(-)-β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis.

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“(-)-β-caryophyllene (BCP), a cannabinoid receptor type 2 (CB2)-selective phytocannabinoid, has already been shown in precedent literature to exhibit both anti-inflammatory and analgesic effects in mouse models of inflammatory and neuropathic pain.

Herein, we endeavored to investigate the therapeutic potential of BCP on experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). Furthermore, we sought to demonstrate some of the mechanisms that underlie the modulation BCP exerts on autoimmune activated T cells, the pro-inflammatory scenery of the central nervous system (CNS), and demyelination.

Our findings demonstrate that BCP significantly ameliorates both the clinical and pathological parameters of EAE. In addition, data hereby presented indicates that mechanisms underlying BCP immunomodulatory effect seems to be linked to its ability to inhibit microglial cells, CD4+ and CD8+ T lymphocytes, as well as protein expression of pro-inflammatory cytokines. Furthermore, it diminished axonal demyelination and modulated Th1/Treg immune balance through the activation of CB2 receptor.

Altogether, our study represents significant implications for clinical research and strongly supports the effectiveness of BCP as a novel molecule to target in the development of effective therapeutic agents for MS.” https://www.ncbi.nlm.nih.gov/pubmed/28368293

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”  http://www.ncbi.nlm.nih.gov/pubmed/23138934

Can Marijuana Cure Cancer? Mom Claims To Have Cured Son’s Leukemia By Secretly Giving Him Weed

deryn

“Boy’s miracle recovery from rare cancer after mum gave him cannabis”  http://metro.co.uk/2017/03/26/boys-miracle-recovery-from-rare-cancer-after-mum-gave-him-cannabis-6534160/

“A mother in England reports that she secretly gave her son marijuana, and credits it with curing his leukemia, and saving the teen’s life. Callie Blackwell chose to secretly give her dying son illegally bought marijuana to help him deal with the pain and anxiety from his aggressive leukemia, because she felt he had “nothing else to lose,” The Independent reported. The drug did far more than the mother could have hoped; it not only relieved Deryn’s pain, it reportedly cured his cancer. Now, Blackwell hopes to share her family’s story in an effort to raise awareness about the healing potential of marijuana.

Deryn was first diagnosed with his severe and aggressive form of leukemia, a type of cancer that originates in the blood cells, at age 10. At 14, doctors informed him that there was nothing more they could do, and the young teen went to live out the rest of his short life in a hospice facility. However, that was three years ago, and now at 17, Deryn has fully recovered from his disease and plans to start a career in the food industry. Callie teamed up with author Karen Hockney to write The Boy in 7 Million, a book detailing the family’s experience and highlighting the potential of marijuana in cancer treatment.

There have been a number of instances where marijuana was suspected of significantly improving, and in some cases even curing cancer, but the science remains inconclusive. Research suggests that cannabinoids—chemicals found in the marijuana plants—can target and kill cancer cells in ways that drugs cannot.” http://www.medicaldaily.com/can-marijuana-cure-cancer-mom-claims-have-cured-sons-leukemia-secretly-giving-414375

“Teenager dying of cancer ‘recovers after mother gives him marijuana'” http://www.independent.co.uk/life-style/health-and-families/health-news/teenager-deryn-boy-dying-cancer-mother-callie-blackwell-recover-medical-marijuana-cannabis-weed-a7652106.html

‘I GAVE MY BOY CANNABIS’. Mum reveals she gave her cancer-stricken son CANNABIS in bid to ease his pain… and now he’s made a miracle recovery. Deryn Blackwell, who was expected to die, has defied doctors by surviving two deadly cancers”  https://www.thesun.co.uk/news/3181956/mum-callie-blackwell-cancer-stricken-son-deryn-cannabis/

“I gave my little boy CANNABIS to help cure his cancer: Mother reveals how her teenage son who was given days to live made a miracle recovery when she gave him the drug behind his doctors’ backs” http://www.dailymail.co.uk/femail/article-4349232/Mother-gave-young-son-cannabis-help-cure-cancer.html

One in 7 Billion: Deryn Blackwell begins his hospital ordeal aged 10

“‘I gave my dying son cannabis to ease his cancer symptoms and he made a miracle recovery’ reveals mum” http://www.mirror.co.uk/news/uk-news/i-gave-dying-son-cannabis-10103387

“I Secretly Gave My Son Cannabis to Save His Life | This Morning”  https://www.youtube.com/watch?v=qqvJOAV7oAc&t=4s

“This Morning fans praise mum who risks prosecution after giving son cannabis cancer drug” http://www.express.co.uk/showbiz/tv-radio/784387/This-Morning-Phillip-Schofield-Holly-Willoughby-cannabis-based-drug-cancer

