Pub Date : 2022-10-17eCollection Date: 2022-01-01DOI: 10.1159/000527080
Nicole E Smolinski, Ruba Sajdeya, Robert Cook, Yan Wang, Almut G Winterstein, Amie Goodin
The Consortium for Medical Marijuana Clinical Outcomes Research, a multi-university collaboration established by the state of Florida in the USA, hosted its second annual Cannabis Clinical Outcomes Research Conference (CCORC) in May 2022. CCORC was held as a hybrid conference, with a scientific program consisting of in-person and virtual sessions. CCORC fostered and disseminated current research on clinical outcomes of medical marijuana while stimulating collaboration and engagement between the scientific community, policymakers, industry representatives, clinicians, and other interested stakeholders. Three themes emerged from conference sessions and speakers: (1) disentangling research findings comparing use and outcomes of medical and nonmedical cannabis, (2) addressing barriers and promoting facilitators for clinical cannabis research, and (3) resolving uncertainties around cannabis dosing. The third annual CCORC is planned for the summer of 2023 in Florida, USA.
{"title":"Proceedings of the 2022 Cannabis Clinical Outcomes Research Conference.","authors":"Nicole E Smolinski, Ruba Sajdeya, Robert Cook, Yan Wang, Almut G Winterstein, Amie Goodin","doi":"10.1159/000527080","DOIUrl":"https://doi.org/10.1159/000527080","url":null,"abstract":"<p><p>The Consortium for Medical Marijuana Clinical Outcomes Research, a multi-university collaboration established by the state of Florida in the USA, hosted its second annual Cannabis Clinical Outcomes Research Conference (CCORC) in May 2022. CCORC was held as a hybrid conference, with a scientific program consisting of in-person and virtual sessions. CCORC fostered and disseminated current research on clinical outcomes of medical marijuana while stimulating collaboration and engagement between the scientific community, policymakers, industry representatives, clinicians, and other interested stakeholders. Three themes emerged from conference sessions and speakers: (1) disentangling research findings comparing use and outcomes of medical and nonmedical cannabis, (2) addressing barriers and promoting facilitators for clinical cannabis research, and (3) resolving uncertainties around cannabis dosing. The third annual CCORC is planned for the summer of 2023 in Florida, USA.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":" ","pages":"138-141"},"PeriodicalIF":0.0,"publicationDate":"2022-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9f/ab/mca-0005-0138.PMC9710315.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35209461","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}
F. Bianchi, J. Wampfler, F. Curtin, J. Desmeules, B. Broers, E. Becher, F. Heimann, F. Grotenhermen
depression associated with opioids, whilst providing many of the desired pain-relieving and sedative effects. Cannabinoid receptors not only mediate immunologic as well as pain signals, but are also expressed in periodontal and gingival tissues, as well as in both osteoblast and osteoclasts, making them potential targets for a number of new technologies: from implantology to anti-plaque mouthwashes. See Table 1 for some of the most researched potential uses.
{"title":"Cannabinoid Conference 2022","authors":"F. Bianchi, J. Wampfler, F. Curtin, J. Desmeules, B. Broers, E. Becher, F. Heimann, F. Grotenhermen","doi":"10.1159/000527113","DOIUrl":"https://doi.org/10.1159/000527113","url":null,"abstract":"depression associated with opioids, whilst providing many of the desired pain-relieving and sedative effects. Cannabinoid receptors not only mediate immunologic as well as pain signals, but are also expressed in periodontal and gingival tissues, as well as in both osteoblast and osteoclasts, making them potential targets for a number of new technologies: from implantology to anti-plaque mouthwashes. See Table 1 for some of the most researched potential uses.","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"5 1","pages":"159 - 198"},"PeriodicalIF":0.0,"publicationDate":"2022-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42190054","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}
Pub Date : 2022-10-10eCollection Date: 2022-01-01DOI: 10.1159/000526769
Riley D Kirk, Toyosi Akanji, Huifang Li, Jie Shen, Saleh Allababidi, Navindra P Seeram, Matthew J Bertin, Hang Ma
Introduction: Cannabinoids including cannabidiol (CBD) have attracted enormous interest as bioactive ingredients for various dermatological and/or cosmeceutical uses. However, topical applications of cannabinoids might be limited without a fundamental understanding of their skin permeability. Herein, we aimed to evaluate the skin permeability of CBD and its topical formulations using artificial skin membrane assays. The solubility and stability of CBD in various surfactants that are commonly used in topical applications were also evaluated.
