Role Of Cannabidiol Research Articles

Selected phytocannabinoids inhibit SN-38- and cytokine-evoked increases in epithelial permeability and improve intestinal barrier function in vitro

Irinotecan use is linked to the development of gastrointestinal toxicity and inflammation, or gastrointestinal mucositis. Selected phytocannabinoids have been ascribed anti-inflammatory effects in models of gastrointestinal inflammation, associated with maintaining epithelial barrier function. We characterised the mucoprotective capacity of the phytocannabinoids: cannabidiol, cannabigerol, cannabichromene and cannabidivarin in a cell-based model of intestinal epithelial stress occurring in mucositis.Transepithelial electrical resistance (TEER) was measured to determine changes in epithelial permeability in the presence of SN-38 (5 μM) or the pro-inflammatory cytokines TNFα and IL-1β (each at 100 ng/mL), alone or with concomitant treatment with each of the phytocannabinoids (1 μM). The DCFDA assay was used to determine the ROS-scavenging ability of each phytocannabinoid following treatment with the lipid peroxidant tbhp (200 μM).Each phytocannabinoid provided significant protection against cytokine-evoked increases in epithelial permeability. Cannabidiol, cannabidivarin and cannabigerol were also able to significantly inhibit SN-38-evoked increases in permeability. None of the tested phytocannabinoids inhibited tbhp-induced ROS generation.These results highlight a novel role for cannabidiol, cannabidivarin and cannabigerol as inhibitors of SN-38-evoked increases in epithelial permeability and support the rationale for the further development of novel phytocannabinoids as supportive therapeutics in the management of irinotecan-associated mucositis.

Involvement of CKS1B in the anti-inflammatory effects of cannabidiol in experimental stroke models

We have previously demonstrated that treatment with cannabidiol (CBD) ameliorates mitochondrial dysfunction and attenuates neuronal injury in rats following cerebral ischemia. However, the role of CBD in the progression of ischemic stroke-induced inflammation and the molecules involved remain unclear. Here, we found that CBD suppressed the production of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), reduced the activation of microglia, ameliorated mitochondrial deficits, and decreased the phosphorylation of nuclear factor κ-B (NF-κB) in BV-2 cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Cyclin-dependent kinase regulatory subunit 1B (CKS1B) expression was decreased in BV-2 cells following OGD/R and this reduction was blocked by treatment with CBD. Knockdown of CKS1B increased the activation of microglia and enhanced the production of IL-1β and TNF-α in BV-2 cells treated with CBD. Moreover, CKS1B knockdown exacerbated mitochondrial deficits and increased NF-κB phosphorylation. CBD treatment also ameliorated brain injury, reduced neuroinflammation, and enhanced the protein levels of mitochondrial transcription factor A and CKS1B in rats following middle cerebral artery occlusion/reperfusion. These data identify CKS1B as a novel regulator of neuroinflammation; and reveals its involvement in the anti-inflammatory effects of CBD. Interventions targeting CKS1B expression are potentially promising for treating in ischemic stroke.

Physician Trainees' Perception of Cannabidiol Use in Medicine: A Survey Study.

Given the ongoing national opiate crisis, physicians have been challenged with mitigating the risk of opiate dependence in their patients. With current physician efforts to mitigate the risks of treating pain with opioid prescriptions, this study evaluates medical students' and residents' understanding and perceptions regarding cannabidiol (CBD) in current medical care and their future medical practice. Orthopedic residents from all American programs and medical students from 50 medical schools, regardless of training year or future specialty plans, were eligible to participate in this survey-based study administered from December 2022 to March 2023. The surveys ask questions about demographic information, what education they receive on CBD utilization in medicine, thoughts on CBD effectiveness in pain control, and future plans on utilizing CBD. A total of 55 residents (1.4%) and 53 medical students (5.1%) responded. Trainees in CBD-legal states were more likely to work with physicians who use CBD in their practice. Most trainees, regardless of location, believe CBD use has a stigma attached to it. Many responders were concerned about the role of CBD in pain control. Finally, most trainees believed that CBD is easy to access if desired and is affordable to purchase. The trajectory of CBD use in the United States indicates that the therapeutic benefits of CBD will be targeted, and future physicians are not always provided adequate educational opportunities to learn about its potential medical uses. Continued training as well as interactions with patients may help decrease the stigma surrounding medical CBD use and help solidify its therapeutic use in pain control.

