Tag Archives: therapeutic

A New Study Suggests Cannabis Could Treat Cervical Cancer

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“A new study suggests that cannabis might be useful in treating cervical cancer.

Through in vitro, or test tube/petri dish, analysis, researchers from the biochemistry department at North-West University in Potchefstroom, South Africa found that the non-psychotropic cannabinoid, or chemical compound, CBD (cannabidiol), taken from a Cannabis sativa extract, could hold anticarcinogenic properties. They pointed out that cannabis acted on the cancerous cells through apoptosis, or a process of cell death, causing only the cancerous cells to kill themselves, and inhibiting their growth.

Cervical cancer is no longer a leading cause of death as much as it used to be in the United States, thanks in large part to the widespread use of pap smears, but it’s still a widespread threat. And in Sub-Saharan Africa, it kills 250,000 women every year. “This makes it the most lethal cancer amongst black women and calls for urgent therapeutic strategies,” the study’s authors wrote in the BMC Complementary and Alternative Medicine journal. “In this study we compare the anti-proliferative effects of crude extract of Cannabis sativa and its main compound cannabidiol on different cervical cancer cell lines.”

It will take much more research before cannabis can be integrated into official cervical cancer treatments in sub-Saharan Africa. But earlier studies also shows that cannabis has been useful in treating not only the symptoms of cancer and chemotherapy, but also the cancer itself.

One study from the journal of Current Clinical Pharmacology found that cannabis served as a preventative agent, reducing inflammation, which researchers also said was useful in reducing the likelihood of cancer. Another study from Oncology Hematology also noted cannabis’ anti-cancer effects, explaining how the plant’s cannabinoids inhibited tumor growth in vitro, such as in a petri dish or test tube, and in vivo, or a living organism.

A handful of other studies have also looked into cannabis as a treatment specifically for cervical cancer. Another from the University Hospital in Geneva, Switzerland, found that the cannabinoids, including the body’s own endocannabinoids, offered “attractive opportunities for the development of novel potent anticancer drugs.”

With that said, often medical marijuana is ingested via capsules, tinctures, vaporizable oils, and other non-smokeable, more pharmaceutical-style forms. Should cannabis eventually become approved for cervical cancer treatment in Africa, it may be up for debate whether whole plant therapy (in which all the cannabinoids work synergistically through the “entourage effect”) or specific cannabinoid therapy is best.”

http://motherboard.vice.com/read/a-new-study-suggests-cannabis-could-treat-cervical-cancer

Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke.

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“Cannabis contains the psychoactive component delta⁸-tetrahydrocannabinol (delta⁸-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol.

It is well-known that delta⁸-THC and other cannabinoid CB₁ receptor agonists are neuroprotective during global and focal ischemic injury.

Additionally, delta⁸-THC also mediates psychological effects through the activation of the CB₁ receptor in the central nervous system.

In addition to the CB₁ receptor agonists, cannabis also contains therapeutically active components which are CB₁ receptor independent.

Of the CB₁ receptor-independent cannabis, the most important is CBD.

In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD.

In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis.

The cerebroprotective action of CBD is CB₁ receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance.

In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.”

https://www.ncbi.nlm.nih.gov/pubmed/27713349

Dendritic Cell Regulation by Cannabinoid-Based Drugs.

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“Cannabinoid pharmacology has made important advances in recent years after the cannabinoid system was discovered.

Studies in experimental models and in humans have produced promising results using cannabinoid-based drugs for the treatment of obesity and cancer, as well as neuroinflammatory and chronic inflammatory diseases.

Moreover, as we discuss here, additional studies also indicates that these drugs have immunosuppressive and anti-inflammatory properties including modulation of immune cell function.

Thus, manipulation of the endocannabinoid system in vivo may provide novel therapeutic strategies against inflammatory disorders.

At least two types of cannabinoid receptors, cannabinoid 1 and cannabinoid 2 receptors are expressed on immune cells such as dendritic cells (DC). Dendritic cells are recognized for their critical role in initiating and maintaining immune responses.

Therefore, DC are potential targets for cannabinoid-mediated modulation.

Here, we review the effects of cannabinoids on DC and provide some perspective concerning the therapeutic potential of cannabinoids for the treatment of human diseases involving aberrant inflammatory processes.”

https://www.ncbi.nlm.nih.gov/pubmed/27713374

Dysregulation of the endocannabinoid signaling system in the cerebellum and brainstem in a transgenic mouse model of spinocerebellar ataxia type-3

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“Spinocerebellar ataxia type-3 (SCA-3) is a rare disease but it is the most frequent type within the autosomal dominant inherited ataxias. The disease lacks an effective treatment to alleviate major symptoms and to modify disease progression.

Our recent findings that endocannabinoid receptors and enzymes are significantly altered in the post-mortemcerebellum of patients affected by autosomal-dominant hereditary ataxias suggest that targeting the endocannabinoid signaling system may be a promising therapeutic option.

