“Anandamide (arachydonylethanolamide) is a naturally-occurring ligand of the canabinoid receptor. When anandamide binds to its receptor, adenylate cyclase is inhibited…
The conclusions are that the motor nerve terminal has a cannabinoid receptor.
The binding of anandamide to this receptor seems to block adenylate cyclase.”
“Two cannabinoid receptors, designated neuronal (or CB1) and peripheral (or CB2), have recently been cloned. Activation of CB1 receptors leads to inhibition of adenylate cyclase and N-type voltage-dependent Ca2+ channels.
Here we show, using a CB2 transfected Chinese hamster ovary cell line, that this receptor binds a variety of tricyclic cannabinoid ligands as well as the endogenous ligand anandamide.
Activation of the CB2 receptor by various tricyclic cannabinoids inhibits adenylate cyclase activity and this inhibition is pertussis toxin sensitive indicating that this receptor is coupled to the Gi/G(o) GTP-binding proteins…
These results characterize the CB2 receptor as a functional and distinctive member of the cannabinoid receptor family.”
http://www.ncbi.nlm.nih.gov/pubmed/7498464
“Extensive structure-activity relationship studies have demonstrated that specific requirements within the cannabinoid structure are necessary to produce potent analgesia.
A three-point association between the agonist and the receptor mediating analgesia consists of: 1) the C ring hydroxyl, 2) the phenolic A ring hydroxyl, and 3) the A ring alkyl hydrophobic side chain. Potent tricyclic and bicyclic structures were synthesized as “nonclassical” cannabinoid analgetics that conform to this agonist-receptor three-point interaction model.
At the cellular level, centrally active cannabinoid drugs inhibit adenylate cyclase activity in a neuroblastoma cell line. The structure-activity relationship profile for inhibition of adenylate cyclase in vitro was consistent with this same three-point association of agonists with the receptor.
A correlation exists between the potency of drugs to produce analgesia in vivo and to inhibit adenylate cyclase in vitro.
Based on the parallels in structure-activity relationships and the enantioselective effects, it is postulated that the receptor that is associated with the regulation of adenylate cyclase in vitro may be the same receptor as that mediating analgesia in vivo.
A conceptualization of the cannabinoid analgetic receptor is presented.”
“The abilities of lipophilic cannabinoid drugs to regulate adenylate cyclase activity in neuroblastoma cell membranes were analyzed by thermodynamic studies…
These data suggest that, for the entropy-driven hormone-stimulated adenylate cyclase enzyme, less disorder of the system occurs in the presence of regulators that inhibit the enzyme via Gi.
In summary, thermodynamic data suggest that cannabidiol can influence adenylate cyclase by increasing membrane fluidity, but that the inhibition of adenylate cyclase by delta 9-tetrahydrocannabinol is not related to membrane fluidization.”
http://www.ncbi.nlm.nih.gov/pubmed/2554920
“delta 9Tetrahydrocannabinol (THC) has been shown to inhibit the activity of adenylate cyclase in the N18TG2 clone of murine neuroblastoma cells. The concentration of delta 9THC exhibiting half-maximal inhibition was 500 nM. delta 8Tetrahydrocannabinol was less active, and cannabinol was only partially active. Cannabidiol, cannabigerol, cannabichromene, olivetol and compounds having a reduced length of the C3 alkyl side chain were inactive. The metabolites of delta 8THC and delta 9THC hydroxylated at the C11 position were more potent than the parent drugs. However, hydroxylation at the C8 position of the terpenoid ring resulted in loss of activity. Compounds hydroxylated along the C3 alkyl side chain were equally efficacious but less potent than delta 9THC. These findings are compared to the pharmacology of cannabinoids reported for psychological effects in humans and behavioral effects in a variety of animal models.”
1942-7611/asset/olalertbanner.jpg?v=1&s=4b27d6a6bed6b58a9935efe70e4f95efc39146bd)
“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.
The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.
In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”
http://www.ncbi.nlm.nih.gov/pubmed/24006213
http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract
“Biological activity of cannabinoids is caused by binding to two cannabinoid receptors CB1 and CB2. Psychoactive is not only tetrahydrocannabinol (THC) but also: cannabidiol, cannabigerol or cannabichromen.
