Journal of Cannabis Research最新文献

{"title":"Cannabinoids in the management of behavioral, psychological, and motor symptoms of neurocognitive disorders: a mixed studies systematic review","authors":"A. Bahji, Natasha Breward, W. Duff, N. Absher, S. Patten, Janet K. Alcorn, D. Mousseau","doi":"10.1186/s42238-022-00119-y","DOIUrl":"https://doi.org/10.1186/s42238-022-00119-y","url":null,"abstract":"","PeriodicalId":15172,"journal":{"name":"Journal of Cannabis Research","volume":"89 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82669634","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":"Growing ganja permission: a real gate-way for Thailand’s promising industrial crop?","authors":"S. Sommano, T. Tangpao, T. Pankasemsuk, Voranate Ponpanumas, Y. Phimolsiripol, P. Rachtanapun, Shashanka K. Prasad","doi":"10.1186/s42238-022-00121-4","DOIUrl":"https://doi.org/10.1186/s42238-022-00121-4","url":null,"abstract":"","PeriodicalId":15172,"journal":{"name":"Journal of Cannabis Research","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83766669","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":"Characteristics that influence purchase choice for cannabis products: a systematic review.","authors":"Jennifer Donnan,&nbsp;Omar Shogan,&nbsp;Lisa Bishop,&nbsp;Michelle Swab,&nbsp;Maisam Najafizada","doi":"10.1186/s42238-022-00117-0","DOIUrl":"https://doi.org/10.1186/s42238-022-00117-0","url":null,"abstract":"<p><strong>Introduction: </strong>When non-medical cannabis use became legal, government regulators implemented policies to encourage safer consumption through access to a regulated market. While this market is growing, sales still occur through unregulated channels. This systematic review identifies factors influencing cannabis purchasing to help policymakers understand why consumers still purchase illicit market cannabis (registered with PROSPERO CRD42020176079).</p><p><strong>Methods: </strong>A comprehensive search strategy included databases in health, business, and social science fields (inception to June 2020). Studies were eligible for inclusion if they were conducted with persons who purchase cannabis and examine at least one attribute that would influence purchase choice and were published in the English language. Studies could be of any methodological design. Two independent reviewers completed two levels of screening, and all extraction was verified by a second reviewer. A qualitative synthesis of the findings was completed. The quality of the included studies was assessed using the Mixed Methods Appraisal Tool.</p><p><strong>Results: </strong>Of the 4839 citations screened, 96 were eligible for full-text review and 35 were included in the final synthesis. Aspects of price were the most common factors (27 studies). Twenty studies measured price elasticity; most studies found that demand was price inelastic. Many other attributes were identified (e.g., product quality, route of administration, product recommendations, packaging), but none were explored in depth. Eleven studies addressed aspects of product quality including demand elasticity based on quality, potency, and aroma. Studies also explored consumer-perceived \"quality\" but provided no definition; differences in quality appeared to impact consumer choice. Smoking cannabis appeared to be the preferred route of administration but was only examined in three studies. There was insufficient data to understand in the impact of other attributes on choice. There appeared to be preference heterogeneity for different attributes based on the consumer's experience, reason for use, and gender.</p><p><strong>Conclusion: </strong>While price influences choices, demand is relatively inelastic. This suggests that consumers may be seeking lowest-cost, unregulated cannabis to avoid reducing consumption. Beyond price, there is a significant gap in our understanding of consumer choices. Perceived quality does appear to impact choice; however, more research is needed due to the lack of a recognized definition for cannabis quality.</p>","PeriodicalId":15172,"journal":{"name":"Journal of Cannabis Research","volume":" ","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39878605","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":"Ethical perspectives of certified public accountants and the cannabis industry.","authors":"G Suzanne Owens-Ott,&nbsp;Johnny Snyder,&nbsp;Richard Ott","doi":"10.1186/s42238-022-00118-z","DOIUrl":"https://doi.org/10.1186/s42238-022-00118-z","url":null,"abstract":"<p><strong>Background: </strong>Certified public accountants must follow very high standards of ethical conduct as set forth by the AICPA Code of Professional Conduct and individual state licensing requirements. A 2019 grounded theory qualitative study posed that CPAs remain largely hesitant to serve the cannabis industry primarily because they fear federal prosecution as long as cannabis remains on the DEA's Schedule I Drug List. The purpose of this research was to determine the perceptions of CPAs regarding providing accounting services to the cannabis industry in states that have legalized cannabis usage. This study investigated whether CPAs would serve the industry, why they might decline to serve the industry, what risks they believe serving the industry posed, and whether they believe serving the cannabis industry would create a moral or ethical issue.