Cannabinoid system in the skin – a possible target for future therapies in dermatology.

“Cannabinoids and their derivatives are group of more than 60 biologically active chemical agents, which have been used in natural medicine for centuries.

The major agent of exogenous cannabinoids is Delta(9)-tetrahydrocannabinol (Delta(9)-THC), natural psychoactive ingredient of marijuana.

Recent discoveries of endogenous cannabinoids (e.g. arachidonoylethanolamide, 2-arachidonoylglycerol or palmithyloethanolamide) and their receptors initiated discussion on the role of cannabinoid system in physiological conditions as well as in various diseases.

Based on the current knowledge, it could be stated that cannabinoids are important mediators in the skin, however their role have not been well elucidated yet.

In our review, we summarized the current knowledge about the significant role of the cannabinoid system in the cutaneous physiology and pathology, pointing out possible future therapeutic targets.”

http://www.ncbi.nlm.nih.gov/pubmed/19664006

New Study Finds Endocannabinoids May Help OCD

OCD and cannabis research

“Obsessive-Compulsive Disorder (OCD) may look different in each affected individual. One person might feel it is necessary to wash their hands constantly while others might feel obligated to count something over and over.

According to the National Institute of Mental Health, OCD is a common disorder in which a person has uncontrollable and reoccurring obsessions and compulsions. Obsessions often cause anxiety in a person, so they feel by doing compulsions, or certain behaviors, they might relieve their anxiety.

There are many treatments and medications used to combat OCD, however research is now showing that endocannabinoids can also play a huge role in OCD. The new study was funded by the The National Institute of Alcohol Abuse and Alcoholism (NIAA) and was conducted with mice. Researchers probed the brain mechanisms that are used when a mouse transitions from goal-directed behavior to habitual behaviors. They then led the mouse to receive food two ways. One way the mice received food was through doing a goal-directed behavior while the second way was through doing a habitual behavior. They then found that by deleting a certain endocannabinoid receptor, mice didn’t form habits.

This discovery led scientists to the conclusion that endocannabinoids, which are natural messengers in our bodies similar to cannabinoids found in cannabis, have a lot to do with how our brains make decisions.

George F. Koob, Ph.D. is the Director of the NIAA stated that their study revealed a mechanism in the brain that controls the transition between goal-directed behaviors and habitual behaviors. He went on to explain, “As we learn more about this mechanism, it could reveal how the brain forms habits and, more specifically, how both endocannabinoids and cannabinoid abuse can influence habitual behavior pathophysiology.”

This conclusion that our bodies natural endocannabinoids and the active ingredients in cannabis can affect memory and decision-making may give scientists a glimpse into new medications and treatments for OCD.” http://ireadculture.com/new-study-finds-endocannabinoids-may-help-ocd/

http://ireadculture.com/new-study-finds-endocannabinoids-may-help-ocd/?utm_content=buffera908b&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer

Allosteric modulation of heterodimeric G-protein-coupled receptors.

“G-protein-coupled receptors (GPCRs) are, and will probably remain, the most tractable class of targets for the development of small-molecule therapeutic medicines.

Currently, all approved GPCR-directed medicines are agonists or antagonists at orthosteric binding sites – except for the calcimimetic cinacalcet, which is a positive allosteric modulator of Ca(2+)-sensing receptors, and maraviroc, an allosteric inhibitor of CC-chemokine receptor (CCR) 5.

It is now widely accepted that GPCRs exist and might function as dimers, and there is growing evidence for the physiological presence and relevance of GPCR heterodimers.

Molecules that can regulate a GPCR within a heterodimer, through allosteric effects between the two protomers of the dimer or between a protomer or protomers and the associated G protein, offer the potential to function in a highly selective and tissue-specific way.

Despite the conceptual attraction of such allosteric regulators of GPCR heterodimers as drugs, they cannot be identified by screening approaches that routinely use a ‘one GPCR target at a time’ strategy.

In our opinion, this will require the development of new approaches for screening and a return to the use of physiologically relevant cell systems at an early stage in compound identification.”

http://www.ncbi.nlm.nih.gov/pubmed/18022255

Treatment of Dravet Syndrome.