Methods: CBD and two CBD-incorporated topical formulations (cream and gel) were prepared for this study. Computational predictions (SwissADME and DERMWIN™) and the parallel artificial membrane permeability assay (PAMPA) were used to evaluate the skin permeability of CBD isolate. The Franz cell diffusion (in vitro release testing) assay was used to evaluate the skin permeability of CBD formulations. The solubility and stability of CBD in surfactants were assessed by high-performance liquid chromatography and mass spectrometry analysis.
Results: CBD isolate showed favorable skin permeability in the SwissADME and DERMWIN™ predictions (-Log Kp of 3.6 and 5.7 cm/s, respectively) and PAMPA (-LogPe value of 5.0 at pH of 6.5 and 7.4). In addition, CBD had higher solubility (378.4 μg/mL) in surfactant Tween 20 as compared to its solubility in polyisobutene. In an acidic environment (pH 5 and 6), Tween 20 maintained the CBD content at 81% and 70% over 30 days, respectively. CBD in the formulations of cream and gel also had moderate skin permeability in the Franz cell diffusion assay.
Conclusion: Data from artificial membrane-based assays support that CBD is a skin permeable cannabinoid and the permeability and stability of its formulations may be influenced by several factors such as surfactant and pH environment. Findings from our study suggest that CBD may have suitable skin permeability for the development of dermatological and/or cosmeceutical applications but further studies using in vivo models are warranted to confirm this.
{"title":"Evaluations of Skin Permeability of Cannabidiol and Its Topical Formulations by Skin Membrane-Based Parallel Artificial Membrane Permeability Assay and Franz Cell Diffusion Assay.","authors":"Riley D Kirk, Toyosi Akanji, Huifang Li, Jie Shen, Saleh Allababidi, Navindra P Seeram, Matthew J Bertin, Hang Ma","doi":"10.1159/000526769","DOIUrl":"https://doi.org/10.1159/000526769","url":null,"abstract":"<p><strong>Introduction: </strong>Cannabinoids including cannabidiol (CBD) have attracted enormous interest as bioactive ingredients for various dermatological and/or cosmeceutical uses. However, topical applications of cannabinoids might be limited without a fundamental understanding of their skin permeability. Herein, we aimed to evaluate the skin permeability of CBD and its topical formulations using artificial skin membrane assays. The solubility and stability of CBD in various surfactants that are commonly used in topical applications were also evaluated.</p><p><strong>Methods: </strong>CBD and two CBD-incorporated topical formulations (cream and gel) were prepared for this study. Computational predictions (SwissADME and DERMWIN™) and the parallel artificial membrane permeability assay (PAMPA) were used to evaluate the skin permeability of CBD isolate. The Franz cell diffusion (in vitro release testing) assay was used to evaluate the skin permeability of CBD formulations. The solubility and stability of CBD in surfactants were assessed by high-performance liquid chromatography and mass spectrometry analysis.</p><p><strong>Results: </strong>CBD isolate showed favorable skin permeability in the SwissADME and DERMWIN™ predictions (-Log Kp of 3.6 and 5.7 cm/s, respectively) and PAMPA (-LogPe value of 5.0 at pH of 6.5 and 7.4). In addition, CBD had higher solubility (378.4 μg/mL) in surfactant Tween 20 as compared to its solubility in polyisobutene. In an acidic environment (pH 5 and 6), Tween 20 maintained the CBD content at 81% and 70% over 30 days, respectively. CBD in the formulations of cream and gel also had moderate skin permeability in the Franz cell diffusion assay.</p><p><strong>Conclusion: </strong>Data from artificial membrane-based assays support that CBD is a skin permeable cannabinoid and the permeability and stability of its formulations may be influenced by several factors such as surfactant and pH environment. Findings from our study suggest that CBD may have suitable skin permeability for the development of dermatological and/or cosmeceutical applications but further studies using in vivo models are warranted to confirm this.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":" ","pages":"129-137"},"PeriodicalIF":0.0,"publicationDate":"2022-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c5/79/mca-0005-0129.PMC9710319.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35209453","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}
