Entries by Michelle Smith

A Delightful Trip Along the Pathway of Cannabinoid and Endocannabinoid Chemistry and Pharmacology

After a traumatic childhood in Europe during the Second World War, I found that scientific research in Israel was a pleasure beyond my expectations. Over the last 65 year, I have worked on the chemistry and pharmacology of natural products. During the last few decades, most of my research has been on plant cannabinoids, the endogenous cannabinoids arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol, and endogenous anandamide-like compounds, all of which are involved in a wide spectrum of physiological reactions.

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The Use of Cannabinoids in the Treatment of Peripheral Neuropathy and Neuropathic Pain: A Systematic Review

Peripheral neuropathies are commonly occurring conditions that are chronic and debilitating for patients. Established nonsurgical treatments have yielded mixed and patient-dependent results. Although cannabinoids have demonstrated efficacy as a treatment for central neuropathic pain, the therapeutic potential of cannabis-based medications for the management of peripheral neuropathic pain caused by nerve injury, trauma, and other noncompressive etiologies has yet to be definitively established. This study aims to determine whether cannabinoids are a potentially effective treatment for pain and symptoms associated with peripheral neuropathy.

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A Comparative In Vitro Study of the Neuroprotective Effect Induced by Cannabidiol, Cannabigerol, and Their Respective Acid Forms: Relevance of the 5-HT1A Receptors

Previous preclinical studies have demonstrated that cannabidiol (CBD) and cannabigerol (CBG), two non-psychotomimetic phytocannabinoids from Cannabis sativa, induce neuroprotective effects on toxic and neurodegenerative processes. However, a comparative study of both compounds has not been reported so far, and the targets involved in this effect remain unknown. The ability of CBD and CBG to attenuate the neurotoxicity induced by two insults involving oxidative stress (hydrogen peroxide, H2O2) and mitochondrial dysfunction (rotenone) was evaluated in neural cell cultures. The involvement of CB-1 and CB-2 or 5-HT1A receptors was investigated. The neuroprotective effect of their respective acids forms, cannabidiolic acid (CBDA) and cannabigerolic acid (CBGA), was also analyzed.

A common genetic variant in fatty acid amide hydrolase is linked to alterations in fear extinction neural circuitry in a racially diverse, nonclinical sample of adults

Poor fear extinction learning and recall are linked to the development of fear-based disorders, like posttraumatic stress disorder, and are associated with aberrant activation of fear-related neural circuitry. This includes greater amygdala activation during extinction learning and lesser hippocampal and ventromedial prefrontal cortex (vmPFC) activation during recall. Emerging data indicate that genetic variation in fatty acid amide hydrolase (FAAH C385A; rs324420) is associated with increased peripheral endocannabinoid (eCB) levels and lesser threat-related amygdala reactivity. Preclinical studies link increased eCB signaling to better extinction learning and recall, thus FAAH C385A may protect against the development of trauma-related psychopathology by facilitating extinction learning.

(Wh)olistic (E)ndocannabinoidome-Microbiome-Axis Modulation through (N)utrition (WHEN) to Curb Obesity and Related Disorders

The discovery of the endocannabinoidome (eCBome) is evolving gradually with yet to be elucidated functional lipid mediators and receptors. The diet modulates these bioactive lipids and the gut microbiome, both working in an entwined alliance. Mounting evidence suggests that, in different ways and with a certain specialisation, lipid signalling mediators such as N-acylethanolamines (NAEs), 2-monoacylglycerols (2-MAGs), and N-acyl-amino acids (NAAs), along with endocannabinoids (eCBs), can modulate physiological mechanisms underpinning appetite, food intake, macronutrient metabolism, pain sensation, blood pressure, mood, cognition, and immunity. This knowledge has been primarily utilised in pharmacology and medicine to develop many drugs targeting the fine and specific molecular pathways orchestrating eCB and eCBome activity. Conversely, the contribution of dietary NAEs, 2-MAGs and eCBs to the biological functions of these molecules has been little studied. In this review, we discuss the importance of (Wh) olistic (E)ndocannabinoidome-Microbiome-Axis Modulation through (N) utrition (WHEN), in the management of obesity and related disorders.

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Effects of oral, smoked, and vaporized cannabis on endocrine pathways related to appetite and metabolism: a randomized, double-blind, placebo-controlled, human laboratory study

As perspectives on cannabis continue to shift, understanding the physiological and behavioral effects of cannabis use is of paramount importance. Previous data suggest that cannabis use influences food intake, appetite, and metabolism, yet human research in this regard remains scant. The present study investigated the effects of cannabis administration, via different routes, on peripheral concentrations of appetitive and metabolic hormones in a sample of cannabis users. This was a randomized, crossover, double-blind, placebo-controlled study. Twenty participants underwent four experimental sessions during which oral cannabis, smoked cannabis, vaporized cannabis, or placebo was administered.

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Substituting Medical Cannabis for Medications Among Patients with Rheumatic Conditions in the United States and Canada

There are numerous reports of people substituting medical cannabis (MC) for medications. Our obejctive was to investigate the degree to which this substitution occurs among people with rheumatic conditions.In a secondary analysis from a cross-sectional survey conducted with patient advocacy groups in the US and Canada, we investigated MC use and medication substitution among people with rheumatic conditions. We subgrouped by whether participants substituted MC for medications and investigated differences in perceived symptom changes and use patterns, including methods of ingestion, cannabinoid content (cannabidiol vs delta-9-tetrahydrocannabinol [THC]), and use frequency.

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Patient-Reported Outcomes of Pain, Stiffness, and Fatigue Reduction in Rheumatoid and Psoriatic Arthritis With Cannabinoid Use

Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are autoimmune conditions that can progressively destroy joints, causing chronic, often debilitating pain, and drastically affecting the quality of life. Novel pharmaceutical remedies have recently been developed, which allow for better symptom management. However, the complex pain experienced is challenging to control fully, leading this patient population to seek alternative treatments.