Perceptions and Opinions on Cannabidiol in the Orthopaedic Sports Medicine Community.

Cannabidiol (CBD) is a known pain modulator that is garnering increased attention in the orthopaedic world. There may be a considerable knowledge gap among orthopaedic sports medicine providers and their perception of its therapeutic value. To (1) examine the knowledge and beliefs of sports medicine orthopaedic providers with respect to CBD, (2) deliver an educational component, and (3) elucidate potential barriers to its widespread application. Cross-sectional study. A 3-component, 25-question online survey was distributed to members of the American Orthopaedic Society for Sports Medicine and the Arthroscopy Association of North America between July and October 2022. The first 20 questions assessed baseline knowledge and opinions regarding CBD, followed by an educational component, and then 5 questions assessing whether the respondents' opinions had changed after learning more about CBD. Responses were compared according to age, practice setting, and state's cannabinoid legalization status using the chi-square test, and changes in opinions from before to after the educational component were compared using the paired t test. There were 101 survey responses, for a response rate of approximately 1%. Most respondents believed that there is a role for CBD in postoperative pain management (76%), acute pain and inflammation after an injury (62%), and chronic pain (94%). Most respondents admitted that they were not knowledgeable about the mechanism of action (89%) or their state's laws (66%) concerning CBD. A minority (25%) believed that CBD has psychoactive properties. While most respondents (76%) did not believe that they would be stigmatized if they were to suggest CBD to a patient, only 48% had ever suggested CBD. Notably, 94% of respondents had encountered patients who reported trying CBD to treat pain. After reading the fact sheet, 51% of respondents stated that their opinion on CBD had changed, and 63% felt inclined to investigate the topic further. Most survey respondents believed that CBD has a role in postoperative and chronic pain management. Although there was a relative familiarity with CBD, there was a knowledge gap, suggesting that increased attention, education, and research are necessary.

Poster 373: Perceptions & Opinions on Cannabidiol Among Sports Medicine Orthopaedic Surgeons

Objectives: Cannabidiol (CBD) is a known pain modulator which is beginning to garner increased attention in the orthopaedic world, with many patients now presenting to clinics having tried CBD for pain relief. However, there may be a considerable knowledge gap with particular reference to orthopedic sports medicine surgeons and how they perceive the use of this therapeutic agent in clinical practice. The purpose of this study is to (1) examine the knowledge and beliefs of sports medicine orthopaedic surgeons with respect to the role of cannabidiol (CBD) in a multi-modal post-operative pain management regimen (2) deliver an educational component regarding CBD to practicing surgeons, and to (3) elucidate potential future barriers to the widespread use of this treatment modality by providing an anonymous forum for surgeons to voice their opinions. Methods: A three-component, 25-question online survey was distributed to fellowship-trained sports medicine orthopaedic surgeons. The first 20 questions were designed to assess baseline knowledge and opinions of sports surgeons regarding cannabidiol. These were followed by a 1-page summary sheet detailing the current legal status of CBD, as well as a brief literature review of its potential role in pain management within the field of orthopaedics. Lastly, 5 additional questions assessed whether the respondents’ opinions had shifted after learning more about CBD. A Visual Analog Scale (VAS) was used for one question (“Please indicate the likelihood you would recommend CBD as part of a pain management regimen.”), which was repeated before and after the summary sheet to see if respondents modified their answer after completing the educational component. Results: One hundred responses were collected from sports medicine surgeons. Most surgeons (76.2%) believe there is a role for CBD in post-operative pain management. While only 62.4% of respondents believe that CBD could be effective in managing acute pain and inflammation following injury, an overwhelming majority (94.1%) believed that CBD has a role in chronic pain management. A large majority stated that CBD would have no effect on soft tissue (89.1%) or bony (90.1%) healing post- operatively. Most surgeons admitted they were not knowledgeable about the mechanism (84.2%), modes of administration (73.3%), or their states’ laws (66.3%) concerning CBD. A minority (24.8%) believe that CBD has psychoactive properties and 18.8% believe CBD has addictive potential. While most surgeons (76.2%) did not believe they would be stigmatized if they were to suggest CBD to a patient, only 47.5% have ever suggested CBD to a patient. Notably, 94.1% of surgeons have encountered patients who reported trying CBD to treat pain. In the optional open-response section, 32 respondents elaborated on their concerns with most sentiments falling into three predominant themes: a) more evidence is required (10, 31.3%); b) stigmatization from patients (8, 25.0%); c) more regulation is required (5, 15.6%). After reading through the fact sheet, 51.4% of the survey respondents stated that their opinion on CBD had changed, and 62.9% stated they felt inclined to investigate the topic further on their own. Conclusions: A majority of sports medicine surgeons believe that CBD has a role in post-operative and chronic pain management. Surgeons are somewhat familiar with CBD, in part due to its remarkable prevalence among their patient populations, however there is clearly a knowledge gap, suggesting more education is necessary involving what is currently known about the subject and that more research should be targeted toward this developing industry. Current barriers to its routine use in clinical practice include unfamiliarity of the mechanism and dosing, limited evidence and regulation, and patient concerns or patient/surgeon stigmatization.

