Cannabinoids in health and disease

Abstract

“Cannabis sativa L. preparations have been used in medicine for millenia. However, concern over the dangers of abuse led to the banning of the medicinal use of marijuana in most countries in the 1930s. Only recently, marijuana and individual natural and synthetic cannabinoid receptor agonists and antagonists, as well as chemically related compounds, whose mechanism of action is still obscure, have come back to being considered of therapeutic value. However, their use is highly restricted. Despite the mild addiction to cannabis and the possible enhancement of addiction to other substances of abuse, when combined with cannabis, the therapeutic value of cannabinoids is too high to be put aside. Numerous diseases, such as anorexia, emesis, pain, inflammation, multiple sclerosis, neurodegenerative disorders (Parkinson’s disease, Huntington’s disease, Tourette’s syndrome, Alzheimer’s disease), epilepsy, glaucoma, osteoporosis, schizophrenia, cardiovascular disorders, cancer, obesity, and metabolic syndrome-related disorders, to name just a few, are being treated or have the potential to be treated by cannabinoid agonists/antagonists/cannabinoid-related compounds. In view of the very low toxicity and the generally benign side effects of this group of compounds, neglecting or denying their clinical potential is unacceptable – instead, we need to work on the development of more selective cannabinoid receptor agonists/antagonists and related compounds, as well as on novel drugs of this family with better selectivity, distribution patterns, and pharmacokinetics, and – in cases where it is impossible to separate the desired clinical action and the psychoactivity – just to monitor these side effects carefully.”

Cancer

“The antiproliferative action of cannabinoids on cancer cells was first noticed in the 1970s. Since then cannabinoids were found to act on various cancer cell lines, through various mechanisms. Cannabinoids were also found to be suppressors of angiogenesis and tumor invasion. Our knowledge on the anticancer activity of cannabinoids is rapidly expanding.”

Conclusion

“Many drugs used today can cause addiction and are misused and abused, for example opiates, cocaine, benzodiazepines, barbiturates, cholinergic agonists, ketamine, dopaminergic agonists, amphetamines, and others. Nevertheless they are still an important part of our pharmacopeia. Marijuana was used for centuries as a medicinal plant, but during the last century, because of its abuse and addictive potential it was taken out of clinical practice. Now, we believe that its constituents and related compounds should be brought back to clinical use. The reasons are: (i) the therapeutic potential of CB1 agonists is huge, as described in this review; (ii) for local action, topical CB1 agonists, or agonists that do not penetrate the blood-brain barrier, can be used; (iii) cannabinoids acting specifically on CB2 receptors, which cause no psychoactivity, may be used on peripheral targets (such as osteoporosis, which is only one of many examples); (iv) there are additional, new cannabinoid targets distinct from the CB1/CB2 receptors which do not cause psychoactivity; (v) there are cannabinoids, such as CBD, which do not cause psychoactivity, but have various therapeutic effects.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202504/

Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis.

 European Journal of Pharmacology “Pneumococcal meningitis is a life-threatening disease characterized by an acute infection affecting the pia matter, arachnoid and subarachnoid space. The intense inflammatory response is associated with a significant mortality rate and neurologic sequelae, such as, seizures, sensory-motor deficits and impairment of learning and memory.

The aim of this study was to evaluate the effects of acute and extended administration of cannabidiol on pro-inflammatory cytokines and behavioral parameters in adult Wistar rats submitted to pneumococcal meningitis.

The extended administration of cannabidiol at different doses reduced the TNF-α level in frontal cortex. Prolonged treatment with canabidiol, 10mg/kg, prevented memory impairment in rats with pneumococcal meningitis.

Although descriptive, our results demonstrate that cannabidiol has anti-inflammatory effects in pneumococcal meningitis and prevents cognitive sequel.”  https://www.ncbi.nlm.nih.gov/pubmed/23085269

“Although descriptive, our results demonstrate that chronic treatment with CBD plays an anti-inflammatory role in pneumococcal meningitis. Furthermore, it prevents cognitive damage, possibly representing a new pharmacological approach towards pneumococcal meningitis.” https://www.sciencedirect.com/science/article/pii/S0014299912008485?via%3Dihub

Ligands that target cannabinoid receptors in the brain: from THC to anandamide and beyond.

