Mechanism of interferon induction by cannabidiol (CBD) and analogues in lung cancer cells

CBD, an FDA approved drug for epilepsy, may have therapeutic potential for other diseases and is currently being tested for efficacy in cancer-related clinical trials. As the literature about CBD, especially in vitro reports, is often contradictory, increasing our understanding of its specific action on a molecular level will allow to determine whether CBD can become a useful therapy or exacerbates specific cancers in a context-dependent manner. Due to its relative lipophilicity, CBD is challenging to dispense at therapeutic concentrations;therefore, one goal is to identify cannabinoid congeners with greater efficacy and reduced drug delivery challenges. We recently showed that CBD activates interferons as a mechanism of inhibiting SARS-CoV-2 replication in lung carcinoma cells. As factors produced by the innate immune system, interferons have been implicated in both pro-survival and growth arrest and apoptosis signaling in cancer. Here we show that CBD induces interferon production and interferon stimulated genes (ISGs) through a mechanism involving NRF2 and MAVS in lung carcinoma cells. We also show that CBDV, which differs from CBD by 2 fewer aliphatic tail carbons, has limited potency, suggesting that CBD specifically interacts with one or more cellular proteins rather than having a non-specific effect. We also identified other CBD-related cannabinoids that are more effective at inducing ISGs. Taken together, these results characterize a novel mechanism by which CBD activates the innate immune system in lung cancer cells and identify related cannabinoids that have possible therapeutic potential in cancer treatment.

A descriptive study of older medical cannabis users in medical cannabis clinics

Introduction: There is a dearth of information on older users (65+ years) of medical cannabis, who may face unique challenges due to altered metabolism with aging, concurrent medication use, and risk of adverse effects. This observational study aimed to describe a large cohort of older medical cannabis users in Canada. Method(s): From Oct 2014 to Oct 2020, a commercial medical cannabis provider based in Canada collected anonymized data for research purposes from patient volunteers. Data included demographic, social, and health details (at intake) and cannabis products, self-perceived changes in symptoms and change in medications (at follow-up, variable duration). Cannabis products were categorized as cannabidiol (CBD) only, tetrahydocannabinol (THC) only or mixed CBD/THC. Of the mixed, formulations could be in 1:1 ratios (CBD+/THC+), predominantly CBD (CBD+/THC-) or predominantly THC (CBD-/THC+). Result(s): In total, 9766 subjects in the older cohort (65+ years old) completed the entire questionnaire (mean age (SD) = 73.6 (6.8) y, 60% female). They represented 23.1% of the total dataset (N = 42,267, mean (SD) =51.5 (16.8) y). The proportion of adults in the older cohort tended to increase over time (pre-2018: 17.6%;2018: 26.7%;2019: 31.2%;2020: 22.7%, when the overall intake decreased from 8869 to 5644). Among the older cohort, 15.5% were previous cannabis users and 67.7% were referred for chronic pain (mainly arthritis, chronic pain, lower back pain). Concomitant analgesic use was common (over-the-counter analgesics: 44.5%;opioids: 28.3%;NSAIDs: 24.5%). 7.9% of the sample (compared to 19.9% in the whole sample) were referred for psychiatric disorders, though 21.4% indicated antidepressant use and 12.3% indicated benzodiazepine use. Another 7% were referred for neurological disorders. Follow-up data were captured in visits (11,992) from 4698 older patients, averaging 2.5 visits per patient. The type of medical cannabis used changed over time, with increasing use of cannabis oil compared to herbal cannabis. In 2020, of 2478 visits, 78.9% use was cannabis oil and 6.7% was herbal forms (pre-2018: 57.6% vs 36.2%). The composition of cannabis oil demonstrated a preference for cannabinoid oil (CBD+) over tetrahydrocannabinol (THC+) in 6043 visits: 45.2% were using CBD+ preparations, only 3.2% were using THC+ preparations, and for CBD/THC combinations, CBD predominated (CBD+/THC-: 30.5%;CBD+/THC+: 16.8%;CBD-/THC+: 4.3%). Adverse-effects (7062 visits) included dry mouth (15.8%), drowsiness (8.6%), dizziness (4%) and hallucinations (0.6%). Patients reported improved pain, sleep and mood over time, though 15-20% reported no improvement or worsening. Medication use was mostly unchanged, though 40% of opioid users reported requiring reduced dosages. Conclusion(s): These data were drawn from a large convenience sample. The data suggest an increasing proportion of older users of medical cannabis, though COVID-19 may have affected recent use. Female users comprised a higher proportion, and cannabis oil containing CBD was preferred. Systematic studies of effectiveness and safety in older users of cannabinoids are needed given its increasing use. Funding(s): No funding was received for this work.Copyright © 2021

