Category Archives: THC (Delta-9-Tetrahydrocannabinol)

The pharmacologic and clinical effects of medical cannabis.

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“Cannabis, or marijuana, has been used for medicinal purposes for many years. Several types of cannabinoid medicines are available in the United States and Canada. Dronabinol (schedule III), nabilone (schedule II), and nabiximols (not U.S. Food and Drug Administration approved) are cannabis-derived pharmaceuticals.

Medical cannabis or medical marijuana, a leafy plant cultivated for the production of its leaves and flowering tops, is a schedule I drug, but patients obtain it through cannabis dispensaries and statewide programs. The effect that cannabinoid compounds have on the cannabinoid receptors (CB(1) and CB(2) ) found in the brain can create varying pharmacologic responses based on formulation and patient characteristics. The cannabinoid Δ(9) -tetrahydrocannabinol has been determined to have the primary psychoactive effects; the effects of several other key cannabinoid compounds have yet to be fully elucidated. Dronabinol and nabilone are indicated for the treatment of nausea and vomiting associated with cancer chemotherapy and of anorexia associated with weight loss in patients with acquired immune deficiency syndrome. However, pain and muscle spasms are the most common reasons that medical cannabis is being recommended.

Studies of medical cannabis show significant improvement in various types of pain and muscle spasticity. Reported adverse effects are typically not serious, with the most common being dizziness. Safety concerns regarding cannabis include the increased risk of developing schizophrenia with adolescent use, impairments in memory and cognition, accidental pediatric ingestions, and lack of safety packaging for medical cannabis formulations. This article will describe the pharmacology of cannabis, effects of various dosage formulations, therapeutics benefits and risks of cannabis for pain and muscle spasm, and safety concerns of medical cannabis use.”

http://www.ncbi.nlm.nih.gov/pubmed/23386598

Medical Cannabis Provides Dramatic Relief for Sufferers of Chronic Ailments, Israeli Study Finds

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“Though controversial, medical cannabis has been gaining ground as a valid therapy, offering relief to suffers of diseases such as cancer, Post-Traumatic Stress Disorder, ALS and more. The substance is known to soothe severe pain, increase the appetite, and ease insomnia where other common medications fail.”

 

“Overall, Klein believes that the healing powers of cannabis are close to miraculous, and has long supported an overhaul in governmental policy…”

Read more: http://www.sciencedaily.com/releases/2013/01/130124123453.htm

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

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

Marijuana’s Medicinal Value Vindicated Once Again, This Time For The Elderly

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Image Credit: Photos.com

Lee Rannals for redOrbit.com – Your Universe Online

“Researchers from Tel Aviv University say that smoking a little marijuana could help provide dramatic relief for the elderly who suffer from a variety of chronic ailments.

The scientists tested the effects of marijuana treatment on 19 residents of the Hadarim nursing home in Israel. During the study, the participants reported dramatic physical results, including healthy weight gain and the reduction of pain and tremors.

According to the study authors, the elderly participants also experienced an immediate improvement in their moods and communication skills after smoking cannabis.

Zach Klein, a graduate of Tel Aviv University’s Department of Film and Television Studies, said that the use of prescription medications was also significantly reduced as a result of using medical marijuana

The active ingredient in marijuana THC was first discovered in Israel by professors Raphael Mechoulam and Yechiel Gaoni. Israel is known as the world leader in medical cannabis research, according to Klein.

During the nursing home study, 19 patents between the ages of 69 and 101 were treated with medical cannabis in the form of powder, oil, vapor or smoke three times daily over the course of a year for conditions like chronic pain, lack of appetite, and muscle spasms and tremors.

Both researchers and nursing home staff members monitored participants for signs of improvement in their conditions as well as their overall quality of life.

Seventeen of the study participants achieved a healthy weight during their use of marijuana and experienced a noticeable reduction in pain, muscle spasms, joint stiffness and tremors. Nearly all of the patients using cannabis slept better, longer and had a reduced incidence of nightmares and flashbacks related to Post-Traumatic Stress Disorder (PTSD).

The researchers also reported a decline in the amount of prescribed medications taken by patients, such as antipsychotics, Parkinson’s treatment, mood stabilizers and pain relievers. Towards the end of the study, researchers found that 72 percent of participants were able to reduce their drug intake by an average of 1.7 medications per day.

For the next phase of his research, Klein wants to study the connection between medical cannabis and an improved ability to swallow. Difficulties in swallowing can lead to a decline in nutrition and, ultimately, premature death. He believes that cannabis will have a positive impact on patients suffering from this disorder, which is known in medical jargon as dysphagia.”

http://www.redorbit.com/news/health/1112770306/medical-benefits-of-marijuana-elderly-012413/

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 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