Category Archives: Uncategorized

Inhibition of Human Neutrophil Chemotaxis by Endogenous Cannabinoids and Phytocannabinoids: Evidence for a Site Distinct from CB1 and CB2

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   “Here, we show a novel pharmacology for inhibition of human neutrophil migration by endocannabinoids, phytocannabinoids, and related compounds. The endocannabinoids virodhamine and N-arachidonoyl dopamine are potent inhibitors of N-formyl-l-methionyl-l-leucyl-l-phenylalanine-induced migration of human neutrophils…”

   “This study reveals that certain endogenous lipids, phytocannabinoids and related ligands are potent inhibitors of human neutrophil migration, and it implicates a novel pharmacological target distinct from cannabinoid CB1 and CB2 receptors; this target is antagonized by the endogenous compound N-arachidoloyl l-serine. These findings corroborate the emerging clinical and animal model data demonstrating that the nonpsychoactive phytocannabinoid, CBD and its structural analogs are effective in alleviating arthritis. Furthermore, our findings have implications for the potential pharmacological manipulation of elements of the endocannabinoid system for the treatment of various inflammatory conditions.”

http://molpharm.aspetjournals.org/content/73/2/441.long

Non-CB1, non-CB2 receptors for endocannabinoids, plant cannabinoids, and synthetic cannabimimetics: focus on G-protein-coupled receptors and transient receptor potential channels.

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Abstract

“The molecular mechanism of action of Delta(9)-tetrahydrocannabinol (THC), the psychotropic constituent of Cannabis, has been a puzzle during the three decades separating its characterization, in 1964, and the cloning, in the 1990s, of cannabinoid CB1 and CB2 receptors. However, while these latter proteins do mediate most of the pharmacological actions of THC, they do not seem to act as receptors for other plant cannabinoids (phytocannabinoids), nor are they the unique targets of the endogenous lipids that were originally identified in animals as agonists of CB1 and CB2 receptors, and named endocannabinoids. Over the last decade, several potential alternative receptors for phytocannabinoids, endocannabinoids, and even synthetic cannabimimetics, have been proposed, often based uniquely on pharmacological evidence obtained in vitro. In particular, the endocannabinoid anandamide, and the other most abundant Cannabis constituent, cannabidiol, seem to be the most “promiscuous” of these compounds. In this article, we review the latest data on the non-CB1, non-CB2 receptors suggested so far for endocannabinoids and plant or synthetic cannabinoids, and lay special emphasis on uncharacterized or orphan G-protein-coupled receptors as well as on transient receptor potential channels.”

http://www.ncbi.nlm.nih.gov/pubmed/19847654

The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin

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  “Cannabis sativa is the source of a unique set of compounds known collectively as plant cannabinoids or phytocannabinoids. This review focuses on the manner with which three of these compounds, (−)-trans-Δ9-tetrahydrocannabinol (Δ9-THC), (−)-cannabidiol (CBD) and (−)-trans-Δ9-tetrahydrocannabivarin (Δ9-THCV), interact with cannabinoid CB1 and CB2 receptors. Δ9-THC, the main psychotropic constituent of cannabis, is a CB1 and CB2 receptor partial agonist and in line with classical pharmacology, the responses it elicits appear to be strongly influenced both by the expression level and signalling efficiency of cannabinoid receptors and by ongoing endogenous cannabinoid release. CBD displays unexpectedly high potency as an antagonist of CB1/CB2 receptor agonists in CB1– and CB2-expressing cells or tissues, the manner with which it interacts with CB2 receptors providing a possible explanation for its ability to inhibit evoked immune cell migration. Δ9-THCV behaves as a potent CB2 receptor partial agonist in vitro. In contrast, it antagonizes cannabinoid receptor agonists in CB1-expressing tissues. This it does with relatively high potency and in a manner that is both tissue and ligand dependent. Δ9-THCV also interacts with CB1 receptors when administered in vivo, behaving either as a CB1 antagonist or, at higher doses, as a CB1 receptor agonist. Brief mention is also made in this review, first of the production by Δ9-THC of pharmacodynamic tolerance, second of current knowledge about the extent to which Δ9-THC, CBD and Δ9-THCV interact with pharmacological targets other than CB1 or CB2 receptors, and third of actual and potential therapeutic applications for each of these cannabinoids.”