“Mum claims cannabis cured son’s cancer after he was given days to live. A MUM has claimed that cannabis cured her son’s terminal cancer.”  http://www.dailystar.co.uk/showbiz-tv/hot-tv/600294/cannabis-cures-cancer-this-morning-holly-willoughby

“As teenage boy ‘beats’ cancer with cannabis oil here are nine illnesses the drug could ‘cure’. Deryn Blackwell’s parents secretly gave him the class B drug to ease his pain and anxiety as he underwent gruelling treatment in hospital for leukaemia and cancer.” http://www.mirror.co.uk/lifestyle/health/after-cannabis-oil-miracle-recovery-10111458

I gave my cancer-stricken son weed and it saved his life” http://nypost.com/2017/03/26/i-gave-my-cancer-stricken-son-weed-and-it-saved-his-life/

“London mother claims cannabis helped her dying son recover from rare cancer” http://www.nydailynews.com/news/world/u-mother-claims-cannabis-helped-dying-son-recover-cancer-article-1.3010404

“Mother gives marijuana to cancer-struck son and he makes full recovery”  http://topexaminer.com/2017/03/28/mother-gives-marijuana-cancer-struck-son-makes-full-recovery/

“CALLIE BLACKWELL SAYS CANNABIS OIL HELPED SON’S CANCER: ‘THE BOY IN 7 BILLION’” http://www.inquisitr.com/4095508/callie-blackwell-says-cannabis-oil-helped-sons-cancer-the-boy-in-7-billion/

“Teenager Dying Of Cancer Survives After His Mother Gives Him A Dose Of Marijuana” http://www.indiatimes.com/health/buzz/teenager-dying-of-cancer-survives-after-his-mother-gives-him-a-dose-of-marijuana-274499.html

“Mother risked 14 years in prison to smuggle cannabis into hospital for dying son – and she claims it saved his life.‘” http://metro.co.uk/2017/10/23/mother-risked-14-years-in-prison-to-smuggle-cannabis-into-hospital-for-dying-son-and-she-claims-it-saved-his-life-7021003/
“Teen boy ‘saved by cannabis’ reveals how his mum’s illegal drug-buying stopped him from dying. Deryn Blackwell, from Norfolk, was sent to a hospice shortly after his 14th birthday to live out his final few days. He was frail and in extraordinary pain after a relentless battle with a one in a billion form of cancer, Langerhans cell sarcoma. But after his parents secretly gave him cannabis oil to ease his pain and anxiety, he made a miracle recovery. Today, Deryn – who had also battled leukaemia – is a happy and healthy 17-year-old student, with friends and a girlfriend.” http://www.mirror.co.uk/tv/tv-news/teen-boy-saved-cannabis-reveals-11393969

http://www.thctotalhealthcare.com/category/leukemia/

Terpene synthases from Cannabis sativa.

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“Cannabis (Cannabis sativa) plants produce and accumulate a terpene-rich resin in glandular trichomes, which are abundant on the surface of the female inflorescence.

Bouquets of different monoterpenes and sesquiterpenes are important components of cannabis resin as they define some of the unique organoleptic properties and may also influence medicinal qualities of different cannabis strains and varieties.

Transcriptome analysis of trichomes of the cannabis hemp variety ‘Finola’ revealed sequences of all stages of terpene biosynthesis. Nine cannabis terpene synthases (CsTPS) were identified in subfamilies TPS-a and TPS-b.

Functional characterization identified mono- and sesqui-TPS, whose products collectively comprise most of the terpenes of ‘Finola’ resin, including major compounds such as β-myrcene, (E)-β-ocimene, (-)-limonene, (+)-α-pinene, β-caryophyllene, and α-humulene.

Transcripts associated with terpene biosynthesis are highly expressed in trichomes compared to non-resin producing tissues. Knowledge of the CsTPS gene family may offer opportunities for selection and improvement of terpene profiles of interest in different cannabis strains and varieties.”

https://www.ncbi.nlm.nih.gov/pubmed/28355238

Cannabis for Pain and Headaches: Primer.

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“Marijuana has been used both medicinally and recreationally since ancient times and interest in its compounds for pain relief has increased in recent years. The identification of our own intrinsic, endocannabinoid system has laid the foundation for further research.

Synthetic cannabinoids are being developed and synthesized from the marijuana plant such as dronabinol and nabilone. The US Food and Drug Administration approved the use of dronabinol and nabilone for chemotherapy-associated nausea and vomiting and HIV (Human Immunodeficiency Virus) wasting. Nabiximols is a cannabis extract that is approved for the treatment of spasticity and intractable pain in Canada and the UK. Further clinical trials are studying the effect of marijuana extracts for seizure disorders.

Phytocannabinoids have been identified as key compounds involved in analgesia and anti-inflammatory effects.  Other compounds found in cannabis such as flavonoids and terpenes are also being investigated as to their individual or synergistic effects.

