Entries by Michelle Smith

Cannabidiol Oil Ingested as Sublingual Drops or Within Gelatin Capsules Shows Similar Pharmacokinetic Profiles in Healthy Males

Cannabidiol (CBD) is a nonintoxicating phytocannabinoid used in clinical treatments and sold widely in consumer products. CBD products may be designed for sublingual or oral delivery, but it is unclear whether either is advantageous for CBD absorption. This study compared CBD pharmacokinetics after providing CBD oil as sublingual drops and within orally ingested gelatin capsules, at a dose relevant to consumer products.

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Cannabinoids for the Treatment of Hair, Scalp, and Skin Disorders: A Systematic Review

Cannabinoid products have been studied in the treatment of various dermatologic conditions. We searched PubMed/MEDLINE for articles published before 1 February 2023 that described the use of cannabinoids in the management of hair, scalp, and skin conditions, identifying 18 original articles that encompassed 1090 patients who used various forms of cannabinoid products. Where specified, topical cannabidiol (CBD) was the most commonly utilized treatment (64.3%, 173/269), followed by oral dronabinol (14.4%, 39/269), oral lenabasum (14.1%, 38/269), and oral hempseed oil (5.9%, 16/269). Using the GRADE approach, we found moderate-quality evidence supporting the efficacy of cannabinoid products in managing atopic dermatitis, dermatomyositis, psoriasis, and systemic sclerosis and moderate-quality evidence supporting a lack of efficacy in treating trichotillomania. There was low to very low quality evidence supporting the efficacy of cannabinoid products in managing alopecia areata, epidermolysis bullosa, hyperhidrosis, seborrheic dermatitis, and pruritus. Our findings suggest that cannabinoids may have efficacy in managing symptoms of certain inflammatory dermatologic conditions. However, the evidence is still limited, and there is no standardized dosage or route of administration for these products. Large randomized controlled trials and further studies with standardized treatment regimens are necessary to better understand the safety and efficacy of cannabinoids.

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Pharmacological blockade of 2-AG degradation ameliorates clinical, neuroinflammatory and synaptic alterations in experimental autoimmune encephalomyelitis

The endocannabinoid system (ECS) is critically involved in the pathophysiology of Multiple Sclerosis (MS), a neuroinflammatory and neurodegenerative disease of the central nervous system (CNS). Over the past decade, the neuroprotective and anti-inflammatory effects of the ECS have been studied, and inhibiting the degradation of the endocannabinoid 2-arachydonoylglycerol (2-AG) is emerging as a promising strategy to counteract brain damage in MS. In this study, a systemic and preventive in vivo treatment with MAGLi 432, the reversible inhibitor of monoacylglycerol lipase (MAGLi), was performed in experimental autoimmune encephalomyelitis (EAE) mice. Clinical, biochemical, electrophysiological and immunofluorescence analyses were carried out to evaluate the impact of the drug on motor disability, neuroinflammation and synaptic damage. MAGLi 432 induced a less severe EAE disease, accompanied by an increase of 2-AG and a reduction of acid arachidonic (AA) and prostaglandins (PGs) brain levels.

Toxicity of Cannabigerol: Examination of Long-Term Toxicity and Lifespan in Caenorhabditis elegans and 14-Day Study in Sprague Dawley Rats

Cannabigerol (CBG) is becoming widely available despite little being known about its potential toxicity or long-term effects. The present investigation involved two distinct studies. The first study explored acute and long-term effects of CBG on toxicity, lifespan, and aging in adult Caenorhabditis elegans (C. elegans). Animals were treated with CBG (0.075 lM–3.75 mM) to determine acute toxicity, mortality, and motility. Acute heat- induced stress survival (thermotolerance; 37°C for 4 h) following CBG administration (0.075–3.75 mM) was measured. Long-term toxicity of lifelong CBG administration (7.5, 75, or 375 lM CBG) was determined through changes in motility and lifespan duration. In the second study, healthy, adult, Sprague Dawley rats received 0, 35, 70, or 140 mg/kg-bw/day CBG (n = 5 per sex per group) daily for 14 days via oral gavage. Signs of gross toxicity and changes in behavior, body weight, food consumption, and serum chemistry were monitored. Liver, kidney, and adrenal gland weights were recorded, and histopathology of select tissues was examined.

