Purified Cannabidiol for Treatment of Refractory Epilepsies in Pediatric Patients with Developmental and Epileptic Encephalopathy.

“A pharmaceutical grade formulation of cannabidiol (CBD) has been approved for the treatment of Dravet syndrome and Lennox-Gastaut syndrome; however, this formulation is not yet available to patients outside the USA. In addition, CBD is thought to have broad anti-seizure properties that may be beneficial for other types of intractable epilepsy.

OBJECTIVE:

The aim of this study was to evaluate the efficacy, safety and tolerability of artisanal medical CBD oil in patients with developmental and epileptic encephalopathy (DEE) at the tertiary epilepsy center of Bambino Gesù Children’s Hospital in Rome, Italy.

RESULTS:

Twenty-nine patients were enrolled in this study (41.4% male). The mean duration of exposure to artisanal CBD was 11.2 months [range 6-25 months; standard deviation (SD) ± 4.4 months]. Mean age at study enrollment was 9.3 years (range 1.9-16.3 years; SD ± 4.7 years). Eleven out of 29 patients (37.9%) had a ≥ 50% improvement in seizure frequency; one patient became seizure free. None of the patients reported worsening seizure frequency; however, 18 patients (62.1%) experienced no beneficial effect regarding seizure frequency. Adverse effects were reported in seven patients (24.14%), most commonly somnolence, decreased appetite and diarrhea. Adverse events were mild and transient, and no dose modification of CBD or other AEDs was required.

CONCLUSIONS:

These data suggest that CBD may have beneficial effects in patients with DEE and an acceptable safety profile. Placebo-controlled randomized trials should be conducted to formally assess the safety and efficacy of CBD in patients with DEE.”

Marijuana as a Substitute for Prescription Medications: A Qualitative Study.

Publication Cover

“Over the past few decades in the United States, marijuana for medical purposes has become increasingly prevalent. Initial qualitative and epidemiological research suggests that marijuana may be a promising substitute for traditional pharmacotherapies.

Objectives: This qualitative study examined perceptions relating to (1) using medical marijuana in comparison to other prescription medications and (2) user perception of policy issues that limit adoption of medical marijuana use.

Results: Three themes emerged related to medical marijuana use, including (1) comparison of medical marijuana to other medications (i.e., better and/or fewer side effects than prescription medications, improves quality of life), (2) substitution of marijuana for other medications (i.e., in addition to or instead of), and (3) how perception of medical marijuana policy impacts use (i.e., stigma, travel, cost, and lack of instruction regarding use).

Conclusions: Several factors prevent pervasive medical marijuana use, including stigma, cost, and the inability for healthcare providers to relay instructions regarding dosing, strain, and method of use. Findings suggest that medical patients consider marijuana to be a viable alternative for opioids and other prescription medications, though certain policy barriers inhibit widespread implementation of marijuana as a treatment option.”

https://www.ncbi.nlm.nih.gov/pubmed/31179810

https://www.tandfonline.com/doi/abs/10.1080/10826084.2019.1618336?journalCode=isum20

Cannabinoids, hippocampal excitability and efficacy for the treatment of epilepsy.

Pharmacology & Therapeutics

“Interest in cannabis and its related cannabinoids THC and CBD for use as anti-convulsant therapy has been progressively increasing. While the destigmatization of cannabis and cannabis related research have progressed in the last few decades, there are still many questions that remain answered. This review seeks to summarize the progress made in cannabis research in the past four decades and to identify possible directions for future research that are critical for the development of cannabinoid-based therapy in epilepsy.”

https://www.ncbi.nlm.nih.gov/pubmed/31176695

https://www.sciencedirect.com/science/article/pii/S0163725819301093?via%3Dihub

What is the evidence for cannabis use in otolaryngology?: A narrative review.

American Journal of Otolaryngology

“A small number of studies exist that suggest cannabis may be a useful therapy for Otolaryngological patients suffering from blepharospasm, the effects of radiation, and the psychological sequelae of receiving a cancer diagnosis.

