CANNABINOIDS INCREASE LUNG CANCER CELL LYSIS BY LYMPHOKINE-ACTIVATED KILLER CELLS VIA UPREGULATION OF ICAM-1.

“Cannabinoids have been shown to promote the expression of the intercellular adhesion molecule 1 (ICAM-1) on lung cancer cells as part of their anti-invasive and antimetastatic action…

Cannabidiol (CBD), a non-psychoactive cannabinoid, enhanced the susceptibility of cancer cells to adhere to and subsequently lysed by LAK cells, with both effects being reversed by a neutralizing ICAM-1 antibody…

ICAM-1-dependent pro-killing effects were further confirmed for the phytocannabinoid Δ9-tetrahydrocannabinol (THC) and R(+)-methanandamide, a stable endocannabinoid analogue…

Altogether, our data demonstrate cannabinoid-induced upregulation of ICAM-1 on lung cancer cells to be responsible for increased cancer cell susceptibility to LAK cell-mediated cytolysis.

These findings provide proof for a novel antitumorigenic mechanism of cannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/25069049

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

The Potential Therapeutic Effects of THC on Alzheimer’s Disease.

“The purpose of this study was to investigate the potential therapeutic qualities of Δ9-tetrahydrocannabinol (THC) with respect to slowing or halting the hallmark characteristics of Alzheimer’s disease…

These sets of data strongly suggest that THC could be a potential therapeutic treatment option for Alzheimer’s disease through multiple functions and pathways.”

http://www.ncbi.nlm.nih.gov/pubmed/25024327

Chemicals in Marijuana May Help Stroke Victims

NewsBriefs

“Scientists at the National Institute of Mental Health (NIMH) said a chemical in marijuana may protect the brain from damage inflicted by a stroke.

Their study was reported in the Proceedings of the National Academy of Sciences (Aidan Hampson, et al., “Cannabidiol and Delta-9-tetrahydrocannabinol Are Neuroprotective Antioxidants,” Proceedings of the National Academy of Sciences, July 7, 1998, Vol. 95, Issue 14, p. 8268; “Pot Chemicals Might Inhibit Breast Tumors, Stroke Damage,” Dallas Morning News, July 13, 1998; Vanessa Thorpe, “Chemicals Help Brain Damage After Stroke,” The Independent (UK), July 19, 1998).

NIMH scientists researched the effects of two cannabinoids, cannabidiol and THC, on the brains of rats. THC is the ingredient in marijuana that causes a psychoactive effect. However, cannabidiol is “a better candidate,” in part, because it does not cause a “high” in the patient, said Aidan Hampson, a neuropharmacologist at NIMH who led the study.

The cannabinoids block a neurochemical, known as glutamate, that leads to the formation of toxic oxidizing molecules that kill brain cells. Glutamate is produced in the brain if the oxygen supply is cut off, for example, as the result of blood clot leading to a stroke.

Researchers found that cannabidiol is a more effective antioxidant than vitamins A and E, which already are known to block the damaging effects of glutamate.”

http://www.ndsn.org/julaug98/medmj1.html

Targeting multiple cannabinoid antitumor pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer.

“The psychoactive cannabinoid Δ9 -tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol(CBD) can both reduce cancer progression each through distinct antitumor pathways.

Our goal was to discover a compound that could efficiently target both cannabinoid antitumor pathways.

KEY RESULTS:

CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogs that could co-target cannabinoid antitumor pathways (CBD- and THC-associated) and discovered the compound O-1663. This analog inhibited Id1, produced a marked stimulation of ROS, upregulated autophagy, and induced apoptosis. Of all compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo.

