Medical Cannabis and Cannabinoids最新文献

{"title":"Chronic Pain and the Endocannabinoid System: Smart Lipids – A Novel Therapeutic Option?","authors":"W. Zieglgänsberger, R. Brenneisen, A. Berthele, C. Wotjak, B. Bandelow, T. Tölle, B. Lutz","doi":"10.1159/000522432","DOIUrl":"https://doi.org/10.1159/000522432","url":null,"abstract":"The development of a high-end cannabinoid-based therapy is the result of intense translational research, aiming to convert recent discoveries in the laboratory into better treatments for patients. Novel compounds and new regimes for drug treatment are emerging. Given that previously unreported signaling mechanisms for cannabinoids have been uncovered, clinical studies detailing their high therapeutic potential are mandatory. The advent of novel genomic, optogenetic, and viral tracing and imaging techniques will help to further detail therapeutically relevant functional and structural features. An evolutionarily highly conserved group of neuromodulatory lipids, their receptors, and anabolic and catabolic enzymes are involved in a remarkable variety of physiological and pathological processes and has been termed the endocannabinoid system (ECS). A large body of data has emerged in recent years, pointing to a crucial role of this system in the regulation of the behavioral domains of acquired fear, anxiety, and stress-coping. Besides neurons, also glia cells and components of the immune system can differentially fine-tune patterns of neuronal activity. Dysregulation of ECS signaling can lead to a lowering of stress resilience and increased incidence of psychiatric disorders. Chronic pain may be understood as a disease process evoked by fear-conditioned nociceptive input and appears as the dark side of neuronal plasticity. By taking a toll on every part of your life, this abnormal persistent memory of an aversive state can be more damaging than its initial experience. All strategies for the treatment of chronic pain conditions must consider stress-related comorbid conditions since cognitive factors such as beliefs, expectations, and prior experience (memory of pain) are key modulators of the perception of pain. The anxiolytic and anti-stress effects of medical cannabinoids can substantially modulate the efficacy and tolerability of therapeutic interventions and will help to pave the way to a successful multimodal therapy. Why some individuals are more susceptible to the effects of stress remains to be uncovered. The development of personalized prevention or treatment strategies for anxiety and depression related to chronic pain must also consider gender differences. An emotional basis of chronic pain opens a new horizon of opportunities for developing treatment strategies beyond the repeated sole use of acutely acting analgesics. A phase I trial to determine the pharmacokinetics, psychotropic effects, and safety profile of a novel nanoparticle-based cannabinoid spray for oromucosal delivery highlights a remarkable innovation in galenic technology and urges clinical studies further detailing the huge therapeutic potential of medical cannabis (Lorenzl et al.; this issue).","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"5 1","pages":"61 - 75"},"PeriodicalIF":0.0,"publicationDate":"2022-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44122802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannx Conference abstracts","authors":"","doi":"10.1159/000522395","DOIUrl":"https://doi.org/10.1159/000522395","url":null,"abstract":"All abstracts are in the attached word document<br />Med Cannabis Cannabinoids 2022;5:36–60","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":" 37","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138515458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Will Cannabis or Cannabinoids Protect You from SARS-CoV-2 Infection or Treat COVID-19?","authors":"Joshua D. Brown, A. Goodin","doi":"10.1159/000522472","DOIUrl":"https://doi.org/10.1159/000522472","url":null,"abstract":"• A recent study reported that two cannabinoids, cannabidiolic acid (CBDA) and cannabigerolic acid (CBGA), could block cellular entry of the virus that causes COVID-19 during in vitro experiments using cell cultures in a laboratory • There is a low likelihood of translating these preclinical research findings to cannabinoid-based therapies due to clinical and pragmatic concerns with dosing that render CBDA and CBGA (as well as other cannabinoids) to be unlikely candidates for further drug development. These include, for example, a short half-life of CBDA, requiring frequent dosing intervals; high doses required at each interval to match the inhibitory concentrations studied; and high cost and lack of availability of CBDA and CBGA. • Replicating the observed effects in the complex