Tag Archives: THC

Update on the Role of Cannabinoid Receptors after Ischemic Stroke

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“The endocannabinoid system is considered as a major modulator of the cerebral blood flow, neuroinflammation, and neuronal survival… Evidence from animal models and in vitro studies suggests a global protective role for cannabinoid receptors agonists in ischemic stroke…Given its potent anti-inflammatory activities on circulating leukocytes, the CB2 activation has been proven to produce protective effects against acute poststroke inflammation. In this paper, we will update evidence on different cannabinoid-triggered avenues to reduce inflammation and neuronal injury in acute ischemic stroke…

Synthetic cannabinoids have been also investigated in animal models showing an improvement of the ischemic injury in the liver, heart, and brain. Furthermore, phytocannabinoids have been also isolated from the Cannabis sativa. Since this plant contains about 80 different cannabinoids, a strong work is still needed to test all these active compounds. This delay in cannabinoid research might be also due to the very low dose of certain cannabinoids in the plant. Thus, since Δ9-tetrahydrocannabidiol (THC) and cannabidiol (CBD) represent up to 40% of the total cannabinoid mass, these compounds have been considered as the most active mediators…

The encouraging therapeutic results of this study are in partial contrast with previous case reports, suggesting a potential relationship between stroke and chronic cannabis abuse in young human beings…

We believe that the “cannabinoid” approach represents an interesting therapeutic strategy still requiring further validations to improve neurologic and inflammatory outcomes in ischemic stroke.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337695/

Increased Severity of Stroke in CB1 Cannabinoid Receptor Knock-Out Mice

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“These findings indicate that endogenous cannabinoid signaling pathways protect mice from ischemic stroke by a mechanism that involves CB1 receptors, and suggest that both blood vessels and neurons may be targets of this protective effect.

 Endogenous cannabinoid signaling pathways have been implicated in protection of the brain from hypoxia, ischemia, and trauma…

Cannabinoids, which include the marijuana constituent Δ9-tetrahydrocannabinol and endogenous cannabinoids (endocannabinoids) produced in the brain, exert many of their effects through the G-protein-coupled CB1 receptor.

Cannabinoids reduce neuronal death from a variety of insults, including excitotoxicity, oxidative stress, hypoxia, ischemic stroke and trauma…

Clinical stroke, which usually results from cerebral ischemia, is a common and frequently incapacitating problem for which satisfactory treatment is generally unavailable. Identifying new endogenous systems that mitigate ischemic brain injury through effects on neurons, blood vessels, or both (such as the endocannabinoid signaling pathway) may help to guide the search for improved therapies.”

Full text: http://www.jneurosci.org/content/22/22/9771.long

Dronabinol for supportive therapy in patients with malignant melanoma and liver metastases.

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“Loss of appetite and nausea can reduce the quality of life of patients with malignant melanoma and liver metastases. Often established antiemetic drugs fail to bring relief. Tetrahydrocannabinol (THC, Marinol), which is the active agent of Indian hemp, has been used successfully in this situation for other malignant tumors.

PATIENTS AND METHODS:

We treated 7 patients with hematogenous metastatic melanoma and liver metastases suffering from extensive loss of appetite and nausea supportively with dronabinol (Marinol. All of these patients had previously received standard antiemetic therapy without adequate relief. Dronabinol is a synthetic Delta-tetrahydrocannabinol. The drug was administered in capsule form. We evaluated the palliative effects of dronabinol with a special patient evaluation form, which was filled out at the beginning of the therapy and again after 4 weeks.

RESULTS:

The majority of patients described a significant increase in appetite and decrease in nausea. These effects remained for some weeks, but then decreased as metastases progressed and the general condition worsened. All of the patients experienced slight to moderate dizziness, but it was not sufficiently troubling to cause interruption or termination of therapy.

CONCLUSION:

Loss of appetite and nausea due to liver metastases of malignant melanoma can be treated in individual cases supportively with Dronabinol.”

http://www.ncbi.nlm.nih.gov/pubmed/16408219

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

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

Cannabinoids Halt Pancreatic Cancer, Breast Cancer Growth, Studies Say

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“Compounds in cannabis inhibit cancer cell growth in human breast cancer cell lines and in pancreatic tumor cell lines, according to a pair of preclinical trials published in the July issue of the journal of the American Association for Cancer Research.

In one trial, investigators at Complutense University in Spain and the Institut National de la Sante et de la Recherche Medicale (INSERM) in France assessed the anti-cancer activity of cannabinoids in pancreatic cancer cell lines and in animals. Cannabinoid administration selectively increased apoptosis (programmed cell death) in pancreatic tumor cells while ignoring healthy cells, researchers found. In addition, “cannabinoid treatment inhibited the spreading of pancreatic tumor cells … and reduced the growth of tumor cells” in animals.

“These findings may contribute to … a new therapeutic approach for the treatment of pancreatic cancer,” authors concluded.