The role of cannabidiol in modulating chronic neuropathic orofacial pain

Chronic neuropathic orofacial pain is an extremely debilitating disorder that poses a burden to patients as well as the economy. Although a common condition, the management and treatment for those affected remains limited. Cannabidiol is a safe, non-psychoactive compound derived from the Cannabis sativa plant, which possesses properties that can modulate pain, including anti-neuropathic, anti-nociception and anti-inflammatory capacities. Although research is limited, cannabidiol may be able to treat chronic orofacial pain in some neurological, neurovascular and idiopathic conditions. This article aims to increase awareness of cannabidiol, and its possible use for future treatment of chronic neuropathic orofacial pain. CPD/Clinical Relevance: Cannabidiol may be useful as a treatment for chronic neuropathic orofacial pain.

Exosomal delivery of cannabinoids against cancer

Exosomes are extracellular vesicles (EVs) originating from endosomes that play a role in cellular communication. These vesicles which mimic the parental cells that release them are promising candidates for targeted drug delivery and therapeutic applications against cancer because of their favorable biocompatibility, specific targeting, low toxicity, and immunogenicity. Currently, Delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD) and other cannabinoids (e.g., CBG, THCV, CBC), are being explored for their anticancer and anti-proliferative properties. Several mechanisms, including cell cycle arrest, proliferation inhibition, activation of autophagy and apoptosis, inhibition of adhesion, metastasis, and angiogenesis have been proposed for their anticancer activity. EVs could be engineered as cannabinoid delivery systems for tumor-specificity leading to superior anticancer effects. This review discusses current techniques for EV isolation from various sources, characterization and strategies to load them with cannabinoids. More extensively, we culminate information available on different sources of EVs that have anticancer activity, mechanism of action of cannabinoids against various wild type and resistant tumors and role of CBD in histone modifications and cancer epigenetics. We have also enumerated the role of EVs containing cannabinoids against various tumors and in chemotherapy induced neuropathic pain.

Cannabidiol attenuates periodontal inflammation through inhibiting TLR4/NF-κB pathway.

Periodontitis is a chronic inflammatory disease involving soft and hard tissue destruction in the periodontal region. Cannabidiol (CBD) is a natural compound isolated from cannabis, which has the effect of inhibiting inflammation. However, the role of CBD in periodontitis remains unclear. The aim of this study was to investigate the anti-inflammatory effects and osteoprotective actions of CBD in periodontitis and its molecular mechanisms. After establishing the rat periodontitis model by ligatures, the specimens were processed for morphometric analysis by Micro-CT. The gingival tissues were collected, and the levels of TNF-α, IL-1β, and TLR4 were measured by enzyme-linked immunosorbent assay. LPS was used to induce the inflammatory response of human periodontal ligament cells (hPDLCs) in vitro. QPCR and western blot were carried out to detect the expression of related inflammatory cytokines and signaling pathways. Cannabidiol significantly inhibits bone loss in experimental rat periodontitis models. CBD downregulated the pro-inflammatory mediator TNF-α, related to the decrease of TLR4 protein expression. Overexpression of TNF-α and TLR4 caused by LPS in hPDLCs. CBD inactivated the TLR4/NF-κB signaling pathway by inhibiting TLR-4 expression and p65 NF-κB phosphorylation. CBD can be considered as a therapeutic agent for periodontitis. Our study demonstrated that CBD attenuates ligature-induced periodontitis in rats and LPS-induced inflammation in hPDLCs by inhibiting TLR4/NF-κB pathway activation. It indicates that topical CBD application is effective in treating periodontitis.