Cannabis and its natural derivatives have emerged as promising therapeutics for multiple pathological and nonpathological medical conditions. For example, cannabinoids, the most popular and biologically active chemicals in cannabis, aid in many clinical ailments, including pain, inflammation, epilepsy, sleep disturbances or insomnia, multiple sclerosis, anorexia, schizophrenia, neurodegenerative diseases, anti-nausea, and most importantly, cancer. Despite the comprehensive benefits, certain aspects of cannabis present unique challenges in the medical cannabis landscape. Recent studies have highlighted the inherent challenges associated with cannabinoids' formulation like low solubility, rapid metabolism, poor bioavailability, and erratic pharmacokinetics - all of which contribute to the limited efficacy of cannabinoids. Several efforts are underway to address the bottlenecks and modify the formulations along with the delivery systems to achieve greater solubility/bioavailability, potency, and efficacy in treatment settings while minding the necessary standards for purity associated with the pharmaceutical industry. The current article presents a perspective on (1) a working knowledge of cannabinoids and their mechanisms of action, (2) the landscape of using medicinal cannabis for cancer-related medical conditions along with adversities, (3) current approaches, formulations, and challenges in medicinal cannabis delivery systems (oral, transdermal, pulmonary, and transmucosal), and lastly, (4) emerging approaches to improve delivery systems.
{"title":"Perspectives on Challenges in Cannabis Drug Delivery Systems: Where Are We?","authors":"Manikandan Palrasu, Lillianne Wright, Manish Patel, Lindsey Leech, Scotty Branch, Shea Harrelson, Saeed Khan","doi":"10.1159/000525629","DOIUrl":"https://doi.org/10.1159/000525629","url":null,"abstract":"<p><p>Cannabis and its natural derivatives have emerged as promising therapeutics for multiple pathological and nonpathological medical conditions. For example, cannabinoids, the most popular and biologically active chemicals in cannabis, aid in many clinical ailments, including pain, inflammation, epilepsy, sleep disturbances or insomnia, multiple sclerosis, anorexia, schizophrenia, neurodegenerative diseases, anti-nausea, and most importantly, cancer. Despite the comprehensive benefits, certain aspects of cannabis present unique challenges in the medical cannabis landscape. Recent studies have highlighted the inherent challenges associated with cannabinoids' formulation like low solubility, rapid metabolism, poor bioavailability, and erratic pharmacokinetics - all of which contribute to the limited efficacy of cannabinoids. Several efforts are underway to address the bottlenecks and modify the formulations along with the delivery systems to achieve greater solubility/bioavailability, potency, and efficacy in treatment settings while minding the necessary standards for purity associated with the pharmaceutical industry. The current article presents a perspective on (1) a working knowledge of cannabinoids and their mechanisms of action, (2) the landscape of using medicinal cannabis for cancer-related medical conditions along with adversities, (3) current approaches, formulations, and challenges in medicinal cannabis delivery systems (oral, transdermal, pulmonary, and transmucosal), and lastly, (4) emerging approaches to improve delivery systems.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":" ","pages":"102-119"},"PeriodicalIF":0.0,"publicationDate":"2022-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ac/84/mca-0005-0102.PMC9710325.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35209429","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}
Pub Date : 2022-06-03eCollection Date: 2022-01-01DOI: 10.1159/000524831
Lydia S Buonomano, Matthew M Mitnick, Thomas R McCalmont, Paulina Syracuse, Karen L Dugosh, David S Festinger, Michelle R Lent
Introduction: Despite the rising availability and use of medical marijuana (MM) in the USA, little is known about the demographics, clinical characteristics, or quality of life of MM patients. This study describes the demographic characteristics and health-related quality of life (HRQoL) of MM patients who are initiating treatment in Pennsylvania.
Methods: Two-hundred adults naive to MM and referred for any of the 23 state-approved qualifying conditions were recruited at three MM dispensaries in Pennsylvania between September 2020 and March 2021. All participants consented to the study; completed semi-structured interviews that included demographic questionnaires, the Short Form-36 (SF-36), and Generalized Anxiety Disorder-7 (GAD-7); provided height and weight measurements; and allowed access their dispensary medical records.
