Tag Archives: Cannabinoids

Treatment of spasticity in multiple sclerosis: new perspectives regarding the use of cannabinoids.

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“Spasticity remains a prevalent symptom in multiple sclerosis, with a significant associated disability and quality of life impairment… Cannabinoids provide a new way for therapy.

A delta-9-tetrahydrocannabinol plus cannabidiol (1:1) association, administered through an oromucosal route, has been approved in several countries including Spain; it causes a specific effect on CB(1) and CB(2) receptors, with traditional psychotropic cannabis actions being minimized.

Randomized, placebo-controlled trials, as well as longer-term open-label extensions, have shown a clear-cut efficacy to reduce spasticity and their associated symptoms in those patients refractory to other therapies, with a good tolerability/safety profile.

No tolerance, abuse or addictive issues have been found…”

http://www.ncbi.nlm.nih.gov/pubmed/23011861

Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial.

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“Clinical reports indicate that cannabinoids may alleviate pain in different pain conditions, including multiple sclerosis related pain…

Randomised double blind placebo controlled crossover trial… To evaluate the effect of the oral synthetic delta-9-tetrahydrocannabinol dronabinol on central neuropathic pain in patients with multiple sclerosis…

CONCLUSIONS:

Dronabinol has a modest but clinically relevant analgesic effect on central pain in patients with multiple sclerosis. Adverse events, including dizziness, were more frequent with dronabinol than with placebo during the first week of treatment.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC498019/

The CB2 cannabinoid receptor signals apoptosis via ceramide-dependent activation of the mitochondrial intrinsic pathway.

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“Delta9-tetrahydrocannabinol and other cannabinoids exert pro-apoptotic actions in tumor cells via the CB2 cannabinoid receptor…

 Here we used the human leukemia cell line Jurkat-that expresses CB2 as the unique CB receptor-to investigate…

 In summary, results presented here show that CB2 receptor activation signals apoptosis via a ceramide-dependent stimulation of the mitochondrial intrinsic pathway.”

http://www.ncbi.nlm.nih.gov/pubmed/16624285

Cannabinoid receptors expression in bone marrow trephine biopsy of chronic lymphocytic leukaemia patients treated with purine analogues.

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“Cannabinoid receptors CB1 and CB2 are part the endocannabinoid system that plays an important role in the process of proliferation and apoptosis of different neoplastic cells. B-cell chronic lymphocytic leukaemia is one of the diseases in which these processes are altered… The aim of our study was the assessment of cannabinoid receptor expression on the B-lymphocytes in bone marrow trephine biopsy from leukaemic patients at diagnosis and after purine analogue treatment….

CONCLUSION:

The study provides original evidence for the existence of cannabinoid receptors on B-lymphocytes in chronic lymphocytic leukaemia patients. The receptors are thought to be a new structure that can modify the course of the disease and may be considered as a new target in leukaemia treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/18004250

Δ9-Tetrahydrocannabinol-Induced Apoptosis in Jurkat Leukemia T Cells Is Regulated by Translocation of Bad to Mitochondria

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“Cannabinoids, the biologically active constituents of marijuana (Cannabis sativa)…

Plant-derived cannabinoids, including Δ9-tetrahydrocannabinol (THC), induce apoptosis in leukemic cells…

cannabinoids were shown to inhibit the proliferation of several human cancer cell lines, including leukemia…

Together, these data suggested that Raf-1/MEK/ERK/RSK-mediated Bad translocation played a critical role in THC-induced apoptosis in Jurkat cells…

THC and other cannabinoids can induce apoptosis in a variety of tumor cell lines, thereby raising the possibility of the use of cannabinoids as novel anticancer agents…”

Full text: http://mcr.aacrjournals.org/content/4/8/549.long

Cannabidiol-Induced Apoptosis in Human Leukemia Cells: A Novel Role of Cannabidiol in the Regulation of p22phox and Nox4 Expression

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“Marijuana has been suggested as a potent therapeutic agent alleviating such complications as intraocular pressure in glaucoma and cachexia, nausea, and pain in AIDS and cancer patients. A number of recent studies now suggest the possible use of these compounds for the treatment of cannabinoid receptor-expressing tumors…

In the current study, we examined the effects of the nonpsychoactive cannabinoid, cannabidiol, on the induction of apoptosis in leukemia cells. Exposure of leukemia cells to cannabidiol led to cannabinoid receptor 2 (CB2)-mediated reduction in cell viability and induction in apoptosis. Furthermore, cannabidiol treatment led to a significant decrease in tumor burden and an increase in apoptotic tumors in vivo…

Together, the results from this study reveal that cannabidiol, acting through CB2 and regulation of Nox4 and p22phox expression, may be a novel and highly selective treatment for leukemia…

In summary, the current study demonstrates that CBD-induced apoptosis may constitute a novel approach to treat malignancies of the immune system…”

Full text: http://molpharm.aspetjournals.org/content/70/3/897.long

Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL-2H3 mast cells

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“Plant-derived cannabinoids, such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the main psychoactive and nonpsychoactive components of cannabis, respectively, possess myriad pharmacological properties…

Cannabidiol (CBD), a prominent psychoinactive component of cannabis with negligible affinity for known cannabinoid receptors, exerts numerous pharmacological actions, including anti-inflammatory and immunosuppressive effects…

Together, these results support existence of yet-to-be identified sites of interaction, i.e., receptors and/or ion channels associated with Ca2+ influx of natural cannabinoids such as CBD and THC, the identification of which has the potential to provide for novel strategies and agents of therapeutic interest.”

Full text: http://www.jleukbio.org/content/81/6/1512.long

Gamma-irradiation enhances apoptosis induced by cannabidiol, a non-psychotropic cannabinoid, in cultured HL-60 myeloblastic leukemia cells.

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“Two non-psychotropic cannabinoids, cannabidiol (CBD) and cannabidiol-dimethylheptyl (CBD-DMH), induced apoptosis in a human acute myeloid leukemia (AML) HL-60 cell line…

  Caspase-3 activation was observed after the cannabinoid treatment, and may represent a mechanism for the apoptosis.

Our data suggest a possible new approach to treatment of AML.”

http://www.ncbi.nlm.nih.gov/pubmed/14692532

Cannabinoids induce incomplete maturation of cultured human leukemia cells.

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“Monocyte maturation markers were induced in cultured human myeloblastic ML-2 leukemia cells after treatment for 1-6 days with 0.03-30 microM delta 9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana…

 Cannabinoids induce incomplete maturation of cultured human leukemia cells…

Findings obtained from this system may have important implications for studies of cannabinoid effects on normal human bone-marrow progenitor cells.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC298868/

Cannabinoid-receptor expression in human leukocytes.

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“Marijuana and many of its constituent cannabinoids influence the central nervous system (CNS), probably through the cannabinoid receptor, which has recently been cloned in rat and human. While numerous reports have also described effects of cannabinoids on the immune system, the observation of both mRNA and cannabinoid receptor has hitherto been exclusively confined to the brain, a reported detection in the testis being the sole example of its presence at the periphery.

Here we report the expression of the cannabinoid receptor on human immune tissues using a highly sensitive polymerase-chain-reaction-based method for mRNA quantification. We show that, although present in a much lower abundance than in brain, cannabinoid receptor transcripts are found in human spleen, tonsils and peripheral blood leukocytes…

The demonstration of cannabinoid-receptor expression at both mRNA and protein levels on human leukocytes provides a molecular basis for cannabinoid action on these cells.”

http://www.ncbi.nlm.nih.gov/pubmed/8508790