Entries by Michelle Smith

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Neuroinflammation, Its Role in Alzheimer’s Disease and Therapeutic Strategies

Neuroinflammation precedes the clinical onset of various neurodegenerative diseases, including Alzheimer’s disease (AD), by years or frequently even decades (1–3). In terms of the underlying physiology, there is a great need for understanding and controlling interactions between the central nervous system (CNS) and the immune system in an attempt to develop approaches to prevent or delay the disease’s progression. Nerve cells have limited motion capability, whereas immune cells can migrate freely via circulation. This difference raises a variety of questions in the context of senile plaque formation and phagocytosis. Broad-scale unbiased genomic studies bring several genetic variants such as sialic acid binding Ig-like lectin 3 (CD33), triggering receptor expressed on myeloid cells 2 (TREM2) or complement receptor type 1 (CR1) into the focus of researchers’ attention as potential risk factors for neuroinflammation. In addition, advanced proteomic analyses have been revealing links between these genetic contributors and complex, malfunctioning signaling pathways (including the upregulation of factors like tumor necrosis factor TNF-α, tumor growth factor TGF-β and interleukin IL-1α) that promote proinflammatory mechanisms via intracellular signaling and trafficking, synaptic function, and cell metabolism/proliferation.

Drug Interactions of Tetrahydrocannabinol and Cannabidiol in Cannabinoid Drugs: Recommendations for Clinical Practice

Cannabinoid drugs containing tetrahydrocannabinol (THC), or its structural analogues, as monotherapeutic agents or as extracts or botanical preparations with or without cannabidiol (CBD) are often prescribed to multimorbid patients who are taking multiple drugs. This raises the question of the risk of drug interactions. This review of the pharmacokinetics and pharmacodynamics of interactions with cannabinoid drugs and their potential effects is based on pertinent publications retrieved by a selective literature search.

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Highly purified cannabidiol in the treatment of drug-resistant epilepsies: A real-life impact on seizure frequency, quality of life, behavior, and sleep patterns from a single Italian center

Seizure frequency in treatment-resistant epilepsies seems to be decreased by cannabidiol (CBD), but contrasting data are available on its effect on sleep, behavior, and quality of life (QoL), and no data is reported on its effect on parental stress in patients with epilepsy (PWE). Thus, we conducted a retrospective study on a cohort of children and adults with drug-resistant epilepsy (DRE) who had been treated with highly purified, pharmaceutical-grade CBD to evaluate its effects on seizure frequency, QoL, behavior, parental stress, and sleep. Eighteen patients (12 adults and 6 children) were included in the cohort and followed for a median of 9 months.

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Therapeutic Use of Cannabinoids in Critically Ill Patients: A Survey of Intensive Care Physicians in Germany

In the course of the legalization of cannabis for therapeutic purposes in Germany, there has been growing interest in the medical use of cannabinoids. To date, the therapeutic potential of cannabinoids for the treatment of critically ill patients has not been explored.This study aims to understand better whether and how frequently cannabinoids have been administered to critically ill patients in recent years.

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Looking Back, Moving Forward in Pain Medicine

Pain is an ancient medical complaint and a clinical riddle that has never been entirely solved. Looking back into history was the springboard to a look into the future of pain medicine. This article was based on a series of presentations given in a recent congress (May 2023) and represents the research, views, and opinions of the authors.

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A type II cannabis extract and a 1:1 blend of Δ(9)-tetrahydrocannabinol and cannabidiol display distinct antinociceptive profiles and engage different endocannabinoid targets when administered into the subarachnoid space

Cannabis extracts are being increasingly used to mitigate chronic pain. Current guidelines for their prescription rely on Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) content as well as the ratio of these major cannabinoids present in the blend. Here we assessed whether these descriptors were representative of product effectiveness to produce a desired outcome such as analgesia.

