Polymorphism rs3123554 in the cannabinoid receptor gene type 2 (CNR2) reveals effects on body weight and insulin resistance in obese subjects.

Endocrinología, Diabetes y Nutrición

“Few studies assessing the relationship between single nucleotide polymorphisms in CNR2 and obesity or its related metabolic parameters are available.

OBJECTIVE:

To investigate the influence of polymorphism rs3123554 in the CNR2 receptor gene on obesity anthropometric parameters, insulin resistance, and adipokines in subjects with obesity.

DESIGN:

The study population consisted of 1027 obese subjects, who were performed bioelectrical impedance analyses, blood pressure measurements, serial assessments of dietary intake during three days, and biochemical tests.

RESULTS:

Genotypes GG, GA, and AA were found in 339 (33.0%), 467 (45.5%), and 221 (21.5%) respectively. Body mass index, weight, fat mass, waist circumference, insulin, HOMA-IR, and triglyceride and leptin levels were higher in A-allele carriers as compared to non A-allele carriers. No differences were seen in these parameters between the GA and AA genotypes. There were no statistical differences in dietary intake.

CONCLUSION:

The main study finding was the association of the minor allele of the SNP rs3123554 in the CNR2 gene with body weight and triglyceride, HOMA-IR, insulin, and leptin levels.”

https://www.ncbi.nlm.nih.gov/pubmed/28895540

http://www.sciencedirect.com/science/article/pii/S2530016417301799?via%3Dihub

The FAAH inhibitor URB597 suppresses hippocampal maximal dentate afterdischarges and restores seizure-induced impairment of short and long-term synaptic plasticity.

“Synthetic cannabinoids and phytocannabinoids have been shown to suppress seizures both in humans and experimental models of epilepsy.

However, they generally have a detrimental effect on memory and memory-related processes. Here we compared the effect of the inhibition of the endocannabinoid (eCB) degradation versus synthetic CB agonist on limbic seizures induced by maximal dentate activation (MDA) acute kindling. Moreover, we investigated the dentate gyrus (DG) granule cell reactivity and synaptic plasticity in naïve and in MDA-kindled anaesthetised rats.

We found that both the fatty acid amide hydrolase (FAAH) inhibitor URB597 and the synthetic cannabinoid agonist WIN55,212-2 displayed AM251-sensitive anti-seizure effects. WIN55,212-2, dose-dependently (0.5-2 mg/kg, i.p.) impaired short-term plasticity (STP) and long-term potentiation (LTP) at perforant path-DG synapses in naïve rats. Strikingly, URB597 (1 mg/kg, i.p.) was devoid of any deleterious effects in normal conditions, while it prevented seizure-induced alterations of both STP and LTP.

Our evidence indicates that boosting the eCB tone rather than general CB1 activation might represent a potential strategy for the development of a new class of drugs for treatment of both seizures and comorbid memory impairments associated with epilepsy.”

https://www.ncbi.nlm.nih.gov/pubmed/28894217

https://www.nature.com/articles/s41598-017-11606-1

[Cannabis use in Epilepsy. Current situation in Argentina and abroad].

Image result for Vertex journal

“Although at present we have over 20 different types of drugs for epilepsy, 30 to 40% of patients continue to have seizures.

Preliminary data from human studies suggest that cannabis, cannabidiol in particular, is effective in the treatment of some patients with epilepsy.

However, the available data are limited and do not allow defnitive conclusions. Only randomized clinical trials with controlled double-blind, placebo-controlled utilizing secure preparations and one or more cannabinoids, will provide comprehensive information on the effcacy and safety of use.

In order to perform these trials it is necessary to have legislation authorizing the use of cannabis on epilepsy.”

Activation of dorsal horn cannabinoid CB2 receptor suppresses the expression of P2Y12 and P2Y13 receptors in neuropathic pain rats.

Image result for journal of neuroinflammation

“More evidence suggests that dorsal spinal cord microglia is an important site contributing to CB2 receptor-mediated analgesia. The upregulation of P2Y12 and P2Y13 purinoceptors in spinal dorsal horn microglia is involved in the development of pain behavior caused by peripheral nerve injury. However, it is not known whether the expression of P2Y12 and P2Y13 receptors at spinal dorsal horn will be influenced after CB2 receptor activation in neuropathic pain rats. Chronic constriction injury (CCI) and intrathecal ADPbetaS injection were performed in rats to induce neuropathic pain.