Abstract

“A major finding–that (-)-trans-Delta(9)-tetrahydrocannabinol (Delta(9)-THC) is largely responsible for the psychotropic effects of cannabis–prompted research in the 1970s and 1980s that led to the discovery that this plant cannabinoid acts through at least two types of cannabinoid receptor, CB(1) and CB(2), and that Delta(9)-THC and other compounds that target either or both of these receptors as agonists or antagonists have important therapeutic applications. It also led to the discovery that mammalian tissues can themselves synthesize and release agonists for cannabinoid receptors, the first of these to be discovered being arachidonoylethanolamide (anandamide) and 2-arachidonoylglycerol. These ‘endocannabinoids’ are released onto their receptors in a manner that appears to maintain homeostasis within the central nervous system and sometimes either to oppose or to mediate or exacerbate the unwanted effects of certain disorders. This review provides an overview of the pharmacology of cannabinoid receptors and their ligands. It also describes actual and potential clinical uses both for cannabinoid receptor agonists and antagonists and for compounds that affect the activation of cannabinoid receptors less directly, for example by inhibiting the enzymatic hydrolysis of endocannabinoids following their release.”

http://www.ncbi.nlm.nih.gov/pubmed/18482430

Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents.

Image result for Best Pract Res Clin Endocrinol Metab

“Cannabinoids (the active components of Cannabis sativa) and their derivatives have received renewed interest in recent years due to their diverse pharmacological activities. In particular, cannabinoids offer potential applications as anti-tumour drugs, based on the ability of some members of this class of compounds to limit cell proliferation and to induce tumour-selective cell death. Although synthetic cannabinoids may have pro-tumour effects in vivo due to their immunosuppressive properties, predominantly inhibitory effects on tumour growth and migration, angiogenesis, metastasis, and also inflammation have been described. Emerging evidence suggests that agonists of cannabinoid receptors expressed by tumour cells may offer a novel strategy to treat cancer. In this chapter we review the more recent results generating interest in the field of cannabinoids and cancer, and provide novel suggestions for the development, exploration and use of cannabinoid agonists for cancer therapy, not only as palliative but also as curative drugs.” https://www.ncbi.nlm.nih.gov/pubmed/19285265

“Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents” http://www.bprcem.com/article/S1521-690X(09)00005-0/abstract

Cannabis-derived substances in cancer therapy–an emerging anti-inflammatory role for the cannabinoids.

“Cannabinoids, the active components of the cannabis plant, have some clinical merit both as an anti-emetic and appetite stimulant in cachexic patients. Recently, interest in developing cannabinoids as therapies has increased following reports that they possess anti-tumour properties.

 Research into cannabinoids as anti-cancer agents is in its infancy, and has mainly focussed on the pro-apoptotic effects of this class of agent. Impressive anti-cancer activities have been reported; actions that are mediated in large part by disruptions to ubiquitous signalling pathways such as ERK and PI3-K. However, recent developments have highlighted a putative role for cannabinoids as anti-inflammatory agents. Chronic inflammation has been associated with neoplasia for sometime, and as a consequence, reducing inflammation as a way of impacting cancer presents a new role for these compounds.

 This article reviews the ever-changing relationship between cannabinoids and cancer, and updates our understanding of this class of agent. Furthermore, the relationship between chronic inflammation and cancer, and how cannabinoids can impact this relationship will be described.”

http://www.ncbi.nlm.nih.gov/pubmed/20925645

Established and potential therapeutic applications of cannabinoids in oncology.

Abstract

“Cannabis occurs naturally in the dried flowering or fruiting tops of the Cannabis sativa plant. Cannabis is most often consumed by smoking marihuana. Cannabinoids are the active compounds extracted from cannabis. Recently, there has been renewed interest in cannabinoids for medicinal purposes. The two proven indications for the use of the synthetic cannabinoid (dronabinol) are chemotherapy-induced nausea and vomiting and AIDS-related anorexia. Other possible effects that may prove beneficial in the oncology population include analgesia, antitumor effect, mood elevation, muscle relaxation, and relief of insomnia. Two types of cannabinoid receptors, CB1 and CB2, have been detected. CB1 receptors are expressed mainly in the central and peripheral nervous system. CB2 receptors are found in certain nonneuronal tissues, particularly in the immune cells. Recent discovery of both the cannabinoid receptors and endocannabinoids has opened a new era in research on the pharmaceutical applications of cannabinoids. The use of cannabinoids should be continued in the areas indicated, and further studies are needed to evaluate other potential uses in clinical oncology.”

http://www.ncbi.nlm.nih.gov/pubmed/12618922

Cannabinoids: potential anticancer agents.

