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Orrin Devinsky, Anup D Patel, Elizabeth A Thiele, Matthew H Wong, Richard Appleton, Cynthia L Harden, Sam Greenwood, Gilmour Morrison, Kenneth Sommerville
OBJECTIVE: To evaluate the safety and preliminary pharmacokinetics of a pharmaceutical formulation of purified cannabidiol (CBD) in children with Dravet syndrome. METHODS: Patients aged 4-10 years were randomized 4:1 to CBD (5, 10, or 20 mg/kg/d) or placebo taken twice daily. The double-blind trial comprised 4-week baseline, 3-week treatment (including titration), 10-day taper, and 4-week follow-up periods. Completers could continue in an open-label extension. Multiple pharmacokinetic blood samples were taken on the first day of dosing and at end of treatment for measurement of CBD, its metabolites 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD, and antiepileptic drugs (AEDs; clobazam and metabolite N -desmethylclobazam [N-CLB], valproate, levetiracetam, topiramate, and stiripentol)...
March 14, 2018: Neurology
Peter M Irving, Tariq Iqbal, Chuka Nwokolo, Sreedhar Subramanian, Stuart Bloom, Neeraj Prasad, Ailsa Hart, Charles Murray, James O Lindsay, Adam Taylor, Rachel Barron, Stephen Wright
Background: Cannabidiol (CBD) exhibits anti-inflammatory properties that could improve disease activity in inflammatory bowel disease. This proof-of-concept study assessed efficacy, safety and tolerability of CBD-rich botanical extract in ulcerative colitis (UC) patients. Methods: Patients aged 18 years or older, with left-sided or extensive UC, Mayo scores of 4-10 (endoscopy scores ≥1), and on stable 5-aminosalicylic acid dosing, were randomized to 10-weeks' CBD-rich botanical extract or placebo capsules...
March 10, 2018: Inflammatory Bowel Diseases
David Neubauer, Mirjana Perković Benedik, Damjan Osredkar
PURPOSE: Refractory epilepsies in children present a major burden for patients and their families. Cannabidiol (CBD) has been suggested as a potential treatment for refractory epilepsies. The aim of this study was to evaluate the effectiveness of add-on therapy with CBD for the treatment of refractory childhood epilepsies. METHOD: Patients with childhood-onset refractory epilepsy, treated at the tertiary epilepsy center of the University Children's Hospital Ljubljana, Slovenia, were included in the study...
March 8, 2018: Epilepsy & Behavior: E&B
Martin Mücke, Tudor Phillips, Lukas Radbruch, Frank Petzke, Winfried Häuser
BACKGROUND: This review is one of a series on drugs used to treat chronic neuropathic pain. Estimates of the population prevalence of chronic pain with neuropathic components range between 6% and 10%. Current pharmacological treatment options for neuropathic pain afford substantial benefit for only a few people, often with adverse effects that outweigh the benefits. There is a need to explore other treatment options, with different mechanisms of action for treatment of conditions with chronic neuropathic pain...
March 7, 2018: Cochrane Database of Systematic Reviews
Emily Stockings, Dino Zagic, Gabrielle Campbell, Megan Weier, Wayne D Hall, Suzanne Nielsen, Geoffrey K Herkes, Michael Farrell, Louisa Degenhardt
Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy. Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL). Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies...
March 6, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
Manoela V Fogaça, Alline C de Campos, Ludmila D Coelho, Ronald S Duman, Francisco S Guimarães
Repeated injections of cannabidiol (CBD), the major non-psychotomimetic compound present in the Cannabis sativa plant, attenuate the anxiogenic effects induced by Chronic Unpredictable Stress (CUS). The specific mechanisms remain to be fully understood but seem to involve adult hippocampal neurogenesis and recruitment of endocannabinoids. Here we investigated for the first time if the behavioral and pro-neurogenic effects of CBD administered concomitant the CUS procedure (14 days) are mediated by CB1 , CB2 or 5HT1A receptors, as well as CBD effects on dendritic remodeling and on intracellular/synaptic signaling (fatty acid amide hydrolase - FAAH, Akt, GSK3β and the synaptic proteins Synapsin Ia/b, mGluR1 and PSD95)...