Formerly, the usefulness of hemp was assessed in the relation to temporary appeasement of the symptoms of some ailments as nausea or vomiting.
Present discoveries indicates that cannabis-based drugs has shown ability to alleviate of autoimmunological disorders such as: Multiple sclerosis (MS), Rheumatoid arthritis (RA) or inflammatory bowel disease.
Another studies indicates that cannabinoids play role in treatment of neurological disorders like Alzheimer disease or Amyotrophic lateral sclerosis (ALS) or even can reduce spreading of tumor cells.
Cannabinoids stand out high safety profile considering acute toxicity, it is low possibility of deadly overdosing and side-effects are comprise in range of tolerated side-effects of other medications.
In some countries marinol and nabilone are used as anti vomiting and nausea drug. First cannabis-based drug containg naturally occurring cannabinoids is Sativex. Sativex is delivered in an mucosal spray for patients suffering from spasticity in MS, pain relevant with cancer and neuropathic pain of various origin.
Cannabis side-effects varies and depend from several factors like administrated dose, rout of administration and present state of mind. After sudden break from long-lasting use, withdrawal symptoms can appear, although they entirely disappear after a week or two.”
“The active ingredient in cannabis can improve the appetites and sense of taste in cancer patients, according to a new study published online in the cancer journal, Annals of Oncology today.
Loss of appetite is common among cancer patients, either because the cancer itself or its treatment affects the sense of taste and smell, leading to decreased enjoyment of food. This, in turn, can lead to weight loss, anorexia, a worse quality of life and decreased survival; therefore, finding effective ways of helping patients to maintain a good diet and consume enough calories is an important aspect of their treatment.
The majority of THC-treated patients (64%) had increased appetite, three patients (27%) showed no change, and one patient’s data was incomplete. No THC-treated patients showed a decrease in appetite. By contrast, the majority of patients receiving placebo had either decreased appetite (50%) or showed no change (20%).
Although there was no difference in the total number of calories consumed by both groups, the THC-treated patients tended to increase the proportion of protein that they ate, and 55% reported that savoury foods tasted better, whereas no patients in the placebo group reported an increased liking for these foods. (Cancer patients often find that meat smells and tastes unpleasant and, therefore, they eat less of it).
In addition, THC-treated patients reported better quality of sleep and relaxation than in the placebo group.”
“Four years following resection of a Clark’s level IV malignant melanoma, a 50-year-old man developed widespred metastatic disease involving the liver, bones, brain, gastrointestinal mucosa, and lungs. One week after whole brain radiation therapy, he was admitted to the hospital for nausea, vomiting, and pain.
He was treated with several antiemetic drugs, but it was not until dronabinol was added that the nausea and vomiting stopped.
Dronabinol was an effective antiemetic used in combination with prochlorperazine in nausea and vomiting unresponsive to conventional antiemetics.”
“First it was a cough. Then it was bronchitis. Then it was time to say goodbye to Michelle Aldrich.
The year 2011 was supposed to be a good one for the 66-year-old. That June, she and her husband, Michael, were feted with a lifetime achievement award by High Times magazine for their four decades of work on marijuana legalization. Yet something was off. She was smoking a lot, maybe more than ever.
And she couldn’t get high.
In the fall of that year — a bad time for the local marijuana movement, as the federal Justice Department began shutting down hundreds of California medical cannabis dispensaries — Aldrich went in to see a series of doctors for what she thought was a flu that just refused to go away.
After six weeks of progressively worse diagnoses — flu became bronchitis, which became pneumonia — a CT scan revealed the cause behind the “heat” she felt in the middle of her chest. A tumor, “poorly-differentiated non-small cell adenocarcinoma.” In other words, stage 3 lung cancer.
Lung cancer is a killer, with nearly 70 percent of new cases resulting in deaths, according to statistics published by the National Cancer Institute. “I thought I was going to die,” Aldrich says from her Marina District apartment. But she didn’t. And now, she is busy telling anyone who will listen that, along with diet and chemotherapy, a concoction of highly concentrated cannabis oil eliminated her cancer in less than four months.”
More: http://www.sfweekly.com/2013-04-24/news/key-words-cannabis-oil-cure-cancer-constance-finley/full/