</p><p><strong>Methods: </strong>This follow-up quantitative study investigated a small convenience sample of approximately one hundred CPAs in Colorado and Washington to learn more about their perceptions of serving the cannabis industry. Data was analyzed using chi-square and Mann-Whitney U tests to determine if there were any differences in perceptions between groups such as states, gender, and age categories.</p><p><strong>Results: </strong>Of the participants, 77% responded that neither they nor their firm provided services to a cannabis-related business client compared to 23% that did serve cannabis clients. More Colorado CPAs were willing to turn down CRB work than were expected and fewer Colorado CPAs would be willing to take on CRB clients than were expected. While in Washington, fewer CPAs would turn down RB clients than expected, and more are willing to accept CRB clients than were expected. The risk due to potential liability coverage issues due to serving the cannabis industry was rated the highest while the risk of losing the CPA license was rated lowest. Data indicated that there was not a statistically significant difference between Colorado and Washington participants related to whether they were morally or religiously opposed to working in the industry or if they viewed serving the industry as an ethical violation.</p><p><strong>Conclusion: </strong>CPAs remain largely unwilling to serve the cannabis industry primarily because CPAs fear federal prosecution as long as cannabis remains on the DEA's Schedule I Drug Listing. The results of this study indicate that while most CPAs are not morally or religiously opposed to serving the industry, about half still believe doing so may constitute an ethical violation for a CPA.</p>","PeriodicalId":15172,"journal":{"name":"Journal of Cannabis Research","volume":" ","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2022-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39738569","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 mixed methods analysis of cannabis use routines for chronic pain management.","authors":"Kevin F Boehnke, Laura Yakas, J Ryan Scott, Melissa DeJonckheere, Evangelos Litinas, Suzanne Sisley, Daniel J Clauw, David A Williams, Jenna McAfee","doi":"10.1186/s42238-021-00116-7","DOIUrl":"10.1186/s42238-021-00116-7","url":null,"abstract":"<p><strong>Background: </strong>The wide heterogeneity of available cannabis products makes it difficult for physicians to appropriately guide patients. In the current study, our objective was to characterize naturalistic cannabis use routines and explore associations between routines and reported benefits from consuming cannabis.</p><p><strong>Methods: </strong>We performed a mixed methods analysis of n=1087 cross-sectional survey responses from adults with self-reported chronic pain using cannabis for symptom management in the USA and Canada. First, we qualitatively analyzed responses to an open-ended question that assessed typical cannabis use routines, including administration routes, cannabinoid content, and timing. We then sub-grouped responses into categories based on inhalation (smoking, vaporizing) vs. non-inhalation (e.g., edibles). Finally, we investigated subgroups perceptions of how cannabis affected pain, overall health, and use of medications (e.g., substituting for opioids, benzodiazepines). Substitutions were treated as a count of medication classes, while responses for both pain and health were analyzed continuously, with - 2 indicating health declining a lot or pain increasing a lot and 2 indicating that health improved a lot or pain decreased a lot.</p><p><strong>Results: </strong>Routines varied widely in terms of administration routes, cannabinoid content, and use timing. Overall, 18.8%, 36.2%, and 45% used non-inhalation, inhalation, and non-inhalation + inhalation routes, respectively. Those who used inhalation routes were younger (mean age 46.5 [inhalation] and 49.2 [non-inhalation + inhalation] vs. 56.3 [inhalation], F=36.1, p<0.001), while a higher proportion of those who used non-inhalation routes were female (72.5% non-inhalation vs. 48.3% inhalation and 65.3% non-inhalation + inhalation, X²=59.6, p<0.001). THC-rich products were typically used at night, while CBD-rich products were more often used during the day. While all participants reported similarly decreased pain, participants using non-inhalation + inhalation administration routes reported larger improvements in health than the non-inhalation (mean difference = 0.32, 95% CI: 0.07-0.37, p<0.001) and inhalation subgroups (mean difference = 0.22, 95% CI: 0.07-0.37, p=0.001). Similarly, the non-inhalation + inhalation group had significantly more medication substitutions than those using non-inhalation (mean difference = 0.62, 95% CI: 0.33-0.90, p<0.001) and inhalation administration routes (mean difference = 0.45, 95% CI: 0.22-0.69, p<0.001), respectively.</p><p><strong>Conclusions: </strong>Subgrouping medical cannabis patients based on administration route profile may provide useful categories for future studies examining the risks and benefits of medical cannabis.