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Cannabinoids and endocannabinoids as therapeutics for nervous system disorders: preclinical models and clinical studies

Cannabinoids are lipophilic substances derived from Cannabis sativa that can exert a variety of effects in the human body. They have been studied in cellular and animal models as well as in human clinical trials for their therapeutic benefits in several human diseases. Some of these include central nervous system (CNS) diseases and dysfunctions such as forms of epilepsy, multiple sclerosis, Parkinson’s disease, pain and neuropsychiatric disorders. In addition, the endogenously produced cannabinoid lipids, endocannabinoids, are critical for normal CNS function, and if controlled or modified, may represent an additional therapeutic avenue for CNS diseases. This review discusses in vitro cellular, ex vivo tissue and in vivo animal model studies on cannabinoids and their utility as therapeutics in multiple CNS pathologies. In addition, the review provides an overview on the use of cannabinoids in human clinical trials for a variety of CNS diseases. Cannabinoids and endocannabinoids hold promise for use as disease modifiers and therapeutic agents for the prevention or treatment of neurodegenerative diseases and neurological disorders.

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Phytochemical characterization and cytotoxic potential of extracts from roots and inflorescences of Cannabis sativa L. cv. Eletta Campana

Cannabis roots have been used in folk medicine for millennia and as nutrient storage systems, contain compounds that may have medicinal value. Despite this, cannabis roots have generally received little attention compared to cannabis flowers, leaves and seeds and were for a long time considered just a waste product. In this paper, for the first time, the extracts of dried roots and in- florescences of Cannabis sativa L. cv Eletta Campana, were chemically investigated in order to compare their metabolite content. The obtained results highlighted a profile rich in fatty acids in the roots and cannabinoids in the inflorescences. Other components such as monoterpenes, sesquiterpenes, diterpenes and triterpenes were also detected. The extracts were also evaluated in terms of cytotoxic activity by using a panel of cancer cell lines derived from different histotypes including melanoma (A375, M14), colon (HCT116, HT29), breast (MDAMB231, MCF7) and non- small cell lung cancer (H1299, A549). Although both extracts significantly reduced the cancer cell viability, the inflorescence extract was more potent. Furthermore, the latter induced a comparable response in all tested cancer cell lines, while melanoma and non-small cell lung cancer were the most sensitive histotypes to the root extract treatment.

Inconsistency in the Composition of the Smoke of a Cannabis Cigarette as Smoking Progresses: Results, Mechanism, and Implications. Cannabis and Cannabinoid Research.

The efficacy of cannabis treatment is determined by the active pharmaceutical ingredients (APIs) of the ingested composition. Despite smoking predominancy in cannabis treatment, very little is known regarding its yield and provision rate of cannabis APIs. Ten experiments were performed, studying changes in APIs content during smoking, using a designated smoking machine. APIs content was evaluated via analysis of a cigarette’s residuals and of the smoke composition; cannabinoid and terpene content were assessed.

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Perceptions and Preoccupations of Patients and Physicians Regarding Use of Medical Cannabis as an Intervention Against Chronic Musculoskeletal Pain: Results from a Qualitative Study

Explore perceptions and preoccupations regarding use of medical cannabis against chronic musculoskeletal pain, among patients and physicians. Qualitative study using interviews with patients and physicians, based on the Theory of Planned Behavior (TPB). The study was conducted in Quebec, Canada, in spring 2020. We included 27 adult patients and 11 physicians (GPs, anesthesiologists, psychiatrists, and a rheumatologist); the mean age of patients was 48.2 years; 59.3% of patients and 36.4% of physicians were women; 59.3% of patients used no medical cannabis at the time of study; 45.5% of physicians had never authorized it.

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Real-Life experience with purified cannabidiol treatment for refractory epilepsy: A multicenter retrospective study

Drug-resistant epilepsy (DRE) significantly affects the development and quality of life of children and young adults. To describe the effectiveness and safety of purified cannabidiol (CBD) in children and young adults with DRE. A retrospective analysis of medical records of 139 children and young adults (54.7% female, median age 12.0 years) with DRE treated with purified CBD from 2018-2022 at 5 medical centers in Israel.