Tag Archives: CBD

Cannabis for Pediatric Epilepsy.

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 Related image“Epilepsy is a chronic disease characterized by recurrent unprovoked seizures. Up to 30% of children with epilepsy will be refractory to standard anticonvulsant therapy, and those with epileptic encephalopathy can be particularly challenging to treat.

The endocannabinoid system can modulate the physiologic processes underlying epileptogenesis. The anticonvulsant properties of several cannabinoids, namely Δ-tetrahydrocannabinol and cannabidiol (CBD), have been demonstrated in both in vitro and in vivo studies.

Cannabis-based therapies have been used for millennia to treat a variety of diseases including epilepsy. Several studies have shown that CBD, both in isolation as a pharmaceutical-grade preparation or as part of a CBD-enriched cannabis herbal extract, is beneficial in decreasing seizure frequency in children with treatment-resistant epilepsy.

Overall, cannabis herbal extracts appear to provide greater efficacy in decreasing seizure frequency, but the studies assessing cannabis herbal extract are either retrospective or small-scale observational studies. The two large randomized controlled studies assessing the efficacy of pharmaceutical-grade CBD in children with Dravet and Lennox-Gastaut syndromes showed similar efficacy to other anticonvulsants. Lack of data regarding appropriate dosing and pediatric pharmacokinetics continues to make authorization of cannabis-based therapies to children with treatment-resistant epilepsy challenging.”

https://www.ncbi.nlm.nih.gov/pubmed/31895184

https://insights.ovid.com/crossref?an=00004691-202001000-00002

Antioxidative and Anti-Inflammatory Properties of Cannabidiol.

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antioxidants-logo“Cannabidiol (CBD) is one of the main pharmacologically active phytocannabinoids of Cannabis sativa L. CBD is non-psychoactive but exerts a number of beneficial pharmacological effects, including anti-inflammatory and antioxidant properties. The chemistry and pharmacology of CBD, as well as various molecular targets, including cannabinoid receptors and other components of the endocannabinoid system with which it interacts, have been extensively studied. In addition, preclinical and clinical studies have contributed to our understanding of the therapeutic potential of CBD for many diseases, including diseases associated with oxidative stress. Here, we review the main biological effects of CBD, and its synthetic derivatives, focusing on the cellular, antioxidant, and anti-inflammatory properties of CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/31881765

https://www.mdpi.com/2076-3921/9/1/21

Medical Cannabis Use in Palliative Care: Review of Clinical Effectiveness and Guidelines – An Update [Internet].

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Cover of Medical Cannabis Use in Palliative Care: Review of Clinical Effectiveness and Guidelines – An Update“Palliative care is defined by the World Health Organization as “an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness…”. The last days and hours of a person’s life can be associated with immense physical as well as emotional suffering Relief of pain and other distressing symptoms, and enhancement of quality of life, are among the essential elements of good palliative care. Palliative care could benefit an estimated 69% to 82% of dying individuals in Canada. As Canada’s population ages, with increasing prevalence of chronic conditions and treatments resulting in prolonged life, it is expected that there will be an increased need for palliative care services.

Approximately 9% of Canadians (or 2.7 million) reported using cannabis for medical purposes in the first half of 2019. Herbal cannabis (cannabis sativa) contains hundreds of pharmacological components, many of which are not well-characterized. Tetrahydrocannabinol (THC) is the most prevalent pharmacologically active compound and is primarily responsible for the psychoactive and physical effects of cannabis. Cannabidiol (also commonly referred to as CBD) is the second most prevalent. It has very little if any psychotropic effects. Quantity and ratio of these and other components can vary considerably between plants and even within the same plant.

Two prescription cannabinoids are currently marketed in Canada: Nabiximols (Sativex) which contains THC and cannabidiol, and Nabilone (Cesamet) which is a synthetic cannabinoid. Dronabinol (Marinol), synthetic THC, was withdrawn from the Canadian market however it is available in other jurisdictions. For the purposes of this report, medical cannabis refers to use of the cannabis plant or its extracts or synthetic cannabinoids for medical purposes.