CONCLUSIONS AND IMPLICATIONS:

O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid antitumor pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/24910342

“Anti-cancer effects of resorcinol derivatives on ascitic and solid forms of Ehrlich carcinoma in mice.” http://www.ncbi.nlm.nih.gov/pubmed/13774935

“Ardisiphenol D, a resorcinol derivative identified from Ardisia brevicaulis, exerts antitumor effect through inducing apoptosis in human non-small-cell lung cancer A549 cells.” http://www.ncbi.nlm.nih.gov/pubmed/24392814

“Antitumor effect of resorcinol derivatives from the roots of Ardisia brevicaulis by inducing apoptosis.” http://www.ncbi.nlm.nih.gov/pubmed/21751842

“Resorcinol derivatives from Ardisia maculosa.”  http://www.ncbi.nlm.nih.gov/pubmed/17885843

“Cannabidiol (CBD) is among the major secondary metabolites of Cannabis devoid of the delta-9-tetra-hydrocannabinol psychoactive effects. It is a resorcinol-based compound with a broad spectrum of potential therapeutic properties, including neuroprotective effects in numerous pathological conditions.” https://www.ncbi.nlm.nih.gov/pubmed/28412918

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

Marijuana can treat autoimmune diseases, scientific study states

“Weed enthusiasts are getting their case for nationwide decriminalization of marijuana bolstered considerably by a new scientific study that promises the controversial plant can treat multiple medical maladies.

Scientists at the University of South Carolina have discovered marijuana’s potential to treat autoimmune diseases — such as arthritis, lupus, colitis and multiple sclerosis — in which chronic inflammation plays a pivotal role.

The Journal of Biological Chemistry published the researchers’ findings that state marijuana’s potential key role in fighting these diseases lies in its capacity to suppress certain immune functions, most particularly inflammation.

The study examined whether marijuana’s main active constituent, tetrahydrocannabinol (THC), could affect DNA through “epigenetic” pathways.

The group of molecules with the capacity to alter DNA and the functioning of genes it controls is collectively referred to as the epigenome. It includes a group of molecules called histones, which are responsible for inflammation, both beneficial and harmful.

The research team, led by Mitzi Nagarkatti, Prakash Nagarkatti and Xiaoming Yang, found that THC can, indeed, affect DNA expression through epigenetic pathways by altering histones.

As recreational and medical use of marijuana become more acceptable in developed countries, more research is being conducted and more potential health applications are being uncovered.

Marijuana already has a variety of medical uses including treatment of chronic pain, nausea, vomiting and the wasting syndrome experienced by some AIDS patients.”

http://atlantadailyworld.com/2014/06/05/marijuana-can-treat-autoimmune-diseases-scientific-study-states/

Marijuana’s potential for treating autoimmune disorders

“A new study provides evidence that THC (tetrahydrocannabinol), a principal ingredient in marijuana, may be beneficial in treating those with autoimmune disorders.

The study is the first to explore how tiny, yet powerful molecules called microRNAs are influenced by THC. The ability to alter microRNA expression could hold the key to successful treatments for a whole host of autoimmune diseases, including arthritis and multiple sclerosis.”

http://www.sciencedaily.com/releases/2013/11/131125121712.htm

Immunoactive effects of cannabinoids: considerations for the therapeutic use of cannabinoid receptor agonists and antagonists

Figure 1

“The active constituents of Cannabis sativa have been used for centuries as recreational drugs and medicinal agents. Today, marijuana is the most prevalent drug of abuse in the United States and, conversely, therapeutic use of marijuana constituents are gaining mainstream clinical and political acceptance.

Given the documented contributions of endocannabinoid signaling to a range of physiological systems, including cognitive function, and the control of eating behaviors, it is unsurprising that cannabinoid receptor agonists and antagonists are showing significant clinical potential.

In addition to the neuroactive effects of cannabinoids, an emerging body of data suggests that both endogenous and exogenous cannabinoids are potently immunoactive.

The central premise of this review article is that the immunological effects of cannabinoids should be considered in the context of each prescribing decision.

We present evidence that the immunological effects of cannabinoid receptor agonists and antagonists are highly relevant to the spectrum of disorders for which cannabinoid therapeutics are currently offered.

Therapeutically relevant cannabinoid receptor ligands include tetra-hydrocannabinol itself, its synthetic forms, and its closely related compounds.