Cannabidiol Treatment Shows Therapeutic Efficacy in a Rodent Model of Social Transfer of Pain in Pair-Housed Male Mice.

Introduction: Prosocial behavior refers to sharing emotions and sensations such as pain. Accumulated data indicate that cannabidiol (CBD), a nonpsychotomimetic component of the Cannabis sativa plant, attenuates hyperalgesia, anxiety, and anhedonic-like behavior. Nevertheless, the role of CBD in the social transfer of pain has never been evaluated. In this study, we investigated the effects of acute systemic administration of CBD in mice that cohabited with a conspecific animal suffering from chronic constriction injury. Furthermore, we assessed whether repeated CBD treatment decreases hypernociception, anxiety-like behavior, and anhedonic-like responses in mice undergoing chronic constriction injury and whether this attenuation would be socially transferred to the partner. Materials and Methods: Male Swiss mice were Housed in pairs for 28 days. On the 14th day of living together, animals were then divided into two groups: cagemate nerve constriction (CNC), in which one animal of each partner was subjected to sciatic nerve constriction; and cagemate sham (CS), subjected to the same surgical procedure but without suffering nerve constriction. In Experiments 1, 2, and 3 on day 28 of living together, the cagemates (CNC and CS) animals received a single systemic injection (intraperitoneally) of vehicle or CBD (0.3, 1, 10, or 30 mg/kg). After 30 min, the cagemates were subjected to the elevated plusmaze followed by exposure to the writhing and sucrose splash tests. For chronic treatment (Exp. 4), sham and chronic constriction injury animals received a repeated systemic injection (subcutaneous) of vehicle or CBD (10 mg/kg) for 14 days after the sciatic nerve constriction procedure. On days 28 and 29 sham and chronic constriction injury animals and their cagemates were behaviorally tested. Results and Conclusion: Acute CBD administration attenuated anxiety-like behavior, pain hypersensitivity, and anhedonic-like behavior in cagemates that cohabited with a pair in chronic pain. In addition, repeated CBD treatment reversed the anxiety-like behavior induced by chronic pain and enhanced the mechanical withdrawal thresholds in Von Frey filaments and the grooming time in the sucrose splash test. Moreover, repeated CBD treatment effects were socially transferred to the chronic constriction injury cagemates.

Cannabidiol-Mediated Sequestration of Alzheimer’s Amyloid-<i>β</i> Peptides in ADDL Oligomers

Cannabidiol (CBD), one of the most studied phytocannabinoids, is non-psychotropic and can induce protective effects on the central nervous system against acute and chronic brain injury. Interestingly, CBD inhibits processes relating to amyloid beta (Aβ)-induced neurotoxicity in mouse models of Alzheimer’s disease, though the detailed molecular mechanism underlying the CBD neurotoxicity modulation is not fully understood. In this study, using atomic force microscopy, we find that CBD promotes the aggregation of Aβ peptides, enhancing the formation of Aβ oligomers, also known as Aβ-derived diffusible ligands (ADDLs). The CBD-mediated sequestration of Aβ monomers in soluble ADDLs could reduce neurotoxicity. This study highlights a possible role of CBD in modulating the formation of ADDL aggregates and provides insight into potentially neuroprotective properties of CBD in Alzheimer’s disease.

The role of Cannabidiol and tetrahydrocannabivarin to overcome doxorubicin resistance in MDA-MB-231 xenografts in athymic nude mice

The significant resistance to currently available chemotherapeutics makes treatment for TNBC a key clinical concern. Herein, we studied the anti-cancer potentials of synthetic cannabidiol (CBD) and Tetrahydrocannabivarin (THCV) when used alone or in combination with doxorubicin (DOX) against MDA-MB-231 resistant cells. Pre-treatment with CBD and THCV significantly increased the cytotoxicity of DOX in MDA-MB-231 2D and 3D cultures that were DOX-resistant. Transcriptomics and Proteomics studies revealed that CBD and THCV, by downregulating PD-L1, TGF-β, sp1, NLRP3, P38-MAPK, and upregulating AMPK induced apoptosis leading to improved DOX's chemosensitivity against DOX resistant MDA-MB-231 tumors in BALB/c nude mice. CBD/THCV in combination with DOX significantly inhibited H3k4 methylation and H2K5 acetylation as demonstrated by western blotting and RT-PCR. Based on these findings, CBD and THCV appear to counteract histone modifications and their subsequent effects on DOX, resulting in chemo-sensitization against MDA-MB-231 resistant cancers.