Current Evidence of Cannabidiol's Potential as an Anxiolytic Agent

This article will summarize the current knowledge and scientific evidence regarding cannabidiol as a possible pharmacological tool for anxiety disorders. Although the use of this substance in medical practice is gaining momentum, gaps can still be found in the current knowledge regarding its molecular targets, drug-to-drug interactions, efficacy in different populations, adequate dosage, duration of treatment, and correct formulation. Moreover, current evidence is still preliminary, lacking robust, blinded, and placebo-controlled clinical trials in many areas of investigation. After reading this article, readers should have a thorough understanding of the current scientific evidence regarding the use of CBD as an anxiolytic drug. [Psychiatr Ann. 2023;53(6):242–246.]

Long COVID, Music, Blood-Brain Barrier, and Nanomedicines

At the beginning of the first COVID-19 wave, it was believed that the life of the patients who had safely survived pulmonary complications caused by SARS-CoV-2 would soon return to normal. Today, we know that this is not for all patients the case. Unfortunately, for many patients, COVID-19 changed into Long COVID – not a life-threatening condition such as the short period of the infection with the coronavirus but with the potential to considerably reduce the quality of life. Notably, Long COVID manifests itself in major pathological alteration in the brain, besides other organs. It is unclear whether the alterations in the brain are reversible. Alterations include but are not limited to cognitive impairment and substantial reduction of grey matter. These clinical findings represent an urgent challenge for the design of nanomedicines targeting the brain and the mode of their application. The challenge comprises a third aspect, which is of physical nature and is the key to a revolution in nanomedicine: the blood-brain barrier (BBB). Even if a nanomedicine is effective in vitro, it remains therapeutically useless if it cannot cross the BBB, which safeguards that neither pathogens nor nanoparticles enter the best-protected organ in our body. Here, we present a theoretical model and discuss experimental results, which coherently indicate that it is possible to transiently open the BBB by its mechanical excitation and/or via chemical modification induced by music. © 2022, Andover House, Inc.. All rights reserved.

Cannabidiol As a Treatment for COVID-19 Symptoms? A Critical Review.

Background: Severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 has caused >211 million infections and >5.5 million deaths within 24 months globally (WHO). Internationally, a debate emerged about potential benefits of cannabidiol (CBD) as treatment of corona virus disease-19 (COVID-19). Objective: To assess the effects of CBD in the treatment of COVID-19-related inflammatory symptoms from the literature. Methods: We searched Cochrane COVID-19 study register, CENTRAL (PubMed, Embase, CINAHL, ClinicalTrials.gov, and the WHO's International Clinical Trials Registry Platform), for studies testing CBD as inflammation intervention. All types of studies and populations were considered. All pre-clinical, clinical, and pharmacological outcomes were of interest. Results: Of 18 articles found, 9 were included: 5 in vivo animal studies, 3 in vitro human tissue studies and, 1 randomized clinical trial. Outcomes in four in vivo animal studies and three human tissue studies were immune response markers, which decreased. One in vivo study showed enhancement of monocytes. One human study did not show group differences in COVID-19 evolution. There was no information on adverse effects or drug interaction. Conclusion: There is not enough evidence to support or refute CBD as a repurpose drug to treat inflammation and other symptoms of COVID-19. Clinical trials are needed to test its efficacy and adverse effects.