Our goal was to investigate the status of the endocannabinoid signaling system in a transgenic mouse model of SCA-3, in the two CNS structures most affected in this disease –cerebellum and brainstem-.

These animals exhibited progressive motor incoordination, imbalance, abnormal gait, muscle weakness, and dystonia, in parallel to reduced in vivobrain glucose metabolism, deterioration of specific neuron subsets located in the dentate nucleus and pontine nuclei, small changes in microglial morphology, and reduction in glial glutamate transporters.

Concerning the endocannabinoid signaling, our data indicated no changes in CB2 receptors. By contrast, CB1 receptors increased in the Purkinje cell layer, in particular in terminals of basket cells, but they were reduced in the dentate nucleus.

We also measured the levels of endocannabinoid lipids and found reductions in anandamide and oleanolamideoyleth in the brainstem. These changes correlated with an increase in the FAAH enzyme in the brainstem, which also occurred in some cerebellar areas, whereas other endocannabinoid-related enzymes were not altered.

Collectively, our results in SCA-3 mutant mice confirm a possible dysregulation in the endocannabinoid system in the most important brain structures affected in this type of ataxia, suggesting that a pharmacological manipulation addressed to correct these changes could be a promising option in SCA-3.”

http://www.sciencedirect.com/science/article/pii/S0306452216305012

Activation of Cannabinoid Receptor 2 Attenuates Mechanical Allodynia and Neuroinflammatory Responses in a Chronic Post-Ischemic Pain Model of Complex Regional Pain Syndrome Type I in Rats.

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“Complex regional pain syndrome type 1 (CRPS-I) remains one of the most clinically challenging neuropathic pain syndromes and its mechanism has not been fully characterized.

Cannabinoid receptor 2 (CB2) has emerged as a promising target for treating different neuropathic pain syndromes.

In neuropathic pain models, activated microglia expressing CB2 receptors are seen in the spinal cord.

Chemokine fractalkine receptor (CX3CR1) plays a substantial role in microglial activation and neuroinflammation.

We hypothesized that CB2 agonist could modulate neuroinflammation and neuropathic pain in an ischemia model of CRPS by regulating CB2 and CX3CR1 signaling.

We used chronic post-ischemia pain (CPIP) as a model of CRPS-I. Rats in the CPIP group exhibited significant hyperemia and edema of the ischemic hindpaw and spontaneous pain behaviors (hindpaw shaking and licking).

Intraperitoneal administration of MDA7 (a selective CB2 agonist) attenuated mechanical allodynia induced by CPIP. MDA7 treatment was found to interfere with early events in the CRPS-I neuroinflammatory response by suppressing peripheral edema, spinal microglial activation and expression of CX3CR1 and CB2 receptors on the microglia in the spinal cord.

MDA7 also mitigated the loss of intraepidermal nerve fibers induced by CPIP. Neuroprotective effects of MDA7 were blocked by a CB2 antagonist, AM630.

Our findings suggest that MDA7, a novel CB2 agonist, may offer an innovative therapeutic approach for treating neuropathic symptoms and neuroinflammatory responses induced by CRPS-I in the setting of ischemia and reperfusion injury.”

https://www.ncbi.nlm.nih.gov/pubmed/27717112

Gingival Stromal Cells as an In Vitro Model: Cannabidiol Modulates Genes Linked with Amyotrophic Lateral Sclerosis.

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“Research in recent years has extensively investigated the therapeutic efficacy of mesenchymal stromal cells in regenerative medicine for many neurodegenerative diseases at preclinical and clinical stages.

However, the success rate of stem cell therapy remains less at translational phase. Lack of relevant animal models that potentially simulate the molecular etiology of human pathological symptoms might be a reason behind such poor clinical outcomes associated with stem cell therapy.

Apparently, self-renewal and differentiation ability of mesenchymal stem cells may help to study the early developmental signaling pathways connected with the diseases, such as Alzheimer’s disease, Amyotrophic lateral sclerosis (ALS), etc., at in vitro level.

Cannabidiol, a non-psychotrophic cannabinoid, has been demonstrated as a potent anti-inflammatory and neuroprotective agent in neurological preclinical models.

In the present study, we investigated the modulatory role of cannabidiol on genes associated with ALS using human gingiva-derived mesenchymal stromal cells (hGMSCs) as an in vitro model system.

Next generation transcriptomic sequencing analysis demonstrated considerable modifications in the expression of genes connected with ALS pathology, oxidative stress, mitochondrial dysfunction, and excitotoxicity in hGMSCs treated with cannabidiol.

Our results suggest the efficacy of cannabidiol to delineate the unknown molecular pathways, which may underlie ALS pathology at early stage using hGMSCs as a compelling in vitro system.”

https://www.ncbi.nlm.nih.gov/pubmed/27714895

Leveraging allostery to improve G protein-coupled receptor (GPCR)-directed therapeutics: cannabinoid receptor 1 as a discovery target.