March 3, 2018: Neuropharmacology
Carmen Navarrete, Francisco Carrillo-Salinas, Belén Palomares, Miriam Mecha, Carla Jiménez-Jiménez, Leyre Mestre, Ana Feliú, Maria L Bellido, Bernd L Fiebich, Giovanni Appendino, Marco A Calzado, Carmen Guaza, Eduardo Muñoz
BACKGROUND: Multiple sclerosis (MS) is characterized by a combination of inflammatory and neurodegenerative processes variously dominant in different stages of the disease. Thus, immunosuppression is the goal standard for the inflammatory stage, and novel remyelination therapies are pursued to restore lost function. Cannabinoids such as9 Δ-THC and CBD are multi-target compounds already introduced in the clinical practice for multiple sclerosis (MS). Semisynthetic cannabinoids are designed to improve bioactivities and druggability of their natural precursors...
March 1, 2018: Journal of Neuroinflammation
Anahita Bassir Nia, Yasmin L Hurd
No abstract text is available yet for this article.
March 1, 2018: American Journal of Psychiatry
Nicola Maggio, Efrat Shavit Stein, Menahem Segal
Epilepsy is a devastating disease, with cognitive and emotional consequences that are not curable. In recent years, it became apparent that cannabinoids help patients to cope with epilepsy. We have studied the effects of cannabidiol (CBD) on the ability to produce long term potentiation (LTP) in stratum radiatum of CA1 region of the mouse hippocampus. Exposure to seizure-producing pilocarpine reduced the ability to generate LTP in the slice. Pre-exposure to CBD prevented this effect of pilocarpine. Furthermore, CBD caused a marked increase in ability to generate LTP, an effect that was blocked by calcium store antagonists as well as by a reduction in serotonin tone...
2018: Frontiers in Molecular Neuroscience
S Ramlugon, R-A Levendal, C L Frost
The objectives of this paper is to investigate, demonstrate, and compare the mechanism of action of phytocannabinoids as antidiabetic and anti-obesity agents in preadipocytes and adipocytes, relative to rosiglitazone and metformin. Briefly, cannabis extract, Δ9 -tetrahydrocannabinol and cannabidiol (in very low dosages) were shown to promote glucose uptake higher or to equivalent levels, reduce fat accumulation, and reverse the insulin-resistant state of 3T3-L1 cells more effectively, relative to rosiglitazone and metformin...
February 21, 2018: Phytotherapy Research: PTR
Benjamin J Whalley, Hong Lin, Lynne Bell, Thomas Hill, Amesha Patel, Roy A Gray, C Elizabeth Roberts, Orrin Devinsky, Michael Bazelot, Claire M Williams, Gary J Stephens
BACKGROUND AND PURPOSE: Numerous claims are made for cannabis' therapeutic utility upon human seizures, but concerns persist about risks. A potential confounder is the presence of both Δ9 -tetrahydrocannabinol (Δ9 -THC), variously reported to be pro- and anti-convulsant, and cannabidiol (CBD), widely confirmed as anticonvulsant. Therefore, we investigated effects of prolonged exposure to different Δ9 -THC/CBD cannabis extracts on seizure activity and associated measures of endocannabinoid (eCB) system signalling...
February 19, 2018: British Journal of Pharmacology
Dinesh Thapa, Elizabeth A Cairns, Anna-Maria Szczesniak, James T Toguri, Meggie D Caldwell, Melanie E M Kelly
Background and Purpose: Corneal injury can result in dysfunction of corneal nociceptive signaling and corneal sensitization. Activation of the endocannabinoid system has been reported to be analgesic and anti-inflammatory. The purpose of this research was to investigate the antinociceptive and anti-inflammatory effects of cannabinoids with reported actions at cannabinoid 1 (CB1 R) and cannabinoid 2 (CB2 R) receptors and/or noncannabinoid receptors in an experimental model of corneal hyperalgesia. Methods: Corneal hyperalgesia (increased pain response) was generated using chemical cauterization of the corneal epithelium in wild-type (WT) and CB2 R knockout (CB2 R-/- ) mice...
