Entries by Michelle Smith

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Neuroinflammation and status epilepticus: a narrative review unraveling a complex interplay

Status epilepticus (SE) is a medical emergency resulting from the failure of the mechanisms involved in seizure termination or from the initiation of pathways involved in abnormally prolonged seizures, potentially leading to long-term consequences, including neuronal death and impaired neuronal networks. It can eventually evolve to refractory status epilepticus (RSE), in which the administration of a benzodiazepine and another anti-seizure medications (ASMs) had been ineffective, and super-refractory status epilepticus (SRSE), which persists for more than 24 h after the administration of general anesthesia. Objective of the present review is to highlight the link between inflammation and SE. Several preclinical and clinical studies have shown that neuroinflammation can contribute to seizure onset and recurrence by increasing neuronal excitability. Notably, microglia and astrocytes can promote neuroinflammation and seizure susceptibility. In fact, inflammatory mediators released by glial cells might enhance neuronal excitation and cause drug resistance and seizure recurrence. Understanding the molecular mechanisms of neuroinflammation could be crucial for improving SE treatment, wich is currently mainly addressed with benzodiazepines and eventually phenytoin, valproic acid, or levetiracetam.

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Medical cannabis for refractory cancer-related pain in a specialised clinical service: a cross-sectional study

Cancer-related pain management in advanced stages presents a significant challenge that often requires a multidisciplinary approach. Although advancements in pharmacological and interventional therapies, a considerable number of patients still suffer from refractory pain, leading to unmet clinical needs. This study shares our experience with medical cannabis (MC) as a potential therapy for this specific population of patients with cancer-related refractory pain.

Empathy-related differences in the anterior cingulate functional connectivity of regular cannabis users when compared to controls

It has been reported that cannabis consumption affects the anterior cingulate cortex (ACC), a structure with a central role in mediating the empathic response. In this study, we compared psychometric scores of empathy subscales, between a group of regular cannabis users (85, users) and a group of non-consumers (51, controls). We found that users have a greater Emotional Comprehension, a cognitive empathy trait involving the understanding of the “other” emotional state. Resting state functional MRI in a smaller sample (users = 46, controls = 34) allowed to identify greater functional connectivity (FC) of the ACC with the left somatomotor cortex (SMC), in users when compared to controls. These differences were also evident within the empathy core network, where users showed greater within network FC. The greater FC showed by the users is associated with emotional representational areas and empathy-related regions. In addition, the differences in psychometric scores suggest that users have more empathic comprehension. These findings suggest a potential association between cannabis use, a greater comprehension of the other’s affective state and the functional brain organization of the users. However, further research is needed to explore such association, since many other factors may be at play.

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Cannabidiol as an Alternative Analgesic for Acute Dental Pain

Odontogenic pain can be debilitating, and nonopioid analgesic options are limited. This randomized placebo-controlled clinical trial aimed to assess the effectiveness and safety of cannabidiol (CBD) as an analgesic for patients with emergency acute dental pain. Sixty-one patients with moderate to severe toothache were randomized into 3 groups: CBD10 (CBD 10 mg/kg), CBD20 (CBD 20 mg/kg), and placebo. We administered a single dose of respective oral solution and monitored the subjects for 3 h. The primary outcome measure was the numerical pain differences using a visual analog scale (VAS) from baseline within and among the groups. Secondary outcome measures included ordinal pain intensity differences, the onset of significant pain relief, maximum pain relief, changes in bite force within and among the groups, psychoactive effects, mood changes, and other adverse events.

Dramatic efficacy of cannabidiol on refractory chronic pain in an adolescent with sickle cell disease

Patients with sickle cell disease (SCD) suffer from both acute and chronic pain, whose pathophysiology involves not only red blood cell sickling with subsequent vaso-occlusion leading to ischemia-reperfusion injury but also neurogenic inflammation, possibly mediated by mast cell activation.Chronic pain affects approximately 40% of patients with SCD, and its management is often a difficult challenge for clinicians. Indeed, morphine, which has long been considered the reference analgesic for acute pain, may paradoxically worsen chronic pain, by promoting mast cell activation and degranulation, leading to the release of mast cell mediators such as substance P or histamine.
Substance P is a pain neurotransmitter and a neuromodulator found to induce peripheral sensitization and neuroinflammation in an SCD effects in SCD by promoting endothelial P-selectin expression. In patients, high levels of plasma histamine have been reported during vaso-occlusive crisis (VOC) but also at steady state, contrasting with
normal or slightly increased tryptase level, which suggests mast celltransgenic mouse model. Histamine may also have deleterious.

