A review of cannabis allergy in the early days of legalization.

Cannabis allergy is a burgeoning field; consequently, research is still in its infancy and allergists' knowledge surrounding this topic is limited. As cannabis legalization expands across the world, it is anticipated that there will be an increase in cannabis use. Thus, we hypothesize that a concomitant rise in the incidence of allergy to this plant can be expected. Initiatives aimed at properly educating health care professionals are therefore necessary. This review presents the most up-to-date information on a broad range of topics related to cannabis allergy. Although the clinical features of cannabis allergy are becoming more well described and recognized, the tools available to make a correct diagnosis are meager and often poorly accessible. In addition, research on cannabis allergy is still taking its first steps, and new and potentially groundbreaking findings in this field are expected to occur in the next few years. Finally, although therapeutic approaches are being developed, patient and physician education regarding cannabis allergy is certainly needed.

Cannabis-related allergies: An international overview and consensus recommendations.

Cannabis is the most widely used recreational drug in the world. Cannabis sativa and Cannabis indica have been selectively bred to develop their psychoactive properties. The increasing use in many countries has been accelerated by the COVID-19 pandemic. Cannabis can provoke both type 1 and type 4 allergic reactions. Officially recognized allergens include a pathogenesis-related class 10 allergen, profilin, and a nonspecific lipid transfer protein. Other allergens may also be relevant, and recognition of allergens may vary between countries and continents. Cannabis also has the potential to provoke allergic cross-reactions to plant foods. Since cannabis is an illegal substance in many countries, research has been hampered, leading to challenges in diagnosis since no commercial extracts are available for testing. Even in countries such as Canada, where cannabis is legalized, diagnosis may rely solely on the purchase of cannabis for prick-to-prick skin tests. Management consists of avoidance, with legal issues hindering the development of other treatments such as immunotherapy. Education of healthcare professionals is similarly lacking. This review aimed to summarize the current status of cannabis allergy and proposes recommendations for the future management of this global issue.

Impact of cannabis knowledge and attitudes on real-world practice.

BACKGROUND: Increased cannabis consumption worldwide challenges allergists because of an upsurge in cannabis allergy and need to discuss cannabis with patients. OBJECTIVE: To determine the knowledge, attitudes, and practices regarding cannabis among allergists and their approach to recognizing and diagnosing suspected cannabis allergy. METHODS: The International Allergist Canna Knowledge, Attitudes, and Practices Survey was completed by members from 3 International Allergy Societies. Survey questions included the following: 13 on cannabis attitudes, 7 on cannabis knowledge, and 4 on real-world allergy practices. Knowledge level was dichotomized and Statistical Package for the Social Sciences TwoStep Cluster Analysis grouped participants by attitudes. Multivariate analysis determined the relationship of knowledge and attitude to practice delivery. RESULTS: Of 570 eligible surveys started, 445 (78.1%) were completed. Participants were 49.7% of female sex, 65.9% aged 24 to 56 years, approximately 70% in practice for more than or equal to 10 years, and 29.2% practicing in an area where cannabis use is illegal. Of the respondents, 43.1% reported consulting on patients with suspected cannabis allergy and 54.7% had undertaken skin prick testing, in vitro cannabis testing, or both. Statistically significant differences were found between the 3 societies for most variables analyzed. Analysis of attitudes revealed 3 clusters named Traditional, Progressive, and Unsure. Those with more progressive attitudes toward cannabis and who had more knowledge were more comfortable speaking to patients about cannabis and more often asked patients on how often and how they used cannabis (all P < .001). CONCLUSION: Varying knowledge and attitudes toward cannabis affecting comfort communicating with patients about cannabis were found in members of 3 allergy societies supporting the need for more cannabis research and education.

Cannabis attitudes and patterns of use among followers of the Allergy & Asthma Network.