The therapeutic potential of purified cannabidiol.

The use of cannabidiol (CBD) for therapeutic purposes is receiving considerable attention, with speculation that CBD can be useful in a wide range of conditions. Only one product, a purified form of plant-derived CBD in solution (Epidiolex), is approved for the treatment of seizures in patients with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex. Appraisal of the therapeutic evidence base for CBD is complicated by the fact that CBD products sometimes have additional phytochemicals (like tetrahydrocannabinol (THC)) present, which can make the identification of the active pharmaceutical ingredient (API) in positive studies difficult. The aim of the present review is to critically review clinical studies using purified CBD products only, in order to establish the upcoming indications for which purified CBD might be beneficial. The areas in which there is the most clinical evidence to support the use of CBD are in the treatment of anxiety (positive data in 7 uncontrolled studies and 17 randomised controlled trials (RCTs)), psychosis and schizophrenia (positive data in 1 uncontrolled study and 8 RCTs), PTSD (positive data in 2 uncontrolled studies and 4 RCTs) and substance abuse (positive data in 2 uncontrolled studies and 3 RCTs). Seven uncontrolled studies support the use of CBD to improve sleep quality, but this has only been verified in one small RCT. Limited evidence supports the use of CBD for the treatment of Parkinson's (3 positive uncontrolled studies and 2 positive RCTs), autism (3 positive RCTs), smoking cessation (2 positive RCTs), graft-versus-host disease and intestinal permeability (1 positive RCT each). Current RCT evidence does not support the use of purified oral CBD in pain (at least as an acute analgesic) or for the treatment of COVID symptoms, cancer, Huntington's or type 2 diabetes. In conclusion, published clinical evidence does support the use of purified CBD in multiple indications beyond epilepsy. However, the evidence base is limited by the number of trials only investigating the acute effects of CBD, testing CBD in healthy volunteers, or in very small patient numbers. Large confirmatory phase 3 trials are required in all indications.

CBD Treatment Improves Fatal Inflammatory Response Exhibited in SEB-Induced ARDS

The novel SARS-CoV-2 virus known to cause the COVID-19 outbreak has resulted in a global healthcare crisis that has persisted the past 3 years. Thus, understanding the mechanisms underlying this disease are vital at this time. While there are issues of research infrastructure to handle the virus and because of the refractoriness of rodents to this disease, the availability of these tools is still limited. The cytokine storm and fatality presented in patients with severe COVID-19 can be mimicked with Staphylococcal enterotoxin B (SEB)-induced Acute Respiratory Distress Syndrome (ARDS). Within ~7 days, the survival rate drops to 0% for C3H/HeJ mice exposed to a dual dose of SEB. In this study, we administered cannabidiol (CBD) intraperitoneally for 3 days pre- and post-SEB dosing and found that the clinical outcomes improved significantly. Initial evaluation of scRNASeq data from lungs comparing naive to SEB-induced ARDS mice illustrated an increase in infiltrating immune cells, and a loss in pulmonary epithelial cells in the latter group. When evaluating the effect of CBD treatment on SEB-induced ARDS, we were able to demonstrate that CBD reduced the macrophage population. To characterize the mechanism by which CBD treatment ameliorated the inflammatory response, we found that CBD treated mice had significant reduction in infiltrating immune cells and alveolar thickening. This same histology and infiltration is presented in ARDS. MicroRNA expression analysis showed a significant increase in the expression mmu-miR-298-5p and mmu-miR- 566 with CBD treatment. Ingenuity Pathway Analysis (IPA) indicated that the dysregulated miRNAs were also implicated in pathways associated with macrophage activation, respiratory disease and inflammation, interferon stimulated genes, as well as genes which have been upregulated in the disease state of this model. These targets include but are not limited to Cebpb, Efhd2, Stat3, Socs3, Cxcl5, Gbp2, and Birc3. This finding offers insights for the development of preventive and therapeutic strategies in the treatment of ARDS, including that induced in COVID-19. Supported by NIH grants P01AT003961, P20GM103641, R01ES003961, R01AI129788, R01AI123947, R01AI160896 to MN and PSN and K99GM147910 to KW.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Aqueous cannabidiol ß-cyclodextrin complexed polymeric micelle nasal spray to attenuate in vitro and ex vivo SARS-CoV-2-induced cytokine storms.

