Tag Archives: cannabinoid

CB1 cannabinoid receptor induction in experimental stroke.

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“Cannabinoids protect cortical neurons from ischemic injury by interacting with CB1 receptors. Because a variety of neuroprotective genes are induced in cerebral ischemia, we examined the effect of experimental stroke, produced by 20 minutes of middle cerebral artery occlusion in rats, on CB1 receptor expression.

Western blotting and immunohistochemistry showed that CB1 expression on neurons was increased in the arterial boundary zone of the cortical mantle, beginning by 2 hours and persisting for 72 hours or more after ischemia.

These findings are consistent with a neuroprotective role for endogenous cannabinoid signaling pathways and with a potential therapeutic role in stroke for drugs that activate CB1 receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/10939579

Endocannabinoids and obesity.

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“A safe and effective antiobesity drug is needed to combat the global obesity epidemic. The discovery of cannabinoids from medicinal herbs has revealed the endocannabinoid system (ECS) in animals and humans, which regulates various physiological activities such as feeding, thermogenesis, and body weight (BW).

Although cannabinoid receptors 1 (CB1) antagonists have shown antiobesity efficacies in animal models and in the clinic, they failed to establish as a treatment due to their psychological side effects.

 Recent studies indicate that CB1 in various peripheral tissues may mediate some of the therapeutic effects of CB1 antagonists, such as improved lipid and glucose homeostasis.

 It rationalizes the development of compounds with limited brain penetration, for minimizing the side effects while retaining the therapeutic efficacies. A survey of the literature has revealed some controversies about how the ECS affects obesity. This review summarizes the research progresses and discusses some future perspectives.”

http://www.ncbi.nlm.nih.gov/pubmed/23374723

Cannabinoid receptors as novel targets for the treatment of melanoma

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“Melanoma causes the greatest number of skin cancer-related deaths worldwide. Here, we evaluated the efficacy of cannabinoid receptor agonists, a new family of potential antitumoral compounds, at skin melanoma. Human melanomas and melanoma cell lines express CB1 and CB2 cannabinoid receptors. Activation of these receptors decreased growth, proliferation, angiogenesis and metastasis, and increased apoptosis, of melanomas in mice. Cannabinoid antimelanoma activity was independent of the immune status of the animal, could be achieved without overt psychoactive effects and was selective for melanoma cells vs. normal melanocytes.

Cannabinoid antiproliferative action on melanoma cells…

 These findings may contribute to the design of new chemotherapeutic strategies for the management of melanoma.

 …the present report, together with the implication of CB2 receptors in the control of processes such as pain initiation, emesis, and inflammation, opens the attractive possibility of finding cannabinoid-based therapeutic strategies devoid of nondesired psychotropic side effects.

Specifically, the antiproliferative effect of cannabinoids reported here may set the basis for a new therapeutic approach for the treatment of malignant melanoma.”

Full text: http://www.fasebj.org/content/20/14/2633.long

Inhibition of basal and ultraviolet B-induced melanogenesis by cannabinoid CB(1) receptors: a keratinocyte-dependent effect.

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“Ultraviolet radiation is the major environmental insult to the skin and stimulates the synthesis of melanin in melanocytes, which then distribute it to the neighboring keratinocytes where it confers photo-protection. Skin color results from the paracrine interaction between these two cell types. Recent studies suggest that endocannabinoids are potential mediators in the skin. Here, we investigated whether cannabinoid drugs play a role in melanogenesis and if ultraviolet radiation modifies the cutaneous endocannabinoid system.

We provide evidence that human melanoma cells (SK-mel-1) express CB(1) receptors… 

Furthermore, ultraviolet-B radiation increased endocannabinoids levels only in keratinocytes, whereas CB(1) cannabinoid receptor expression was up-regulated only in melanoma cells.

Our results collectively suggest that ultraviolet radiation activates paracrine CB(1)-mediated endocannabinoid signaling to negatively regulate melanin synthesis.

The endocannabinoid system in the skin may be a possible target for future therapies in pigmentary disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/21298280

The antimitogenic effect of the cannabinoid receptor agonist WIN55212-2 on human melanoma cells is mediated by the membrane lipid raft.