Further research is required to determine the potential therapeutic roles and adverse effects of cannabis on conditions related to Otolaryngology.”

https://www.ncbi.nlm.nih.gov/pubmed/31174932

https://www.sciencedirect.com/science/article/abs/pii/S0196070919304685?via%3Dihub

“Otolaryngology is a medical specialty which is focused on the ears, nose, and throat.”  http://www.entcolumbia.org/about-us/what-otolaryngology

The cannabinoid receptor 2 agonist, β-caryophyllene, improves working memory and reduces circulating levels of specific proinflammatory cytokines in aged male mice.

Behavioural Brain Research“Age-related cognitive decline has been associated with proinflammatory cytokines, yet the precise relationship between cognitive decline and cytokine load remains to be elucidated. β-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist with established anti-inflammatory effects that is known to improve memory and increase lifespan. It is of interest to explore the potential of BCP to reduce age-related cognitive decline and proinflammatory cytokine load. In this study, we assessed changes in circulating cytokines across the lifespan, memory performance in young and aged mice, and the effects of BCP on memory function and cytokine load. The plasma levels of 12 cytokines were assessed in male Swiss-Webster mice at 3, 12, and 18 months of age using multiplexed flow cytometry. Working memory was compared in 3 and 12 month-old mice using spontaneous alternations. A dose-response function (100-300 mg/kg, subchronic administration) for BCP-induced memory restoration was determined in 3 and 12 month-old mice. Finally, the effects on cytokine levels of the peak memory enhancing dose of BCP was assessed in 18 month-old mice. Circulating levels of several cytokines significantly increased with age. Multilinear regression analysis showed that IL-23 levels were most strongly associated with age. Aged mice showed deficits in working memory and higher levels of IL-23, both of which were reversed by BCP treatment. BCP appears to reverse age-associated impairments in memory and modulates cytokine production. IL-23 may play a significant role in the aging process, and future research should determine whether it has utility as a biomarker for novel anti-aging therapeutics.”

https://www.ncbi.nlm.nih.gov/pubmed/31173795

https://www.sciencedirect.com/science/article/pii/S0166432819304516?via%3Dihub

“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

“Beta-caryophyllene is a dietary cannabinoid.”   https://www.ncbi.nlm.nih.gov/pubmed/18574142

Pharmacokinetics of oral and intravenous cannabidiol and its antidepressant-like effects in chronic mild stress mouse model.

Environmental Toxicology and Pharmacology

“Cannabidiol (CBD) exhibits significant efficacy in mental and inflammatory diseases. Several studies have recently reported on the rapid antidepressant-like effects of CBD, suggesting that CBD is a potential anti-depressant or anti-stress drug. However, CBD is mainly administered orally or by inhalation with poor bioavailability, resulting in high costs. We aim to explore the efficacy of long-term periodic administration of CBD in chronic mild stress (CMS) via two routes and its pharmacokinetics. We treated ICR mice with CBD administered orally and intravenously and then determined the kinetic constants. A single bolus intravenous injection of CBD resulted in a half-life of 3.9 h, mean residence time of 3.3 h, and oral bioavailability of about 8.6%. The antidepressant-like effects of periodically administered CBD on the chronic mild stress mouse model are evaluated. Results demonstrated that such treatment at a high dose of 100 mg/kg CBD (p.o.) or a low dose of 10 mg/kg CBD (i.v.), elicited significant antidepressant-like behavioral effects in forced swim test, following increased mRNA expression of brain-derived neurotrophic factor (BDNF) and synaptophysin in the prefrontal cortex and the hippocampus. Our findings are expected to provide a reference for the development of intravenous antidepressant formulations of CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/31173966