As a final point, the application of CB1 antagonists may be immunostimulative…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804300/

Towards a therapeutic use of selective CB2 cannabinoid receptor ligands for atherosclerosis.

“Atherosclerosis remains the primary cause of heart disease and stroke, causing approximately 50% of all deaths in Western countries. The identification of promising novel anti-atherosclerotic therapies is therefore of great interest and represents a continued challenge to the medical community.

Cannabinoids, such as Delta9-tetrahydrocannabinol (THC), which is the major psychoactive compound of marijuana, modulate immune functions and might therefore be of therapeutic use for the treatment of inflammatory diseases.

The authors have demonstrated recently that oral treatment with low dose THC inhibits atherosclerosis progression in mice through pleiotropic immunomodulatory effects on inflammatory cells. All these effects were mediated via the cannabinoid receptor CB(2), the main cannabinoid receptor expressed on immune cells.

The identification and characterization of cannabinoid derivative that selectively activate CB(2) receptors and are devoid of adverse effects might offer a novel therapeutic strategy for the treatment of atherosclerosis.”

http://www.ncbi.nlm.nih.gov/pubmed/19804131

https://www.futuremedicine.com/doi/abs/10.2217/14796678.2.1.49

“Researchers suggest that THC and other cannabinoids, which are active at CB2, the cannabinoid receptor expressed on immune cells, may be valuable in treating atherosclerosis.” https://www.medscape.com/viewarticle/787468

Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders.

“Cannabis has been used to treat disease since ancient times. Δ9 -Tetrahydrocannabinol (Δ9 -THC) is the major psychoactive ingredient and CBD is the major nonpsychoactive ingredient in cannabis.

Cannabis and Δ9 -THC are anticonvulsant in most animal models but can be proconvulsant in some healthy animals. The psychotropic effects of Δ9 -THC limit tolerability.

CBD is anticonvulsant in many acute animal models, but there are limited data in chronic models.

The antiepileptic mechanisms of CBD are not known, but may include effects on the equilibrative nucleoside transporter; the orphan G-protein-coupled receptor GPR55; the transient receptor potential of vanilloid type-1 channel; the 5-HT1a receptor; and the α3 and α1 glycine receptors.

CBD has neuroprotective and antiinflammatory effects, and it appears to be well tolerated in humans, but small and methodologically limited studies of CBD in human epilepsy have been inconclusive.

More recent anecdotal reports of high-ratio CBD:Δ9 -THC medical marijuana have claimed efficacy, but studies were not controlled.

CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction, and neonatal hypoxic-ischemic encephalopathy.”

http://www.ncbi.nlm.nih.gov/pubmed/24854329

The case for medical marijuana in epilepsy.

“Charlotte, a little girl with SCN1A-confirmed Dravet syndrome, was recently featured in a special that aired on CNN. Through exhaustive personal research and assistance from a Colorado-based medical marijuana group (Realm of Caring), Charlotte’s mother started adjunctive therapy with a high concentration cannabidiol/Δ9 -tetrahydrocannabinol (CBD:THC) strain of cannabis, now known as Charlotte’s Web. This extract, slowly titrated over weeks and given in conjunction with her existing antiepileptic drug regimen, reduced Charlotte’s seizure frequency from nearly 50 convulsive seizures per day to now 2-3 nocturnal convulsions per month. This effect has persisted for the last 20 months, and Charlotte has been successfully weaned from her other antiepileptic drugs. We briefly review some of the history, preclinical and clinical data, and controversies surrounding the use of medical marijuana for the treatment of epilepsy, and make a case that the desire to isolate and treat with pharmaceutical grade compounds from cannabis (specifically CBD) may be inferior to therapy with whole plant extracts. Much more needs to be learned about the mechanisms of antiepileptic activity of the phytocannabinoids and other constituents of Cannabis sativa.”

http://www.ncbi.nlm.nih.gov/pubmed/24854149

“Marijuana stops child’s severe seizures”  http://www.cnn.com/2013/08/07/health/charlotte-child-medical-marijuana/

http://www.thctotalhealthcare.com/category/dravet-syndome/