Cannabidiol Protects Striatal Neurons by Attenuating Endoplasmic Reticulum Stress.

Introduction: The aggregation of misfolded proteins in the endoplasmic reticulum (ER) is a pathological trait shared by many neurodegenerative disorders. This aggregation leads to the persistent activation of the unfolded protein response (UPR) and ultimately apoptosis as a result of ER stress. Cannabidiol (CBD) has been demonstrated to be neuroprotective in various cellular and animal models of neurodegeneration, which has been attributed to its antioxidant and anti-inflammatory properties. However, little is known about the role of CBD in the context of protein folding and ER stress. The purpose of this study was to investigate whether CBD is neuroprotective against an in vitro model of ER stress. Materials and Methods: Using different exposure models, mouse striatal STHdhQ7/Q7 cells were exposed to either the ER stress inducer thapsigargin (TG) and/or CBD. Cell viabilities assays were used to investigate the effect of CBD pre-treatment, co-treatment, and post-treatment on TG-induced cell death. Real-time quantitative polymerase chain reaction was used to measure changes in ER stress regulators and UPR genes such as glucose-regulated protein-78 (GRP78), mesencephalic astrocyte-derived neurotrophic factor (MANF), B cell lymphoma 2 (BCL-2), BCL-2 interacting mediator of cell death (BIM), and caspase-12. Results: Cell viability increased significantly when cells were pre-treated with CBD before TG exposure. An increase in the gene expression of pro-survival ER chaperone GRP78 and ER-resident neurotrophic factor MANF coincided with this effect and decreased ER-mediated pro-apoptotic markers such as BIM, and caspase-12 was observed. Conclusions: These data suggest that CBD pre-treatment is neuroprotective against TG-induced cell death. Understanding the role of ER stress in CBD-driven neuroprotection provides insight into the therapeutic potential of CBD and the role of ER dysfunction in neurodegenerative disorders.

The Role of Cannabidiol (CBD) in a Cisplatin‐Induced Model of Chronic Neuropathic Pain

Cannabinoid‐based therapies offer a safer, non‐opioid alternative for the management of chronic pain. While most studies focus on the analgesic potential of the main psychoactive component of marijuana, Δ9‐tetrahydrocannabinol, fewer studies have investigated the role of the non‐psychoactive component, cannabidiol (CBD). CBD has been purported to have analgesic, anti‐inflammatory, anticonvulsant, and anxiolytic effects. In addition to having actions at both cannabinoid receptors (CB1 and CB2), CBD has been shown to interact with both the transient receptor potential vanilloid‐1 (TRPV1) and serotonergic (5‐HT) receptors. Clinically, CBD’s lack of psychoactivity and decreased abuse liability make it an appealing pharmacotherapeutic for the management of chronic pain. Therefore, the purpose of the current study was to determine whether CBD sex‐ or dose‐dependently reverses antinociception in an acute model of thermal pain and/or mechanical allodynia in a model of cisplatin‐induced chronic neuropathic pain. Furthermore, we observed the degree to which CB1, CB2, 5‐HT, and TRPV1 receptors may be mediating these anti‐allodynic responses. Male and female wild‐type mice were assessed for either the anti‐allodynic effects of 0, 1, 3, 10, and 30 mg/kg CBD in a cisplatin‐induced model of neuropathic pain or the antinociceptive effects of 0, 1, 3, 10, 30, and 100 mg/kg CBD in a model of acute thermal (tail‐flick) pain 60 minutes following CBD administration. To determine the relative contributions of each receptor subtype in mediating the anti‐allodynic effects of CBD, male and female mice were pretreated with either: vehicle, the CB1 inverse agonist SR141716A (10 mg/kg), the CB2 antagonist SR144528 (10 mg/kg), the TRPV1 antagonist capsazepine (10 mg/kg), or the 5‐HT2 antagonist methysergide (4 mg/kg) 30 minutes prior to treatment with CBD. Mice were assessed for the effects of the pretreatment alone and in combination with CBD. CBD at a dose of 3 mg/kg was able to partially reverse cisplatin‐induced allodynia in male and female mice, while doses of 10 and 30 mg/kg resulted in nearly complete reversal. Our preliminary findings showed that the anti‐allodynic effects of 30 mg/kg CBD were completely blocked following pretreatment with SR141716A and SR144528, and partially blocked by capsazepine in both male and female mice. Interestingly, pretreatment with methysergide partially attenuated the anti‐allodynic effects of CBD in females alone. In contrast, CBD (0‐100 mg/kg) failed to induce antinociception on the tail‐flick assay. CBD did induce mild hypothermia with males showing a greater degree of CBD‐mediated hypothermia than female mice. Taken together, these findings suggest that CBD may be a more effective treatment option for the management of chronic pain. This study highlights the therapeutic potential of CBD in a model of neuropathic pain and suggests that these effects may have clinical implications for the use of cannabinoids in chronic pain management.