</p>","PeriodicalId":15172,"journal":{"name":"Journal of Cannabis Research","volume":"4 1","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2022-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9364001","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":"Case report: Medical cannabis-warfarin drug-drug interaction.","authors":"Tyan F Thomas, Evdokia S Metaxas, Thu Nguyen, Whitni Bennett, Kathryn V Skiendzielewski, Diane H Quinn, Alice L Scaletta","doi":"10.1186/s42238-021-00112-x","DOIUrl":"10.1186/s42238-021-00112-x","url":null,"abstract":"<p><strong>Aim: </strong>A case of an 85-year-old patient with concurrent use of warfarin and medical cannabis containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is described. Warfarin continues to be a cornerstone of anticoagulation treatment despite the recent addition of FDA-approved anticoagulant agents. It is well known that warfarin has numerous drug interactions; however, much remains unknown about its interaction with THC and CBD. A literature review was conducted to identify documented cases of possible interactions between cannabis and warfarin. The case reports we identified noted that cannabis may potentially increase warfarin's effect. Therefore, we aimed to determine why an effect was not seen on our patient's warfarin dose despite daily use of medical cannabis.</p><p><strong>Case: </strong>This case report describes an 85-year-old patient who despite starting an oromucosal medical cannabis regimen of THC and CBD (which provided 0.3 mg of THC and 5.3 mg CBD once daily and an additional 0.625 mg of THC and 0.625 mg CBD once daily as needed) had minimal INR fluctuations from October 2018 to September 2019.</p><p><strong>Conclusion: </strong>Despite the introduction and use of medical cannabis therapy, with both THC and CBD components, an elderly patient with concurrent warfarin use did not see major INR fluctuations, in contrast to published literature. The potential for warfarin and THC/CBD interactions may be dependent on route of administration and dose of the cannabis product.</p>","PeriodicalId":15172,"journal":{"name":"Journal of Cannabis Research","volume":" ","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2022-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8744571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39669937","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":"Identifying archetypal cannabis consumers to inform drug policy design: a Q-sort assessment of young adults' attitudes in Mexico City's metropolitan area.","authors":"Salvador Espinosa,&nbsp;Charles Marks,&nbsp;Gustavo Fondevila","doi":"10.1186/s42238-021-00107-8","DOIUrl":"https://doi.org/10.1186/s42238-021-00107-8","url":null,"abstract":"<p><strong>Background: </strong>As the legalization of cannabis moves forward in many countries, it is important to highlight the potential harm that excessive use can cause on young consumers. Crafting effective policy interventions to reduce the harm stemming from excessive use requires an understanding of the attitudes and motivations of young consumers.</p><p><strong>Methods: </strong>This article uses Q methodology to study four aspects of cannabis use among young adults from Mexico City's metropolitan area: motivations for use, perceived consequences of use, reasons that would increase willingness to reduce consumption, and attitudes towards government regulation. A total of 110 cannabis users between 18 and 21 years old were recruited using chain-referral sampling. Using a Q methodology, we captured the relative importance that participants assigned to a series of statements and identified archetypal profiles of young adults who use cannabis for each of the four aspects mentioned above.</p><p><strong>Results: </strong>The sample for this research study included 76 men and 34 women. The average age of participants was 20 years old, and the average age when cannabis consumption started was 15 years old. For each of the four Q-sort factor analyses, we identified 4 distinct factors based on explained variance and interpretability. The Q factor analysis indicated that attenuation of a negative affect (i.e., anxiety, stress) and relaxation were primary motivations for cannabis use. Understood consequences of cannabis use ranged across aspect-archetype, reflecting legal (i.e., interacting with law enforcement), financial, familial (i.e., disappointing family members), and educational performance concerns. Participants indicated that finding alternative relaxation strategies, receiving credible evidence of the health harms of cannabis use, increased financial burden of purchasing, and increased inaccessibility of cannabis products would motivate reductions in use. Across archetypes, participants indicated a willingness to comply with cannabis policies which are simple and easy to understand, which do not lead to discrimination or law enforcement involvement, and which provide for legal places to purchase and use safe (i.e., free of adulterants) cannabis products.