Cannabidiol (CBD) has a number of biological effects by acting on the cannabinoid receptors CB1 and CB2. CBD may be involved in anti-inflammatory processes via CB1 and CB2 receptors, resulting in a decrease of pro-inflammatory cytokines. However, CBD's poor aqueous solubility is a major issue in pharmaceutical applications. The aim of the present study was to develop and evaluate a CBD nasal spray solution. A water-soluble CBD was prepared by complexation with ß-cyclodextrin (ß-CD) at a stoichiometric ratio of 1:1 and forming polymeric micelles using poloxamer 407. The mixture was then lyophilized and characterized using FT-IR, DSC, and TGA. CBD-ß-CD complex-polymeric micelles were formulated for nasal spray drug delivery. The physicochemical properties of the CBD-ß-CD complex-polymeric micelle nasal spray solution (CBD-ß-CDPM-NS) were assessed. The results showed that the CBD content in the CBD-ß-CD complex polymeric micelle powder was 102.1 ± 0.5% labeled claim. The CBD-ß-CDPM-NS was a clear colorless isotonic solution. The particle size, zeta potential, pH value, and viscosity were 111.9 ± 0.7 nm, 0.8 ± 0.1 mV, 6.02 ± 0.02, and 12.04 ± 2.64 cP, respectively. This formulation was stable over six months at ambient temperature. The CBD from CBD-ß-CDPM-NS rapidly released to 100% within 1 min. Ex vivo permeation studies of CBD-ß-CDPM-NS through porcine nasal mucosa revealed a permeation rate of 4.8 µg/cm2/min, which indicated that CBD was effective in penetrating nasal epithelial cells. CBD-ß-CDPM-NS was tested for its efficacy and safety in terms of cytokine production from nasal immune cells and toxicity to nasal epithelial cells. The CBD-ß-CDPM-NS was not toxic to nasal epithelial at the concentration of CBD equivalent to 3.125-50 µg/mL. When the formulation was subjected to bioactivity testing against monocyte-like macrophage cells, it proved that the CBD-ß-CDPM-NS has the potential to inhibit inflammatory cytokines. CBD-ß-CDPM-NS demonstrated the formulation's ability to reduce the cytokine produced by S-RBD stimulation in ex vivo porcine nasal mucosa in both preventative and therapeutic modes.

Tocilizumab-coated solid lipid nanoparticles loaded with cannabidiol as a novel drug delivery strategy for treating COVID-19: A review.

Commonly used clinical strategies against coronavirus disease 19 (COVID-19), including the potential role of monoclonal antibodies for site-specific targeted drug delivery, are discussed here. Solid lipid nanoparticles (SLN) tailored with tocilizumab (TCZ) and loading cannabidiol (CBD) are proposed for the treatment of COVID-19 by oral route. TCZ, as a humanized IgG1 monoclonal antibody and an interleukin-6 (IL-6) receptor agonist, can attenuate cytokine storm in patients infected with SARS-CoV-2. CBD (an anti-inflammatory cannabinoid and TCZ agonist) alleviates anxiety, schizophrenia, and depression. CBD, obtained from Cannabis sativa L., is known to modulate gene expression and inflammation and also shows anti-cancer and anti-inflammatory properties. It has also been recognized to modulate angiotensin-converting enzyme II (ACE2) expression in SARS-CoV-2 target tissues. It has already been proven that immunosuppressive drugs targeting the IL-6 receptor may ameliorate lethal inflammatory responses in COVID-19 patients. TCZ, as an immunosuppressive drug, is mainly used to treat rheumatoid arthritis, although several attempts have been made to use it in the active hyperinflammatory phase of COVID-19, with promising outcomes. TCZ is currently administered intravenously. It this review, we discuss the potential advances on the use of SLN for oral administration of TCZ-tailored CBD-loaded SLN, as an innovative platform for managing SARS-CoV-2 and related infections.