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“Here are reported the antiproliferative effects of the cannabinoid agonist WIN upon human melanoma cells expressing mRNA and protein for both CB1 and CB2 receptors.

While WIN exerted antimitogenic effects, selective CB1 or CB2 agonists were unable to reproduce such effects and selective CB1 and CB2 antagonists did not inhibit WIN-induced cell death. Cells treated with WIN, preincubated with the lipid raft disruptor methylcyclodestrin, were rescued from death. WIN induced activation of caspases and phosphorylation of ERK that were attenuated in cultures treated with methylcyclodestrin.

 Membrane lipid raft complex-mediated antimitogenic effect of WIN in melanoma could represents a potential targets for a melanoma treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/21807457

Cannabidiol Inhibits Growth and Induces Programmed Cell Death in Kaposi Sarcoma–Associated Herpesvirus-Infected Endothelium

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“Kaposi sarcoma is the most common neoplasm caused by Kaposi sarcoma–associated herpesvirus (KSHV). Current treatments for Kaposi sarcoma can inhibit tumor growth but are not able to eliminate KSHV from the host. When the host’s immune system weakens, KSHV begins to replicate again, and active tumor growth ensues. New therapeutic approaches are needed.

Cannabidiol (CBD), a plant-derived cannabinoid, exhibits promising antitumor effects without inducing psychoactive side effects. CBD is emerging as a novel therapeutic for various disorders, including cancer.

In this study, we investigated the effects of CBD both on the infection of endothelial cells (ECs) by KSHV and on the growth and apoptosis of KSHV-infected ECs, an in vitro model for the transformation of normal endothelium to Kaposi sarcoma….

Cannabidiol (CBD) was first isolated in 1940. It is a major component of the plant Cannabis sativa, which is also the source of Δ9-tetrahydrocannabinol (Δ9-THC). Due to its multiple biological activities, CBD has been identified as a potential clinical agent. Moreover, CBD affects these activities without the psychoactive side effects that typify Δ9-THC. Recent studies have documented the potential antitumorigenic properties of CBD in the treatment of various neoplasms, including breast cancer, lung cancer, bladder cancer, glioblastoma,and leukemia.CBD induces these effects through a variety of mechanisms and signaling pathways

CBD has been evaluated clinically for the treatment of various conditions, including anxiety, psychosis, and pain. In contrast to other members of the cannabinoid family, CBD has a strong safety profile and induces no psychotropic effects.Therefore, it has become an attractive agent in the search for new anticancer therapies.Our current study demonstrated that CBD preferentially enhanced apoptosis and inhibited the proliferation of KSHV-infected endothelial cells. This selective targeting of KSHV-induced neoplasia suggests that CBD may have a desirable therapeutic index when used to treat cancer. Moreover, a recent study demonstrated that CBD can be delivered effectively by nasal and transdermal routes, which may be particularly valuable for the treatment of Kaposi sarcoma oral or skin lesions.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527984/

New Study: Cannabidiol, a non- THC compound derived from Marijuana effectively treats schizophrenia.

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“A certain marijuana compound known as cannabidiol (CBD) can treat schizophrenia as well as antipsychotic drugs, with far fewer side effects, according to a preliminary clinical trial. Cannabidiol differs from THC which is the much publicized intoxicating chemical in THC.”

 “The results were amazing,” said Daniel Piomelli, Ph.D., professor of pharmacology at the University of California-Irvine and a co-author of the study. “Not only was [CBD] as effective as standard antipsychotics, but it was also essentially free of the typical side effects seen with antipsychotic drugs.””

Read more: http://www.classicalmedicinejournal.com/the-classical-medicine-journal/2012/6/18/new-study-cannabidiol-a-non-thc-compound-derived-from-mariju.html

Cannabidiol Relieves Psychosis in Schizophrenia, Why is it Illegal?