“Dravet syndrome is among the most challenging electroclinical syndromes. There is a high likelihood of recurrent status epilepticus; seizures are medically refractory; and patients have multiple co-morbidities, including intellectual disability, behaviour and sleep problems, and crouch gait. Additionally, they are at significant risk of sudden unexplained death.

This review will focus predominantly on the prophylactic medical management of seizures, addressing both first-line therapies (valproate and clobazam) as well as second-line (stiripentol, topiramate, ketogenic diet) or later options (levetiracetam, bromides, vagus nerve stimulation). Sodium channel agents-including carbamazepine, oxcarbazepine, phenytoin and lamotrigine-should be avoided, as they typically exacerbate seizures.

Several agents in development may show promise, specifically fenfluramine and cannabidiol, but they need further evaluation in randomized, controlled trials.

In addition to prophylactic treatment, all patients need home-rescue medication and a status epilepticus protocol that can be carried out in their local hospital. Families must be counselled on non-pharmacologic strategies to reduce seizure risk, including avoidance of triggers that commonly induce seizures (including hyperthermia, flashing lights and patterns).

In addition to addressing seizures, holistic care for a patient with Dravet syndrome must involve a multidisciplinary team that includes specialists in physical, occupational and speech therapy, neuropsychology, social work and physical medicine.”

http://www.ncbi.nlm.nih.gov/pubmed/27264138

http://www.thctotalhealthcare.com/category/dravet-syndome/

Marihuana as Medicine

“BETWEEN 1840 and 1900, European and American medical journals published more than 100 articles on the therapeutic use of the drug known then as Cannabis indica (or Indian hemp) and now as marihuana.

It was recommended as an appetite stimulant, muscle relaxant, analgesic, hypnotic, and anticonvulsant. As late as 1913 Sir William Osler recommended it as the most satisfactory remedy for migraine.

Today the 5000-year medical history of cannabis has been almost forgotten.

Its use declined in the early 20th century because the potency of preparations was variable, responses to oral ingestion were erratic, and alternatives became available—injectable opiates and, later, synthetic drugs such as aspirin and barbiturates.

In the United States, the final blow was struck by the Marihuana Tax Act of 1937. Designed to prevent nonmedical use, this law made cannabis so difficult to obtain for medical purposes that it was removed from the pharmacopeia.”

http://jama.jamanetwork.com/article.aspx?articleid=388943#Abstract

The use of cannabis as a mood stabilizer in bipolar disorder: anecdotal evidence and the need for clinical research.

“The authors present case histories indicating that a number of patients find cannabis (marihuana) useful in the treatment of their bipolar disorder.

Some used it to treat mania, depression, or both. They stated that it was more effective than conventional drugs, or helped relieve the side effects of those drugs.

One woman found that cannabis curbed her manic rages; she and her husband have worked to make it legally available as a medicine. Others described the use of cannabis as a supplement to lithium (allowing reduced consumption) or for relief of lithium’s side effects.

Another case illustrates the fact that medical cannabis users are in danger of arrest, especially when children are encouraged to inform on parents by some drug prevention programs.

An analogy is drawn between the status of cannabis today and that of lithium in the early 1950s, when its effect on mania had been discovered but there were no controlled studies.

In the case of cannabis, the law has made such studies almost impossible, and the only available evidence is anecdotal. The potential for cannabis as a treatment for bipolar disorder unfortunately can not be fully explored in the present social circumstances.”

http://www.ncbi.nlm.nih.gov/pubmed/9692379

The endogenous cannabinoid system protects against colonic inflammation

“Excessive inflammatory responses can emerge as a potential danger for organisms’ health.

Our results indicate that the endogenous cannabinoid system represents a promising therapeutic target for the treatment of intestinal disease conditions characterized by excessive inflammatory responses.

The major active constituent of the plant Cannabis sativa (marijuana), Δ9-tetrahydrocannabinol, and a variety of natural and synthetic cannabinoids have been shown to possess antinociceptive and anti-inflammatory activities.

For millennia, Cannabis preparations have been used in folk medicine for the treatment of a wide variety of disorders, including those affecting the gastrointestinal tract. A century ago, extracts of Cannabis were used in the US to treat gastrointestinal pain of different origins, gastroenteritis, and diarrhea. There are also anecdotal reports suggesting that marijuana may be effective in alleviating symptoms of Crohn disease.