Results: Participants had a mean age of 48.5 ± 15.6 years, predominantly identified as female (67.5%), and were most commonly referred for chronic pain (63.5%) and/or anxiety (58.5%). Additionally, 46.0% were living with obesity as determined by BMI. Relative to a normative sample, participants reported diminished HRQoL in several domains, most notably in role limitations due to physical health (M = 46.0 ± 42.0), role limitations due to emotional problems (M = 52.5 ± 42.3), energy and fatigue (M = 39.8 ± 20.2), and pain (M = 49.4 ± 26.0).
Discussion/conclusion: Patients initiating MM treatment experienced low HRQoL in multiple domains. Future studies could evaluate the relationship between HRQoL and patients' decisions to pursue MM treatment, as well as changes in HRQoL with MM use over time.
{"title":"Clinical Characteristics and Quality of Life in Adults Initiating Medical Marijuana Treatment.","authors":"Lydia S Buonomano, Matthew M Mitnick, Thomas R McCalmont, Paulina Syracuse, Karen L Dugosh, David S Festinger, Michelle R Lent","doi":"10.1159/000524831","DOIUrl":"https://doi.org/10.1159/000524831","url":null,"abstract":"<p><strong>Introduction: </strong>Despite the rising availability and use of medical marijuana (MM) in the USA, little is known about the demographics, clinical characteristics, or quality of life of MM patients. This study describes the demographic characteristics and health-related quality of life (HRQoL) of MM patients who are initiating treatment in Pennsylvania.</p><p><strong>Methods: </strong>Two-hundred adults naive to MM and referred for any of the 23 state-approved qualifying conditions were recruited at three MM dispensaries in Pennsylvania between September 2020 and March 2021. All participants consented to the study; completed semi-structured interviews that included demographic questionnaires, the Short Form-36 (SF-36), and Generalized Anxiety Disorder-7 (GAD-7); provided height and weight measurements; and allowed access their dispensary medical records.</p><p><strong>Results: </strong>Participants had a mean age of 48.5 ± 15.6 years, predominantly identified as female (67.5%), and were most commonly referred for chronic pain (63.5%) and/or anxiety (58.5%). Additionally, 46.0% were living with obesity as determined by BMI. Relative to a normative sample, participants reported diminished HRQoL in several domains, most notably in role limitations due to physical health (<i>M</i> = 46.0 ± 42.0), role limitations due to emotional problems (<i>M</i> = 52.5 ± 42.3), energy and fatigue (<i>M</i> = 39.8 ± 20.2), and pain (<i>M</i> = 49.4 ± 26.0).</p><p><strong>Discussion/conclusion: </strong>Patients initiating MM treatment experienced low HRQoL in multiple domains. Future studies could evaluate the relationship between HRQoL and patients' decisions to pursue MM treatment, as well as changes in HRQoL with MM use over time.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":" ","pages":"95-101"},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247440/pdf/mca-0005-0095.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40617079","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}
Introduction: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are two cholinergic enzymes catalyzing the reaction of cleaving acetylcholine into acetate and choline at the neuromuscular junction. Abnormal hyperactivity of AChE and BChE can lead to cholinergic deficiency, which is associated with several neurological disorders including cognitive decline and memory impairments. Preclinical studies support that some cannabinoids including cannabidiol (CBD) and tetrahydrocannabinol (THC) may exert pharmacological effects on the cholinergic system, but it remains unclear whether cannabinoids can inhibit AChE and BChE activities. Herein, we aimed to evaluate the inhibitory effects of a panel of cannabinoids including CBD, Δ8-THC, cannabigerol (CBG), cannabigerolic acid (CBGA), cannabicitran (CBT), cannabidivarin (CBDV), cannabichromene (CBC), and cannabinol (CBN) on AChE and BChE activities. Methods: The inhibitory effects of cannabinoids on the activities of AChE and BChE enzymes were evaluated with the Ellman method using acetyl- and butyryl-thiocholines as substrates. The inhibition mechanism of cannabinoids on AChE and BChE was studied with enzyme kinetic assays including the Lineweaver-Burk and Michaelis-Menten analyses. In addition, computational-based molecular docking experiments were performed to