</p><p><strong>Conclusions: </strong>We posit that these archetypes could be useful to inform cannabis policy design. As the study reveals, participants' cannabis use was primarily motivated by perceived improvements to mental health. Furthermore, participant responses indicated that they viewed cannabis use as a health matter, not a criminal one. Policies which aim to promote alternative mental health wellness and relaxation mechanisms, which aim to improve communication of potential health harms of cannabis, and which allow for the safe and legal purchase and use of cannabis may be effective in reducing cannabis-associated harms. Though our findings shed light on important aspects of can","PeriodicalId":15172,"journal":{"name":"Journal of Cannabis Research","volume":" ","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2022-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39798218","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":"UK Medical Cannabis Registry palliative care patients cohort: initial experience and outcomes.","authors":"Devaki Nimalan,&nbsp;Michal Kawka,&nbsp;Simon Erridge,&nbsp;Mehmet Ergisi,&nbsp;Michael Harris,&nbsp;Oliver Salazar,&nbsp;Rayyan Ali,&nbsp;Katerina Loupasaki,&nbsp;Carl Holvey,&nbsp;Ross Coomber,&nbsp;Michael Platt,&nbsp;James J Rucker,&nbsp;Shaheen Khan,&nbsp;Mikael H Sodergren","doi":"10.1186/s42238-021-00114-9","DOIUrl":"https://doi.org/10.1186/s42238-021-00114-9","url":null,"abstract":"<p><strong>Introduction: </strong>Palliative care aims to improve quality of life through optimal symptom control and pain management. Cannabis-based medicinal products (CBMPs) have a proven role in the treatment of chemotherapy-induced nausea and vomiting. However, there is a paucity of high-quality evidence with regards to the optimal therapeutic regimen, safety, and effectiveness of CBMPs in palliative care, as existing clinical trials are limited by methodological heterogeneity. The aim of this study is to summarise the outcomes of the initial subgroup of patients from the UK Medical Cannabis Registry who were prescribed CBMPs for a primary indication of palliative care, cancer pain and chemotherapy-induced nausea and vomiting, including effects on health-related quality of life and clinical safety.</p><p><strong>Methods: </strong>A case series from the UK Medical Cannabis Registry of patients, who were receiving CBMPs for the indication of palliative care was undertaken. The primary outcome consisted of changes in patient-reported outcome measures including EQ-5D-5L, General Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), Pain Visual Analog Scale (VAS) and the Australia-Modified Karnofsky Performance Scale at 1 and 3 months compared to baseline. Secondary outcomes included the incidence and characteristics of adverse events. Statistical significance was defined by p-value< 0.050.</p><p><strong>Results: </strong>Sixteen patients were included in the analysis, with a mean age of 63.25 years. Patients were predominantly prescribed CBMPs for cancer-related palliative care (n = 15, 94%). The median initial CBD and THC daily doses were 32.0 mg (Range: 20.0-384.0 mg) and 1.3 mg (Range: 1.0-16.0 mg) respectively. Improvements in patient reported health outcomes were observed according to SQS, EQ-5D-5L mobility, pain and discomfort, and anxiety and depression subdomains, EQ-5D-5L index, EQ-VAS and Pain VAS validated scales at both 1-month and 3-months, however, the changes were not statistically significant. Three adverse events (18.75%) were reported, all of which were either mild or moderate in severity.</p><p><strong>Conclusion: </strong>This small study provides an exploratory analysis of the role of CBMPs in palliative care in the first cohort of patients since CBMPs legalisation in the UK. CBMPs were tolerated with few adverse events, all of which were mild or moderate and resolved spontaneously. Further long-term safety and efficacy studies involving larger cohorts are needed to establish CBMPs role in palliative care, including comparisons with standard treatments.</p>","PeriodicalId":15172,"journal":{"name":"Journal of Cannabis Research","volume":" ","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2022-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39784581","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":"Delta-8-THC: Delta-9-THC's nicer younger sibling?","authors":"Jessica S Kruger,&nbsp;Daniel J Kruger","doi":"10.1186/s42238-021-00115-8","DOIUrl":"https://doi.org/10.1186/s42238-021-00115-8","url":null,"abstract":"<p><strong>Background: </strong>Products containing delta-8-THC became widely available in most of the USA following the 2018 Farm Bill and by late 2020 were core products of hemp processing companies, especially where delta-9-THC use remained illegal or required medical authorization. Research on experiences with delta-8-THC is scarce, some state governments have prohibited it because of this lack of knowledge.</p><p><strong>Objective: </strong>We conducted an exploratory study addressing a broad range of issues regarding delta-8-THC to inform policy discussions and provide directions for future systematic research.