Abstract

“Cannabinoids – the active components of Cannabis sativa and their derivatives – exert palliative effects in cancer patients by preventing nausea, vomiting and pain and by stimulating appetite. In addition, these compounds have been shown to inhibit the growth of tumour cells in culture and animal models by modulating key cell-signalling pathways. Cannabinoids are usually well tolerated, and do not produce the generalized toxic effects of conventional chemotherapies. So, could cannabinoids be used to develop new anticancer therapies?”

http://www.ncbi.nlm.nih.gov/pubmed/14570037

 

Search: Study says marijuana fights cancer

“Researchers in Madrid say the main psychoactive ingredient in marijuana (what is it?) and other “cannabinoids” (what are those?) could help slow cancer growth, as well as manage many cancer symptoms (like what?).  Scientists studied cancer cells (which type?) that grow faster than normal cells, and discovered that the cancer cells died whenever they were exposed to the pot ingredient.”

http://specials.msn.com/a-list/healthyliving/marijuana-fights-cancer-popular-pages

Marijuana compound could help fight breast cancer – ABC News

“There may be a new weapon in the fight against aggressive forms of breast cancer in the future, and it comes from an unlikely source: Marijuana. Researchers at California Pacific Medical Center in San Francisco believe a compound in marijuana may help.

The research funded by the California Breast Cancer Research Program builds on more than a decade of studies involving the genes responsible for the spread of cancer. Now scientists have found at the cellular level, a compound in cannabis inhibits the gene that controls the spread of cancer.

“The problem is not the cancer itself, the problem is the spread of the cancer,” said cancer researcher Yvez Desprez, Ph.D.

Cancer researcher Pierre Desprez points to the gene ID-1 as the trigger.

“When this type of gene is expressed, the cells basically go crazy and they’re very aggressive and they metastasize everywhere in the body,” said Desprez.

“We could expect that if we create really effective inhibitors against it, we could potentially treat many types of aggressive cancers,” said cancer researcher Sean McAllister, Ph.D.

Their research in breast cancer cell lines focused on using a non-toxic compound in cannabis to target the ID-1 gene.

“What we found was cannabidiol is a particularly good inhibitor of this gene that’s responsible for the ability of cancer cells to become very aggressive,” said McAllister.”

http://abclocal.go.com/kgo/story?section=news/health&id=5771385

Scientists believe marijuana compound could fight cancer

“Scientists in California believe they may have discovered a compound in marijuana that can reduce the aggressiveness of some forms of cancer.

The San Francisco Gate reports on the data that has been years in the making. While marijuana has been shown to help reduce nausea and pain in cancer patients, scientists believe that a compound in marijuana has the ability to “turn off” the activity of a gene responsible for metastasis in breast and other types of cancers.

The research team is working out of San Francisco’s California Pacific Medical Center Research Institute and have been working for years on the study. The compound they’re focused on, called cannabidiol, does not produce the psychotropic high associated with marijuana.

Last year, the team published a small study showing the positive effects of cannabidiol on mice. New data is about to be released that expands upon the previous results that the researchers hope will help propel the study even further.

“The preclinical trial data is very strong, and there’s no toxicity. There’s really a lot of research to move ahead with and to get people excited,” said Sean McAllister, who is working alongside scientist Pierre Desprez in the study.

Desprez and McAllister believe that their merging of separate areas of study was serendipitous.

Desprez had been studying the protein ID-1, which he found to play an important role in how cancer could spread. McAllister, on the other hand, was focused on studying anabolic steroids in drug abuse. He soon became focused on with the role non-psychotropic cannabidiol, or CBD, interacts with cancer.

McAllister, after hearing an internal seminar from Desprez on his studies of ID-1, came up with the question “How effective would cannabidiol be on targeting metastatic cancer cells?”

The two then teamed up, with Desprez armed with ID-1 cancer-causing protein, and McAllister with CBD, his cancer-fighting compound.

For their experimentation, the doctors exposed ID-1 to CBD in a petri dish. In a shocking result, the ID-1, the cancer-causing protein, reverted to a normal state and stopped acting “crazy.”

“We thought we did the experiment the wrong way,” McAllister said of the overwhelming results.

However, their results proved to be consisted.

“I told Sean, ‘Maybe your drug is working through my gene,’ ” Desprez said.

What the researchers have discovered thus far in their research is that CBD turns off the overexpression of ID-1, which prevents it from traveling to foreign tissues. Thus, the metastasization – cancer’s fatal ability – is blocked.

In the wake of their positive results, the doctors were forced to emphasize that the CBD will only work in the presence of high levels of ID-1 and these do not include all cancerous tumors but, rather, aggressive, metastatic cells. High levels have been found in leukemia, colorectal, pancreatic, lung, ovarian, brain and other cancers.”
Read more: http://www.irishcentral.com/news/Scientists-believe-marijuana-compound-could-fight-cancer-170689736.html#ixzz29rQbc2oS