Medical cannabis may be of value for a number of conditions, including but not limited to pain, nausea and vomiting, depression, anxiety and appetite stimulation. Adverse effects of cannabis are very common, developing in 80% to 90% of patients. These include but are not limited to psychiatric disturbances, sedation, speech disorders, impaired memory, dizziness, ataxia, addiction, irritability, and driving impairment. Risk of adverse effects is likely lower with cannabidiol alone as compared to THC. The potential for drug interactions is also an important concern. These risks must be considered along with the an apparent lack of evidence surrounding effectiveness of medical cannabis in many conditions for which its use is promoted.

This report updates and expands on a previous summary of abstracts report.9 The objective of the report is to review evidence and guidelines for use of medical cannabis in the palliative care setting.”

https://www.ncbi.nlm.nih.gov/pubmed/31873991

https://www.ncbi.nlm.nih.gov/books/NBK551867/

Medicinal and Synthetic Cannabinoids for Pediatric Patients: A Review of Clinical Effectiveness and Guidelines [Internet].

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Cover of Medicinal and Synthetic Cannabinoids for Pediatric Patients: A Review of Clinical Effectiveness and Guidelines“Cannabinoids are pharmacologically active agents extracted from the cannabis plant. Cannabidiol and tetrahydrocannabinol (THC) are the most studied cannabinoids and both interact with endocannabinoid receptors in various human tissues. The endocannabinoid system moderates physiological functions, such as neurodevelopment, cognition, and motor control.

The products naturally derived from cannabis include marijuana (dried leaves and flowers, mostly for smoking) and oral cannabinoid extracts with varying concentrations of cannabinoids, including cannabidiol and THC. THC is the main psychoactive constituent and cannabidiol seems to have no psychoactive properties. In addition, there are two synthetical cannabinoids approved by the Food and Drug Administration (FDA) in the United States, dronabinol and nabilone, which are molecules similar to a type of THC (δ-9-THC)1 Nabilone is also approved in Canada. Dronabinol is indicated for chemotherapy-induced nausea and vomiting in children. The use of nabilone in children is not recommended.

In Canada, the minimum age for cannabis consumption varies by provinces and territories, and is either 18 or 19 years. A prescription is required to administer cannabinoids among children. Clinically, cannabis has been used to treat children with epilepsy, cancer palliation and primary treatment, chronic pain, and Parkinson disease.

The adverse events that clinicians need to monitor for include negative psychoactive sequelae and development of tolerance. Psychoactive sequelae may be positive, such as relaxation and euphoria, or negative, such as anxiety and irritability. In 2016, CADTH completed a Summary of Abstracts report on the use of cannabis in children with medical conditions such as attention deficit hyperactivity disorder, autism spectrum disorder, Tourette syndrome, epilepsy, posttraumatic stress disorder, or neurodegenerative diseases, and five non-randomized studies were identified. However, there were no control groups in the five studies included in the report.

It is unclear whether there is new evidence or clinical guidance for the use of medical cannabis in children with mental health conditions, neurodegenerative diseases, or pain disorders, particularly in comparison with other possible therapies for those conditions. There is a need to review the clinical effectiveness of cannabis for pediatric care, as well as clinical guidelines.”

https://www.ncbi.nlm.nih.gov/pubmed/31873990

https://www.ncbi.nlm.nih.gov/books/NBK551866/

Cannabis and Neuropsychiatric Disorders: An Updated Review.

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 Image result for Acta Neurol Taiwan. journal“Cannabis plant has the scientific name called Cannabis sativa L. Cannabis plant has many species, but there are three main species including Cannabis sativa, Cannabis indica and Cannabis ruderalis. Over 70 compounds isolated from cannabis species are called cannabinoids (CBN).

Cannabinoids produce over 100 naturally occurring chemicals. The most abundant chemicals are delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD). THC is psychotropic chemical that makes people feel “high” while CBD is nonpsychotropic chemical. However, cannabinoid chemicals are not found only in the cannabis plant, they are also produced by the mammalian body, called endocannabinoids and in the laboratory, called synthesized cannabinoids.

Endocannabinoids are endogenous lipid-based retrograde neurotransmitters that bind to cannabinoid receptors, and cannabinoid receptor proteins that are expressed throughout the mammalian central nervous system including brain and peripheral nervous system. There are at least two types of endocannabinoid receptors (CB1 and CB2) which are G-protein coupled receptors.