In CCI- and ADPbetaS-treated rats, AM1241 pretreatment could efficiently activate CB2 receptor, while inhibiting p38MAPK and NF-kappaB activation in the dorsal spinal cord. CB2 receptor stimulation decreased P2Y13 receptor expression via p38MAPK/NF-kappaB signaling. On the other hand, CB2 receptor activation decreased P2Y12 receptor expression via p38MAPK-independent NF-kappaB signaling pathway.”

https://www.ncbi.nlm.nih.gov/pubmed/28899427

Effects of coadministration of low dose cannabinoid type 2 receptor agonist and morphine on vanilloid receptor 1 expression in a rat model of cancer pain.

“Morphine is widely used as an analgesic to treat moderate to severe pain, but chronic morphine use is associated with development of tolerance and dependence, which limits its analgesic efficacy. Our previous research has showed that nonanalgetic dose of a cannabinoid type 2 (CB2) receptor agonist reduced morphine tolerance in cancer pain. A previous study showed the colocalization of CB2 and transient receptor potential vanilloid 1 (TRPV1) in human and rat dorsal root ganglia (DRG) sensory neurons. Whether coadministration of a CB2 receptor agonist and morphine could reduce TRPV1 expression in morphine‑induced antinociception and tolerance in cancer pain is unclear. Therefore, we investigated the effects of coadministration of a CB2 receptor agonist AM1241 and morphine on TRPV1 expression and tolerance in cancer pain. Coadministration of AM1241 and morphine for 8 days significantly reduced morphine tolerance, as assessed by measuring paw withdrawal latency to a radiant heat stimulation, in Walker 256 tumor‑bearing rats. Repeated morphine treatment for a period of 8 days induced upregulation of the TRPV1 protein expression levels in the DRG in the tumor‑bearing rats, although no change in mRNA expression. Pretreatment with AM1241 reduced this morphine‑induced upregulation of TRPV1 and the effect was reversed by the CB2 receptor antagonist AM630. Our findings suggest that coadministration of a CB2 receptor agonist AM1241 and morphine reduced morphine tolerance possibly through regulation of TRPV1 protein expression in the DRG in cancer pain.”

https://www.ncbi.nlm.nih.gov/pubmed/28901432

https://www.spandidos-publications.com/10.3892/mmr.2017.7479

Olivia Newton-John champions the use of ‘magical, miracle’ medicinal cannabis

Cannabis is a "magical miracle plant" says singer Olivia Newton-John.“Let’s get medicinal, says Olivia Newton-John, who has spoken out about the use of medicinal cannabis on a recent visit to Australia. “I will do what I can to encourage it. It’s an important part of treatment and it should be available,” the singer, who announced a second battle with breast cancer in May, told News Corp Australia. The Australian entertainer said the drug – which is legal in her home state of California – had helped her during her second fight against cancer.” https://www.stuff.co.nz/entertainment/celebrities/96702731/olivia-newtonjohn-champions-the-use-of-magical-miracle-medicinal-cannabis

“OLIVIA NEWTON-JOHN TELLS HOW MARIJUANA IS HELPING HER BEAT CANCER”.“I use medicinal cannabis, which is really important for pain and healing,” “It’s a plant that has been maligned for so long, and has so many abilities to heal.”“I will do what I can to encourage it,” “It’s an important part of treatment, and it should be available. I use it for the pain and it’s also a medicinal thing to do — the research shows it’s really helpful.”” http://www.dailytelegraph.com.au/news/nsw/olivia-newtonjohn-tells-how-marijuana-is-helping-her-beat-cancer/news-story/12705dfadc0579a1139472271aa03bf8

 “It’s a magical miracle plant:’ Olivia Newton-John reveals husband John Easterling grows marijuana to aid her breast cancer battle… as star recalls her struggle to tell daughter Chloe about heartbreaking diagnosis. In an emotional interview with Karl Stefanovic on 60 Minutes, Olivia revealed that the controversial plant has helped her immeasurably in her cancer battle. ”It’s been a maligned plant all these years and it really is a magical miracle plant.”” http://www.dailymail.co.uk/tvshowbiz/article-4869940/Olivia-Newton-John-benefits-medical-marijuana.html