Can Cannabinoids Suppress the Cytokines Cascade in Patients with Coronavirus Disease COVID-19? A Mini-Review

Coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, started in Wuhan, China in December 2019 and became a global pandemic. According to WHO, more than fourteen million cases were reported and thousands of casualties worldwide (until July 18, 2020). Most of the COVID-19 patients have symptoms such as fever, tiredness, and dry cough. Some people may also experience body aches, nasal congestion, a runny nose, and diarrhea. So far, doctors have been using treatment to relieve symptoms and give patients' immune systems time to regain control of this virus. Many studies have high-lighted the important role of cytokine cascades in the death rate in COVID-19 patients. Therefore, inhibi-tion of this phenomenon has become a very important target in the clinical management of this disease. With this idea, in this mini-review, we will focus on the potential role of cannabinoids in the suppression of cytokines cascades in patients with COVID-19 and their importance in the clinical management of this disease.Copyright © 2021 Bentham Science Publishers.

Exploring young adults' e-cigarette use behavior during COVID-19.

INTRODUCTION: Changes in daily life related to COVID-19 have impacted e-cigarette use, particularly in young adults. This cross-sectional mixed-methods study explored young adults' perceptions regarding how COVID-19 influenced their e-cigarette use. METHODS: We analyzed Fall 2020 survey data from 726 past 6-month e-cigarette users (mean age=24.15 years, 51.1% female, 35.5% sexual minority, 4.4% Black, 10.2% Asian, 12.1% Hispanic) and Spring 2021 semi-structured interview data among a subset of 40 participants (mean age=26.30 years, 35.0% female, 45.0% sexual minority, 5.0% Black, 22.5% Asian, 12.5% Hispanic). Participants were drawn from 6 metropolitan statistical areas with varied tobacco and cannabis legislative contexts. RESULTS: Among survey participants, 44.4% also smoked cigarettes, 54.0% other tobacco products, and 60.1% used cannabis. They reported various changes in their daily lives, including changes in the nature and/or status of employment (e.g. 15.3% were laid off, 72.8% experienced household income loss). Regarding changes in e-cigarette use since COVID-19, 22.6% tried to cut down and 16.0% tried to quit. Interview participants commonly indicated that they increased their use due to stress, boredom, changes in accessibility, and/or changes to daily environment that made e-cigarette use more feasible. CONCLUSIONS: Results highlight the importance of promoting opportunities for young adults to build relationships to decrease stress, foster a sense of belonging, and increase quality of life (e.g. increasing the accessibility to mental health and social support services, intentionally engaging young adults in pandemic-appropriate community-building and extracurricular activities). This research may help to inform future e-cigarette cessation interventions that consider the unique challenges of societal stressors, such as pandemics.

Detecting Tweets Containing Cannabidiol-Related COVID-19 Misinformation Using Transformer Language Models and Warning Letters From Food and Drug Administration: Content Analysis and Identification.

Background: COVID-19 has introduced yet another opportunity to web-based sellers of loosely regulated substances, such as cannabidiol (CBD), to promote sales under false pretenses of curing the disease. Therefore, it has become necessary to innovate ways to identify such instances of misinformation. Objective: We sought to identify COVID-19 misinformation as it relates to the sales or promotion of CBD and used transformer-based language models to identify tweets semantically similar to quotes taken from known instances of misinformation. In this case, the known misinformation was the publicly available Warning Letters from Food and Drug Administration (FDA). Methods: We collected tweets using CBD- and COVID-19-related terms. Using a previously trained model, we extracted the tweets indicating commercialization and sales of CBD and annotated those containing COVID-19 misinformation according to the FDA definitions. We encoded the collection of tweets and misinformation quotes into sentence vectors and then calculated the cosine similarity between each quote and each tweet. This allowed us to establish a threshold to identify tweets that were making false claims regarding CBD and COVID-19 while minimizing the instances of false positives. Results: We demonstrated that by using quotes taken from Warning Letters issued by FDA to perpetrators of similar misinformation, we can identify semantically similar tweets that also contain misinformation. This was accomplished by identifying a cosine distance threshold between the sentence vectors of the Warning Letters and tweets. Conclusions: This research shows that commercial CBD or COVID-19 misinformation can potentially be identified and curbed using transformer-based language models and known prior instances of misinformation. Our approach functions without the need for labeled data, potentially reducing the time at which misinformation can be identified. Our approach shows promise in that it is easily adapted to identify other forms of misinformation related to loosely regulated substances.

