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

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 Dronabinol (Marinol), synthetic THC, was withdrawn from the Canadian market however it is available in other jurisdictions.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].

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/

Pharmacists and the future of cannabis medicine.

“To summarize the history and evolution of cannabis use and policies and to review current therapeutic uses, safety, and the central role pharmacists can play.

SUMMARY:

Cannabis regulation and use have evolved over the centuries and are becoming more widely accepted, with over two-thirds of states in the United States having an approved cannabis program. However, changing policy and a paucity of controlled clinical trials has led to questions on the safety and effectiveness of cannabinoid therapies. Although there are conditions for which cannabinoids may be helpful, potential contraindications, adverse effects, and drug-drug interactions should be taken into account.

CONCLUSION:

Pharmacists are in a unique position based on their accessibility, knowledge, and skills to guide product selection, dosing, and discuss drug interactions and adverse effects to educate patients on safe cannabis use, whether it be delta-9-tetrahydrocannabinol, cannabidiol, or a combination thereof. Pharmacists and pharmacy organizations, moreover, should advocate for an integral role in the medical cannabis movement to ensure patient safety and evaluate cannabinoid pharmacology, pharmacokinetics, drug-drug interactions, safety, and efficacy through rigorous investigations.”

https://www.ncbi.nlm.nih.gov/pubmed/31870860

https://www.japha.org/article/S1544-3191(19)30513-8/fulltext

Cannabis and Neuropsychiatric Disorders: An Updated Review.

 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

Endocannabinoid system and adult neurogenesis: a focused review.

Current Opinion in Pharmacology“The endocannabinoid system (eCB) is a ubiquitous lipid signaling system composed of at least two receptors, their endogenous ligands, and the enzymes responsible for their synthesis and degradation. Within the brain, the eCB system is highly expressed in the hippocampus and controls basic biological processes, including neuronal proliferation, migration and differentiation, which are intimately linked with embryonal neurogenesis. Accumulated preclinical evidence has indicated that eCBs play a major role also in regulating adult neurogenesis. Increased cannabinoid receptor activity, either by increased eCB content or by pharmacological blockade of their degradation, produces neurogenic effects alongside rescue of phenotypes in animal models of different psychiatric and neurological disorders. Therefore, in the light of the higher therapeutic potential of adult neurogenesis compared to the embryonic one, here we sought to summarize the most recent evidence pointing towards a neurogenic role for eCBs in the adult brain, both under normal and pathological conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/31864101

“The endocannabinoid system is involved in all aspects of the biology of neural stem cells. Selective CB1 and CB2 agonism produces pro-neurogenic effects in different models of brain insults. Further research is needed to characterize the eCB system as a new druggable target for neurogenesis-related diseases.”

https://www.sciencedirect.com/science/article/pii/S1471489219301122?via%3Dihub

The impact of cannabis access laws on opioid prescribing.

Journal of Health Economics“While recent research has shown that cannabis access laws can reduce the use of prescription opioids, the effect of these laws on opioid use is not well understood for all dimensions of use and for the general United States population. Analyzing a dataset of over 1.5 billion individual opioid prescriptions between 2011 and 2018, which were aggregated to the individual provider-year level, we find that recreational and medical cannabis access laws reduce the number of morphine milligram equivalents prescribed each year by 11.8 and 4.2 percent, respectively. These laws also reduce the total days’ supply of opioids prescribed, the total number of patients receiving opioids, and the probability a provider prescribes any opioids net of any offsetting effects. Additionally, we find consistent evidence that cannabis access laws have different effects across types of providers, physician specialties, and payers.”

https://www.ncbi.nlm.nih.gov/pubmed/31865260

“The results of this study suggest that passing cannabis access laws reduces the use of prescription opioids across several different measures of opioid prescriptions. Thus, the passage of Recreational cannabis laws (RCLs) or Medical cannabis laws (MCLs) may be a valid policy option for combating the ongoing opioid epidemic, even if these laws were not originally conceived for that purpose.”

https://www.sciencedirect.com/science/article/pii/S0167629618309020?via%3Dihub

THC exposure during adolescence does not modify nicotine reinforcing effects and relapse in adult male mice.

 This study investigated the effects of adolescent exposure to the main psychoactive component of cannabis, ∆9-tetrahydrocannabinol (THC), in the reinforcing properties of nicotine in adult male mice. Possible alterations in relapse to nicotine-seeking behaviour in adult animals due to THC adolescent exposure were also evaluated.

