Cannabidiol reduced frequency of convulsive seizures in drug resistant Dravet syndrome.

BMJ Journals

“Study design

Design: Multinational double-blinded placebo-controlled trial. Patients randomised in 1:1 ratio to receive cannabidiol or placebo, in addition to stable antiepileptic treatment regime.

Study question

Setting: Twenty-three centres in Europe and USA.

 Patients: Patients aged 2 years to 18 years with established diagnosis of Dravet syndrome having at least four convulsive seizures during the 28-day baseline period despite regular antiepileptic medication.

Intervention: Adjunctive cannabidiol or placebo oral solution at 20 mg per kilogram of body weight per day.

Primary outcome: Percentage change in median frequency of convulsive seizures per month.

Follow-up period: Outcome measured over a 14-week treatment period in comparison to a 4-week baseline period.

Patient follow-up: One hundred and eight (90%) completed the trial: 85% (52/61) in the cannabidiol group and …”

http://ep.bmj.com/content/early/2017/09/22/archdischild-2017-313700

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Medical marijuana for the treatment of vismodegib-related muscle spasm

JAAD Case Reports

“Basal cell carcinoma (BCC) arises from loss-of-function mutations in tumor suppressor patched homologue 1, which normally inhibits smoothened homologue in the sonic hedgehog signaling pathway. Vismodegib, a smoothened homologue inhibitor, is US Food and Drug Administration (FDA) approved for metastatic or locally advanced BCC that has recurred after surgery or for patients who are not candidates for surgery and radiation. Common adverse effects of vismodegib are muscle spasms, alopecia, dysgeusia, nausea, and weight loss. Muscle spasms worsen with duration of drug administration and may lead to drug discontinuation.

We report a case of vismodegib-related muscle spasm that was successfully treated with medical marijuana (MM).

During the first week of vismodegib and radiation, the patient started MM, having heard of its indication in the treatment of muscle cramps. She smoked 3 to 4 joints daily of Trainwreck strain, containing 18.6% tetrahydrocannabinol (THC), 0.0% cannabidiol (CBD), and 0.0% cannabinol. Her muscle spasms resolved immediately. She continued MM for 3.5 weeks, until the cost of MM became prohibitive. She reported no adverse effects from MM. Complete resolution of muscle spasms was sustained through the remaining 3.5 weeks of vismodegib. Complete blood count, comprehensive metabolic panel, and lactate dehydrogenase level were monitored throughout the study with no significant changes. As of 18 months posttreatment, the patient had a complete clinical response of her BCC.

One marijuana joint contains, on average, 0.66 g of marijuana, although the definition of a joint is highly variable. With any MM formulation, patients should start at a low dose and gradually titrate to effect. Additional studies could confirm safety and efficacy and better specify the optimal cannabinoid subtypes, preparations, and dosages that may be most beneficial for vismodegib-induced muscle spasms.”

http://www.jaadcasereports.org/article/S2352-5126(17)30124-8/fulltext

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Efficacy of Cannabis-Based Medicines for Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

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“The management of chronic pain is a complex challenge worldwide. Cannabis-based medicines (CBMs) have proven to be efficient in reducing chronic pain, although the topic remains highly controversial in this field.

OBJECTIVES:

This study’s aim is to conduct a conclusive review and meta-analysis, which incorporates all randomized controlled trials (RCTs) in order to update clinicians’ and researchers’ knowledge regarding the efficacy and adverse events (AEs) of CBMs for chronic and postoperative pain treatment.

CONCLUSIONS:

The current systematic review suggests that CBMs might be effective for chronic pain treatment, based on limited evidence, primarily for neuropathic pain (NP) patients. Additionally, GI AEs occurred more frequently when CBMs were administered via oral/oromucosal routes than by inhalation.”

https://www.ncbi.nlm.nih.gov/pubmed/28934780

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Effects of Cannabinoid Agonists and Antagonists on Sleep and Breathing in Sprague-Dawley Rats.

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“There are no pharmacological treatments for obstructive sleep apnea syndrome, but dronabinol showed promise in a small pilot study. In anesthetized rats, dronabinol attenuates reflex apnea via activation of cannabinoid (CB) receptors located on vagal afferents; an effect blocked by cannabinoid type 1 (CB1) and/or type 2 (CB2) receptor antagonists. Here, using a natural model of central sleep apnea, we examine the effects of dronabinol, alone and in combination with selective antagonists in conscious rats chronically instrumented to stage sleep and measure cessation of breathing.

RESULTS:

Dronabinol decreased the percent time spent in rapid eye movement (REM) sleep. CB receptor antagonists did not reverse this effect. Dronabinol also decreased apneas during sleep, and this apnea suppression was reversed by CB1 or CB1/CB2 receptor antagonism.

CONCLUSIONS:

Dronabinol’s effects on apneas were dependent on CB1 receptor activation, while dronabinol’s effects on REM sleep were CB receptor-independent.”

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[Delta-9-tetrahydrocannabinol-cannabidiol in the treatment of spasticity in chronic spinal cord injury: a clinical experience].

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“Spasticity in chronic spinal cord injury is a condition that can have negative repercussions on the patient’s quality of life. Its treatment is complex and sometimes the outcome is insufficient.

Cannabinoids have recently been used in multiple sclerosis to successfully treat spasticity that is refractory to other therapies.

AIM:

To quantify the clinical response of a group of patients with spastic chronic spinal cord injury to the orally administered drug delta-9-tetrahydrocannabinol-cannabidiol (Sativex ®) as medication for use in special situations.