Effects of Cannabidiol on Innate Immunity: Experimental Evidence and Clinical Relevance.

Cannabidiol (CBD) is the main non-psychotropic cannabinoid derived from cannabis (Cannabis sativa L., fam. Cannabaceae). CBD has received approval by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome. However, CBD also has prominent anti-inflammatory and immunomodulatory effects; evidence exists that it could be beneficial in chronic inflammation, and even in acute inflammatory conditions, such as those due to SARS-CoV-2 infection. In this work, we review available evidence concerning CBD's effects on the modulation of innate immunity. Despite the lack so far of clinical studies, extensive preclinical evidence in different models, including mice, rats, guinea pigs, and even ex vivo experiments on cells from human healthy subjects, shows that CBD exerts a wide range of inhibitory effects by decreasing cytokine production and tissue infiltration, and acting on a variety of other inflammation-related functions in several innate immune cells. Clinical studies are now warranted to establish the therapeutic role of CBD in diseases with a strong inflammatory component, such as multiple sclerosis and other autoimmune diseases, cancer, asthma, and cardiovascular diseases.

Cannabinoids as Immune System Modulators: Cannabidiol Potential Therapeutic Approaches and Limitations.

Introduction: Cannabidiol (CBD) is the second most abundant Phytocannabinoid in Cannabis extracts. CBD has a binding affinity for several cannabinoid and cannabinoid-associated receptors. Epidiolex (oral CBD solution) has been lately licensed by the Food and Drug Administration (FDA) for the treatment of pediatric epileptic seizures. Methods: In this review, we discussed the most promising applications of CBD for chronic inflammatory conditions, namely CBD's anti-inflammatory effects during inflammatory bowel disease, coronavirus disease (antiviral effect), brain pathologies (neuroprotective and anti-inflammatory properties), as well as CBD immunomodulatory and antitumoral activities in the tumor microenvironment. Special focus was shed on the main therapeutic mechanisms of action of CBD, particularly in the control of the immune system and the endocannabinoid system. Results: Findings suggest that CBD is a potent immunomodulatory drug as it has manifested immunosuppressive properties in the context of sterile inflammation (e.g., inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative diseases), and immunoprotective effects during viral infections (e.g. COVID-19) Similarly, CBD has exhibited a selective response toward cancer types by engaging different targets and signaling pathways. These results are in favor of the primary function of the endocannabinoid system which is homeostatic maintenance. Conclusion: The presented evidence suggests that the endocannabinoid system is a prominent target for the treatment of inflammatory and autoimmune diseases, rheumatoid diseases, viral infections, neurological and psychological pathologies, and cancer. Moreover, the antitumoral activities of CBD have been suggested to be potentially used in combination with chemo- or immunotherapy during cancer. However, clinical results are still lacking, which raises a challenge to apply translational cannabis research to the human immune system.

Analyzing the Perspectives of Health Professionals and Legal Cannabis Users on the Treatment of Chronic Pain With Cannabidiol: Protocol for a Scoping Review.