</p><p><strong>Methods: </strong>We developed an online survey for delta-8-THC consumers, including qualities of delta-8-THC experiences, comparisons with delta-9-THC, and open-ended feedback. The survey included quantitative and qualitative aspects to provide a rich description and content for future hypothesis testing. Invitations to participate were distributed by a manufacturer of delta-8-THC products via social media accounts, email contact list, and the Delta8 Reddit.com discussion board. Participants (N = 521) mostly identified as White/European American (90%) and male (57%). Pairwise t tests compared delta-8-THC effect rating items; one-sample t tests examined responses to delta-9-THC comparison items.</p><p><strong>Results: </strong>Most delta-8-THC users experienced a lot or a great deal of relaxation (71%); euphoria (68%) and pain relief (55%); a moderate amount or a lot of cognitive distortions such as difficulty concentrating (81%), difficulties with short-term memory (80%), and alerted sense of time (74%); and did not experience anxiety (74%) or paranoia (83%). Participants generally compared delta-8-THC favorably with both delta-9-THC and pharmaceutical drugs, with most participants reporting substitution for delta-9-THC (57%) and pharmaceutical drugs (59%). Participant concerns regarding delta-8-THC were generally focused on continued legal access.</p><p><strong>Conclusions: </strong>Delta-8-THC may provide much of the experiential benefits of delta-9-THC with lesser adverse effects. Future systematic research is needed to confirm participant reports, although these studies are hindered by the legal statuses of both delta-8-THC and delta-9-THC. Cross-sector collaborations among academics, government officials, and representatives from the cannabis industry may accelerate the generation of knowledge regarding delta-8-THC and other cannabinoids. A strength of this study is that it is the first large survey of delta-8 users, limitations include self-report data from a self-selected convenience sample.</p>","PeriodicalId":15172,"journal":{"name":"Journal of Cannabis Research","volume":" ","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2022-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39643326","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":"Olivetolic acid, a cannabinoid precursor in Cannabis sativa, but not CBGA methyl ester exhibits a modest anticonvulsant effect in a mouse model of Dravet syndrome.","authors":"Lyndsey L Anderson,&nbsp;Michael Udoh,&nbsp;Declan Everett-Morgan,&nbsp;Marika Heblinski,&nbsp;Iain S McGregor,&nbsp;Samuel D Banister,&nbsp;Jonathon C Arnold","doi":"10.1186/s42238-021-00113-w","DOIUrl":"https://doi.org/10.1186/s42238-021-00113-w","url":null,"abstract":"<p><strong>Objective: </strong>Cannabigerolic acid (CBGA), a precursor cannabinoid in Cannabis sativa, has recently been found to have anticonvulsant properties in the Scn1a^+/- mouse model of Dravet syndrome. Poor brain penetration and chemical instability of CBGA limits its potential as an anticonvulsant therapy. Here, we examined whether CBGA methyl ester, a more stable analogue of CBGA, might have superior pharmacokinetic and anticonvulsant properties. In addition, we examined whether olivetolic acid, the biosynthetic precursor to CBGA with a truncated (des-geranyl) form, might possess minimum structural requirements for anticonvulsant activity. We also examined whether olivetolic acid and CBGA methyl ester retain activity at the epilepsy-relevant drug targets of CBGA: G-protein-coupled receptor 55 (GPR55) and T-type calcium channels.</p><p><strong>Methods: </strong>The brain and plasma pharmacokinetic profiles of CBGA methyl ester and olivetolic acid were examined following 10 mg/kg intraperitoneal (i.p.) administration in mice (n = 4). The anticonvulsant potential of each was examined in male and female Scn1a^+/- mice (n = 17-19) against hyperthermia-induced seizures (10-100 mg/kg, i.p.). CBGA methyl ester and olivetolic acid were also screened in vitro against T-type calcium channels and GPR55 using intracellular calcium and ERK phosphorylation assays, respectively.</p><p><strong>Results: </strong>CBGA methyl ester exhibited relatively limited brain penetration (13%), although somewhat superior to that of 2% for CBGA. No anticonvulsant effects were observed against thermally induced seizures in Scn1a^+/- mice. Olivetolic acid also showed poor brain penetration (1%) but had a modest anticonvulsant effect in Scn1a^+/- mice increasing the thermally induced seizure temperature threshold by approximately 0.4°C at a dose of 100 mg/kg. Neither CBGA methyl ester nor olivetolic acid displayed pharmacological activity at GPR55 or T-type calcium channels.</p><p><strong>Conclusions: </strong>Olivetolic acid displayed modest anticonvulsant activity against hyperthermia-induced seizures in the Scn1a^+/- mouse model of Dravet syndrome despite poor brain penetration. The effect was, however, comparable to the known anticonvulsant cannabinoid cannabidiol in this model. Future studies could explore the anticonvulsant mechanism(s) of action of olivetolic acid and examine whether its anticonvulsant effect extends to other seizure types.</p>","PeriodicalId":15172,"journal":{"name":"Journal of Cannabis Research","volume":" ","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2022-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39784586","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}