RESULTS:

Fifteen patients took part in this study. A significant improvement was observed on three of the scales recorded: modified Ashworth scale (z = -2.97; p = 0.003), Penn spasm frequency scale (z = -2.76; p = 0.006) and Numeric Rating Scale (z = -3.21; p = 0.001).

CONCLUSIONS:

Sativex can be considered an alternative in patients with spasticity associated with chronic spinal cord injury for whom other therapeutic measures have been insufficient. Further studies need to be conducted before the use of this drug can be recommended and so as to define a complete profile of its long-term side effects.”

https://www.ncbi.nlm.nih.gov/pubmed/28929471

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Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids

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“Nanotechnology has opened up a new, previously unimaginable world in cancer diagnosis and therapy, leading to the emergence of cancer nanomedicine and nanoparticle-aided radiotherapy. These nanoparticle drones can be programmed to deliver therapeutic payloads to tumor sites to achieve optimal therapeutic efficacy.

In this article, we examine the state-of-the-art and potential of nanoparticle drones in targeting lung cancer. Inhalation (INH) (air) versus traditional intravenous (“sea”) routes of navigating physiological barriers using such drones is assessed. Results and analysis suggest that INH route may offer more promise for targeting tumor cells with radiosensitizers and cannabinoids from the perspective of maximizing damage to lung tumors cells while minimizing any collateral damage or side effects.

As discussed earlier, nanoparticle drones are particularly attractive because they can also be loaded with drugs payload like cannabinoids. Cannabinoids, which are the bioactive components of Cannabis sativa and their derivatives, may exert palliative effects in cancer patients by preventing nausea, vomiting, and pain and by stimulating appetite .

Furthermore, studies indicate that cannabinoids can inhibit cancer cell growth in in vitro and in vivo. A Nature Reviews Cancer article and other recently published work highlight the potential of cannabinoids for treating cancer, working in synergy with radiotherapy and serving as radiosensitzers to enhance damage to lung tumor cells in particular. Consistent with this, our own experiments have confirmed the potential of cannabinoids in treating lung cancer, with results confirming that cannabinoids can enhance damage to cancer cells.

Overall, the use of nanoparticle drones administered via INH to enhance NRT, as highlighted in this article, may provide a good strategy for maximizing therapeutic efficacy in external beam NRT for lung cancer. Also there is growing evidence that cannabinoids can serve as radiosensitizers, enhance damage to tumor cells, slow tumor growth, and work synergistically with radiotherapy in cancer treatment.”

http://journal.frontiersin.org/article/10.3389/fonc.2017.00208/full

“Cannabis Science Announces Publication of Initial Research Results Using Nanoparticle Drones to Target Lung Cancer With Radiosensitizers and Cannabinoids in the Renowned Journal Frontiers in Oncology” https://ca.finance.yahoo.com/news/cannabis-science-announces-publication-initial-120522920.html

“Cannabis Science “Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids” Full Publication Released Today In Frontiers In Oncology” http://www.marketwired.com/press-release/cannabis-science-nanoparticle-drones-target-lung-cancer-with-radiosensitizers-cannabinoids-2234167.htm

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Re-visiting the Endocannabinoid System and Its Therapeutic Potential in Obesity and Associated Diseases.

 Current Diabetes Reports

“The purpose of the review was to revisit the possibility of the endocannabinoid system being a therapeutic target for the treatment of obesity by focusing on the peripheral roles in regulating appetite and energy metabolism.

Previous studies with the global cannabinoid receptor blocker rimonabant, which has both central and peripheral properties, showed that this drug has beneficial effects on cardiometabolic function but severe adverse psychiatric side effects. Consequently, focus has shifted to peripherally restricted cannabinoid 1 (CB1) receptor blockers as possible therapeutic agents that mitigate or eliminate the untoward effects in the central nervous system.

Targeting the endocannabinoid system using novel peripheral CB1 receptor blockers with negligible penetrance across the blood-brain barrier may prove to be effective therapy for obesity and its co-morbidities.

Perhaps the future of blockers targeting CB1 receptors will be tissue-specific neutral antagonists (e.g., skeletal muscle specific to treat peripheral insulin resistance, adipocyte-specific to treat fat excess, liver-specific to treat fatty liver and hepatic insulin resistance).”

https://www.ncbi.nlm.nih.gov/pubmed/28913816

https://link.springer.com/article/10.1007%2Fs11892-017-0924-x

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Endocannabinoid mechanism in amphetamine-type stimulant use disorders: A short review.

Journal of Clinical Neuroscience Home

“Recent evidence shows that the endocannabinoid system is involved in amphetamine-type stimulants (ATS) use disorders. To elucidate the role of the endocannabinoid system in ATS addiction, we reviewed results of studies using cannabinoid receptor agonists, antagonists as well as knockout model.

The endocannabinoid system seems to play a role in reinstatement and relapse of ATS addiction and ATS-induced psychiatric symptoms. The molecular mechanisms of this system remains unclear, the association with dopamine system in nucleus accumbens is most likely involved. However, the function of the endocannabinoid system in anxiety and anti-anxiety effects induced by ATS is more complicated.

These findings suggest that the endocannabinoid system may play an important role in the mechanism of ATS addiction and provide new idea for treating ATS addiction.”

https://www.ncbi.nlm.nih.gov/pubmed/28912087

http://www.jocn-journal.com/article/S0967-5868(17)30989-X/fulltext

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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

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

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“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.”

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