BACKGROUND: Cannabis use in patients with allergy/asthma, a high-risk group for adverse effects to cannabis, is unknown. OBJECTIVE: To determine the patterns of use and attitudes toward cannabis in patients with allergy/asthma. METHODS: An anonymous online survey on cannabis attitudes and use was conducted through the Adult Allergy & Asthma Network. The Asthma Control Test assessed asthma burden. Cluster analyses determined group phenotypes and factor analyses condensed cannabis subjective effects into similar response patterns. RESULTS: A total of 88 of 489 respondents (18.0%) currently use cannabis with most at the age of less than 50 years old, of female sex, and of White race. Of the noncannabis users (N = 401), 2.5% reported cannabis allergy. Cluster analysis revealed that a liberal attitude toward cannabis was associated with current cannabis use (P < .001). Among current cannabis users, 40.9% of their physicians inquired on cannabis use; only 37.5% of users wanted to discuss cannabis. In addition, 65.9% used cannabis for medical or medical/recreational purposes. Cannabinoids used were tetrahydrocannabinol (33.0%), cannabidiol (19.3%), or both (47.7%). Smoked and vaped cannabis were reported by 53.4% and 35.2%, respectively. Furthermore, 51 cannabis users (58.0%) reported current asthma with 39.2% uncontrolled; of these, 50% smoked cannabis. Compared with current participants with asthma not using cannabis, those currently using cannabis experienced similar levels of asthma control, quality of life, and frequency of asthma exacerbations. Positive effects were endorsed more than negative effects to cannabis (P < .001). Moreover, 19.3% of cannabis users reported coughing that was associated with smoking cannabis (P < .001). CONCLUSION: Cannabis was used by less than 20% of the respondents with positive effects more frequent than negative effects. Half of cannabis users with uncontrolled asthma smoke cannabis, but only a minority of the physicians inquire about its use.

Exercise-induced bronchoconstriction update-2016.

The first practice parameter on exercise-induced bronchoconstriction (EIB) was published in 2010. This updated practice parameter was prepared 5 years later. In the ensuing years, there has been increased understanding of the pathogenesis of EIB and improved diagnosis of this disorder by using objective testing. At the time of this publication, observations included the following: dry powder mannitol for inhalation as a bronchial provocation test is FDA approved however not currently available in the United States; if baseline pulmonary function test results are normal to near normal (before and after bronchodilator) in a person with suspected EIB, then further testing should be performed by using standardized exercise challenge or eucapnic voluntary hyperpnea (EVH); and the efficacy of nonpharmaceutical interventions (omega-3 fatty acids) has been challenged. The workgroup preparing this practice parameter updated contemporary practice guidelines based on a current systematic literature review. The group obtained supplementary literature and consensus expert opinions when the published literature was insufficient. A search of the medical literature on PubMed was conducted, and search terms included pathogenesis, diagnosis, differential diagnosis, and therapy (both pharmaceutical and nonpharmaceutical) of exercise-induced bronchoconstriction or exercise-induced asthma (which is no longer a preferred term); asthma; and exercise and asthma. References assessed as relevant to the topic were evaluated to search for additional relevant references. Published clinical studies were appraised by category of evidence and used to document the strength of the recommendation. The parameter was then evaluated by Joint Task Force reviewers and then by reviewers assigned by the parent organizations, as well as the general membership. Based on this process, the parameter can be characterized as an evidence- and consensus-based document.

Crystal Structure of Carboxyltransferase from Staphylococcus aureus Bound to the Antibacterial Agent Moiramide B.

The dramatic increase in the prevalence of antibiotic-resistant bacteria has necessitated a search for new antibacterial agents against novel targets. Moiramide B is a natural product, broad-spectrum antibiotic that inhibits the carboxyltransferase component of acetyl-CoA carboxylase, which catalyzes the first committed step in fatty acid synthesis. Herein, we report the 2.6 Å resolution crystal structure of moiramide B bound to carboxyltransferase. An unanticipated but significant finding was that moiramide B bound as the enol/enolate. Crystallographic studies demonstrate that the (4S)-methyl succinimide moiety interacts with the oxyanion holes of the enzyme, supporting the notion that an anionic enolate is the active form of the antibacterial agent. Structure-activity studies demonstrate that the unsaturated fatty acid tail of moiramide B is needed only for entry into the bacterial cell. These results will allow the design of new antibacterial agents against the bacterial form of carboxyltransferase.

Design, radiosynthesis, and evaluation of radiotracers for positron emission tomography imaging of stearoyl-CoA desaturase-1.