https://www.sciencedirect.com/science/article/pii/S1382668919300687?via%3Dihub

Medical Marijuana in the Pediatric Population With Epilepsy—What You Should Know

Journal of Pediatric Health Care Home

“This article discusses the controversial but promising topic of medical marijuana (MM) use in the pediatric population with epilepsy. Included is the importance of MM throughout history, the pharmacodynamics and pharmacokinetics, and a literature review that provides anecdotal evidence of the positive effect MM has on children suffering from seizures. From this literature review, dosage for treatment and management is provided. Also discussed is the recent FDA-approved pharmaceutical grade CBD product, Epidiolex, for treatment of two pediatric-onset seizure syndromes, Lennox-Gastaut and Dravet. Clinical implications regarding adverse side effects of MM use are also discussed. The aim of this article is to arm providers with contemporary knowledge on the risks and benefits of MM use in the pediatric population with epilepsy, which may boost their skills and confidence in educating and advocating for children with seizures. This novel, ever-changing medication is in the forefront of history and the news, making this topic especially important for review.”

l-α-Lysophosphatidylinositol (LPI) aggravates myocardial ischemia/reperfusion injury via a GPR55/ROCK-dependent pathway.

Pharmacology Research & Perspectives banner

“The phospholipid l-α-lysophosphatidylinositol (LPI), an endogenous ligand for GPR55, is elevated in patients with acute coronary syndrome, and a GPR55 antagonist cannabidiol (CBD) reduces experimental ischemia/reperfusion (I/R) injury.”

https://www.ncbi.nlm.nih.gov/pubmed/31149342

https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1002/prp2.487

The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake.

Addiction Biology banner“The administration of cannabidiol has shown promising evidence in the treatment of some neuropsychiatric disorders, including cocaine addiction. However, little information is available as to the mechanisms by which cannabidiol reduces drug use and compulsive seeking.

We investigated the role of adult hippocampal neurogenesis in reducing cocaine voluntary intake produced by repeated cannabidiol treatment in mice.

Cannabidiol (20 mg/kg) reduced cocaine self-administration behaviour acquisition and total cocaine intake and enhanced adult hippocampal neurogenesis.

The present study confirms that adult hippocampal neurogenesis is one of the mechanisms by which cannabidiol lowers cocaine reinforcement and demonstrates the functional implication of adult hippocampal neurogenesis in cocaine voluntary consumption in mice.

Such findings highlight the possible use of cannabidiol for developing new pharmacotherapies to manage cocaine use disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31162770

https://onlinelibrary.wiley.com/doi/abs/10.1111/adb.12778

Bipolar disorder and the endocannabinoid system.

 Image result for acta neuropsychiatrica“Bipolar disorder (BD) is a debilitating, lifelong neuropsychiatric illness characterised by unsteady mood states which vacillate from (hypo)mania to depression. Despite the availability of pharmaceutical agents which can be effective in ameliorating the acute affective symptoms and prevent episodic relapse, BD is inadequately treated in a subset of patients.

The endocannabinoid system (ECS) is known to exert neuromodulatory effects on other neurotransmitter systems critical in governing emotions. Several studies ranging from clinical to molecular, as well as anecdotal evidence, have placed a spotlight on the potential role of the ECS in the pathophysiology of BD. In this perspective, we present advantages and disadvantages of cannabis use in the management of illness course of BD and provide mechanistic insights into how this system might contribute to the pathophysiology of BD.

RESULTS:

We highlight the putative role of selective cannabinoid receptor 2 (CB2) agonists in BD and briefly discuss findings which provide a rationale for targeting the ECS to assuage the symptoms of BD. Further, data encourage basic and clinical studies to determine how cannabis and cannabinoids (CBs) can affect mood and to investigate emerging CB-based options as probable treatment approaches.

CONCLUSION:

The probable role of the ECS has been almost neglected in BD; however, from data available which suggest a role of ECS in mood control, it is justified to support conducting comprehensive studies to determine whether ECS manipulation could positively affect BD. Based on the limited available data, we suggest that activation of CB2 may stabilise mood in this disorder.”

https://www.ncbi.nlm.nih.gov/pubmed/31159897

https://www.cambridge.org/core/journals/acta-neuropsychiatrica/article/bipolar-disorder-and-the-endocannabinoid-system/0C3191AF7BECA6D5A6EBED3C94CAA57B