant), but has a higher binding affinity with a Ki value of 7.5nM.”  http://en.wikipedia.org/wiki/List_of_AM_cannabinoids

Propagation through alginate encapsulation of axillary buds of Cannabis sativa L. — an important medicinal plant

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“Cannabis sativa L. (Cannabaceae) is an important medicinal plant well known for its pharmacologic and therapeutic potency…

These plants are selected to be used in mass cultivation for the production of biomass as a starting material for the isolation of THC as a bulk active pharmaceutical.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3550375/

http://www.thctotalhealthcare.com/category/thc-delta-9-tetrahydrocannabinol/

 

New Approaches in the Design and Development of Cannabinoid Receptor Ligands: Multifunctional and Bivalent Compounds.

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“Since the identification of the endocannabinoid system, two G protein-coupled receptors (GPCRs) of this complex system were identified and characterized: cannabinoid receptors type 1 (CB1R) and type 2 (CB2R).

In addition to orthosteric and subsequently allosteric ligands, new strategies have been used to target CBRs.

Bivalent ligands and multifunctional ligands acting at diverse biological targets have been designed, synthesized, and characterized for both CBRs. Due to their altered receptor binding and pharmacological profiles, they are interesting tools to explore CBR functions and their interactions with other physiological systems.

Moreover, this approach may bear therapeutic advantages in the therapy of CBR-related disorders, especially multifactorial diseases.

Promising prospects include anorectics with fewer side effects, analgesics with decreased tolerance, and therapeutics with multiple pharmacological activities for the treatment of cancer, inflammation, multiple sclerosis, Huntington’s and Alzheimer’s diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/25820617