Cannabidiol and SARS-CoV-2 Infection.

Cannabidiol (CBD) can prevent the inflammatory response of SARS-CoV-2 spike protein in Caco-2-cells. This action is coupled with the inhibition of IL-1beta, IL-6, IL-18, and TNF-alpha, responsible for the inflammatory process during SARS-CoV-2 infection. CBD can act on the different proteins encoded by SARS-CoV-2 and as an antiviral agent to prevent the viral infection. Furthermore, recent studies have shown the possible action of CBD as an antagonist of cytokine release syndromes. In the SARS-CoV-2 pathophysiology, the angiotensin-converting enzyme 2 (ACE2) seems to be the key cell receptor for SARS-CoV-2 infection. The WNT/β-catenin pathway and PPARγ interact in an opposite manner in many diseases, including SARS-CoV-2 infection. CBD exerts its activity through the interaction with PPARγ in SARS-CoV-2 infection. Thus, we can hypothesize that CBD may counteract the inflammatory process of SARS-CoV-2 by its interactions with both ACE2 and the interplay between the WNT/β-catenin pathway and PPARγ. Vaccines are the only way to prevent COVID-19, but it appears important to find therapeutic complements to treat patients already affected by SARS-CoV-2 infection. The possible role of CBD should be investigated by clinical trials to show its effectiveness.

Role of Cannabidiol and Tetrahydrocannabivarin on Paclitaxel-induced neuropathic pain in rodents

The purpose of this study was to evaluate if phytocannabinoids, synthetic cannabidiol (CBD), and tetrahydrocannabivarin (THCV), and their combination, could protect mice from Paclitaxel-induced peripheral neuropathy (PIPN). Six groups of C57BL/6J mice (n = 6) were used in this study. The mice were given paclitaxel (PTX) (8 mg/kg/day, i.p.) on days 1, 3, 5, and 7 to induce neuropathy. Mice were evaluated for behavioral parameters, and dorsal root ganglions (DRG) were collected from the animals and subjected to RNA sequencing and westernblot analysis at the end of the study. On cultured DRGs derived from adult male rats, immunocytochemistry and mitochondrial functional assays were also performed. When compared to individual treatments, the combination of CBD and THCV improved thermal and mechanical neurobehavioral symptoms in mice by twofold. Targets for CBD and THCV therapy were identified by KEGG (RNA sequencing). PTX reduced the expression of p-AMPK, SIRT1, NRF2, HO1, SOD2, and catalase while increasing the expression of PI3K, p-AKT, p-P38 MAP kinase, BAX, TGF-β, NLRP3 inflammasome, and caspase 3 in DRG homogenates of mice. Combination therapy outperformed monotherapy in reversing these protein expressions. The addition of CBD and THCV to DRG primary cultures reduced mitochondrial superoxides while increasing mitochondrial membrane potentials. WAY100135 and rimonabant altered the neuroprotective effects of CBD and THCV respectively by blocking 5-HT1A and CB1 receptors in mice and DRG primary cultures. The entourage effect of CBD and THCV against PIPN appears to protect neurons in mice via 5HT1A and CB1 receptors respectively.

Cannabidiol (CBD) for relief from pain, anxiety, and epilepsy: A review

Cannabis or marijuana (Cannabis sativa) contains more than one hundred chemical compounds. Of these, tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most common chemicals. THC is the chemical that gives a “high” and has various psychoactive characteristics. Cannabidiol, on the other hand, has no intoxicating qualities yet provides all the medical benefits, such as relief from anxiety, depression, insomnia, cancer, neuropathic pain, epilepsy, acute respiratory distress syndrome, Parkinson’s disease, Alzheimer’s disease, etc. In the present article, CBD oil extraction techniques, the mechanism of action of cannabinoids, and the role of CBD in relief from pain, anxiety, depression, and epilepsy have been reviewed.

