Tag Archives: cannabis

Endocannabinoid signaling in female reproductive events: a potential therapeutic target?

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“Nearly 30 years after the discovery in 1964 of the psychoactive ingredient of cannabis (Cannabis sativa), Δ9-tetrahydrocannabinol, its endogenous counterparts were discovered and collectively termed endocannabinoids (eCBs): N-arachidonoylethanolamine (anandamide) in 1992 and 2-arachidonoylglycerol in 1995.

Since then, intense research has identified additional eCBs and an ensemble of proteins that bind, synthesize and degrade them, the so-called eCB system.

Altogether, these new compounds have been recognized as key mediators of several aspects of human pathophysiology, and in particular of female fertility.

Here, the main features of the eCB system are presented, in order to put in a better perspective the relevance of eCB signaling in virtually all steps of human reproduction and to highlight emerging hopes that elements of this system might indeed become novel targets to combat fertility problems.”

http://www.ncbi.nlm.nih.gov/pubmed/26126134

Δ-9 Tetrahydrocannabinol inhibits growth and metastasis of lung cancer.

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“Lung cancer is the major cause of cancer-related mortality worldwide.

Many of these over-express epidermal growth factor receptor (EGFR), and are usually highly aggressive and resistant to chemotherapy.

Recent studies have shown that Δ-9 Tetrahydrocannabinol (THC), the major component of Cannabis sativa, possess anti-tumor properties against various types of cancers.

However, not much is known about its effect on lung cancer. In this study, we sought to characterize the effect of THC on EGF-induced growth and metastasis of human non small lung cancer cell (NSCLC) lines A549 and SW-1573.

We demonstrate that these cell lines and primary tumor samples derived from lung cancer patients express cannabinoids receptors CB1 and CB2, the known targets for THC action.

We further show that THC inhibits EGF-induced growth in these cell lines.

In addition THC attenuated EGF-stimulated chemotaxis and chemoinvasion.

Next we characterized the effect of THC on in vivo lung cancer growth and metastasis in a murine model. A549 cells were implanted in SCID mice (n=6 per group) through subcutaneous and intravenous injections to generate subcutaneous and lung metastatic cancer, respectively. THC (5mg/kg body wt.) was administered once daily through intraperitoneal injections for 21 days. The mice were analyzed for tumor growth and lung metastasis.

A significant reduction (~50%) in tumor weight and volume were observed in THC treated animals compared to the vehicle treated animals.

THC treated animals also showed a significant (~60%) reduction in macroscopic lesions on the lung surface in comparison to vehicle treated control.

Immunohistochemical analysis of the tumor samples from THC treated animals revealed anti-proliferative and anti-angiogenic effects of THC with significant reduction in staining for Ki67, a proliferative marker and CD31, an endothelial marker indicative of vascularization. Investigation into the signaling events associated with reduced EGF-induced functional effects revealed that THC also inhibits EGF-induced Akt phosphorylation. Akt is a central signaling molecule of EGFR-mediated signaling pathways and it regulates a diverse array of cellular functions, including proliferation, angiogenesis, invasion and apoptosis.

Cumulatively, these studies indicate that THC has anti-tumorigenic and anti-metastatic effects against lung cancer. Novel therapies against EGFR overexpressing, aggressive and chemotherapy resistant lung cancers may include targeting the cannabinoids receptors.”

http://cancerres.aacrjournals.org/content/67/9_Supplement/4749.short

http://www.thctotalhealthcare.com/category/lung-cancer/

Ultralow doses of cannabinoid drugs protect the mouse brain from inflammation-induced cognitive damage.

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“In our previous studies, we found that a single ultralow dose of tetrahydrocannabinol (THC)… protects the brain from different insults that cause cognitive deficits.

Because various insults may trigger a neuroinflammatory response that leads to secondary damage to the brain, the current study tested whether this extremely low dose of THC could protect the brain from inflammation-induced cognitive deficits…

Our results suggest that an ultralow dose of THC that lacks any psychotrophic activity protects the brain from neuroinflammation-induced cognitive damage and might be used as an effective drug for the treatment of neuroinflammatory conditions, including neurodegenerative diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/25042014

Chronic administration of Δ9-tetrahydrocannabinol induces intestinal anti-inflammatory microRNA expression during acute simian immunodeficiency virus infection of rhesus macaques.

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“Recreational and medical use of cannabis among human immunodeficiency virus (HIV)-infected individuals has increased in recent years. In simian immunodeficiency virus (SIV)-infected macaques, chronic administration of Δ9-tetrahydrocannabinol (Δ9-THC) inhibited viral replication and intestinal inflammation and slowed disease progression…

These results support a role for differential miRNA induction in THC-mediated suppression of intestinal inflammation. Whether similar miRNA modulation occurs in other tissues requires further investigation.