CB1 receptors are particularly abundant in the frontal cortex, hippocampus, basal ganglia, hypothalamus and cerebellum, spinal cord and peripheral nervous system. They are present in inhibitory GABA-ergic neurons and excitatory glutamatergic neurons. CB2 receptor is most abundantly found on cells of the immune system, hematopoietic cells and glia cells. CB2 is mainly expressed in the periphery under normal healthy condition, but in conditions of disease or injury, this upregulation occurs within the brain, and CB2 is therefore expressed in the brain in unhealthy states.

Cannabis and cannabinoid are studied in different medical conditions. The therapeutic potentials of both cannabis and cannabinoid are related to the effects of THC, CBD and other cannabinoid compounds. However, the “high” effect of THC in cannabis and cannabinoid may limit the clinical use, particularly, the study on the therapeutic potential of THC alone is more limited.

This review emphasizes the therapeutic potential of CBD and CBD with THC. CBD has shown to have benefit in a variety of neuropsychiatric disorders including autism spectrum disorder, anxiety, psychosis, neuropathic pain, cancer pain, HIV, migraine, multiple sclerosis, Alzheimer disease, Parkinson disease, Huntington disease, hypoxic-ischemic injury and epilepsy. CBD is generally well tolerated. Most common adverse events are diarrhea and somnolence. CBD also shows significantly low abuse potential.”

https://www.ncbi.nlm.nih.gov/pubmed/31867704

Use of cannabidiol in anxiety and anxiety-related disorders.

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“Cannabidiol (CBD) has a proposed novel role in the management of anxiety owing to its actions on the endocannabinoid system.

The purpose of this systematic review was to evaluate the current evidence on the safety and efficacy of CBD in anxiety and anxiety-related disorders.

RESULTS:

Eight articles were included in the review: 6 small, randomized controlled trials; 1 case series; and 1 case report. These studies examined the role of CBD in the anxiety response of healthy volunteers; in generalized anxiety disorder; in social anxiety disorder; and in the anxiety component of posttraumatic stress syndrome. No articles that evaluated CBD in panic disorder, specific phobia, separation anxiety, and obsessive-compulsive disorder were identified. In the studies, CBD was administered orally as a capsule or as a sublingual spray and as either monotherapy or adjunctive therapy. Doses varied widely, with studies employing fixed CBD doses ranging from 6 mg to 400 mg per dose. Various anxiety assessment scales were used in the studies to assess efficacy, with CBD demonstrating improved clinical outcomes among the instruments. In general, CBD was well-tolerated and associated with minimal adverse effects, with the most commonly noted adverse effects being fatigue and sedation.

CONCLUSION:

CBD has a promising role as alternative therapy in the management of anxiety disorders. However, more studies with standardized approaches to dosing and clinical outcome measurements are needed to determine the appropriate dosing strategy for CBD and its place in therapy.”

https://www.ncbi.nlm.nih.gov/pubmed/31866386

https://www.japha.org/article/S1544-3191(19)30514-X/fulltext

Cannabis-based products for pediatric epilepsy: An updated systematic review.

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Seizure - European Journal of Epilepsy Home“To provide an up-to-date summary of the benefits and harms of cannabis-based products for epilepsy in children.

METHODS:

We updated our earlier systematic review, by searching for studies published up to May 2019. We included randomized controlled trials (RCTs) and non-randomized studies (NRS) involving cannabis-based products administered to children with epilepsy. Outcomes were seizure freedom, seizure frequency, quality of life, sleep, status epilepticus, death, gastrointestinal adverse events, and emergency room visits.

RESULTS:

Thirty-five studies, including four RCTs, have assessed the benefits and harms of cannabis-based products in pediatric epilepsy (12 since April 2018). All involved cannabis-based products as adjunctive treatment, and most involved cannabidiol. In the RCTs, there was no statistically significant difference between cannabidiol and placebo for seizure freedom (relative risk 6.77, 95 % confidence interval [CI] 0.36-128.38), quality of life (mean difference [MD] 0.6, 95 %CI -2.6 to 3.9), or sleep disruption (MD -0.3, 95 %CI -0.8 to 0.2). Data from both RCTs and NRS suggest that cannabidiol reduces seizure frequency and increases treatment response; however, there is an increased risk of gastrointestinal adverse events.