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“Allosteric modulators of G-protein coupled receptors (GPCRs) hold the promise of improved pharmacology and safety over typical orthosteric GPCR ligands.

These features are particularly relevant to the cannabinoid receptor 1 (CB1R) GPCR, since typical orthosteric CB1R ligands are associated with adverse events that limit their translational potential.

Areas covered: The contextual basis for applying allostery to CB1R is considered from pharmacological, drug-discovery, and medicinal standpoints.

Rational design of small-molecule CB1R allosteric modulators as potential pharmacotherapeutics would be greatly facilitated by direct experimental characterization of structure-function correlates underlying the biological activity of chemically-diverse CB1R allosteric modulators, CB1R allosteric ligand-binding binding pockets, and amino acid contact residues critical to allosteric ligand engagement and activity.

In these regards, designer covalent probes exhibiting well-characterized molecular pharmacology as CB1R allosteric modulators are emerging as valuable molecular reporters enabling experimental interrogation of CB1R allosteric site(s) and informing the design of new CB1R agents as drugs.

Expert opinion: Synthesis and pharmacological profiling of CB1R allosteric ligands will continue to provide valuable insights into CB1R structure-function correlates. The resulting data should expand the repertoire of novel agents capable of exerting therapeutic benefit by modulating CB1R-dependent signaling.”

 https://www.ncbi.nlm.nih.gov/pubmed/27712124

Cannabinoids and GI Disorders: Endogenous and Exogenous.

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“Despite the political and social controversy affiliated with it, the medical community must come to the realization that cannabinoids exist as a ubiquitous signaling system in many organ systems. Our understanding of cannabinoids and how they relate not only to homeostasis but also in disease states must be furthered through research, both clinically and in the laboratory. The identification of the cannabinoid receptors in the early 1990s have provided us with the perfect target of translational research. Already, much has been done with cannabinoids and the nervous system. Here, we explore the implications it has for the gastrointestinal tract. Most therapeutics currently on the market presently target only one aspect of the cannabinoid system. Our main purpose here is to highlight areas of research and potential avenues of discovery that the cannabinoid system has yet to reveal.”

https://www.ncbi.nlm.nih.gov/pubmed/27699625

Acute and chronic effects of cannabidiol on Δ⁹-tetrahydrocannabinol (Δ⁹-THC)-induced disruption in stop signal task performance.

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“Recent clinical and preclinical research has suggested that cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) have interactive effects on measures of cognition; however, the nature of these interactions is not yet fully characterized.

To address this, we investigated the effects of Δ9-THC and CBD independently and in combination with proposed therapeutic dose ratios of 1:1 and 1:3 Δ9-THC:CBD in adult rhesus monkeys performing a stop signal task (SST).

These results indicate that CBD, when combined with Δ9-THC in clinically available dose ratios, does not exacerbate and, under restricted conditions may even attenuate, Δ9-THC’s behavioral effects.”

https://www.ncbi.nlm.nih.gov/pubmed/27690502

β-caryophyllene and β-caryophyllene oxide-natural compounds of anticancer and analgesic properties.

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Cancer Biology & Medicine

“Natural bicyclic sesquiterpenes, β-caryophyllene (BCP) and β-caryophyllene oxide (BCPO), are present in a large number of plants worldwide.

Both BCP and BCPO (BCP(O)) possess significant anticancer activities, affecting growth and proliferation of numerous cancer cells.

In addition, both compounds potentiate the classical drug efficacy by augmenting their concentrations inside the cells.

BCP is a phytocannabinoid with strong affinity to cannabinoid receptor type 2 (CB2 ), but not cannabinoid receptor type 1 (CB1 ). In opposite, BCP oxidation derivative, BCPO, does not exhibit CB1/2 binding, thus the mechanism of its action is not related to endocannabinoid system (ECS) machinery.

It is known that BCPO alters several key pathways for cancer development, such as mitogen-activated protein kinase (MAPK), PI3K/AKT/mTOR/S6K1 and STAT3 pathways. In addition, treatment with this compound reduces the expression of procancer genes/proteins, while increases the levels of those with proapoptotic properties.

The selective activation of CB2 may be considered a novel strategy in pain treatment, devoid of psychoactive side effects associated with CB1 stimulation. Thus, BCP as selective CB2 activator may be taken into account as potential natural analgesic drug.

Moreover, due to the fact that chronic pain is often an element of cancer disease, the double activity of BCP, anticancer and analgesic, as well as its beneficial influence on the efficacy of classical chemotherapeutics, is particularly valuable in oncology.

This review is focused on anticancer and analgesic activities of BCP and BCPO, the mechanisms of their actions, and potential therapeutic utility.”

https://www.ncbi.nlm.nih.gov/pubmed/27696789

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”  http://www.ncbi.nlm.nih.gov/pubmed/23138934