Entries by Michelle Smith

,

Medicinal cannabis for Australian patients with chronic refractory pain including arthritis

To examine the tolerability and effectiveness of medicinal cannabis prescribed to patients for chronic, refractory pain, with a subset analysis on arthritis. This was an interim analysis of the CA Clinics Observational Study investigating self-reported adverse events (AEs) and changes in health-related quality of life (HRQoL) outcomes over time after commencing medicinal cannabis. Patients were prescribed medicinal cannabis by a medical practitioner, containing various ratios of Δ9-tetrahydrocannabinol (THC) and/or cannabidiol (CBD).

,

Potential, Limitations and Risks of Cannabis-Derived Products in Cancer Treatment

It is easy to find success stories on the internet of patients with cancer who seem to benefit from using cannabis products. However, scientific substantiation is usually lacking. Therefore, there are critical questions among clinicians and other healthcare providers about the potential of cannabis products in cancer care. In this article, we aim to give direction for making choices about the responsible use of cannabis products in oncology by addressing the following questions: How does cannabis work? What is medicinal cannabis? What kind of cannabis products are in use? What is their legal status? Is there evidence for therapeutic effects in patients with cancer? What is the risk–benefit balance in terms of adverse effects, (potential) drug interactions, symptom management and antitumour activity? May cannabis products provide added value in the treatment of patients with cancer? We end up with an outlook and perspective determining the place of cannabis products in oncology.

Cannabis use preferences in women with myofascial pelvic pain: A cross-sectional study

Myofascial tenderness is present in most chronic pelvic pain conditions and causes significant distress to patients. Treatment is challenging and often not curative. Cannabis is often used for self-management of chronic pelvic pain. However, we do not know which concentrations and routes of administration are most acceptable to users. We aimed to investigate patterns and willingness of cannabis product use among both habitual users and non-users with myofascial pelvic pain (MPP), to inform therapeutic development.

Vaping Induced Cannabidiol (CBD) Oxidation Product CBD Quinone Forms Protein Adducts with KEAP1 and Activates KEAP1-Nrf2 Genes

Cannabidiol (CBD) vaping products have become widely available in the U.S. since their legalization in 2018. However, little is known about their respiratory health effects. Here we show that aerosolization of commercial CBD vaping products generates a reactive CBD quinone (CBDQ) which forms adducts with protein cysteine residues. Using click chemistry and a novel in vitro vaping product exposure system (VaPES), we further demonstrate that CBDQ forms adducts with human bronchial epithelial cell proteins including Keap1 and activates KEAP1-Nrf2 stress response pathway genes. These results suggest that vaping CBD alters protein function and induces cellular stress pathways in the lung.

,

Clinical Practice Guidelines for Cannabis and Cannabinoid-Based Medicines in the Management of Chronic Pain and Co-Occurring Conditions

The interest in the pharmacological applications of cannabinoids is largely increasing in a wide range of medical areas. Recently, research on its potential role in eye conditions, many of which are chronic and/or disabling and in need of new alternative treatments, has intensified. However, due to cannabinoids’ unfavorable physicochemical properties and adverse systemic effects, along with ocular biological barriers to local drug administration, drug delivery systems are needed. Hence, this review focused on the following: (i) identifying eye disease conditions potentially subject to treatment with cannabinoids and their pharmacological role, with emphasis on glaucoma, uveitis, diabetic retinopathy, keratitis and the prevention of Pseudomonas aeruginosa infections; (ii) reviewing the physicochemical properties of formulations that must be controlled and/or optimized for successful ocular administration; (iii) analyzing works evaluating cannabinoid-based formulations for ocular administration, with emphasis on results and limitations; and (iv) identifying alternative cannabinoid- based formulations that could potentially be useful for ocular administration strategies. Finally, an overview of the current advances and limitations in the field, the technological challenges to overcome and the prospective further developments, is provided.

Cannabinoid-Based Ocular Therapies and Formulations

The interest in the pharmacological applications of cannabinoids is largely increasing in a wide range of medical areas. Recently, research on its potential role in eye conditions, many of which are chronic and/or disabling and in need of new alternative treatments, has intensified. However, due to cannabinoids’ unfavorable physicochemical properties and adverse systemic effects, along with ocular biological barriers to local drug administration, drug delivery systems are needed. Hence, this review focused on the following: (i) identifying eye disease conditions potentially subject to treatment with cannabinoids and their pharmacological role, with emphasis on glaucoma, uveitis, diabetic retinopathy, keratitis and the prevention of Pseudomonas aeruginosa infections; (ii) reviewing the physicochemical properties of formulations that must be controlled and/or optimized for successful ocular administration; (iii) analyzing works evaluating cannabinoid-based formulations for ocular administration, with emphasis on results and limitations; and (iv) identifying alternative cannabinoid- based formulations that could potentially be useful for ocular administration strategies. Finally, an overview of the current advances and limitations in the field, the technological challenges to overcome and the prospective further developments, is provided.

The Case for Cannabis

EPs are trained to treat medication-related toxicities. I was fortunate enough to have a toxicology rotation in my residency program, where snake bites and overdose consults were standard. Learning how individuals overdose and die by suicide really is something that should have a psychologic screening before a rotation.

But I digress. Toxicology is a cornerstone of emergency medicine. We are strong and capable of treating these issues when they land in our EDs, but we often lack follow-up and prevention. What happens after a patient comes in with acetaminophen toxicity? We treat the patient, often report it to poison control, and then discharge or admit. But does the manufacturing company know of these issues? At which point is it their responsibility to address the toxicity and then change or be held accountable?

, ,

Cannabidiol in the acute phase of Febrile Infection-Related Epilepsy Syndrome (FIRES)

Febrile infection-related epilepsy syndrome (FIRES) is a prolonged refractory status epilepticus (SE) that develops among healthy individuals after a febrile infection.