2018: Cannabis and Cannabinoid Research
David J Potter, Kathy Hammond, Shaun Tuffnell, Christopher Walker, Marta Di Forti
BACKGROUND: In 2005 and 2008, studies reported that cannabis in England had become dominated by the sinsemilla (unseeded female) form. The average potency (Δ9-tetrahydrocannabinol [THC] content) of this material had doubled over the previous decade. Cannabis resin then circulating contained approximately equal ratios of THC and cannabidiol (CBD), whereas sinsemilla was almost devoid of CBD. Despite raised health concerns regarding sinsemilla use and the development of psychotic disorders, no update on street cannabis potency has been published since 2008...
February 14, 2018: Drug Testing and Analysis
Kerrie-Anne Chen, Michelle A Farrar, Michael Cardamone, John A Lawson
Research is expanding for the use of cannabidiol as an anticonvulsant drug. The mechanism of cannabidiol in paediatric epilepsy is unclear but is thought to play a role in modulation of synaptic transmission. Evidence for its efficacy in treating epilepsy is limited but growing, with a single pharmaceutical company-funded randomised double-blind controlled trial in children with Dravet syndrome. Progress towards the use of medicinal cannabinoids incorporates a complex interplay of social influences and political and legal reform...
February 19, 2018: Medical Journal of Australia
A L Uhernik, Z T Montoya, C D Balkissoon, J P Smith
Cannabidiol (CBD) is thought to have therapeutic potential for treating psychiatric conditions that affect cognitive aspects of learning and memory, including anxiety and post-traumatic stress disorder (PTSD). Studies have shown that CBD enhances extinction of fear memory when given after conditioning. This led us to hypothesize that CBD, if administered prior to fear conditioning, might modulate cognitive learning and memory processes in additional ways that would further guide its potential use for treating PTSD...
February 9, 2018: Neurobiology of Learning and Memory
Giulia S Porcari, Cary Fu, Emily D Doll, Emma G Carter, Robert P Carson
Medically refractory epilepsy continues to be a challenge worldwide, and despite an increasing number of medical therapies, approximately 1 in 3 patients continues to have seizures. Cannabidiol (CBD), one of many constituents of the Cannabis sativa or marijuana plant, has received renewed interest in the treatment of epilepsy. While highly purified CBD awaits Food and Drug Administration (FDA) approval, artisanal formulations of CBD are readily available and are seeing increased use in our patient population...
February 8, 2018: Epilepsy & Behavior: E&B
Antonella Smeriglio, Salvatore V Giofrè, Enza M Galati, Maria T Monforte, Nicola Cicero, Valeria D'Angelo, Gianpaolo Grassi, Clara Circosta
Aldose reductase (ALR2) is a key enzyme involved in diabetic complications and the search for new aldose reductase inhibitors (ARIs) is currently very important. The synthetic ARIs are often associated with deleterious side effects and medicinal and edible plants, containing compounds with aldose reductase inhibitory activity, could be useful for prevention and therapy of diabetic complications. Non-psychotropic phytocannabinoids exert multiple pharmacological effects with therapeutic potential in many diseases such as inflammation, cancer, diabetes...
February 7, 2018: Fitoterapia
Sophia Varadkar
No abstract text is available yet for this article.
January 25, 2018: Lancet
Elizabeth A Thiele, Eric D Marsh, Jacqueline A French, Maria Mazurkiewicz-Beldzinska, Selim R Benbadis, Charuta Joshi, Paul D Lyons, Adam Taylor, Claire Roberts, Kenneth Sommerville
BACKGROUND: 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. METHODS: In this randomised, double-blind, placebo-controlled trial done at 24 clinical sites in the USA, the Netherlands, and Poland, we investigated the efficacy of cannabidiol as add-on therapy for drop seizures in patients with treatment-resistant Lennox-Gastaut syndrome...
January 25, 2018: Lancet
Leslie Grayson, Brannon Vines, Kate Nichol, Jerzy P Szaflarski
•An interaction between warfarin and cannabidiol is described•The mechanisms of cannabidiol and warfarin metabolism are reviewed•Mechanism of the interaction is proposed•INR should be monitored in patients when cannabinoids are introduced.
2018: Epilepsy & Behavior Case Reports
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