human body is unlikely due to the interplay of these compounds within the endocannabinoid system, and there are known and hypothesized safety concerns for the doses required. • Cannabinoids, including CBDA and CBGA, are not recommended for the treatment or prevention of SARS-CoV-2 infection. • Recreational or medical use of currently available cannabis-derived products are at doses much lower than those studied and are unlikely to provide any benefit against SARS-CoV-2 infection. DOI: 10.1159/000522472","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"5 1","pages":"32 - 35"},"PeriodicalIF":0.0,"publicationDate":"2022-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46945580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medicinal Cannabis for the Treatment of Chronic Refractory Pain: An Investigation of the Adverse Event Profile and Health-Related Quality of Life Impact of an Oral Formulation.","authors":"Sarah Abelev,&nbsp;Leon N Warne,&nbsp;Melissa Benson,&nbsp;Mark Hardy,&nbsp;Sunny Nayee,&nbsp;John Barlow","doi":"10.1159/000521492","DOIUrl":"https://doi.org/10.1159/000521492","url":null,"abstract":"<p><strong>Introduction: </strong>Medicinal cannabis is prescribed in Australia for patients with chronic refractory pain conditions. However, measures of safety and effectiveness of different cannabinoids are lacking. We designed an observational study to capture effectiveness, adverse events (AEs), and health-related quality of life (HRQoL) measures in patients prescribed an oral medicinal cannabis formulation at Cannabis Access Clinics through the Cannabis Access Clinics Observational study (CACOS).</p><p><strong>Objectives: </strong>We aimed to evaluate effectiveness, reported AEs, and change in patient-reported outcomes in individuals prescribed a cannabinoid oil formulation for management of chronic pain.</p><p><strong>Methods: </strong>A cross-sectional analysis was conducted on patients prescribed an oil formulation of Δ9-tetrahydrocannabinol and cannabidiol for pain symptoms of at least 3-month duration. Clinician-reported AEs were organized by system, organ, class, and frequency. Analysis of patient-reported responses to a questionnaire was conducted using published minimal clinically important differences to determine meaningful change in HRQoL over time.</p><p><strong>Results: </strong>More than half (<i>n</i> = 91/151, 60.3%) of the participants experienced at least one AE during the observation period (mean 133 ± 116 days). No serious AEs were reported. Patient-reported pain impact scores were significantly reduced across the cohort (<i>p</i> = 0.034), and pain intensity scores verged on significance (<i>p</i> = 0.053). The majority of patients saw meaningful improvements in sleep (49.3%) and fatigue (35.6%).</p><p><strong>Conclusion: </strong>This analysis presents real-world data collected as part of standard of care. More than one-third of patients benefited from oral medicinal cannabis, which is impactful given the refractory nature of their pain. Amelioration of the impact of pain confirms continued prescribing of this formulation and validates our observational methodology as a tool to determine the therapeutic potency of medicinal cannabinoids.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":" ","pages":"20-31"},"PeriodicalIF":0.0,"publicationDate":"2022-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235063/pdf/mca-0005-0020.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40617080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase I Trial to Determine the Pharmacokinetics, Psychotropic Effects, and Safety Profile of a Novel Nanoparticle-Based Cannabinoid Spray for Oromucosal Delivery","authors":"S. Lorenzl, Franz Gottwald, Angelika Nistler, Laura Brehm, Renate Grötsch, Georg Haber, Christian Bremm, Christiane Weck, Carina Trummer, Werner Brand","doi":"10.1159/000521352","DOIUrl":"https://doi.org/10.1159/000521352","url":null,"abstract":"Introduction: A phase I, open-label clinical trial in healthy male subjects was conducted to assess the pharmacokinetic and safety profile of an oromucosal cannabinoid spray (AP701) containing a lipid-based nanoparticular drug formulation standardized to ∆-9-tetrahydrocannabinol (THC). Methods: Twelve healthy male subjects received a single dose of AP701 (12 sprays) containing 3.96 mg THC. Plasma samples were drawn 10 min–30 h post dose for analysis of THC and the active metabolite 11-hydroxy-∆-9-THC (11-OH-THC). Results: The single dose of the applied oromucosal cannabinoid spray AP701 (12 sprays, 3.96 mg THC) resulted in a mean maximum plasma concentration (Cmax) of 2.23 ng/mL (90% CI 1.22–3.24) and a mean overall exposure (area under the concentration-time curve from time 0 to last measurable concentration [AUC0–t]) of 7.74 h × ng/mL (90% CI 5.03–10.45) for THC. For the active metabolite 11-OH-THC, a Cmax of 2.09 mg/mL (90% CI 1.50–2.68) and AUC0–t of 10.4 h × ng/mL (90% CI 7.03–13.77) was found. The oromucosal cannabinoid spray AP701 caused only minor psychotropic effects despite the relatively high dosage applied by healthy subjects. No serious adverse effects occurred. Overall, the oromucosal cannabinoid spray AP701 was well tolerated. Conclusion: Compared to currently available drugs on the market, higher AUC values could be detected for the oromucosal cannabinoid spray AP701 despite administration of a lower dose. These comparatively higher blood levels caused only minor psychotropic adverse effects. The oromucosal cannabinoid spray AP701 was well tolerated at a single dose of 3.96 mg THC. The oromucosal administration may provide an easily applicable and titratable drug formulation with a high safety and tolerability profile.","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"5 1","pages":"9 - 19"},"PeriodicalIF":0.0,"publicationDate":"2022-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45718044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabinoids as Cocrystals","authors":"C. N. Filer","doi":"10.1159/000521137","DOIUrl":"https://doi.org/10.1159/000521137","url":null,"abstract":"Dear Editor, The fascinating portfolio of Cannabis cannabinoids (phytocannabinoids) [1] continues to grow with new members continually added [2]. Interest in these intriguing natural products has accelerated in recent years, fueled by their potential as medicinal agents [3]. However, along with the promising pharmaceutical opportunity for cannabinoids come some challenging chemistry issues. The first concern is a common property shared by most cannabinoids, namely, their physical state as lipophilic, low melting point semisolids. This physical nature has profound implications. Since crystalline substances are usually more stable than amorphous solids, many cannabinoids have stability limitations. Acidic cannabinoids (functionalized with an aromatic carboxyl [CO2H] group) are especially prone to decarboxylation, but even neutral cannabinoids (lacking a carboxyl group) can be unstable to heat or light. With an estimated 70% of pharmaceuticals given as tablets [4], the low melting point-semisolid state of most cannabinoids has certainly complicated this convenient administration route for them. Another consequence of the cannabinoid lipophilic nature is their lack of water solubility. In fact, limited water solubility with accompanying delay of drug absorption and bioavailability has been a major problem for many candidate pharmaceuticals like the cannabinoids [5]. Finally, the large number (but smaller individual amounts) of “minor cannabinoids” as a complex mixture in the Cannabis trichomes has confounded their purification and hindered their pharmaceutical development. The purpose of this note is to highlight a recent and exciting alternative approach to these various technical challenges. Ongoing efforts by cannabinoid chemists to address these daunting obstacles have usually focused on each of them individually. However, the recent return to the 19th century chemistry of “cocrystallization” may well be able to solve some of them simultaneously. This transformative technique is significantly different from traditional crystallization. Cocrystallization involves the intermolecular noncovalent bonding of a molecule of interest (like a cannabinoid) with a companion neutral partner molecule (often termed a “coformer”), crystallizing as a stoichiometric pair in a well-defined and repeating 3-dimensional cocrystal lattice. The discovery of cocrystals is widely attributed to noted German chemist Friedrich Wohler [6] in 1844 and his preparation of quinhydrone, a cocrystal redox couple of quinone and hydroquinone. Wohler was likely unaware of his discovery’s significance and the full characterization of quinhydrone as a cocrystal (by X-ray crystal analysis) took more than a century to accomplish. Cocrystal technology with its many synthetic methods has now been eagerly embraced by the pharmaceutical sector to improve drug stability and bioavailability [7]. Interestingly, early indications that cannabinoids might","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"5 1","pages":"7 - 8"},"PeriodicalIF":0.0,"publicationDate":"2022-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48520845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabis for the Treatment of Attention Deficit Hyperactivity Disorder: A Report of 3 Cases.","authors":"Holly Mansell,&nbsp;Declan Quinn,&nbsp;Lauren E Kelly,&nbsp;Jane Alcorn","doi":"10.1159/000521370","DOIUrl":"https://doi.org/10.1159/000521370","url":null,"abstract":"<p><p>Attention deficit hyperactivity