Therapeutic Symptomatic Strategies in the Parasomnias.

Current Treatment Options in Neurology

“The purpose of this review was to discuss the currently available pharmacologic and non-pharmacologic treatment options for parasomnias.

Cannabinoids proved to be effective in some of parasomnias, as in many other neurological disorders.

Prazosin and cannabinoids are effective in nightmare disorder.”

“Parasomnias are a category of sleep disorders that involve abnormal movements, behaviors, emotions, perceptions, and dreams that occur while falling asleep, sleeping, between sleep stages, or during arousal from sleep.”  https://en.wikipedia.org/wiki/Parasomnia
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Cannabis for Chronic Pain: Challenges and Considerations.

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy banner

“The National Academies of Sciences, Engineering, and Medicine has found substantial evidence that cannabis (plant) is effective for the treatment of chronic pain in adults, and moderate evidence that oromucosal cannabinoids (extracts, especially nabiximols) improve short-term sleep disturbances in chronic pain. ”

https://www.ncbi.nlm.nih.gov/pubmed/29637590

https://onlinelibrary.wiley.com/doi/abs/10.1002/phar.2115

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Prospective analysis of safety and efficacy of medical cannabis in large unselected population of patients with cancer

Cover image volume 49, Issue

“Cancer is a major public health problem as the leading cause of death. Palliative treatment aimed to alleviate pain and nausea in patients with advanced disease is a cornerstone of oncology.

In 2007, the Israeli Ministry of Health began providing approvals for medical cannabis for the palliation of cancer symptoms. The aim of this study is to characterize the epidemiology of cancer patients receiving medical cannabis treatment and describe the safety and efficacy of this therapy.

Methods

We analyzed the data routinely collected as part of the treatment program of 2970 cancer patients treated with medical cannabis between 2015 and 2017.

Results

The average age was 59.5 ± 16.3 years, 54.6% women and 26.7% of the patients reported previous experience with cannabis. The most frequent types of cancer were: breast (20.7%), lung (13.6%), pancreatic (8.1%) and colorectal (7.9%) with 51.2% being at stage 4. The main symptoms requiring therapy were: sleep problems (78.4%), pain (77.7%, median intensity 8/10), weakness (72.7%), nausea (64.6%) and lack of appetite (48.9%). After six months of follow up, 902 patients (24.9%) died and 682 (18.8%) stopped the treatment. Of the remaining, 1211 (60.6%) responded; 95.9% reported an improvement in their condition, 45 patients (3.7%) reported no change and four patients (0.3%) reported deterioration in their medical condition.

Conclusions

Cannabis as a palliative treatment for cancer patients seems to be well tolerated, effective and safe option to help patients cope with the malignancy related symptoms.”

https://www.ncbi.nlm.nih.gov/pubmed/29482741

http://www.ejinme.com/article/S0953-6205(18)30023-2/pdf

“Cannabis to be a “Safe,” “Effective” Medical Treatment in First-of-its-Kind, Peer-Reviewed Study of Thousands of Cancer Patients Using Tikun Olam™ Strains”  http://markets.businessinsider.com/news/stocks/cannabis-to-be-a-safe-effective-medical-treatment-in-first-of-its-kind-peer-reviewed-study-of-thousands-of-cancer-patients-using-tikun-olam-strains-1017297749

“For the first time, a major scientific study has confirmed what cannabis advocates have known for decades: that cannabis can be a safe and effective palliative treatment in patients suffering from the debilitating effects of cancer.”  https://www.prnewswire.com/news-releases/cannabis-to-be-a-safe-effective-medical-treatment-in-first-of-its-kind-peer-reviewed-study-of-thousands-of-cancer-patients-using-tikun-olam-strains-300604361.html

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Cannabidiol inhibits pathogenic T cells, decreases spinal microglial activation and ameliorates multiple sclerosis-like disease in C57BL/6 mice.

British Journal of Pharmacology

“Cannabis extracts and several cannabinoids have been shown to exert broad anti-inflammatory activities in experimental models of inflammatory CNS degenerative diseases.

Clinical use of many cannabinoids is limited by their psychotropic effects. However, phytocannabinoids like cannabidiol (CBD), devoid of psychoactive activity, are, potentially, safe and effective alternatives for alleviating neuroinflammation and neurodegeneration.

Treatment with CBD during disease onset ameliorated the severity of the clinical signs of EAE.

CBD, a non-psychoactive cannabinoid, ameliorates clinical signs of EAE in mice, immunized against MOG. Suppression of microglial activity and T-cell proliferation by CBD appeared to contribute to these beneficial effects.”

https://www.ncbi.nlm.nih.gov/pubmed/21449980

“In summary, we have shown that CBD administered to MOG-immunized C57BL/6 mice, at the onset of EAE disease, reduced the severity of the clinical signs of EAE. CBD treatment was accompanied by diminished axonal loss and inflammation (infiltration of T cells and microglial activation). Moreover, CBD prevented proliferation of myelin-specific T cells in vitro. These observations suggest that CBD may have potential for alleviating MS-like pathology.” http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01379.x/full

“Study Shows Cannabidiol (CBD) Improves MS-Like Symptoms”  http://www.prohealth.com/library/showarticle.cfm?libid=31211

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Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial.