In the second trial, investigators at Spain’s Complutense University reported that THC administration “reduces human breast cancer cell proliferation [in vitro] by blocking the progression of the cell cycle and by inducing apoptosis.” Authors concluded that their findings “may set the bases for a cannabinoid therapy for the management of breast cancer.”

Previous preclinical data published in May in the Journal of Pharmacological and Experimental Therapeutics reported that non-psychoactive cannabinoids, particularly cannabidiol (CBD), dramatically halt the spread of breast cancer cells and recommended their use in cancer therapy.

Separate trials have also shown cannabinoids to reduce the size and halt the spread of glioma (brain tumor) cells in animals and humans in a dose dependent manner. Additional preclinical studies have demonstrated cannabinoids to inhibit cancer cell growth and selectively trigger malignant cell death in skin cancer cells, leukemic cells, lung cancer cells, and prostate carcinoma cells, among other cancerous cell lines.”

http://norml.org/news/2006/07/06/cannabinoids-halt-pancreatic-cancer-breast-cancer-growth-studies-say

Cannabinoids and anxiety.

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“The term cannabinoids encompasses compounds produced by the plant Cannabis sativa, such as delta9-tetrahydrocannabinol, and synthetic counterparts. Their actions occur mainly through activation of cannabinoid type 1 (CB1) receptors. Arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol (2-AG) serve as major endogenous ligands (endocannabinoids) of CB1 receptors. Hence, the cannabinoid receptors, the endocannabinoids, and their metabolizing enzymes comprise the endocannabinoid system. Cannabinoids induce diverse responses on anxiety- and fear-related behaviors. Generally, low doses tend to induce anxiolytic-like effects, whereas high doses often cause the opposite. Inhibition of endocannabinoid degradation seems to circumvent these biphasic effects by enhancing CB1 receptor signaling in a temporarily and spatially restricted manner, thus reducing anxiety-like behaviors. Pharmacological blockade or genetic deletion of CB1 receptors, in turn, primarily exerts anxiogenic-like effects and impairments in extinction of aversive memories. Interestingly, pharmacological blockade of Transient Receptor Potential Vanilloid Type-1 (TRPV1) channel, which can be activated by anandamide as well, has diametrically opposite consequences. This book chapter summarizes and conceptualizes our current knowledge about the role of (endo)cannabinoids in fear and anxiety and outlines implications for an exploitation of the endocannabinoid system as a target for new anxiolytic drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/21309120

Pharmacological exploitation of the endocannabinoid system: new perspectives for the treatment of depression and anxiety disorders?

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 “Animal experiments suggest that drugs promoting endocannabinoid action may represent a novel strategy for the treatment of depression and anxiety disorders.

Because of its analgesic, antiemetic and tranquilizing effects, the herb Cannabis sativa has been used for medical purposes for centuries. In addition, preparations of cannabis, such as marijuana, hashish or skunk, have a long history as drugs of abuse.1 Typical effects of cannabis abuse are amnesia, sedation and a feeling of well-being described as “bliss”.2 In the middle of the last century, Raphael Mechoulam and colleagues identified Δ9-tetrahydrocannabinol (Δ9-THC) as the main psychoactive ingredient of this herb. Today, it is known that Cannabis sativa contains more than 60 substances, such as cannabidiol, cannabinol and cannabicromene, which are referred to as phytocannabinoids.3 Their lipid nature posed a significant obstacle to chemical experiments, which might explain why the discovery of phytocannabinoids occurred late compared to other natural compounds (e.g. morphine was isolated from opium in the XIX century). The molecular structure rendered it likely that Δ9-THC exerts its effects primarily by changing physico-chemical characteristics of cell membranes. Therefore it came as a surprise that specific binding sites could be identified within the mammalian brain,4 followed by isolation and characterization of endogenous binding substances, named endocannabinoids.5 The development of novel pharmacological compounds targeting receptors or ligand synthesis and degradation revealed a number of complex brain functions, which are tightly controlled by the endocannabinoid system. The aim of the present review is to briefly introduce this system and its pharmacology, to discuss its involvement in psychopathology and to illustrate its therapeutic potential.

 Conclusion

 Malfunctions in the endocannabinoid system may promote the development and maintenance of psychiatric disorders such as depression, phobias and panic disorder. Thus, CB1 agonists or inhibitors of anandamide hydrolysis are expected to exert antidepressant and anxiolytic effects. Future studies should consider 1) the development of CB1 antagonists that cannot readily cross the blood-brain barrier, 2) shifts in the balance of CB1 vs. TRPV1 signalling, 3) the allosteric site of CB1 receptor and 4) the potential involvement of CB2 receptor in mood regulation. Striking similarities in (endo)cannabinoid action in animals and men render it likely that the new pharmacological principle outlined in the present article may find their way into clinical practice.”

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462010000500004&lng=en&nrm=iso&tlng=en