Design, radiosynthesis, and biological evaluation of two radiotracers (N-(3-[(18)F]fluoropropyl)-6-(4-(trifluoromethyl)benzoyl)-piperazin-1-yl)pyridazine-3-carboxamide ((18)F-FPPPT) and (N-(4-[(18)F]fluoroaniline)-6-(4-(trifluoromethyl)benzoyl)-piperazin-1-yl)pyridazine-3-carboxamide ((18)F-FAPPT)) are described for noninvasive assessment of stearoyl-CoA desaturase-1 (SCD-1). The overexpression of SCD-1 in multiple solid tumors associates with poor survival in cancer patients. The two radiotracers, (18)F-FPPPT and (18)F-FAPPT, were each prepared in three steps in radiochemical yields of 21% and 3%, respectively. The practicality of imaging SCD-1 with (18)F-FPPPT was tested in two mouse models bearing xenograft tumors with different levels of SCD-1 expression, which afforded a 1.8-fold uptake difference correspondingly. Our work indicates that it is possible to develop SCD-1 specific imaging probes from previously reported SCD-1 inhibitors.

Oxidoreductase-Facilitated Visualization and Detection of Human Cancer Cells.

Achieving highly selective and sensitive detection/visualization of intracellular biological events through the use of cell-penetrable, bioanalyte-activatable, turn-on probes is dependent on the presence of specific event-linked cellular biomarkers, if and only if there exist activatable probes that appropriately respond to the biomarker analyte. Here is described the evaluation of, and use in cellular imaging studies, a previously undisclosed naphthalimide probe QMeNN, whose fluorescence is deactivated by photoinduced electron transfer (PeT) quenching that results from the presence of a covalently linked biomarker-specific quinone trigger group. Highly selective and rapid activation of the quinone group by the human cancer tumor-linked NAD(P)H: quinone oxido-reductase isozyme 1 (hNQO1) results in fast trigger group removal to yield a highly fluorescent green-energy-range reporter that possesses a high molar absorptivity; there is a 136-fold increase in brightness for the enzymatically produced reporter versus probe precursor, a value 4 times greater than previously reported for the hNQO1 analyte. The novel probe is taken up and activated rapidly within only hNQO1-positive human cancer cells; addition of an hNQO1 inhibitor prevents the selective activation of the probe. Comparison of cytosolic fluorescence intensity in positive cells versus background in negative cells yields a quantitative metric (positive-to-negative ratio, PNR) for judging hNQO1 activity. We show it is possible to determine hNQO1 presence in previously studied colorectal cancer cells and the unexplored ovarian cancer cell line NIH:OVCAR-3, with respective PNR values of 926 and 34 being obtained. Even with 10 min probe incubation, ready discrimination of positive cells from negative cells is achieved. Cell viability is unaffected by probe presence, thereby highlighting the practicality of probe use in live-cell imaging applications.

Profluorogenic reductase substrate for rapid, selective, and sensitive visualization and detection of human cancer cells that overexpress NQO1.

Achieving the vision of identifying and quantifying cancer-related events and targets for future personalized oncology is predicated on the existence of synthetically accessible and economically viable probe molecules fully able to report the presence of these events and targets in a rapid and highly selective and sensitive fashion. Delineated here are the design and evaluation of a newly synthesized turn-on probe whose intense fluorescent reporter signature is revealed only through probe activation by a specific intracellular enzyme present in tumor cells of multiple origins. Quenching of molecular probe fluorescence is achieved through unique photoinduced electron transfer between the naphthalimide dye reporter and a covalently attached, quinone-based enzyme substrate. Fluorescence of the reporter dye is turned on by rapid removal of the quinone quencher, an event that immediately occurs only after highly selective, two-electron reduction of the sterically and conformationally restricted quinone substrate by the cancer-associated human NAD(P)H:quinone oxidoreductase isozyme 1 (hNQO1). Successes of the approach include rapid differentiation of NQO1-expressing and -nonexpressing cancer cell lines via the unaided eye, flow cytometry, fluorescence imaging, and two-photon microscopy. The potential for use of the turn-on probe in longer-term cellular studies is indicated by its lack of influence on cell viability and its in vitro stability.