BACKGROUND: Medical cannabis is one of the most commonly reported treatments for chronic pain. The wide acceptance and research in alternative medicine have put medical cannabis in the limelight, where researchers are widely examining its therapeutic benefits, including treatment of chronic pain. OBJECTIVE: The purpose of this scoping review is to provide an overview of the perspectives on cannabidiol as an alternative treatment for chronic pain among health professionals and legal cannabis users. METHODS: The framework of Arksey and O'Malley guides the design of this scoping review, and the elements reported use the recommended guidelines of the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews). A comprehensive literature search accessed the databases CINAHL Complete and MEDLINE via EBSCO, Australia/New Zealand Reference Centre, PsycINFO, Ovid Emcare, Wiley Online Library, Scopus, Informit New Zealand Collection, and Google Scholar for published literature, and then it was extended to include gray literature. Gray literature searches included searching the databases Australia/New Zealand Reference Centre, Informit New Zealand Collection, INNZ: Index New Zealand, ProQuest Dissertations & Theses Global, and AUT Tuwhera Research Repository, and the website nzresearch.org.nz. The studies included in this scoping review were assessed for eligibility for inclusion using the following criteria: published in English after 2000, conducted in New Zealand (NZ) or Australia, and aimed to investigate the perspectives of health professionals and medical cannabis users using interviews for data collection. Studies were screened for inclusion using Covidence, a software tool to filter search results, and the risk of bias was assessed using the Critical Appraisal Skills Programme tool. Although this is not a required step for scoping reviews, it added an element of strength to this scoping review. Data will be analyzed using thematic analysis guided by Braun and Clarke. The findings from the data analysis will be presented in a table, which will then inform the key themes for discussion. RESULTS: The database search started in October 2021 and was completed in December 2021. The total number of studies included in this review is 5 (n=5). Studies included were conducted in NZ or Australia and examined the perspectives using participant interviews. This scoping review is anticipated to be submitted for publication in December 2022. CONCLUSIONS: Using perspectives is a valuable tool to understand the challenges experienced by health professionals and medical cannabis users associated with medical cannabis treatment. Addressing these challenges through interventions that are highlighted through perspectives such as educating health professionals to increase access to medical cannabis in NZ may aid in policy reformulation for medical cannabis in the context of NZ. Thus, this scoping review highlights the importance of medical cannabis research and suggests recommendations to guide and inform medical cannabis policy in the context of NZ. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37697.

Parent and Caregiver Perspectives towards Cannabidiol as a Treatment for Fragile X Syndrome.

Cannabidiol (CBD) is a non-intoxicating chemical in cannabis plants that is being investigated as a candidate for treatment in Fragile X Syndrome (FXS), a leading known cause of inherited intellectual developmental disability. Studies have shown that CBD can reduce symptoms such as anxiety, social avoidance, hyperactivity, aggression, and sleep problems. This is a qualitative study that utilized a voluntary-anonymous survey that consisted of questions regarding demographics, medical information, the form, type, brand, dose, and frequency of CBD use, the rationale for use, the perception of effects, side effects, and costs. The full survey contained a total of 34 questions, including multiple-choice, Likert-scale, and optional free-response questions. This research revealed that there are a wide range of types, brands, and doses of CBD being administered to individuals with FXS by their parents and caregivers. There were many reasons why CBD was chosen, the most common ones being that respondents had heard positive things about CBD from members of the community, the perception that CBD had fewer side effects than other medications, and because respondents felt that CBD was a more natural substance. Most of the parents and caregivers who responded agreed that CBD improved some of the symptoms of FXS and made a positive difference overall. CBD has the therapeutic potential to help relieve some FXS symptoms. Future research is necessary to understand the benefits of CBD in FXS.

An Overview of Legal Issues and Regulations Affecting CBD-Based Franchise Systems