A Two-Phase, Dose-Ranging, Placebo-Controlled Study of the Safety and Preliminary Test of Acute Effects of Oral D8-Tetrahydrocannabivarin in Healthy Participants

Tetrahydrocannabivarin (THCV) is an understudied cannabinoid that appears to have effects that vary as a function of dose. No human study has evaluated the safety and nature of effects in a wide range of THCV doses. This was a two-phase, dose-ranging, placebo-controlled trial of the D8 isomer of oral THCV in healthy adults. Phase 1 utilized an unblinded, single-ascending dose design (n = 3). Phase 2 used a double-blind, random- ized, within-participant crossover design (n = 18). Participants received single acute doses of placebo and 12.5, 25, 50, 100, and 200 mg of THCV. Safety measures and subjective and cognitive effects were assessed predose and up to 8 h postdose.

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The Use of Dispensary-Obtained Tetrahydrocannabinol as a Treatment for Neuropsychiatric Symptoms of Dementia

Neuropsychiatric symptoms (NPS) of dementia represent a large driver of health care costs, caregiver burden, and institutionalization of people with dementia. Management options are limited, and antipsychotics are often used, although they carry a significant side effect profile. One novel option is tetrahydrocannabinol (THC); however, in the US, to obtain THC for patients with dementia, caregivers have to go to a commercial dispensary. We evaluated the effectiveness of dispensary-obtained THC for patients with dementia and NPS. Two independent reviewers reviewed charts of patients with diagnosed dementia (N = 50) seen in geriatric psychiatry between 2017 and 2021 for whom dispensary-obtained THC was recommended. The primary outcome was effectiveness in treating NPS; secondary outcomes were the proportion of caregivers who obtained and administered THC (uptake), post-THC antipsychotic use, and adverse reactions leading to treatment discontinuation.

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Medical Cannabis Alleviates Chronic Neuropathic Pain Effectively and Sustainably without Severe Adverse Effect: A Retrospective Study on 99 Cases

Medical cannabis may provide a treatment option for chronic neuropathic pain. However, empirical disease-specific data are scarce. This is a retrospective observational study including 99 patients with chronic neuropathic pain. These patients received medical cannabis by means of inhaling dried flowers with tetrahydrocannabinol content of <12–22% at a maximal daily dose of 0.15–1 g. Up to six follow-ups were carried out at intervals of 4–6 weeks. Pain severity, sleep disturbance, general improvement, side effects, and therapy tolerance at the follow-up consultations were assessed in interviews and compared with the baseline data using non-parametric Wilcoxon signed-rank test.

Targeting Trauma-Induced Endocannabinoid System Dysfunction: A Novel Neuroprotective Approach For Traumatic Brain Injury

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. The primary injury results in neuronal damage and initiates secondary injuries like neuroinflammation, excitotoxicity, oxidative stress and blood-brain barrier disruption. This results in long-term cognitive, behavioral and motor deficits. Existing therapeutic options for TBI focus on symptomatic management rather than directly addressing the cellular processes that drive secondary damage. Novel neuroprotective therapies are urgently needed. The endocannabinoid system (ECS) is a promising therapeutic target for TBI. The ECS comprises the endocannabinoids anandamide and 2-AG, cannabinoid receptors CB1 and CB2, and metabolic enzymes like fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). It is involved in synaptic function, neuroinflammation, excitotoxicity, blood-brain barrier disruption, oxidative stress and neuronal loss. Modulation the ECS through receptor agonists/antagonists, inhibitors of endocannabinoid catabolism, or combination approaches represents a novel neuroprotective strategy in TBI.

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Real-World evidence on the use of cannabidiol for the treatment of drug resistant epilepsy not related to Lennox-Gastaut syndrome, Dravet syndrome or Tuberous Sclerosis Complex

Highly purified cannabidiol (CBD) has a broad spectrum of action and could be useful for the treatment of drug resistant epilepsy regardless of etiology or syndrome. Multicenter retrospective study that evaluated the efficacy and safety of CBD for the treatment of drug resistant epilepsy of different etiologies in patients >2 years of age.