IMPORTANCE:

Gastrointestinal (GI) tract disease/inflammation is a hallmark of HIV/SIV infection.

Previously, we showed that chronic treatment of SIV-infected macaques with Δ9-tetrahydrocannabinol (Δ9-THC) increased survival and decreased viral replication and infection-induced gastrointestinal inflammation.

Here, we show that chronic THC administration to SIV-infected macaques induced an anti-inflammatory microRNA expression profile in the intestine…

Overall, our results show that selective upregulation of anti-inflammatory miRNA expression contributes to THC-mediated suppression of gastrointestinal inflammation and maintenance of intestinal homeostasis.”

http://www.ncbi.nlm.nih.gov/pubmed/25378491

http://www.thctotalhealthcare.com/category/hivaids/

Psychological and social sequelae of cannabis and other illicit drug use by young people: a systematic review of longitudinal, general population studies.

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“Use of illicit drugs, particularly cannabis, by young people is widespread and is associated with several types of psychological and social harm. These relations might not be causal. Causal relations would suggest that recreational drug use is a substantial public health problem…

All these associations seemed to be explicable in terms of non-causal mechanisms.

Available evidence does not strongly support an important causal relation between cannabis use by young people and psychosocial harm…

The lack of evidence of robust causal relations prevents the attribution of public health detriments to illicit drug use.”

http://www.ncbi.nlm.nih.gov/pubmed/15145631

Biomedical benefits of cannabinoids?

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“Cannabinoids appear to be of therapeutic value as antiemetics, antispasmodics, analgesics and appetite stimulants and may have potential uses in epilepsy, glaucoma and asthma.

This paper reviews the clinical trials which have been carried out with cannabinoids including Δ⁹-tetrahydrocannabinol (THC) and synthetic cannabinoids such as nabilone and levonantradol, and discusses the advantages and adverse effects of cannabinoids in clinical use.

The place of cannabinoids in modern medicine remains to be properly evaluated, but present evidence suggests that they could be valuable, particularly as adjuvants, for symptom control in a range of conditions for which standard drugs are not fully satisfactory.”

Evaluation of Serum Cytokines Levels and the Role of Cannabidiol Treatment in Animal Model of Asthma.

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“Asthma represents a public health problem and traditionally is classified as an atopic disease, where the allergen can induce clinical airway inflammation, bronchial hyperresponsiveness, and reversible obstruction of airways.

Studies have demonstrated the presence of T-helper 2 lymphocytes in the lung of patients with asthma. These cells are involved in cytokine production that regulates immunoglobulin synthesis.

Recognizing that T cell interaction with antigens/allergens is key to the development of inflammatory diseases, the aim of this study is to evaluate the anti-inflammatory potential of cannabidiol (CBD) in this setting.

CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL-10 levels.

CBD seems to be a potential new drug to modulate inflammatory response in asthma.” http://www.ncbi.nlm.nih.gov/pubmed/26101464

“In conclusion, we here demonstrate that the administration of CBD in an animal model of asthma could blunt the serum cytokine response to OVA in sensitized animals. These effects suggest a potential for a new asthma treatment since CBD controls the exaggerated inflammatory response observed in this model.” https://www.hindawi.com/journals/mi/2015/538670/

Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems: A Clinical Review.

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“Use of marijuana for chronic pain, neuropathic pain, and spasticity due to multiple sclerosis is supported by high-quality evidence.

Several of these trials had positive results, suggesting that marijuana or cannabinoids may be efficacious for these indications.

CONCLUSIONS AND RELEVANCE:

Medical marijuana is used to treat a host of indications, a few of which have evidence to support treatment with marijuana and many that do not. Physicians should educate patients about medical marijuana to ensure that it is used appropriately and that patients will benefit from its use.”

http://www.ncbi.nlm.nih.gov/pubmed/26103031

Cannabinoids for Medical Use: A Systematic Review and Meta-analysis.

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“Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear.

To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids.

There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome.

Cannabinoids were associated with an increased risk of short-term AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination.”

http://www.ncbi.nlm.nih.gov/pubmed/26103030

http://jama.jamanetwork.com/article.aspx?articleid=2338251

Cardioprotective effect of cannabidiol in rats exposed to doxorubicin toxicity.

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“The potential protective effect of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated against doxorubicin cardiotoxicity in rats.

Histopathological examination showed that cannabidiol ameliorated doxorubicin-induced cardiac injury.

Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin in cardiac tissue of doxorubicin-treated rats.

These results indicate that cannabidiol represents a potential protective agent against doxorubicin cardiac injury.”

http://www.ncbi.nlm.nih.gov/pubmed/23721741