explore the interactions between the cannabinoids and the enzyme proteins. Results: Cannabinoids including CBD, Δ8-THC, CBG, CBGA, CBT, CBDV, CBC, and CBN (at 200 µM) inhibited the activities of AChE and BChE by 70.8, 83.7, 92.9, 76.7, 66.0, 79.3, 13.7, and 30.5%, and by 86.8, 80.8, 93.2, 87.1, 77.0, 78.5, 27.9, and 22.0%, respectively. The inhibitory effects of these cannabinoids (with IC50 values ranging from 85.2 to >200 µM for AChE and 107.1 to >200 µM for BChE) were less potent as compared to the positive control galantamine (IC50 1.21 and 6.86 µM for AChE and BChE, respectively). In addition, CBD, as a representative cannabinoid, displayed a competitive type of inhibition on both AChE and BChE. Data from the molecular docking studies suggested that cannabinoids interacted with several amino acid residues on the enzyme proteins, which supported their overall inhibitory effects on AChE and BChE. Conclusion: Cannabinoids showed moderate inhibitory effects on the activities of AChE and BChE enzymes, which may contribute to their modulatory effects on the cholinergic system. Further studies using cell-based and in vivo models are warranted to evaluate whether cannabinoids’ neuroprotective effects are associated with their anti-cholinesterase activities.
{"title":"Inhibitory Effects of Cannabinoids on Acetylcholinesterase and Butyrylcholinesterase Enzyme Activities","authors":"Tess Puopolo, Chang Liu, Hang Ma, N. Seeram","doi":"10.1159/000524086","DOIUrl":"https://doi.org/10.1159/000524086","url":null,"abstract":"Introduction: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are two cholinergic enzymes catalyzing the reaction of cleaving acetylcholine into acetate and choline at the neuromuscular junction. Abnormal hyperactivity of AChE and BChE can lead to cholinergic deficiency, which is associated with several neurological disorders including cognitive decline and memory impairments. Preclinical studies support that some cannabinoids including cannabidiol (CBD) and tetrahydrocannabinol (THC) may exert pharmacological effects on the cholinergic system, but it remains unclear whether cannabinoids can inhibit AChE and BChE activities. Herein, we aimed to evaluate the inhibitory effects of a panel of cannabinoids including CBD, Δ8-THC, cannabigerol (CBG), cannabigerolic acid (CBGA), cannabicitran (CBT), cannabidivarin (CBDV), cannabichromene (CBC), and cannabinol (CBN) on AChE and BChE activities. Methods: The inhibitory effects of cannabinoids on the activities of AChE and BChE enzymes were evaluated with the Ellman method using acetyl- and butyryl-thiocholines as substrates. The inhibition mechanism of cannabinoids on AChE and BChE was studied with enzyme kinetic assays including the Lineweaver-Burk and Michaelis-Menten analyses. In addition, computational-based molecular docking experiments were performed to explore the interactions between the cannabinoids and the enzyme proteins. Results: Cannabinoids including CBD, Δ8-THC, CBG, CBGA, CBT, CBDV, CBC, and CBN (at 200 µM) inhibited the activities of AChE and BChE by 70.8, 83.7, 92.9, 76.7, 66.0, 79.3, 13.7, and 30.5%, and by 86.8, 80.8, 93.2, 87.1, 77.0, 78.5, 27.9, and 22.0%, respectively. The inhibitory effects of these cannabinoids (with IC50 values ranging from 85.2 to >200 µM for AChE and 107.1 to >200 µM for BChE) were less potent as compared to the positive control galantamine (IC50 1.21 and 6.86 µM for AChE and BChE, respectively). In addition, CBD, as a representative cannabinoid, displayed a competitive type of inhibition on both AChE and BChE. Data from the molecular docking studies suggested that cannabinoids interacted with several amino acid residues on the enzyme proteins, which supported their overall inhibitory effects on AChE and BChE. Conclusion: Cannabinoids showed moderate inhibitory effects on the activities of AChE and BChE enzymes, which may contribute to their modulatory effects on the cholinergic system. Further studies using cell-based and in vivo models are warranted to evaluate whether cannabinoids’ neuroprotective effects are associated with their anti-cholinesterase activities.","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"5 1","pages":"85 - 94"},"PeriodicalIF":0.0,"publicationDate":"2022-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42104819","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}
Xiaoxue Li, Jegason P. Diviant, Sarah S. Stith, Franco Brockelman, Keenan Keeling, Branden Hall, J. Vigil