CONCLUSION:

Newly available evidence supports earlier findings that cannabidiol probably reduces the frequency of seizures among children with drug-resistant epilepsy.”

https://www.ncbi.nlm.nih.gov/pubmed/31865133

https://www.seizure-journal.com/article/S1059-1311(19)30733-2/fulltext

Potential role of cannabidiol for seizure control in a patient with recurrent glioma.

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Journal of Clinical Neuroscience Home“Glioma-related epilepsy significantly impact on patients’ quality of life, and can often be difficult to treat. Seizures cause significant morbidity for example neurocognitive deterioration, which may result from seizures themselves or due to adverse effects from antiepileptic drugs. Management of tumour with surgery, radiotherapy and chemotherapy may contribute to seizure control, but tumour related epilepsy is often refractory despite adequate treatment with standard anti-epileptic medications. Given the increasing interest in medicinal cannabis (or cannabidiol or CBD) as an anti-epileptic drug, CBD may help with seizure control in glioma patients with treatment-refractory seizures. Here we present a case of a young lady with recurrent glioma who had refractory seizures despite multiple anti-epileptic agents, who had significant benefit with CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/31848037

“CBD could potentially be a management option in treatment-refractory epilepsy in glioma patients.”

https://www.jocn-journal.com/article/S0967-5868(19)31306-2/fulltext

Exploiting cannabinoid and vanilloid mechanisms for epilepsy treatment.

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“This review focuses on the possible roles of phytocannabinoids, synthetic cannabinoids, endocannabinoids, and “transient receptor potential cation channel, subfamily V, member 1” (TRPV1) channel blockers in epilepsy treatment.

The phytocannabinoids are compounds produced by the herb Cannabis sativa, from which Δ9-tetrahydrocannabinol (Δ9-THC) is the main active compound. The therapeutic applications of Δ9-THC are limited, whereas cannabidiol (CBD), another phytocannabinoid, induces antiepileptic effects in experimental animals and in patients with refractory epilepsies.

Synthetic CB1 agonists induce mixed effects, which hamper their therapeutic applications. A more promising strategy focuses on compounds that increase the brain levels of anandamide, an endocannabinoid produced on-demand to counteract hyperexcitability. Thus, anandamide hydrolysis inhibitors might represent a future class of antiepileptic drugs. Finally, compounds that block the TRPV1 (“vanilloid”) channel, a possible anandamide target in the brain, have also been investigated.

In conclusion, the therapeutic use of phytocannabinoids (CBD) is already in practice, although its mechanisms of action remain unclear. Endocannabinoid and TRPV1 mechanisms warrant further basic studies to support their potential clinical applications.”

https://www.ncbi.nlm.nih.gov/pubmed/31839498

“Cannabidiol is in clinical use for refractory epilepsies.”

https://www.epilepsybehavior.com/article/S1525-5050(19)30373-7/fulltext

The influence of carboxylesterase 1 polymorphism and cannabidiol on the hepatic metabolism of heroin.

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Chemico-Biological Interactions“Heroin (diamorphine) is a highly addictive opioid drug synthesized from morphine. The use of heroin and incidence of heroin associated overdose death has increased sharply in the US.

Heroin is primarily metabolized via deacetylation (hydrolysis) forming the active metabolites 6-monoacetylmorphine (6-MAM) and morphine. A diminution in heroin hydrolysis is likely to cause higher drug effects and toxicities.

In this study, we sought to determine the contribution of the major hepatic hydrolase carboxylesterase 1 (CES1) to heroin metabolism in the liver as well as the potential influence of one of its known genetic variants, G143E (rs71647871).

Furthermore, given the potential therapeutic application of cannabidiol (CBD) for heroin addiction and the frequent co-abuse of cannabis and heroin, we also assessed the effects of CBD on heroin metabolism.

CBD exhibited potent in vitro inhibition toward both heroin and 6-MAM hydrolysis, which may be of potential clinical relevance.”

https://www.ncbi.nlm.nih.gov/pubmed/31837295

“Cannabidiol is a potent in vitro inhibitor of the two-step hydrolysis of heroin.”

https://www.sciencedirect.com/science/article/abs/pii/S0009279719317259?via%3Dihub