“…cannabis is a source not only of Δ9-THC, CBD and Δ9-THCV but also of at least 67 other phytocannabinoids and as such can be regarded as a natural library of unique compounds. The therapeutic potential of many of these ligands still remains largely unexplored prompting a need for further preclinical and clinical research directed at establishing whether phytocannabinoids are indeed ‘a neglected pharmacological treasure trove’. As well as leading to a more complete exploitation of Δ9-THC and CBD as therapeutic agents and establishing the clinical potential of Δ9-THCV more clearly, such research should help to identify any other phytocannabinoids that have therapeutic applications per se or that constitute either prodrugs from which semisynthetic medicines might be manufactured or lead compounds from which wholly synthetic medicines might be developed.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219532/

Naturally occurring and related synthetic cannabinoids and their potential therapeutic applications.

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Abstract

“Naturally occurring cannabinoids (phytocannabinoids) are biosynthetically related terpenophenolic compounds uniquely produced by the highly variable plant, Cannabis sativa L. Natural and synthetic cannabinoids have been extensively studied since the discovery that the psychotropic effects of cannabis are mainly due to Delta(9)-THC. However, cannabinoids exert pharmacological actions on other biological systems such as the cardiovascular, immune and endocrine systems. Most of these effects have been attributed to the ability of these compounds to interact with the cannabinoid CB1 and CB2 receptors. The FDA approval of Marinol, a product containing synthetic Delta(9)-THC (dronabinol), in 1985 for the control of nausea and vomiting in cancer patients receiving chemotherapy, and in 1992 as an appetite stimulant for AIDS patients, has further intensified the research interest in these compounds. This article reviews patents (2003-2007) that describe methods for isolation of cannabinoids from cannabis, chemical and chromatographic methods for their purification, synthesis, and potential therapeutic applications of these compounds.”

http://www.ncbi.nlm.nih.gov/pubmed/19519560

Fungal biotransformation of cannabinoids: potential for new effective drugs.

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Abstract

“Phytocannabinoids from the plant Cannabis sativa induce a variety of physiological and pharmacological responses in living systems, including anti-inflammatory, antinociceptive, anti-ulcer and antitumor activities. The discovery of the cannabinoid receptors CB1 and CB2 led to the development of agonists and antagonists of these receptors for the treatment of a variety of diseases. Nabilone, a synthetic derivative of Delta9-tetrahydrocannabinol (Delta9-THC), which is the main natural psychotropic constituent of C sativa, was approved by the US FDA for the treatment of nausea and as an anti-emetic for patients undergoing chemotherapy. Delta9-THC and related cannabinoids are involved in a variety of signal transduction pathways; thus, reducing or removing the psychotropic effects of these compounds would enhance their therapeutic spectra. Compound synthesis and qualitative SAR studies are time-consuming activities; however, microbes are effectively the most inventive synthetic chemists because of their metabolic plasticity. This review discusses the potential of C sativa mycoflora, which is pathogenic as well as endophytic, to remove the psychotropic effects of Delta9-THC and related cannabinoids, and describes the development of a model system for the rapid and cost-effective commercial production of cannabinoids through fermentation pathways.”

http://www.ncbi.nlm.nih.gov/pubmed/19333876

A molecular basis of the therapeutic and psychoactive properties of cannabis (delta9-tetrahydrocannabinol).

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Abstract

“All of the therapeutic properties of marihuana (analgesic, antiemetic, appetite stimulant, antiglaucoma) have been duplicated by the tetrahydrocannabinol (THC) molecule or its synthetic derivatives. Today, the molecular mechanisms of action of these compounds have led to a general understanding of the pharmacological effects of marihuana and of its therapeutic properties. These mechanisms involve the specific binding of THC to the 7-transmembrane (7TM) domain G protein-linked receptor, a molecular switch which regulates signal transduction in the cell membrane. The natural ligand of the 7TM receptor is an eicosanoid, arachidonylethanolamide (AEA), generated in the membrane and derived from arachidonic acid. THC acts as a substitute ligand to the 7TM receptor site of AEA. THC would deregulate the physiological function of the 7TM receptor and of its ligand AEA. As a result, the therapeutic effects of the drug may not be separated from its adverse psychoactive and cardiovascular effects. The binding of THC to the 7TM receptor site of AEA induces allosteric changes in the receptor sites of neurotransmitter and opiates resulting in variable interactions and pharmacological responses. The pharmacokinetics of THC with its prolonged storage in fat and its slow release result in variable and delayed pharmacological response, which precludes precise dosing to achieve timely therapeutic effects. The experimental use of THC and of its synthetic analogues, agonists, and antagonists has provided novel information in the nature of molecular signaling in the cell membrane. As a result, the relationships between allosteric receptor responsiveness, molecular configuration of proteins, and physiological regulation of cellular and organ function may be further investigated.”