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“A molecule in cannabis (CBD) has shown to relieve anxiety and symptoms of psychosis in people diagnosed with schizophrenia, though many patients are denied or discouraged from this medicine with fewer side effects than pharmaceutical products because the DEA has deemed the cannabis plant to be “illegal”. The U.S. government needs to answer “why?” this medicine warrents time in prison when nobody is being harmed.

 Investigators concluded, “Our results provide evidence that the non-cannabimimetic constituent of marijuana, cannabidiol, exerts clinically relevant antipsychotic effects that are associated with marked tolerability and safety, when compared with current medications. … The results … potentially represent a completely new mechanism in the treatment of schizophrenia.”

 “Studies have suggested a wide range of possible therapeutic effects of cannabidiol on several conditions, including Parkinson’s disease, Alzheimer’s disease, cerebral ischemia, diabetes, rheumatoid arthritis, other inflammatory diseases, nausea and cancer,” Zuardi writes. Let’s look at a few of these in detail, shall we?

1. Antiepileptic action
“In 1973, a Brazilian group reported that CBD was active in … blocking convulsions produced in experimental animals.”

2. Sedative action
“In humans with insomnia, high doses of CBD increased sleep duration compared to placebo.”

3. Anxiolytic action
“CBD induce[s] a clear anxiolytic effect and a pattern of cerebral activity compatible with an anxiolytic activity.”

4. Antipsychcotic action
“[C]linical studies suggest that CBD is an effective, safe and well-tolerated alternative treatment for schizophrenic patients.”

5. Antidystonic action
“CBD … had antidystonic effects in humans when administered along with standard medication to five patients with dystonia, in an open study.”

6. Antioxidative action
“[I]t was demonstrated that CBD can reduce hydroperoxide-induced oxidative damage as well as or better than other antioxidants. CBD was more protective against glutamate neurotoxicity than either ascorbate or a-tocopherol, indicating that this drug is a potent antioxidant.”

7. Neuroprotective action
“A marked reduction in the cell survival was observed following exposure of cultured rat pheochromocytoma PC12 cells to beta-A peptide. Treatment of the cells with CBD prior to beta-A exposure significantly elevated the cell survival.”

8. Antiinflammatory action
“CBD, administered i.p. or orally, has blocked the progression of arthritis.”

9. Cardioprotective action
“CBD induces a substantial cardioprotective effect.”

10. Action on diabetes
“CBD treatment of NOD (non-obese diabetic) mice before the development of the disease reduced its incidence from 86% in the non-treated control mice to 30% in CBD-treated mice. … It was also observed that administration of CBD to 11-14 week old female NOD mice, which were either in a latent diabetes stage or had initial symptoms of diabetes, ameliorated the manifestations of the disease.”

11. Antiemetic action
“The expression of this conditioned retching reaction was completely suppressed by CBD and delta9-THC, but not by ondansetron, [an] antagonist that interferes with acute vomiting.”

12. Anticancer action
“A study of the effect of different cannabinoids on eight tumor cell lines, in vitro, has clearly indicated that, of the five natural compounds tested, CBD was the most potent inhibitor of cancer cell growth.”

In sum, the past 45 years of scientific study on CBD has revealed the compound to be non-toxic, non-psychoactive, and to possess a multitude of therapeutic properties. Yet, to this day it remains illegal to possess or use (and nearly impossible to study in US clinical trials) simply because it is associated with marijuana.

What possible advancements in medical treatment may have been achieved over the past decades had US government officials chosen to advance — rather than inhibit — clinical research into CBD (which, under federal law, remains a Schedule I drug defined as having “no currently accepted medical use”)? Perhaps it’s time someone asks John Walters or the DEA?” 

Read more: http://rinf.com/alt-news/latest-news/cannabidiol-relieves-psychosis-in-schizophrenia-why-is-it-illegal/17827/

Local Delivery of Cannabinoid-Loaded Microparticles Inhibits Tumor Growth in a Murine Xenograft Model of Glioblastoma Multiforme

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“Treatment with cannabinoid-loaded microparticles activates apoptosis and inhibits tumor angiogensis. The aim of the present study was therefore to evaluate the antitumor efficacy of biodegradable polymeric microparticles allowing the controlled release of the phytocannabinoids THC and CBD. Our findings show that administration of cannabinoid-loaded microparticles reduces the growth of glioma xenografts supporting that this method of administration could be exploited for the design of cannabinoid-based anticancer treatments.