“OLIVIA NEWTON-JOHN TELLS ALL ON HER CANCER BATTLE & WHY WEED IS HER ‘HEALING PLANT'” http://okmagazine.com/photos/olivia-newton-john-cancer-weed-today-show/

“Olivia Newton-John on Being a Cancer ‘Thriver’ and Using Weed to Cope with Her Relapse: It’s a ‘Healing Plant’” http://people.com/music/olivia-newton-john-cancer-relapse-weed/

Image may contain: 1 person, text

Olivia Newton-John credits weed for helping cancer battle http://pagesix.com/2017/09/21/olivia-newton-john-credits-weed-for-helping-cancer-battle/

“Olivia Newton-John’s cancer battle is going well… Thanks to cannabis oil!” http://lifestyle.one/closer/celebrity/news/olivia-newton-john-daughter-chloe-lattanzi-cannabis-oil-cancer/

“Olivia Newton-John is Using Cannabis Oil for her Breast Cancer—Here’s How It Could Help” http://www.health.com/breast-cancer/cannabis-cancer-treatment-olivia-newton-john

“Cannabis Oil Will Help Olivia Newton-John Battle Breast Cancer”  https://thefreshtoast.com/celebrity/olivia-newton-john-will-use-cannabis-oil-in-battling-second-breast-cancer-diagnosis/

“Olivia Newton-John Is Using Cannabis Oil To Treat Her Cancer”  https://www.inverse.com/article/32780-cannabis-oil-cancer-treatment-cannabinoid-chemotherapy

“OLIVIA NEWTON-JOHN USES MEDICINAL CANNABIS IN CANCER FIGHT”  http://www.wsfm.com.au/entertainment/the-feed/olivia-newton-john-uses-medicinal-cannabis-in-cancer-fight

Olivia Newton-John is using medical marijuana during her battle with breast cancer” http://www.kansascity.com/entertainment/article171116417.html
“Olivia Newton-John reveals marijuana helping her beat cancer” http://www.9news.com.au/national/2017/09/03/08/58/olivia-newton-john-backs-medicinal-cannabis
“Newton-John backs medicinal cannabis”

“‘I use cannabis’: Olivia Newton-John talks cancer treatment”  https://startsat60.com/health/big-issues/cancer/i-use-cannabis-olivia-newton-john-opens-up-on-cancer-treatment

Image may contain: 1 person, smiling, text

 “”I use medicinal cannabis, which is really important for pain and healing. It’s a plant that has been maligned for so long and has so many abilities to heal,” Newton-John told the Daily Telegraph in a recent interview. Newton-John does not have a problem with her supplies of cannabis oil as her daughter, Chloe Lattanzi, owns a cannabis farm in Oregon, and can be easily obtained in her home state of California, where the use of medical marijuana is legal. However, as many parts of the world are still pessimistic about the medical use of marijuana, Newton-John has declared that she will advocate for its use, including in her home country Australia, where obtaining permits to use it still requires a long process even after it was legalized earlier this year. “I will do what I can to encourage it. It’s an important part of treatment, and it should be available. I use it for the pain and it’s also a medicinal thing to do — the research shows it’s really helpful,” Newton John said.” http://www.christianpost.com/news/olivia-newton-john-news-70s-icon-reveals-advocates-use-of-cannabis-oil-to-deal-with-cancer-pain-197915/
 “Olivia Newton-John champions use of medicinal cannabis in breast cancer battle” http://www.ibtimes.co.uk/olivia-newton-john-champions-use-medicinal-cannabis-breast-cancer-battle-1637729
“Newton-John champions medicinal cannabis use after it helped her cancer battle” https://thewest.com.au/news/health/newton-john-champions-medicinal-cannabis-use-after-it-helped-her-cancer-battle-ng-b88588000z
‘It’s really important and should be available’: Olivia Newton-John speaks for the first time about how ‘medical cannabis’ is helping her beat breast cancer” http://www.dailymail.co.uk/tvshowbiz/article-4846664/Olivia-Newton-John-talks-cannabis-use-time.html
“Grammy-winning singer/songwriter and actor Olivia Newton-John has opened up about her use of marijuana. “I use medicinal cannabis, which is really important for pain and healing,”“I will do what I can to encourage it. It’s an important part of treatment, and it should be available.”” https://www.civilized.life/articles/medicinal-cannabis-olivia-newton-john/
Image may contain: 1 person, smiling, meme and text