disorder (ADHD) is a chronic neurobehavioral disorder that is highly prevalent in children and adults. An increasing number of patients with ADHD are self-medicating with cannabis, despite a lack of evidence on efficacy and safety. This case report describes 3 males (ages 18, 22, and 23) who have integrated cannabis into their treatment regimen with positive results. Semistructured interviews conducted with the patients describe subjective improvements in symptoms and on quality of life. Improvements on validated rating scales conducted post-cannabis initiation, compared to pre-cannabis initiation obtained from the medical chart, corroborated their personal accounts. Scores on the PHQ-9 (measuring depression) improved by 8-22 points (30-81%), and the SCARED (measuring anxiety) ranged from 0 to 27 points (up to 33%). Improvements on the CEER-9 scale (measuring regulation) ranged from 2 to 7 points (22-78%), and the 9-item SNAP scale (measuring inattention) showed improvements of 2-8 points (7-30%). Mild adverse events including short-term memory problems, dry mouth, and sleepiness were reported. Blood samples were also collected from the patients to determine the plasma concentrations of the cannabinoids and relevant metabolites before and after a cannabis administration. After cannabis use, the plasma levels for CBD and THC ranged from 0 to 15.29 ng/mL and 1.32 to 13.76 ng/mL, respectively. Cannabinoids, however, were not detected prior to dosing, suggesting that cannabis played a complimentary role in the therapeutic regimen of these 3 patients. Clinical trials are recommended to confirm the efficacy of cannabis in the treatment of ADHD.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"5 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832253/pdf/mca-0005-0001.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10376591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.1159/000527071","DOIUrl":"https://doi.org/10.1159/000527071","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1159/000521370.].</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"5 1","pages":"128"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/06/5f/mca-0005-0128.PMC9732506.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10323623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Considerations for Cannabis Use and Cardiovascular Health.","authors":"Ruba Sajdeya,&nbsp;Sebastian Jugl,&nbsp;Robert Cook,&nbsp;Joshua D Brown,&nbsp;Amie Goodin","doi":"10.1159/000526731","DOIUrl":"https://doi.org/10.1159/000526731","url":null,"abstract":"aConsortium for Medical Marijuana Clinical Outcomes Research, University of Florida, Gainesville, FL, USA; bDepartment of Epidemiology, University of Florida, Gainesville, FL, USA; cCenter for Drug Evaluation and Safety (CoDES), Department of Pharmaceutical Outcomes & Policy, University of Florida, Gainesville, FL, USA Received: June 14, 2022 Accepted: August 13, 2022 Published online: September 28, 2022","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"5 1","pages":"120-127"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1e/0d/mca-0005-0120.PMC9710318.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9340293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Cannabis on Cardiovascular System: The Good, the Bad, and the Many Unknowns","authors":"A. E. Dabiri, G. Kassab","doi":"10.1159/000519775","DOIUrl":"https://doi.org/10.1159/000519775","url":null,"abstract":"Cannabis is currently the most consumed illicit substance in the world, and gradual legalization in the USA makes it important to understand the health consequences of the use of this substance. With growing body of evidence that some cannabis ingredients may be beneficial in various aspects of hemostasis, additional research is clearly needed in various clinical areas. In addition to understanding the efficacy, research efforts should also include studies that address any harmful effects of the compounds or administration methods that may result in adverse effects. This review is focused on the cardiometabolic effects of cannabis use. Cardiometabolic diseases are among the leading causes of death in the USA and around the world. The purpose of this review was to provide an overview of the known medicinal benefits of selected cannabis cannabinoids and the known side effects or contraindications. More importantly, we have proposed new questions and signposts in cannabis research to uncover additional medicinal benefits and identify the health hazards with focus on cardiovascular disease.","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"4 1","pages":"75 - 85"},"PeriodicalIF":0.0,"publicationDate":"2021-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45017147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}