S. Lorenzl, Franz Gottwald, Angelika Nistler, Laura Brehm, Renate Grötsch, Georg Haber, Christian Bremm, Christiane Weck, Carina Trummer, Werner Brand
{"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}
Holly Mansell, Declan Quinn, Lauren E Kelly, Jane Alcorn
{"title":"Cannabis for the Treatment of Attention Deficit Hyperactivity Disorder: A Report of 3 Cases.","authors":"Holly Mansell, Declan Quinn, Lauren E Kelly, 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}
Ruba Sajdeya, Sebastian Jugl, Robert Cook, Joshua D Brown, Amie Goodin
{"title":"Clinical Considerations for Cannabis Use and Cardiovascular Health.","authors":"Ruba Sajdeya, Sebastian Jugl, Robert Cook, Joshua D Brown, 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}
{"title":"Abstracts of the 2021 Cannabis Clinical Outcomes Research Conference","authors":"","doi":"10.1159/000519038","DOIUrl":"https://doi.org/10.1159/000519038","url":null,"abstract":"","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"4 1","pages":"125 - 142"},"PeriodicalIF":0.0,"publicationDate":"2021-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46152769","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}
A. Goodin, Debbie L. Wilson, Robert L. Cook, Yan Wang, Joshua D. Brown, A. Winterstein
{"title":"Proceedings of the 2021 Cannabis Clinical Outcomes Research Conference","authors":"A. Goodin, Debbie L. Wilson, Robert L. Cook, Yan Wang, Joshua D. Brown, A. Winterstein","doi":"10.1159/000519037","DOIUrl":"https://doi.org/10.1159/000519037","url":null,"abstract":"The Cannabis Clinical Outcomes Research Conference (CCORC) 2021 was held virtually on April 8 and 9, 2021. The conference was hosted by the Consortium for Medical Marijuana Clinical Outcomes Research, a research organization instituted by the state legislature of Florida in the United States. The inaugural annual CCORC 2021 was organized as a scientific meeting to foster and disseminate research on medical marijuana (MM) clinical outcomes, while promoting engagement among MM researchers, patients, clinicians, policymakers, and industry partners. Key conference themes included: (a) the disconnect between policy, practice, and evidence and steps towards reconciliation, (b) approaches to overcome common barriers to MM research, and (c) the use of focused translational approaches utilizing both mechanistic and clinical research methodology to tackle the complexities of MM outcomes. CCORC 2022 is planned for spring 2022 in Orlando, Florida, United States.","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"4 1","pages":"143 - 146"},"PeriodicalIF":0.0,"publicationDate":"2021-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42782329","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":"Measuring the Change in Health-Related Quality of Life in Patients Using Marijuana for Pain Relief","authors":"A. Peterson, Christine Le, Tyler Dautrich","doi":"10.1159/000517857","DOIUrl":"https://doi.org/10.1159/000517857","url":null,"abstract":"Introduction: Current evidence suggests that cannabinoids are safe with minimal side effects and are effective in managing chronic pain. Data also show that medical marijuana (MM) may improve quality of life (QoL) among patients. However, there are little data showing the health-related QoL (HRQoL) benefit in MM patients using it for pain. The purpose of this study was to determine if there is a relationship between HRQol and MM use in patients using it to relieve pain. Methods: All pain patients aged 18 years or older enrolled in the Pennsylvania MM program were eligible for inclusion. Recruited subjects completed 4 surveys – at enrollment (baseline) then 2, 4, and 8 weeks post-enrollment. We used the EQ-5D survey tool for measuring HRQoL. The primary outcome measure was the change in the EQ-5D Index Score from survey 2 to survey 4 (6 week difference). Secondary outcomes included self-reported pain and health scores. Data were analyzed using a paired t test and repeated-measures multivariable analysis to control for both gender and length of time between surveys. Results: 1,762 people responded to the screening request, and 1,393 (79%) met screening criteria. Of those, 353 (25.3%) agreed to participate and 51% completed all 4 surveys, for a final sample of 181 with 85 male and 95 female and one nonbinary subject. The average age was 41.21 (SD = 12.9) years, with no difference between genders. The adjusted HRQoL score improved from 0.722 to 0.747 (p = 0.011) from survey 2 to survey 4, as did the self-reported pain and health scores. The EQ-5D subscales revealed no change in mobility or usual activities, significant improvement in anxiety and pain, and a significant worsening in self-care. Conclusion: The results show a significant improvement in HRQoL among patients using MM for pain. The EQ-5D subscales validated the pain improvement and also showed an improvement in anxiety. However, the decline in the self-care subscale may have tempered the overall improvement in HRQoL, and further research into which aspects of self-care are impacted by MM use in this population is warranted. Overall, there is a positive relationship between MM use and HRQoL in patients using it for pain.","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"4 1","pages":"114 - 120"},"PeriodicalIF":0.0,"publicationDate":"2021-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46328575","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}
J. Jean-Jacques, Robert Cook, A. Winterstein, A. Goodin, Joshua D. Brown, S. Jugl, Yan Wang
{"title":"Priorities for Medical Marijuana Research from the Perspective of Physicians, Dispensary Owners/Staff, and Patients: A Survey Study","authors":"J. Jean-Jacques, Robert Cook, A. Winterstein, A. Goodin, Joshua D. Brown, S. Jugl, Yan Wang","doi":"10.1159/000518105","DOIUrl":"https://doi.org/10.1159/000518105","url":null,"abstract":"Objective: More patients are turning to medical marijuana as an alternative treatment, yet there are apparent knowledge gaps on the risk benefit of medical marijuana for a variety of indications. This study aimed to determine the priorities for medical marijuana research from the perspective of multiple stakeholders including patients, clinicians, and industry representatives. Methods: An anonymous survey was administered to attendees of the 2019 American Medical Marijuana Physicians Association annual meeting in Orlando, Florida. Respondents completed the survey on paper or smartphone via Qualtrics. The survey included questions on demographics and medical marijuana research priorities under the following broad categories: clinical conditions, safety issues, marijuana types, populations, and others. Results: Forty-six participants (56.5% female, mean age = 51.6 ± 14.1) responded to the survey. A majority were medical marijuana qualified physicians in Florida (56.5%), 30.5% other physicians or clinicians, and 21.7% medical marijuana patients (multiple choices allowed). The top conditions prioritized for research by this group were chronic pain, cancer, and anxiety, and the top priority safety issues were dosing/product choice, complications from smoking/vaping, and drug interactions. Regarding marijuana types, the group prioritized research on THC/CBD ratios, different modes of consumption, and terpenes. Conclusions: Findings from this survey indicate that medical marijuana stakeholders perceived a broad range of research topics as priorities. More research is needed to advance the evidence in these areas and provide guidance to patients, physicians, and the medical marijuana industry.","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"4 1","pages":"107 - 113"},"PeriodicalIF":0.0,"publicationDate":"2021-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43297109","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}