The Lancet logo

“Patients with Lennox-Gastaut syndrome, a rare, severe form of epileptic encephalopathy, are frequently treatment resistant to available medications.

No controlled studies have investigated the use of cannabidiol for patients with seizures associated with Lennox-Gastaut syndrome.

We therefore assessed the efficacy and safety of cannabidiol as an add-on anticonvulsant therapy in this population of patients.

Add-on cannabidiol is efficacious for the treatment of patients with drop seizures associated with Lennox-Gastaut syndrome and is generally well tolerated.

https://www.ncbi.nlm.nih.gov/pubmed/29395273

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)30136-3/fulltext

“This study is registered with ClinicalTrials.gov, number NCT02224690.”

“Cannabidiol for drop seizures in Lennox-Gastaut syndrome”  http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)30135-1/fulltext

“Cannabidiol Reduces Drop Seizures in Lennox-Gastaut Syndrome”  https://www.neurologyadvisor.com/epilepsy/cannabidiol-reduces-drop-seizures-in-lennox-gastaut-syndrome/article/739544/

“Cannabidiol helps reduce drop attacks in people with Lennox-Gastaut syndrome, study shows” https://www.epilepsy.org.uk/news/news/cannabidiol-helps-reduce-drop-attacks-people-lennox-gastaut-syndrome-study-shows-68090

“‘Pharma Grade’ CBD Effective in Lennox-Gastaut”  https://www.medscape.com/viewarticle/891810

“Cannabidiol Efficacious for Lennox-Gastaut Drop Seizures”  https://www.doctorslounge.com/index.php/news/pb/78004

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Cannabidiol restores intestinal barrier dysfunction and inhibits the apoptotic process induced by Clostridium difficile toxin A in Caco-2 cells.

 SAGE Journals

“Clostridium difficile toxin A is responsible for colonic damage observed in infected patients.

Drugs able to restore Clostridium difficile toxin A-induced toxicity have the potential to improve the recovery of infected patients. Cannabidiol is a non-psychotropic component of Cannabis sativa, which has been demonstrated to protect enterocytes against chemical and/or inflammatory damage and to restore intestinal mucosa integrity.

The purpose of this study was to evaluate (a) the anti-apoptotic effect and (b) the mechanisms by which cannabidiol protects mucosal integrity in Caco-2 cells exposed to Clostridium difficile toxin A.

RESULTS:

Clostridium difficile toxin A significantly decreased Caco-2 cells’ viability and reduced transepithelial electrical resistence values and RhoA guanosine triphosphate (GTP), bax, zonula occludens-1 and occludin protein expression, respectively. All these effects were significantly and concentration-dependently inhibited by cannabidiol, whose effects were completely abolished in the presence of the cannabinoid receptor type 1 (CB1) antagonist, AM251.

CONCLUSIONS:

Cannabidiol improved Clostridium difficile toxin A-induced damage in Caco-2 cells, by inhibiting the apoptotic process and restoring the intestinal barrier integrity, through the involvement of the CB1 receptor.”

https://www.ncbi.nlm.nih.gov/pubmed/29238589

“In the last decade, cannabinoids extracted from the marijuana plant (Cannabis sativa) and synthetic cannabinoids have shown numerous beneficial effects on gastrointestinal (GI) functions. Non-psychotropic phytocannabinoid cannabidiol (CBD) is one of the most interesting compounds, since it exerts a wide range of beneficial pharmacological actions on GI functions, ranging from antioxidant to antinflammatory activities. CBD has been shown to act as a non-competitive negative allosteric modulator of CB1 receptors. Notably, CBD is able to restore in vitro intestinal permeability increased by ethylenediaminetetraacetic acid (EDTA) or pro-inflammatory stimuli.

Clostridium difficile infection is the leading cause of hospital-acquired diarrhoea and pseudomembranous colitis. Clostridium difficile-Toxin A significantly affects enterocytes permeability leading to apoptosis and colonic mucosal damage.

In the present study, we showed that Cannabidiol, a non-psychotropic component of Cannabis sativa significantly inhibit the apoptosis rate in TcdA-exposed cells and restores barrier function by a significant RhoA GTP rescue.

We also provide evidence that the effects of Cannabidiol are mediated by CB-1 receptor.

Given the absence of any significant toxic effect in humans, cannabidiol may ideally represent an effective adjuvant treatment for Clostridium difficile-associated colitis.”   http://journals.sagepub.com/doi/10.1177/2050640617698622

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Cannabidiol as a treatment for epilepsy

Journal of Neurology

“Despite an increasing number of anti-epileptic drugs (AEDs), the proportion of drug-resistant cases of epilepsy has remained fairly static at around 30% and the search for new and improved AEDs continues.

Cannabis has been used as a medical treatment for epilepsy for thousands of years; it contains many active compounds, the most important being tetrahydrocannabinol, which has psychoactive properties, and cannabidiol, which does not.