Cannabinoids, the active components of marijuana and their derivatives, are currently investigated due to their potential therapeutic application for the management of many different diseases, including cancer. Specifically, Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) – the two major ingredients of marijuana – have been shown to inhibit tumor growth in a number of animal models of cancer, including glioma. Although there are several pharmaceutical preparations that permit the oral administration of THC or its analogue nabilone or the oromucosal delivery of a THC- and CBD-enriched cannabis extract, the systemic administration of cannabinoids has several limitations in part derived from the high lipophilicity exhibited by these compounds. In this work we analyzed CBD- and THC-loaded poly-ε-caprolactone microparticles as an alternative delivery system for long-term cannabinoid administration in a murine xenograft model of glioma. In vitro characterization of THC- and CBD-loaded microparticles showed that this method of microencapsulation facilitates a sustained release of the two cannabinoids for several days. Local administration of THC-, CBD- or a mixture (1:1 w:w) of THC- and CBD-loaded microparticles every 5 days to mice bearing glioma xenografts reduced tumour growth with the same efficacy than a daily local administration of the equivalent amount of those cannabinoids in solution. Moreover, treatment with cannabinoid-loaded microparticles enhanced apoptosis and decreased cell proliferation and angiogenesis in these tumours. Our findings support that THC- and CBD-loaded microparticles could be used as an alternative method of cannabinoid delivery in anticancer therapies.

Δ9-Tetrahydrocannabinol (THC), the main active component of the hemp plant Cannabis sativa, exerts a wide variety of biological effects by mimicking endogenous substances – the endocannabinoids – that bind to and activate specific cannabinoid receptors. So far, two G protein–coupled cannabinoid-specific receptors have been cloned and characterized from mammalian tissues: CB1, abundantly expressed in the brain and at many peripheral sites, and CB2, expressed in the immune system and also present in some neuron subpopulations and glioma cells. One of the most active areas of research in the cannabinoid field is the study of the potential application of cannabinoids in the treatment of different pathologies. Among these therapeutic applications, cannabinoids are being investigated as anti-tumoral agents. Thus, cannabinoid administration curbs the growth of several types of tumor xenografts in rats and mice including gliomas. Based on this preclinical evidence, a pilot clinical trial has been recently run to investigate the anti-tumor action of THC on recurrent gliomas. The mechanism of THC anti-tumoral action relies on the ability of this compound to: (i) promote the apoptotic death of cancer cells (ii) to inhibit tumour angiogenesis and (iii) to reduce the migration of cancer cells.

Conclusions

Data presented in this manuscript show for the first time that in vivo administration of microencapsulated cannabinoids efficiently reduces tumor growth thus providing a proof of concept for the utilization of this formulation in cannabinoid-based anti-cancer therapies.”

Full text: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0054795. 

Cannabinoids for Cancer Treatment: Progress and Promise

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Cancer Research: 68 (2)

“Cannabinoid refers to a group of chemicals naturally found in the marijuana plant Cannabis sativa L. and includes compounds that are either structurally or pharmacologically similar to Δ(9)-tetrahydrocannabinol or those that bind to the cannabinoid receptors. Although anticancer effects of cannabinoids were shown as early as 1975 in Lewis lung carcinoma, renewed interest was generated little after the discovery of the cannabinoid system and cloning of the specific cannabinoid receptors.

Cannabinoids are a class of pharmacologic compounds that offer potential applications as antitumor drugs, based on the ability of some members of this class to limit inflammation, cell proliferation, and cell survival. In particular, emerging evidence suggests that agonists of cannabinoid receptors expressed by tumor cells may offer a novel strategy to treat cancer. Here, we review recent work that raises interest in the development and exploration of potent, nontoxic, and nonhabit forming cannabinoids for cancer therapy.”

Full Text: http://cancerres.aacrjournals.org/content/68/2/339.long