Cannabidiol’s neuroprotective properties and potential treatment of traumatic brain injuries

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Cannabidiol (CBD) has numerous pharmacological targets that initiate anti-inflammatory, antioxidative, and antiepileptic properties. These neuroprotective benefits have generated interest in CBD’s therapeutic potential against the secondary injury cascade from traumatic brain injury (TBI). There are currently no effective broad treatment strategies for combating the damaging mechanisms that follow the primary injury and lead to lasting neurological consequences or death. However, CBD’s effects on different neurotransmitter systems, the blood brain barrier, oxidative stress mechanisms, and the inflammatory response provides mechanistic support for CBD’s clinical utility in TBI. This review describes the cascades of damage caused by TBI and CBD’s neuroprotective mechanisms to counter them. We also present challenges in the clinical treatment of TBI and discuss important future clinical research directions for integrating CBD in treatment protocols. The mechanistic evidence provided by pre-clinical research shows great potential for CBD as a much-needed improvement in the clinical treatment of TBI. Upcoming clinical trials sponsored by major professional sport leagues are the first attempts to test the efficacy of CBD in head injury treatment protocols and highlight the need for further clinical research.

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Efficacy and safety of topical 0.1% cannabidiol for managing recurrent aphthous ulcers: a randomized controlled trial

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Although topical steroids constitute the first-line therapy for recurrent aphthous ulcers (RAUs), their long-term use often leads to candidiasis. Although cannabidiol (CBD) can be an alternative for pharmacologically managing RAUs due to its analgesic and anti-inflammatory in vivo effects, there is a lack of clinical and safety trials concerning its use. The aim of this study was to evaluate the clinical safety and efficacy of topical 0.1% CBD for managing RAU. A CBD patch test was performed on 100 healthy subjects. CBD was applied on the normal oral mucosa of 50 healthy subjects 3 times/day for 7 days. Oral examination, vital signs, and blood tests were performed pre- and post-CBD use. Another 69 RAU subjects randomly received one of three topical interventions: 0.1% CBD, 0.1% triamcinolone acetonide (TA), or placebo. These were applied on the ulcers 3 times/day for 7 days. The ulcer and erythematous size were measured on day 0, 2, 5, and 7. Pain ratings were recorded daily. The subjects rated their satisfaction with the intervention and completed a quality-of-life questionnaire (OHIP-14).

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Cannabis-Assisted Psychotherapy for Complex Dissociative Posttraumatic Stress Disorder: A Case Report

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A dissociative subtype of posttraumatic stress disorder, known as “D-PTSD”, has been included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. In addition to meeting criteria for PTSD, patients endorse prominent dissociative symptoms, namely depersonalization and derealization, or detachment from one’s self and surroundings. At present, this population is supported by a highly heterogeneous and undeveloped literature. Targeted interventions are therefore lacking, and those indicated for PTSD are limited by poor efficacy, delayed onset of action, and low patient engagement. Here, we introduce cannabis-assisted psychotherapy (CAP) as a novel treatment for D-PTSD, drawing parallels to psychedelic therapy. Case presentation: A 28-year-old female presented with complex D-PTSD. In a naturalistic setting, she underwent 10 sessions of CAP, scheduled twice monthly over 5 months, coupled with integrative cognitive behavioral therapy. An autonomic and relational approach to CAP was leveraged, specifically psychedelic somatic interactional psychotherapy. Acute effects included oceanic boundlessness, ego dissolution, and emotional breakthrough.

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Cannabis for Anxiety and PTSD

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Anxiety disorders are the most common type of psychiatric disorders, and they’re one of the most common conditions for which people use cannabis. One review found that among 6665 cannabis users with data collected from 13 different studies, 52% of the subjects reported using cannabis for anxiety, making it the second most commonly treated symptom, following pain (1). Anxiety disorders come in many forms, including generalized anxiety, social anxiety, and panic disorders.

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Table 2 Descriptions of frequently consumed Cannabis flower chemovar index codes

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Little is known about the frequency with which different combinations of phytochemicals (chemovars) arise in Cannabis flower or whether common chemovars are associated with distinct pharmacodynamics and patient health outcomes. This study created a clinically relevant, user-friendly, scalable chemovar indexing system summarizing primary cannabinoid and terpene contents and tested whether the most frequently consumed chemovars differ in their treatment effectiveness and experienced side effects.