This article will review relevant literature regarding medical use of marijuana and cannabinoid pharmaceuticals with an emphasis on pain and headaches.”

https://www.ncbi.nlm.nih.gov/pubmed/28281107

Endocannabinoids: A Promising Impact for Traumatic Brain Injury.

 

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“The endogenous cannabinoid (endocannabinoid) system regulates a diverse array of physiological processes and unsurprisingly possesses considerable potential targets for the potential treatment of numerous disease states, including two receptors (i.e., CB1 and CB2 receptors) and enzymes regulating their endogenous ligands N-arachidonoylethanolamine (anandamide) and 2-arachidonyl glycerol (2-AG).

Increases in brain levels of endocannabinoids to pathogenic events suggest this system plays a role in compensatory repair mechanisms.

Traumatic brain injury (TBI) pathology remains mostly refractory to currently available drugs, perhaps due to its heterogeneous nature in etiology, clinical presentation, and severity. Here, we review pre-clinical studies assessing the therapeutic potential of cannabinoids and manipulations of the endocannabinoid system to ameliorate TBI pathology.

Specifically, manipulations of endocannabinoid degradative enzymes (e.g., fatty acid amide hydrolase, monoacylglycerol lipase, and α/β-hydrolase domain-6), CB1and CB2 receptors, and their endogenous ligands have shown promise in modulating cellular and molecular hallmarks of TBI pathology such as; cell death, excitotoxicity, neuroinflammation, cerebrovascular breakdown, and cell structure and remodeling.

TBI-induced behavioral deficits, such as learning and memory, neurological motor impairments, post-traumatic convulsions or seizures, and anxiety also respond to manipulations of the endocannabinoid system.

As such, the endocannabinoid system possesses potential drugable receptor and enzyme targets for the treatment of diverse TBI pathology.

Yet, full characterization of TBI-induced changes in endocannabinoid ligands, enzymes, and receptor populations will be important to understand that role this system plays in TBI pathology.

Promising classes of compounds, such as the plant-derived phytocannabinoids, synthetic cannabinoids, and endocannabinoids, as well as their non-cannabinoid receptor targets, such as TRPV1 receptors, represent important areas of basic research and potential therapeutic interest to treat TBI.”

Marijuana and other cannabinoids as a treatment for posttraumatic stress disorder: A literature review.

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“Posttraumatic stress disorder (PTSD) is common in the general population, yet there are limitations to the effectiveness, tolerability, and acceptability of available first-line interventions.

We review the extant knowledge on the effects of marijuana and other cannabinoids on PTSD.

Potential therapeutic effects of these agents may largely derive from actions on the endocannabinoid system and we review major animal and human findings in this area.

Preclinical and clinical studies generally support the biological plausibility for cannabinoids‘ potential therapeutic effects, but underscore heterogeneity in outcomes depending on dose, chemotype, and individual variation.

Treatment outcome studies of whole plant marijuana and related cannabinoids on PTSD are limited and not methodologically rigorous, precluding conclusions about their potential therapeutic effects.

Although controlled research on marijuana and other cannabinoids‘ effects on PTSD remains limited, rapid shifts in the legal landscape may now enable such studies, potentially opening new avenues in PTSD treatment research.”

https://www.ncbi.nlm.nih.gov/pubmed/28245077

The endocannabinoid system modulating levels of consciousness, emotions and likely dream contents.

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“Cannabinoids are derivatives that are either compounds occurring naturally in the plant, Cannabis sativa or synthetic analogs of these molecules. The first and most widely investigated of the cannabinoids is ∆9-tetrahydrocannabinol (Δ9-THC), which is the main psychotropic constituent of cannabis and undergoes significant binding to cannabinoid receptors.

These cannabinoid receptors are seven-transmembrane receptors that received their name from the fact that they respond to cannabinoid compounds, including Δ9-THC. The cannabinoid receptors have been described in rat, human and mouse brains and they have been named as the CB1 and CB2 cannabinoid receptors.

Later, an endogenous molecule that exerts pharmacological effects similar to those described by ∆9-THC and binds to the cannabinoid receptors was discovered. This molecule, named anandamide, was the first of five endogenous cannabinoid receptor agonists described to date in the mammalian brain and other tissues. Of these endogenous cannabinoids or endocannabinoids, the most thoroughly investigated to date have been anandamide and 2-arachidonoylglycerol (2-AG).

Over the years, a significant number of articles have been published in the field of endogenous cannabinoids, suggesting a modulatory profile in multiple neurobiological roles of endocannabinoids. The general consensus accepts that the endogenous cannabinoid system includes natural ligands (such as anandamide and 2-AG), receptors (CB1 and CB2), and the main enzymes responsible for the hydrolysis of anandamide and 2-AG (fatty acid amide hydrolase [FAAH] and monoacylglycerol lipase [MAGL], respectively) as well as the anandamide membrane transporter (AMT).