In conclusion, this study shows that the endogenous cannabinoid system is physiologically involved in the protection against excessive inflammation in the colon, both by dampening smooth muscular irritation caused by inflammation and by controlling cellular pathways leading to inflammatory responses.

These results strongly suggest that modulation of the physiological activity of the endogenous cannabinoid system during colonic inflammation might be a promising therapeutic tool for the treatment of several diseases characterized by inflammation of the gastrointestinal tract.”

https://www.jci.org/articles/view/19465

“A mouse study demonstrated that endogenous cannabinoid system signaling is likely to provide intrinsic protection against colonic inflammation. As a result, a hypothesis that phytocannabinoids and endocannabinoids may be useful in the risk reduction and treatment of colorectal cancer has been developed.” http://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq#section/_7

Marijuana is medicine, Journal of the American Medical Association concludes

“Marijuana is one hundred percent a form of medicine, researchers conclude in a bombshell series of reports released by the Journal of the American Medical Association. Cannabis has been used medicinally for thousands of years” http://blog.sfgate.com/smellthetruth/2015/06/23/marijuana-is-medicine-journal-of-the-american-medical-association-concludes/

http://blog.sfgate.com/smellthetruth/2015/06/23/marijuana-is-medicine-journal-of-the-american-medical-association-concludes/

“Cannabinoids for Medical Use. A Systematic Review and Meta-analysis.”  http://jama.jamanetwork.com/article.aspx?articleid=2338251

Natural Phytochemicals in the Treatment and Prevention of Dementia: An Overview.

“The word dementia describes a class of heterogeneous diseases which etiopathogenetic mechanisms are not well understood. There are different types of dementia, among which, Alzheimer’s disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) are the more common.

Currently approved pharmacological treatments for most forms of dementia seem to act only on symptoms without having profound disease-modifying effects. Thus, alternative strategies capable of preventing the progressive loss of specific neuronal populations are urgently required.

In particular, the attention of researchers has been focused on phytochemical compounds that have shown antioxidative, anti-amyloidogenic, anti-inflammatory and anti-apoptotic properties and that could represent important resources in the discovery of drug candidates against dementia.

In this review, we summarize the neuroprotective effects of the main phytochemicals belonging to the polyphenol, isothiocyanate, alkaloid and cannabinoid families in the prevention and treatment of the most common kinds of dementia.

We believe that natural phytochemicals may represent a promising sources of alternative medicine, at least in association with therapies approved to date for dementia.”

http://www.ncbi.nlm.nih.gov/pubmed/27110749

Integrating cannabis into clinical cancer care.

“Cannabis species have been used as medicine for thousands of years; only since the 1940s has the plant not been widely available for medical use.

However, an increasing number of jurisdictions are making it possible for patients to obtain the botanical for medicinal use.

For the cancer patient, cannabis has a number of potential benefits, especially in the management of symptoms. Cannabis is useful in combatting anorexia, chemotherapy-induced nausea and vomiting, pain, insomnia, and depression.

Cannabis might be less potent than other available antiemetics, but for some patients, it is the only agent that works, and it is the only antiemetic that also increases appetite.

Inhaled cannabis is more effective than placebo in ameliorating peripheral neuropathy in a number of conditions, and it could prove useful in chemotherapy-induced neuropathy.

A pharmacokinetic interaction study of vaporized cannabis in patients with chronic pain on stable doses of sustained-release opioids demonstrated no clinically significant change in plasma opiates, while suggesting the possibility of synergistic analgesia.

Aside from symptom management, an increasing body of in vitro and animal-model studies supports a possible direct anticancer effect of cannabinoids by way of a number of different mechanisms involving apoptosis, angiogenesis, and inhibition of metastasis.

Despite an absence of clinical trials, abundant anecdotal reports that describe patients having remarkable responses to cannabis as an anticancer agent, especially when taken as a high-potency orally ingested concentrate, are circulating.

Human studies should be conducted to address critical questions related to the foregoing effects.”

http://www.ncbi.nlm.nih.gov/pubmed/27022315