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Cannabidiol Negatively Regulates Androgenic Signal in Prostate Cancer Cells and Fine-Tunes the Tumorigenesis by Modulating Endoplasmic Reticulum-Associated Degradation, Unfolded Protein Response, and Autophagy

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Cannabis sativa L., Cannabaceae, has been used as a herbal medicine for several thousand years in many cultures and it has more than 540 metabolites that provide therapeutic effects. Cannabinoids are the major compounds derived from the Cannabis species. There are over 120 isolated and identified cannabinoids from C. sativa and (−)-cannabidiol is one of the most well-researched among them. Recent studies have focused on the expanding usage of cannabidiol in many therapeutic areas as well as cancer. Studies demonstrated a negative correlation between cannabidiol administration and the growth of various cancer types, including prostate cancer. However, the detailed mode of action of cannabidiol on prostate cancer remains unclear. In the present study, we investigated the molecular mechanism of cannabidiol prostate cancer cells. For this aim, we examined the effect of cannabidiol on autophagy, endoplasmic reticulum-associated degradation, endoplasmic reticulum stress, unfolded protein response, epithelial-mesenchymal transition, angiogenesis, and androgenic signaling in vitro. We found that cannabidiol remarkably inhibited autophagy. Also, it strongly induced unfolded protein response and endoplasmic reticulum-associated degradation mechanisms. Moreover, it exerted anti-cancer activity by reducing epithelial-mesenchymal transition and causing cell cycle arrest. Additionally, cannabidiol importantly disrupted androgenic signaling by affecting basal androgen receptor levels and inhibiting nuclear translocation of this receptor.

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Cannabidiol as a potential novel treatment for endometriosis by its anti-inflammatory, antioxidative and antiangiogenic effects in an experimental rat model

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Endometrial implants were surgically induced in 36 female Wistar albino rats. After confirmation of endometriotic foci, the rats were randomized into four groups. In the leuprolide acetate group, rats were given a single 1 mg/kg s.c. leuprolide acetate injection. The other groups were 5 mg/kg CBD (CBD5), saline solution and 20 mg/kg CBD (CBD20); daily i.p. injections were administered for 7 days. After 21 days, the rats were euthanised, and total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) measurements in blood and peritoneal fluid samples, and immunohistochemical staining for TNF-α, IL-6 and vascular endothelial growth factor (VEGF) of endometriotic tissues were evaluated.

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Assessment of Orally Administered Δ9-Tetrahydrocannabinol When Coadministered With Cannabidiol on Δ9-Tetrahydrocannabinol Pharmacokinetics and Pharmacodynamics in Healthy Adults: A Randomized Clinical Trial

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Are there acute pharmacokinetic or pharmacodynamic differences between oral ingestion of a Δ9-tetrahydrocannabinol (Δ9-THC)-dominant cannabis extract compared with a cannabidiol (CBD)-dominant extract at the same Δ9-THC dose (20 mg) in healthy adults who use cannabis infrequently? In this randomized clinical trial including 18 adult participants, ingestion of 20 mg Δ9-THC + 640 mg CBD resulted in stronger subjective drug effects, greater impairment of cognitive and psychomotor ability, and greater increase in heart rate relative to 20 mg Δ9-THC alone and placebo. These effects appear to be mediated by CBD inhibition of Δ9-THC and 11-OH-Δ9-THC metabolism.

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Cannabidiol modulates excitatory-inhibitory ratio to counter hippocampal hyperactivity

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Rosenberg et al. reveal a potential mechanism by which cannabidiol (CBD) reduces seizures. They discover that CBD restores the hippocampal excitatory-to- inhibitory ratio by preventing the actions of the lipid LPI at the receptor GPR55. Seizures acutely potentiate the GPR55- LPI axis, providing a target for CBD’s anti- seizure action.

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Chemical transformation of cannabidiol into psychotropic cannabinoids under acidic reaction conditions: Identifification of transformed products by GC-MS

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Recently, cannabidiol (CBD), one of the major components of the Cannabis species, has been a focus in the cannabis industry due to its various pharmacological effects. Interestingly, CBD can be converted into several psychoactive cannabinoids, such as 9-tetrahydrocannabinol (D9-THC) and its structural isomers, under acidic reaction conditions. In this study, chemical transformation of CBD in ethanol solution was conducted with variation in pH at 2.0, 3.5, and 5.0 by addition of 0.1 M hydrochloric acid (HCl). These resulting solutions were derivatized with trimethylsilyl (TMS) reagent and analyzed using GC/MS-scan mode. Time profiles of CBD degradation and transformation of products were examined according to variations in pH and temperature.

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

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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.

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The Use of Cannabinoids in the Treatment of Inflammatory Bowel Disease (IBD): A Review of the Literature

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Around the world, about 15 to 40% of individuals with inflammatory bowel disease (IBD) rely on cannabis and cannabinoids to reduce the need for other medications, as well as increase appetite and reduce pain. Whereas more and more patients continue to report benefits accruing from cannabis and cannabinoid usage in IBD, agreement relative to the use of cannabis and its derivatives in IBD remains unclear. This paper reviewed the interplay between cannabinoid use and IBD disease treatment, remission, or symptom relief. The study was conducted from a systematic review perspective. It involved consulting literature from published original research articles, noting outcomes, and performing a meta-analysis to identify trends and draw conclusions. The selected articles were those that had been published in a 10-year period ranging between 2012 and 2022. The motivation was to ensure recency and also relevance to contemporary scientific research and clinical environment practices.

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