FIRES treatment is challenging due to its poor response to anti-seizure medications (ASMs) and anesthetic drugs. The use of cannabidiol (CBD) as an adjunctive treatment has been suggested, albeit data about its role in the acute phase is lacking. This report describes the use of purified CBD in the acute phase of two pediatric cases of FIRES and their long-term outcome.

Both children were treated with several ASMs, immunomodulators, anesthetics, and non-pharmacological treatment (ketogenic diet). CBD was administered, as an adjunctive treatment, through nasogastric tube about 30 days after onset. SE resolved within three days of reaching the target dose and both were seizure-free for one year after.

Although it is difficult to define the extent to which each previous therapy contributed to recovery, in both cases CBD therapy was a turning point, reinforcing its potential role as add-on treatment in the acute phase of FIRES.

, ,

The Polypharmacological Effects of Cannabidiol

Cannabidiol (CBD) is a major phytocannabinoid present in Cannabis sativa (Linneo, 1753). This naturally occurring secondary metabolite does not induce intoxication or exhibit the characteristic profile of drugs of abuse from cannabis like Δ9-tetrahydrocannabinol (∆9-THC) does. In contrast to ∆9-THC, our knowledge of the neuro-molecular mechanisms of CBD is limited, and its pharmacology, which appears to be complex, has not yet been fully elucidated. The study of the pharmacological effects of CBD has grown exponentially in recent years, making it necessary to generate frequently updated reports on this important metabolite. In this article, a rationalized integration of the mechanisms of action of CBD on molecular targets and pharmacological implications in animal models and human diseases, such as epilepsy, pain, neuropsychiatric disorders, Alzheimer’s disease, and inflammatory diseases, are presented. We identify around 56 different molecular targets for CBD, including enzymes and ion channels/metabotropic receptors involved in neurologic conditions. Herein, we compiled the knowledge found in the scientific literature on the multiple mechanisms of actions of CBD. The in vitro and in vivo findings are essential for fully understanding the polypharmacological nature of this natural product.

,

Tetrahydrocannabivarin (THCV) Protects Adipose-Derived Mesenchymal Stem Cells (ASC) against Endoplasmic Reticulum Stress Development and Reduces Inflammation during Adipogenesis

The endoplasmic reticulum (ER) fulfills essential duties in cell physiology, and impairment of this organelle’s functions is associated with a wide number of metabolic diseases. When ER stress is generated in the adipose tissue, it is observed that the metabolism and energy homeostasis of the adipocytes are altered, leading to obesity-associated metabolic disorders such as type 2 diabetes (T2D). In the present work, we aimed to evaluate the protective effects of ∆9-tetrahydrocannabivarin (THCV, a cannabinoid compound isolated from Cannabis sativa L.) against ER stress in adipose-derived mesenchymal stem cells. Our results show that pre-treatment with THCV prevents the subcellular alteration of cell components such as nuclei, F-actin, or mitochondria distribution, and restores cell migration, cell proliferation and colony-forming capacity upon ER stress. In addition, THCV partially reverts the effects that ER stress induces regarding the activation of apoptosis and the altered anti- and pro-inflammatory cytokine profile. This indicates the protective characteristics of this cannabinoid compound in the adipose tissue. Most importantly, our data demonstrate that THCV decreases the expression of genes involved in the unfolded protein response (UPR) pathway, which were upregulated upon induction of ER stress. Altogether, our study shows that the cannabinoid THCV is a promising compound that counters the harmful effects triggered by ER stress in the adipose tissue. This work paves the way for the development of new therapeutic means based on THCV and its regenerative properties to create a favorable environment for the development of healthy mature adipocyte tissue and to reduce the incidence and clinical outcome of metabolic diseases such as diabetes.

,

The Effects of Long-Term Self-Dosing of Cannabidiol on Drowsiness, Testosterone Levels, and Liver Function

Previous research indicated that cannabidiol (CBD) may result in low levels of male total testosterone (TT), elevations in liver tests (LTs), and daytime drowsiness (DD). We investigated the prevalences of TT and LT in a large adult sample self-administering CBD and determined the effect self- dosing of CBD has on the severity of DD. Methods: Adult participants (18–75 years of age) who self-dose CBD orally for a minimum of 30 days were recruited for this decentralized observational study from companies that offer CBD products. Participants were sent their usual CBD regimen. A clinical study platform was used on a phone app to obtain consent and collect study data.

,

Cannabidiol-associated hepatotoxicity: A systematic review and meta-analysis

Inflammatory bowel diseases (IBDs) are chronic conditions of unknown cause or cure. Treatment seeks to reduce symptoms and induce and maintain remission. Many patients have turned to alternatives, such as cannabis, to alleviate living with IBD. This study reports the demographics, prevalence, and perception on cannabis use of patients attending an IBD clinic. Patients agreed to participate and completed an anonymous survey during their visit or online. Descriptive analysis, Fisher’s exact test, and Wilcoxon-Mann-Whitney rank-sum test were used. One hundred and sixty- two adults (85 males, 77 with CD) completed the survey. Sixty (37%) reported use of cannabis, of which 38 (63%) used it to relieve their IBD. A value of 77% reported low to moderate knowledge about cannabis, and 15% reported little to no knowledge. Among cannabis users, 48% had discussed use with their physician, but 88% said they would feel comfortable discussing medical cannabis for IBD. Most saw improvement of their symptoms (85.7%). A considerable number of patients with IBD use medical cannabis for their disease, unknown to their physician. The study reinforces the importance that physicians understand the role of cannabis in the treatment of IBD in order to appropriately counsel patients.