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Phytochemical investigation of anti-proliferative active fractions of Cannabis sativa leads to isolate a new Compound Canniprene A and other bioactive compounds through bioassay guided fractionation and HPLC assisted puri�cation

Phytocannabinoids and synthetic cannabinoids have been explored as the lead due to their anti-proliferative nature and can be anti-cancer agents. These were found to activate numerous pharmacological targets to generate new therapies in alleviating specic symptoms or delaying the disease of Cancer. However, the comprehensive anti-cancer activities of cannabinoid acids and non-cannabinoids are not fully explored. Herein we report simple extraction, faster bioassay-guided fractionation, and HPLC-assisted purication of bioactive secondary metabolite and their identication.

Confronting The Harms Caused By Racism In Perinatal Drug Testing

Today, you are the doctor in the well-baby nursery. As you walk from one hospital room to the next, talking with new parents, most of your patients are healthy. Your job is to ensure that rare but serious health problems don’t go undetected before these babies go home with their parents. As you walk by the nurses’ station, a nurse pulls you aside.

“The baby in room 7 is jittery,” she tells you. “And he just seems fussy. The resident had me check his blood sugar and calcium levels. Both were normal.”

You stand silent for an extra beat, waiting to see what else the nurse might say.

“Has anyone asked the mom how she thinks her baby is doing?” You say this because a parent’s perspective always matters.

“I don’t know,” the nurse offers.

“Thank you for letting me know your concerns. Let me go look at him.”

You knock, open the door, sit down beside this mother, and offer congratulations on the birth of her child. You ask if you can examine him.

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Therapeutic Potential of Minor Cannabinoids in Dermatological Diseases—A Synthetic Review

Dermatological diseases pose a significant burden on the quality of life of individuals and can be challenging to treat effectively. In this aspect, cannabinoids are gaining increasing importance due to their therapeutic potential in various disease entities including skin diseases. In this synthetic review, we comprehensively analyzed the existing literature in the field of potential dermatological applications of a lesser-known subgroup of cannabinoids, the so-called minor cannabinoids, such as cannabidivarin (CBDV), cannabidiforol (CBDP), cannabichromene (CBC), tetrahydrocannabivarin (THCV), cannabigerolic acid (CBGA), cannabigerol (CBG), cannabielsoin (CBE), cannabimovone (CBM) or cannabinol (CBN), while drawing attention to their unique pharmacological properties. We systematically searched the available databases for relevant studies and analyzed the data to provide an overview of current thematic knowledge.

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Dispensary personnel’s views and experiences regarding oncologic cannabis and the counsel they offer adults with cancer

A minority of oncologists feel qualified to advise adults with can- cer on issues pertaining to medicinal cannabis. Adults with cancer frequently ac- cess medicinal cannabis information from non-medical sources such as cannabis dispensaries. We explored dispensary personnel’s views and experiences regard- ing oncologic cannabis and the counsel they extend individuals with cancer. Methods: Snowball sampling in this qualitative study facilitated recruitment across 13 states (N = 26). Semi-structured phone interviews ceased with thematic saturation. A multi-stage thematic analysis combined inductive and deductive codes.

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Cannabis Extracts on Glioblastoma Cell Lines: Chemical Composition and Pharmacologic Insights

Glioblastoma multiforme (GBM), also called grade IV astrocytoma, is an aggressive, malignant brain tumor with a low treatment success rate, particularly in patients with immune checkpoint-active tumors. These types of tumors are associated with a 5-year survival rate of <3%. Targeted treatments specifically designed for GBM are urgently needed. The aim of this study was to evaluate the effects of chemovar-specific cannabis extractions (CSCEs) in patients with GBM using liquid chromatography-mass spectrometry (LC-MS).

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The potential for medicinal cannabis to help manage challenging behaviour in people with intellectual disability: A perspective review

Around 2% of the population have intellectual disabilities. Over one-third people with intellectual disabilities (PwID) present with ‘challenging behaviour’, which nosologically and diagnostically is an abstract concept. Challenging behaviour is influenced by a range of bio-psycho-social factors in a population, which is unable to suitably comprehend and/or communicate concerns. This predisposes to poor health and social outcomes. There is no evidence-based treatments for managing challenging behaviour. Cannabidiol (CBD) and tetrahydrocannabinol (THC) are being trialled for a range of disorders, which are over-represented in PwID and provoke challenging behaviours, such as severe epilepsy, spasticity, post-traumatic stress disorder, social phobia, pain, etc.