RESULTS:

Adolescent THC treatment did not modify acquisition and extinction of nicotine self-administration in adulthood. Moreover, THC exposure did not alter relapse to nicotine seeking induced by stress or nicotine-associated cues.

CONCLUSIONS:

These results suggest that a history of exposure to THC during adolescence under these particular conditions does not modify the reinforcing effects and seeking behaviour of nicotine in the adult period.”

https://www.ncbi.nlm.nih.gov/pubmed/31858159

https://link.springer.com/article/10.1007%2Fs00213-019-05416-8

Stress-induced modulation of endocannabinoid signaling leads to delayed strengthening of synaptic connectivity in the amygdala.

Image result for pnas“Even a brief exposure to severe stress strengthens synaptic connectivity days later in the amygdala, a brain area implicated in the affective symptoms of stress-related psychiatric disorders. However, little is known about the synaptic signaling mechanisms during stress that eventually culminate in its delayed impact on the amygdala. Hence, we investigated early stress-induced changes in amygdalar synaptic signaling in order to prevent its delayed effects.

Whole-cell recordings in basolateral amygdala (BLA) slices from rats revealed higher frequency of miniature excitatory postsynaptic currents (mEPSCs) immediately after 2-h immobilization stress. This was replicated by inhibition of cannabinoid receptors (CB1R), suggesting a role for endocannabinoid (eCB) signaling.

Stress also reduced N-arachidonoylethanolamine (AEA), an endogenous ligand of CB1R. Since stress-induced activation of fatty acid amide hydrolase (FAAH) reduces AEA, we confirmed that oral administration of an FAAH inhibitor during stress prevents the increase in synaptic excitation in the BLA soon after stress.

Although stress also caused an immediate reduction in synaptic inhibition, this was not prevented by FAAH inhibition. Strikingly, FAAH inhibition during the traumatic stressor was also effective 10 d later on the delayed manifestation of synaptic strengthening in BLA neurons, preventing both enhanced mEPSC frequency and increased dendritic spine-density.

Thus, oral administration of an FAAH inhibitor during a brief stress prevents the early synaptic changes that eventually build up to hyperexcitability in the amygdala. This framework is of therapeutic relevance because of growing interest in targeting eCB signaling to prevent the gradual development of emotional symptoms and underlying amygdalar dysfunction triggered by traumatic stress.”

https://www.ncbi.nlm.nih.gov/pubmed/31843894

https://www.pnas.org/content/early/2019/12/13/1910322116

Cannabinoids and dystonia: an issue yet to be defined.

 “Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal movements and postures. Besides motor manifestations, patients with dystonia also display non-motor signs and symptoms including psychiatric and sensory disturbances.

Symptomatic treatment of motor signs in dystonia largely relies on intramuscular botulinum toxin injections and, in selected cases, on deep brain stimulation. Oral medications and physical therapy offer a few benefits only in a minority of patients.

Cannabinoids have been shown to be a complementary treatment in several neurological disorders but their usefulness in dystonia have not been systematically assessed. Given recent policy changes in favor of cannabis use in clinical practice and the request for alternative treatments, it is important to understand how cannabinoids may impact people with dystonia.

Reviewing the evidence so far available and our own experience, cannabinoids seem to be effective in single cases but further studies are required to improve our understanding on their role as complementary treatment in dystonia.”

https://www.ncbi.nlm.nih.gov/pubmed/31848779

https://link.springer.com/article/10.1007%2Fs10072-019-04196-5

Medicinal Use of Cannabis in Children and Pregnant Women.

 Image result for Rambam Maimonides Med J.“The increasing medicinal use of cannabis during recent years has largely overlooked children and pregnant women due to litigious and ethical concerns.

However, over the last few years medicine has observed increasing numbers of children treated with cannabis for autism spectrum disorder (ASD) and fetal alcohol spectrum disorder (FASD), and pregnant women treated for hyperemesis gravidarum (HG).

This review provides an account of major findings discovered through this research.

Specifically, cannabis may offer therapeutic advantages to behavioral symptoms of autism spectrum disorder and fetal alcohol spectrum disorder, and to the severe nausea and vomiting in hyperemesis gravidarum.

The use of medical cannabis in children and pregnant women should be further discussed and researched in this patient population.”

https://www.ncbi.nlm.nih.gov/pubmed/31826800