Objectives: We measure for the first time how commercially available Cannabis flower products affect feelings of fatigue. Methods: A total of 1,224 people recorded 3,922 Cannabis flower self-administration sessions between June 6, 2016, and August 7, 2019, using the Releaf App. Usage sessions included real-time subjective changes in fatigue intensity levels prior to and following Cannabis consumption, Cannabis flower characteristics (labeled phenotype, cannabinoid potency levels), combustion method, and any potential experienced side effects. Results: On average, 91.94% of people experienced decreased fatigue following consumption with an average symptom intensity reduction of 3.48 points on a 0–10 visual analog scale (SD = 2.70, d = 1.60, p < 0.001). While labeled plant phenotypes (“C. indica,” “C. sativa,” or “hybrid”) did not differ in symptom relief, people that used joints to combust the flower reported greater symptom relief than pipe or vaporizer users. Across cannabinoid levels, tetrahydrocannabinol, and cannabidiol levels were generally not associated with changes in symptom intensity levels. Cannabis use was associated with several negative side effects that correspond to increased feelings of fatigue (e.g., feeling unmotivated, couch-locked) among a minority of users (<24% of users), with slightly more users (up to 37%) experiencing a positive side effect that corresponds to increased energy (e.g., feeling active, energetic, frisky, or productive). Conclusions: The findings suggest that the majority of patients experience decreased fatigue from consumption of Cannabis flower consumed in vivo, although the magnitude of the effect and extent of side effects experienced likely vary with individuals’ metabolic states and the synergistic chemotypic properties of the plant.
{"title":"The Effects of Consuming Cannabis Flower for Treatment of Fatigue","authors":"Xiaoxue Li, Jegason P. Diviant, Sarah S. Stith, Franco Brockelman, Keenan Keeling, Branden Hall, J. Vigil","doi":"10.1159/000524057","DOIUrl":"https://doi.org/10.1159/000524057","url":null,"abstract":"Objectives: We measure for the first time how commercially available Cannabis flower products affect feelings of fatigue. Methods: A total of 1,224 people recorded 3,922 Cannabis flower self-administration sessions between June 6, 2016, and August 7, 2019, using the Releaf App. Usage sessions included real-time subjective changes in fatigue intensity levels prior to and following Cannabis consumption, Cannabis flower characteristics (labeled phenotype, cannabinoid potency levels), combustion method, and any potential experienced side effects. Results: On average, 91.94% of people experienced decreased fatigue following consumption with an average symptom intensity reduction of 3.48 points on a 0–10 visual analog scale (SD = 2.70, d = 1.60, p < 0.001). While labeled plant phenotypes (“C. indica,” “C. sativa,” or “hybrid”) did not differ in symptom relief, people that used joints to combust the flower reported greater symptom relief than pipe or vaporizer users. Across cannabinoid levels, tetrahydrocannabinol, and cannabidiol levels were generally not associated with changes in symptom intensity levels. Cannabis use was associated with several negative side effects that correspond to increased feelings of fatigue (e.g., feeling unmotivated, couch-locked) among a minority of users (<24% of users), with slightly more users (up to 37%) experiencing a positive side effect that corresponds to increased energy (e.g., feeling active, energetic, frisky, or productive). Conclusions: The findings suggest that the majority of patients experience decreased fatigue from consumption of Cannabis flower consumed in vivo, although the magnitude of the effect and extent of side effects experienced likely vary with individuals’ metabolic states and the synergistic chemotypic properties of the plant.","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"5 1","pages":"76 - 84"},"PeriodicalIF":0.0,"publicationDate":"2022-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42729199","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}
W. Zieglgänsberger, R. Brenneisen, A. Berthele, C. Wotjak, B. Bandelow, T. Tölle, B. Lutz
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).
{"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}
• 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
{"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}
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