To date, diverse pieces of evidence have shown that the endocannabinoid system controls multiple functions such as feeding, pain, learning and memory and has been linked with various diseases, such as Parkinson´s disease. Among the modulatory properties of the endocannabinoid system, current data indicate that the sleep-wake cycle is under the influence of endocannabinoids since the blocking of the CB1 cannabinoid receptor or the pharmacological inhibition of FAAH activity promotes wakefulness whereas the obstruction of AMT function enhances sleep. However, no solid evidence is available regarding the role of the endocannabinoid system in an unquestionable emotional component of the sleep: Dream activity.

Since dreaming is a mental activity that occurs during sleep (characterized by emotions, sensory perceptions, and bizarre components) and the endocannabinoid system modulates neurobiological processes involving consciousness, such as learning and memory, attention, pain perception, emotions and sleep, it is acceptable to hypothesize that the endocannabinoid system might be modulating dream activity. In this regard, an accumulative body of evidence in human and animal models has been reported regarding the role of the endocannabinoid system in the control of emotional states and dreams.

Moreover, preliminary studies in humans have indicated that treatment with cannabinoids may decrease post-traumatic stress disorder symptoms, including nightmares. Thus, based on a review of the literature available in PubMed, this article hypothesizes a conceptual framework within which the endocannabinoid system might influence the generation of dream experiences.”

https://www.ncbi.nlm.nih.gov/pubmed/28240187

Cannabinoids and Cystic Fibrosis

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“Cannabis stimulates appetite and food intake. This property has been exploited to benefit AIDS and cancer patients suffering from wasting disease, by administering the whole plant or its major active ingredient ?-tetrahydrocannabinol (THC). Endogenous cannabinoids (“endocannabinoids”) are found in maternal milk. We have recently shown that endocannabinoids are critical for milk ingestion and survival of newborns because blocking CB1 receptors resulted in death from malnutrition. Lack of appetite resulting in malnutrition is a contributing factor to mortality in many Cystic Fibrosis (CF) patients. It is proposed here for the first time, to administer THC to CF patients. It is hoped that the cannabinoid will alleviate malnutrition and thus help prevent wasting in CF patients. Recent findings suggest that a lipid imbalance (high arachidonic acid/low DHA) is a primary factor in the etiology of CF and that defective CFTR (CF transmembrane conductor regulator) that characterizes the CF condition is responsible for the dysregulation. Endocannabinoids are all fatty acid derivatives. Therefore, it is further proposed here that the CFTR gene product also modulates endocannabinoid synthesis, through regulation of fatty acid biosynthesis. According to this hypothesis, CF patients display decreased levels of endocannabinoids and by elevating these levels, symptoms may improve. Indeed, a number of physiological mechanisms of cannabinoids and endocannabinoids coincide with the pathology of CF. Thus it is suggested that potential benefits from THC treatment, in addition to appetite stimulation, will include antiemetic, bronchodilating, anti-inflammatory, anti-diarrheal and hypo-algesic effects.” https://www.researchgate.net/publication/233294071_Cannabinoids_and_Cystic_Fibrosis

“Cannabinoids and Cystic Fibrosis. A Novel Approach to Etiology and Therapy”  http://www.tandfonline.com/doi/abs/10.1300/J175v02n01_03

Effects of tetrahydrocannabinol on glucose uptake in the rat brain.

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“Δ9-Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain.

The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain.

Low blood THC levels of <1 ng/ml corresponded to an increased glucose uptake while blood THC levels > 10 ng/ml coincided with a decreased glucose uptake. The effective concentration in this region was estimated 2.4 ng/ml.

This glucose PET study showed that stimulation of CB1 receptors by THC affects the glucose uptake in the rat brain, whereby the effect of THC is regionally different and dependent on dose – an effect that may be of relevance in behavioural studies.”

https://www.ncbi.nlm.nih.gov/pubmed/28219717

The potential for clinical use of cannabinoids in treatment of cardiovascular diseases.

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“Cannabinoids, the constituents of the marijuana plant and their analogs, have not only neurobehavioral but also cardiovascular effects. Great advances in the last couple of decades have led to better understanding of the physiological effects of the cannabinoids and of their role in various cardiovascular pathologies. The potential therapeutic use of cannabinoids in various cardiac diseases, such as ischemic injury, heart failure, and cardiac arrhythmias, has been studied in animal models. The purpose of this article is to review the physiological cardiovascular properties of cannabinoids and to summarize the knowledge related to their potential therapeutic use.” https://www.ncbi.nlm.nih.gov/pubmed/20946323

“Cannabinoid system as a potential target for drug development in the treatment of cardiovascular disease.” https://www.ncbi.nlm.nih.gov/pubmed/15320476