Role of Cannabidiol and Tetrahydrocannabivarin on Paclitaxel-Induced Neuropathic Pain in Rodents

Role of Cannabidiol and Tetrahydrocannabivarin on Paclitaxel-Induced Neuropathic Pain in Rodents

Cannabidiol Attenuates MK-801-Induced Cognitive Symptoms of Schizophrenia in the Passive Avoidance Test in Mice.

Schizophrenia is a chronic mental disorder that disturbs feelings and behavior. The symptoms of schizophrenia fall into three categories: positive, negative, and cognitive. Cognitive symptoms are characterized by memory loss or attentional deficits, and are especially difficult to treat. Thus, there is intense research into the development of new treatments for schizophrenia-related responses. One of the possible strategies is connected with cannabidiol (CBD), a cannabinoid compound. This research focuses on the role of CBD in different stages of memory (acquisition, consolidation, retrieval) connected with fear conditioning in the passive avoidance (PA) learning task in mice, as well as in the memory impairment typical of cognitive symptoms of schizophrenia. Memory impairment was provoked by an acute injection of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (animal model of schizophrenia). Our results revealed that an acute injection of CBD (30 mg/kg; intraperitoneally (i.p.) improved all phases of long-term fear memory in the PA test in mice. Moreover, the acute injection of non-effective doses of CBD (1 or 5 mg/kg; i.p.) attenuated the memory impairment provoked by MK-801 (0.6 mg/kg; i.p.) in the consolidation and retrieval stages of fear memory, but not in the acquisition of memory. The present findings confirm that CBD has a positive influence on memory and learning processes in mice, and reveals that this cannabinoid compound is able to attenuate memory impairment connected with hypofunction of glutamate transmission in a murine model of schizophrenia.

A Research Domain Criteria Approach to Gambling Disorder and Behavioral Addictions: Decision-Making, Response Inhibition, and the Role of Cannabidiol.

Gambling Disorder (GD) has been recently re-classified in the DSM-5 under the “substance-related and addictive disorders,” in light of its genetic, endophenotypic, and phenotypic resemblances to substance dependence. Diminished control is a core defining concept of psychoactive substance dependence or addiction and has given rise to the concept of “behavioral” addictions, which are syndromes analogous to substance addiction, but with a behavioral focus other than ingestion of a psychoactive substance. The main symptom clusters are represented by loss of control, craving/withdrawal, and neglect of other areas of life, whereas in a Research Domain Criteria (RDoC) perspective, GD patients exhibit deficits in the domain of “Positive valence systems,” particularly in the “Approach motivation” and “Reward learning” constructs, as well as in the “Cognitive systems,” primarily in the “Cognitive control” construct. In the Addictions Neuroclinical Assessment (ANA), three relevant domains for addictions emerge: “Incentive salience,” “Negative Emotionality,” and “Executive Function.” The endocannabinoid system (ECS) may largely modulate these circuits, presenting a promising pharmaceutical avenue for treating addictions. Up to now, research on cannabidiol has shown some efficacy in Attention Deficit/Hyperactivity Disorder (ADHD), whereas in behavioral addictions its role has not been fully elucidated, as well as its precise action on RDoC domains. Herein, we review available evidence on RDoC domains affected in GD and behavioral addictions and summarize insights on the use of cannabidiol in those disorders and its potential mechanisms of action on reward, decisional, and sensorimotor processes.

The Role of Cannabidiol in Neurological Disorders.

Cannabis has been used for both recreational and medicinal purposes for more than 4 millennia. Cannabis has been studied in various medical disorders including neurological disorders. There are well-known risks of long-term use of cannabis, including low motivation, lowered cognitive capabilities, and diminished IQ and brain mass. Cannabinoids are compounds in cannabis that are known to have therapeutic potential. The most abundant chemicals in cannabinoids are delta-9-tetrahydrocannabinol and cannabidiol. Delta-9-tetrahydrocannabinol has psychotropic effects that limits its use as a pharmacotherapeutic agent. Cannabidiol is a nonpsychotropic chemical and therefore has become a compound of interest for clinical researchers to study its therapeutic potential. This article reviews the efficacy and safety of cannabidiol in various neurological disorders in humans.