“Olivia Newton-John Admits to Using Home-Grown Medical Marijuana to Battle Cancer” http://popculture.com/2017/09/11/olivia-newton-john-medical-marijuana-breast-cancer/

 “Grassed Lightning: Olivia Newton-John is using cannabis instead of popping pills for breast cancer pain relief” http://www.mirror.co.uk/3am/celebrity-news/grassed-lightning-olivia-newton-john-11158137

“WEED ALL ABOUT IT.  Olivia Newton-John reveals she is drinking cannabis extract to ease her back pain as she battles cancer”  https://www.thesun.co.uk/fabulous/4454398/olivia-newton-john-reveals-she-is-drinking-cannabis-extract-to-ease-her-back-pain-as-she-battles-cancer/

“Olivia Newton-John Reveals She Was Unable to Walk After Cancer Relapse – and She’s Using Marijuana to Ease Pain” http://people.com/music/olivia-newton-john-cancer-update-couldnt-walk-australian-60-minutes/

“Olivia Newton-John uses medical marijuana to treat cancer”  https://www.buzz.ie/celebs/olivia-newton-john-drinks-cannabis-extract-numb-pain-cancer-253796

“Olivia Newton-John Talks Using Medical Marijuana In Cancer Treatment. “I use medical cannabis, which is really important to pain and healing. It’s an important part of treatment, and it should be available.”” https://www.thefix.com/olivia-newton-john-talks-using-medical-marijuana-cancer-treatment

“I’m really hoping that you will have it accessible to people. Particularly for people who are in pain. It’s not just cancer, it’s many, many illnesses. In children with epilepsy, parents are going to jail for trying to help their children, by giving them medicinal cannabis. That has to change, and I think it will. I think people are realizing this has been a maligned plant but it’s a healing plant with lots of wonderful properties. It can help alot of people. And they’re doing alot of research into the healing properties of cannabis, it’s not just for pain but to cure things. So it’s a very exciting time in the research as well.” –Olivia Newton-John http://www.dailymail.co.uk/video/tvshowbiz/video-1537789/Olivia-Newton-John-wants-medical-cannabis-legal-Australia.html

Image may contain: 1 person, smiling, meme, text and outdoor

 “Actress and singer Olivia Newton-John believes in the ‘healing properties’ of medical cannabis and hopes it will become legal, including for children.” http://www.dailymail.co.uk/video/tvshowbiz/video-1537789/Olivia-Newton-John-wants-medical-cannabis-legal-Australia.html

“‘It’s a magical miracle plant:’ Olivia Newton-John reveals husband John Easterling grows marijuana to aid her breast cancer battle” http://www.dailymail.co.uk/tvshowbiz/article-4869940/Olivia-Newton-John-benefits-medical-marijuana.html

“A picture of health! Olivia Newton-John beams at the ONJ Wellness Walk and Research Run in Melbourne as she battles cancer for the second time”   http://www.dailymail.co.uk/tvshowbiz/article-4892342/Olivia-Newton-John-cancer-fun-run.html

What’s the harm? Alcohol and marijuana use and perceived risks of unprotected sex among adolescents and young adults.

Addictive Behaviors

“The link between substance use and risky sexual behavior, particularly unprotected sex, among adolescents and young adults has been well established in the literature; however, less is known regarding how different patterns and types of substance use differentially relate to unprotected sex and perceived risks of unprotected sex.

The current study examined perceived risks and unprotected sex among adolescents and young adults, and examined whether marijuana use, alcohol use, and dual marijuana and alcohol use were differentially linked to unprotected sex and perceived risks of unprotected sex.