Animal models and clinical data to date have suggested that cannabidiol is more useful in treating epilepsy; there is limited evidence that tetrahydrocannabinol has some pro-convulsant effects in animal models. The mechanism by which cannabidiol exerts its anti-convulsant properties is currently unclear.

Conclusion. The evidence is increasing that cannabidiol is an effective treatment option for childhood onset severe treatment-resistant epilepsies with a tolerable side effect and safety profile. Further evidence is needed before cannabidiol can be considered in more common or adult onset epilepsies. Longer-term safety data for cannabidiol, particularly considering its effects on the developing brain, are also required.”

https://link.springer.com/article/10.1007%2Fs00415-017-8663-0

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Reversal of age-related cognitive impairments in mice by an extremely low dose of tetrahydrocannabinol.

Neurobiology of Aging

“This study was designed to test our hypothesis that an ultra-low dose of delta-9 tetrahydrocannabinol (THC) reverses age-dependent cognitive impairments in old mice and to examine the possible biological mechanisms that underlie this behavioral effect. These findings suggest that extremely low doses of THC that are devoid of any psychotropic effect and do not induce desensitization may provide a safe and effective treatment for cognitive decline in aging humans.”  https://www.ncbi.nlm.nih.gov/pubmed/29107185

“Cognitive decline is an integral aspect of aging. The idea that age-related cognitive decline can be reversed and that the old brain can be revitalized is not new. It has been previously suggested that the endocannabinoid system is part of an antiaging homeostatic defense system.  In previous studies, we have shown that ultra-low doses of tetrahydrocannabinol (THC, the main psychotropic ingredient in cannabis) protected young mice from cognitive impairments that were evoked by various insults. In the present study, we tested our hypothesis that a single ultra-low dose of THC can reverse age-dependent cognitive decline in mice. Here, we show that a single extremely low dose of THC devoid of any psychotropic activity can trigger an endogenous compensatory mechanism that improves cognitive functioning in old mice and that this effect lasts for at least several weeks. Since THC in high doses (dronabinol, 1–10 mg) is already approved for medical treatments in humans, and since its safety profile is well characterized, we believe that the initiation of clinical trials with ultra-low doses of THC designed to reverse cognitive decline in elderly patients should be straightforward.”  http://www.sciencedirect.com/science/article/pii/S0197458017303214

“Reversal of age-related cognitive impairments in mice by an extremely low dose of tetrahydrocannabinol. These findings suggest that extremely low doses of THC that are devoid of any psychotropic effect and do not induce desensitization may provide a safe and effective treatment for cognitive decline in aging humans.”   http://www.neurobiologyofaging.org/article/S0197-4580(17)30321-4/fulltext

Neurobiology of Aging Home

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Reprint of: survey of medicinal cannabis use among childbearing women: patterns of its use in pregnancy and retroactive self-assessment of its efficacy against ‘morning sickness’.

Complementary Therapies in Clinical Practice

“A majority of women experience some nausea and/or vomiting during pregnancy. This condition can range from mild nausea to extreme nausea and vomiting, with 1-2% of women suffering from the life-threatening condition hyperemesis gravidarum.

Cannabis (Cannabis sativa) may be used therapeutically to mitigate pregnancy-induced nausea and vomiting.

This paper presents the results of a survey of 84 female users of medicinal cannabis, recruited through two compassion societies in British Columbia, Canada. Of the seventy-nine respondents who had experienced pregnancy, 51 (65%) reported using cannabis during their pregnancies. While 59 (77%) of the respondents who had been pregnant had experienced nausea and/or vomiting of pregnancy, 40 (68%) had used cannabis to treat the condition, and of these respondents, 37 (over 92%) rated cannabis as ‘extremely effective’ or ‘effective.’

Our findings support the need for further investigations into cannabis therapy for severe nausea and vomiting during pregnancy.”

https://www.ncbi.nlm.nih.gov/pubmed/19880090

“Marijuana use is common in pregnancy but may not be an independent risk factor for poor neonatal outcomes in term pregnancies.”  http://www.sciencedirect.com/science/article/pii/S000293781500527X

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Cannabis and Cannabinoids for Chronic Pain.

Current Rheumatology Reports

“The purpose of this study was to provide the most up-to-date scientific evidence of the potential analgesic effects, or lack thereof, of the marijuana plant (cannabis) or cannabinoids, and of safety or tolerability of their long-term use.

RECENT FINDINGS:

We found that inhaled (smoked or vaporized) cannabis is consistently effective in reducing chronic non-cancer pain.

Oral cannabinoids seem to improve some aspects of chronic pain (sleep and general quality of life), or cancer chronic pain, but they do not seem effective in acute postoperative pain, abdominal chronic pain, or rheumatoid pain.

The available literature shows that inhaled cannabis seems to be more tolerable and predictable than oral cannabinoids. Cannabis or cannabinoids are not universally effective for pain. Continued research on cannabis constituents and improving bioavailability for oral cannabinoids is needed. Other aspects of pain management in patients using cannabis require further open discussion: concomitant opioid use, medical vs. recreational cannabis, abuse potential, etc.”

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