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Increased Hippocampal Blood Flow in People at Clinical High Risk for Psychosis and Effects of Cannabidiol

Hippocampal hyperperfusion has been observed in people at Clinical High Risk for Psychosis (CHR), is associated with adverse longitudinal outcomes and represents a potential treatment target for novel pharmacotherapies. Whether cannabidiol (CBD) has ameliorative effects on hippocampal blood flow (rCBF) in CHR patients remains unknown. Using a double-blind, parallel-group design, 33 CHR patients were randomised to a single oral 600mg dose of CBD or placebo; 19 healthy controls did not receive any drug. Hippocampal rCBF was measured using Arterial Spin Labelling. We examined differences relating to CHR status (controls vs placebo), effects of CBD in CHR (placebo vs CBD) and linear between-group relationships, such that placebo>CBD>controls or controls>CBD>placebo, using a combination of hypothesis-driven and exploratory wholebrain analyses.

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Cannabidiol in Sports: Insights on How CBD could improve performance and recovery

Damage caused by physical exertion (anti-inflammatory) (Gamelin et al., 2020;Kennedy, 2017;Stone et al., 2023;Villanueva et al., 2022), and reduce pain caused by high physical demands (pain and soreness reliever) (see figure 1) (Gamelin et al., 2020;Henson et al., 2022;Kennedy, 2017). substances promote sleep controlled by the endocannabinoid system, which we can activate by consuming CBD (McCartney et al., 2020;Rojas-Valverde, 2021).Sleep management requires a precise balance of neurotransmitters, and CBD’s actions on the endocannabinoid system contribute to this balance. CBD interacts with adenosine receptors, which is significant since adenosine is a neurotransmitter that promotes sleep and relaxation.CBD promotes tranquillity and preparedness for sleep by boosting adenosine signalling.Furthermore, CBD’s effect on GABAergic neurotransmission adds to its sleep-enhancing properties (Kaul et al., 2021;Kesner & Lovinger, 2020). GABA is an inhibitory neurotransmitter that promotes relaxation and drowsiness by lowering neuronal excitability.CBD’s effect on GABA receptors can promote deeper, more comfortable sleep. Furthermore, CBD’s ability to relieve anxiety and stress, which are significant causes of sleep disruption, indirectly supports greater sleep quality (Blessing et al., 2015;Moltke & Hindocha, 2021;Ortiz Rios et al., 2022). CBD provides a biological foundation for its action via modifying endocannabinoid system signalling, increasing adenosine effects, and regulating GABAergic neurotransmission (Martinez Naya et al., 2023;Yarar, 2020;Zou & Kumar, 2018).

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Cannabidiol alters mitochondrial bioenergetics via VDAC1 and triggers cell death in hormone-refractory prostate cancer

In spite of the huge advancements in both diagnosis and interventions, hormone refractory prostate cancer (HRPC) remains a major hurdle in prostate cancer (PCa). Metabolic reprogramming plays a key role in PCa oncogenesis and resistance. However, the dynamics between metabolism and oncogenesis are not fully understood. Here, we demonstrate that two multi-target natural products, cannabidiol (CBD) and cannabigerol (CBG), suppress HRPC development in the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model by reprogramming metabolic and oncogenic signaling. Mechanistically, CBD increases glycolytic capacity and inhibits oxidative phosphorylation in enzalutamide-resistant HRPC cells. This action of CBD originates from its effect on metabolic plasticity via modulation of VDAC1 and hexokinase II (HKII) coupling on the outer mitochondrial membrane, which leads to strong shifts of mitochondrial functions and oncogenic signaling pathways. The effect of CBG on enzalutamide-resistant HRPC cells was less pronounced than CBD and only partially attributable to its action on mitochondria. However, when optimally combined, these two cannabinoids exhibited strong anti-tumor effects in TRAMP mice, even when these had become refractory to enzalutamide, thus pointing to their therapeutical potential against PCa.