http://www.ncbi.nlm.nih.gov/pubmed/12188105

Marijuana Smokers Breathe Easy Says The University of Alabama

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   “As of January 10, 2012, a new study has been published in the Journal of the American Medical Association exonerating marijuana from the bad reputation of being as harmful to your lungs when smoked as tobacco cigarettes. Researchers at the University of California San Francisco and the University of Alabama at Birmingham completed a twenty-year study between 1986 and 2006 on over 5,000 adults over the age of 21 in four American cities. Study co-author Dr. Stefan Kertesz is a professor of preventive medicine at the University of Alabama at Birmingham. He explained that the studies measured the pulmonary obstruction in individuals with up to seven joint-years of lifetime exposure (one joint per day for seven years or one joint per week for 49 years). “What this study clarifies,” Kertesz explains in a released video, “is that the relationship to marijuana and lung function changes depending on how much a person has taken in over the course of a lifetime.”

“…findings suggest that occasional use of marijuana may not be linked with unfavorable consequences on pulmonary function.  Marijuana is designated by the U.S. government as a Schedule I drug, which declares it has no medicinal purposes.  Previous studies have shown that the drug can be used to treat multiple sclerosis, glaucoma, nausea, and pain.  It has been known to have beneficial effects on pain control, mood, appetite, and managing of other chronic symptoms.  Despite these facts, marijuana continues to be depicted as more damaging to us than it’s legal counterpart tobacco. Marijuana activists, medical patients, and recreational users alike will rejoice knowing the evidence shows otherwise.”

Read more: http://nugs.com/article/marijuana-smokers-breathe-easy-says-the-university-of-alabama.html

Study: Smoking Marijuana Not Linked with Lung Damage – TIME

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“Marijuana does not impair lung function—at least not in the doses inhaled by the majority of users, according to the largest and longest study ever to consider the issue, which was published today in the Journal of the American Medical Association.

Researchers working on a long-term study of risk factors for cardiovascular disease (the Coronary Artery Risk Development in Young Adults or CARDIA study) tested the lung function of 5115 young adults over the course of 20 years, starting in 1985 when they were aged 18 to 30.

The study was “well conducted” and is “essentially confirmatory of the findings from several previous studies that have examined the association between marijuana smoking and lung function,” says Dr. Donald Tashkin, professor of medicine at UCLA and a leading scientist in the area. He was not associated with the new research.

“The major strengths of this study are that it included a far larger number of subjects followed for longer than any of these previous studies,” he adds.”

Read more: http://healthland.time.com/2012/01/10/study-smoking-marijuana-not-linked-with-lung-damage/

Casual Marijuana Smoking Not Harmful to Lungs

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“It wouldn’t have mattered if Bill Clinton inhaled, as far as his lungs are concerned. Smoking up to a joint per day doesn’t seem to decrease lung function, according to a study published in Jan. 11 edition of Journal of the American Medical Association.

In fact, occasional marijuana use was associated with slight increases in lung airflow rates and increases in lung volume, the study found.

Far from a license to light up, the study eases the worry among some health professionals that daily use of marijuana for medical reasons could have negative, long-term implications on pulmonary health.”

Read more: http://www.scientificamerican.com/article.cfm?id=casual-marijuana-smoking&fb_action_ids=462987810404532&fb_action_types=og.likes&fb_source=aggregation&fb_aggregation_id=288381481237582

Casual Pot Smoking Not Harmful: Study – NBC

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“Tokers rejoice – a new study shows occasional marijuana smoking does not harm your lungs. It also shows that smoking pot is not as bad for you as smoking cigarettes.

The UC San Francisco research shows smoking marijuana once a week does not harm lungs. The results bolsters evidence that weed doesn’t damage your health like tobacco.

The study’s conclusion was printed like this:  “Occasional and low cumulative marijuana use was not associated with adverse effects on pulmonary function.””

Read more: http://www.nbcbayarea.com/news/local/Casual-Pot-Smoking-Not-Harmful-Study-137045308.html