[...]in Oregon and Florida, consumers can purchase CBD in their coffee.2 Following declassification of hemp as a Schedule I drug, a recent Gallup poll found that one in seven Americans use hemp-derived CBD products (although CBD derived from marijuana is still illegal under federal law and will not be addressed here). "3 CBD products are available at a variety of mainstream retailers including CVS, Walgreens, GNC, Kroger, Ulta Beauty, Abercrombie & Fitch, and American Eagle Outfitters.4 Industry research firms estimate that by 2024, CBD sales will exceed twenty billion dollars in the United States.5 Another study projects a twenty-five percent compound annual growth rate in the CBD edible market between 2020 and 2027.6 Many consumers rely on CBD to treat anxiety, pain, and insomnia.7 Other common usages include over-the-counter treatment for depression, muscle contractions, skin conditions, and digestive concerns.8 A third of pet owners have purchased CBD-infused treats, food, or other items for their cats and dogs, and purchases of CBD pet products are rapidly increasing as pet owners begin to return to the office following the nationwide lifting of COVID-19 restrictions.9 Considering this clear market demand and the likelihood that states will continue to ease restrictions on sale of CBD and other hemp-derived related products, franchisors may find entering the CBD market an irresistible opportunity-either through creating a new franchised system that primarily sells CBD products or by adding them as a new or additional product line in an existing system. [...]Section IV addresses many of the unique challenges associated with franchises selling CBD and proposes best practices for both franchisors and franchisees. "25 Guy believed a cannabis product with low levels of THC but high levels of CBD would be appealing for these users.26 By the late 1990s, several Northern California cannabis growers were cultivating high CBD/low THC strains and distributing both the seeds and their research about its effects at marijuana shops and fairs on the West Coast.27 In 2010, a group of medical marijuana researchers and cannabis growers founded Project CBD, a nonprofit corporation with the goal of collecting and promoting medical research regarding the benefits of CBD.28 In August 2013, CNN aired Dr. Sanjay Gupta's documentary Weed, which contained a segment describing the successful use of a CBD oil developed by the Stanley Brothers, called "Charlotte's Web," to reduce seizures in fiveyear old Charlotte Figi.29 After the segment, the wait list for the oil grew to 15,000 people, families moved to Colorado with the hope of using the oil, and the Food and Drug Administration fast-tracked trials of GW Pharmaceutical's CBD-based medication, Epidiolex.30 Popular culture acceptance and demand for CBD has continued to increase in the last decade.

Cannabidiol as a personalized treatment for anxiety: clinical cases in Mexico.

Anxiety-related disorders are one of the most common mental health issues worldwide. Mexico has reported an increase in the prevalence of these ailments secondary to the confinement derived from the COVID-19 pandemic. Given the limitations of commonly used treatments for these disorders, a need arises to develop new pharmacological treatments for these patients. This paper has the primary objective of evaluating the efficacy and safety of cannabidiol isolate in drug compounding used as a personalized treatment in patients with anxiety disorders through the presentation of four clinical cases.

Cannabidiol Treatment for Neurological, Cognitive, and Psychiatric Symptoms in Sturge-Weber Syndrome.

BACKGROUND: A prior drug trial of cannabidiol for treatment-resistant epilepsy in patients with Sturge-Weber syndrome (SWS), a rare neurovascular condition, implicated improvements in neurological, quality of life (QOL), neuropsychologic, psychiatric, and motor outcomes. METHODS: Ten subjects with SWS brain involvement, controlled seizures, and cognitive impairments received study drug in this Johns Hopkins institutional review board-approved, open-label, prospective drug trial. Oral cannabidiol was taken for six months (dose ranged from 5 to 20 mg/kg/day). SWS neuroscore, port-wine birthmark score, QOL, and adverse events were recorded every four to 12 weeks. Neuropsychologic, psychiatric, and motor assessments were administered at baseline and six months' follow-up. Most evaluations were conducted virtually due to the coronavirus disease 2019 pandemic. RESULTS: Cannabidiol was generally well tolerated. Six subjects reported mild to moderate side effects related to study drug and continued on drug; one subject withdrew early due to moderate side effects. No seizures were reported. Significant improvements in SWS neuroscore, patient-reported QOL, anxiety and emotional regulation, and report of bimanual ability use were noted. Migraine QOL scores were high at baseline in these subjects, and remained high. Neuropsychologic and other QOL and motor outcomes remained stable, with some within-subject improvements noted. CONCLUSIONS: Further studies are needed to determine whether Epidiolex can improve quality of life and be beneficial for neurological, anxiety, and motor impairments in SWS independent of seizure control. Large multicentered studies are needed to extend these preliminary findings.