In a hierarchical logistic regression, only alcohol use was related to having unprotected sex at last intercourse (b=0.25, p<0.001). The second multinomial logistic regression showed that the interaction of alcohol and marijuana use was significantly related to lower levels of perceived risk of unprotected sex (moderate risk: b=0.06, p=0.04, OR=1.07; no/slight risk: b=0.07, p=0.03).

While dual marijuana and alcohol use was related to lower perceived risk of unprotected sex, only alcohol use only was associated with a higher likelihood of unprotected sex.”

https://www.ncbi.nlm.nih.gov/pubmed/28886577

http://www.sciencedirect.com/science/article/pii/S0306460317303325?via%3Dihub

Restless Genital Syndrome (ReGS) should be distinguished from Spontaneous Orgasms: A case report of Cannabis induced spontaneous orgasm.

Publication Cover

“A case is described of a 40 year old woman with persistent spontaneous orgasms after use of Cannabis and five hour hard pounding sexual activity. She presented with severe anxiety in particular to suffer from Restless Genital Syndrome (ReGS). However, she did not fulfill to any of the five criteria of ReGS. It was concluded that her spontaneous orgasms were the result of the use of Cannabis combined with long duration of previous sexual activity. This is not only important for physicians but alsof for highly exposed subjects like those active in the sex industry.”

11-nor-9-carboxy-Δ9-tetrahydrocannabinol glucuronide exhibits acyl-migration isomers.

Journal of Pharmaceutical and Biomedical Analysis

“11-nor-Δ9-Tetrahydrocannabinol-9-carboxylic acid glucuronide (THCCOOH-glucuronide) is an 1-β-O-acyl glucuronide which degrades not only to 11-nor-9-carboxy-Δ9-THC (THCCOOH) but, additionally, to an isomer with a currently unknown structure. The present study was carried out to examine whether acyl glucuronide isomers are formed by acyl migration and if they are involved in formation of this isomer. THCCOOH-glucuronide was incubated in phosphate buffer (pH 7.4, 37°C, 7days) and a variety of glucuronide cleavage procedures were performed. Samples of the incubation mixture and of different biological specimens from cannabis users were analyzed using liquid chromatography-mass spectrometry (LC-MS/MS). A total of six chromatographically separated isomeric acyl glucuronides were detected during incubation of THCCOOH-glucuronide reference substance. In biological specimens of cannabis users, two additional isomers were found. However, the main glucuronide present in human specimens was different from that of a commercially available reference substance. Both, the commercial and the authentic glucuronide were cleaved by β-glucuronidases, the other formed isomers by alkaline hydrolysis only. Mass spectrometric investigations (i.e. product ion, precursor ion and neutral loss scans) confirmed identity. The THCCOOH isomer was detected in all authentic samples, but not in those after buffer incubation. By analyzing THCCOOH-glucuronide in authentic samples, it has to be taken into account that the authentic glucuronide is different from that of the commercial reference standard. THCCOOH-glucuronide undergoes acyl migration and some isomers occur to minor extents in biological specimens. Acyl migration does not lead to the formation of the THCCOOH isomer.”

https://www.ncbi.nlm.nih.gov/pubmed/28892757

http://www.sciencedirect.com/science/article/pii/S0731708517317090?via%3Dihub

Challenges towards Revitalizing Hemp: A Multifaceted Crop.

Image result for cell journal

“Hemp has been an important crop throughout human history for food, fiber, and medicine. Despite significant progress made by the international research community, the basic biology of hemp plants remains insufficiently understood. Clear objectives are needed to guide future research. As a semi-domesticated plant, hemp has many desirable traits that require improvement, including eliminating seed shattering, enhancing the quantity and quality of stem fiber, and increasing the accumulation of phytocannabinoids. Methods to manipulate the sex of hemp plants will also be important for optimizing yields of seed, fiber, and cannabinoids. Currently, research into trait improvement is hindered by the lack of molecular techniques adapted to hemp. Here we review how addressing these limitations will help advance our knowledge of plant biology and enable us to fully domesticate and maximize the agronomic potential of this promising crop.”

https://www.ncbi.nlm.nih.gov/pubmed/28886910

http://www.cell.com/trends/plant-science/fulltext/S1360-1385(17)30177-2?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1360138517301772%3Fshowall%3Dtrue