A Call to Commemorate International Holocaust Remembrance Day, January 27, in All Health Science Schools.

This viewpoint proposes why and how Holocaust Remembrance Day, January 27, should be honored in all health professions schools. A public letter, from which this viewpoint is adapted, has been endorsed by over 50 teachers of medicine, ethics, and history.

Teaching Health Professions Students About the Holocaust.

The legacy of health professionals' roles in the Holocaust is fundamental to understanding modern health care ethics, but teaching it is difficult. The University of Colorado Center for Bioethics and Humanities has developed a program that addresses 4 main pedagogical challenges of this content. This article identifies 3 core lessons and proposes 5 specific learning objectives related to health professionals' involvement in the Holocaust for any health professional training program.

Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT.

Copper-67 (t1/2 = 2.58 days) decays by ß- ([Formula: see text]: 562 keV) and γ-rays (93 keV and 185 keV) rendering it with potential for both radionuclide therapy and single-photon emission computed tomography (SPECT) imaging. Prompted by the recent breakthrough of 67Cu production with high specific activity, high radionuclidic purity, and sufficient quantities, the interest in the theranostic potential of 67Cu has been rekindled. This work addresses the practicability of developing 67Cu-labeled antibodies with substantially improved quality for cancer radioimmunotheranostics. Proof of concept is demonstrated with pertuzumab, a US-FDA-approved monoclonal antibody for combination therapies of HER2-positive breast cancer. With an average number of 1.9 chelators coupled to each antibody, we achieved a two-order of magnitude increase in radiolabeling efficiency compared to literature reports. In a preclinical therapeutic study, mice (n = 4-7/group) bearing HER2+ xenografts exhibited a 67Cu-dose dependent tumor-growth inhibition from 67Cu-labeled-Pertuzumab co-administered with trastuzumab. Furthermore, greater tumor size reduction was observed with 67Cu-labeled-pertuzumab formulations of higher specific activity. The potential of SPECT imaging with 67Cu radiopharmaceuticals was tested after 67Cu-labeled-Pertuzumab administration. Impressively, all tumors were clearly visualized by SPECT imaging with 67Cu-labeled-Pertuzumab even at day 5 post injection. This work demonstrates it is practical to use 67Cu radioimmunoconjugates for cancer radioimmunotheranostics.

Attitudes about cannabis mediate the relationship between cannabis knowledge and use in active adult athletes.

BACKGROUND: Little is known about how cannabis knowledge and attitudes impact cannabis use behavior. OBJECTIVE: To test the knowledge-attitudes-behavior paradigm in active adult athletes. DESIGN: The Athlete Pain, Exercise, and Cannabis Experience (PEACE) Survey, a cross-sectional survey study, used social media and email blasts to recruit participants and SurveyGizmo to collect data. PARTICIPANTS: Self-defined active adult athletes (n = 1161). MAIN MEASURES: Knowledge about cannabis was evaluated with four questions. Attitudes toward cannabis was evaluated with 11 questions. The attitudes questions were used in a TwoStep Cluster analysis in SPSS to assign group membership by attitudes. Chi-square was used to determine if there were differences in cluster membership by demographic factors and if knowledge about cannabis differed by cluster membership. Regression analysis was performed to determine if cannabis attitudes mediated the relationship between cannabis knowledge and cannabis use. KEY RESULTS: A three-cluster solution was the best fit to the data. The clusters were named Conservative (n = 374, 32.2%), Unsure (n = 533, 45.9%), and Liberal (n = 254, 21.9). There was a significant difference among the clusters for all 11 attitudes items (all p < 0.001). Attitude cluster membership was significantly different by age (p < 0.001), primary sport (p < 0.05), and knowledge about cannabis (p < 0.001). Athletes in the liberal cluster answered the knowledge questions correctly most often. Attitudes mediated the relationship between cannabis knowledge and cannabis use [Never (32.4%), Past (41.6%), Current (26.0%)] with athletes in the liberal cluster showing more knowledge and greater likelihood to be a current cannabis user (p < 0.001). Among current cannabis users there were differential patterns of cannabis use depending on their attitudes and knowledge; liberal athletes tended to co-use THC and CBD and used cannabis longer. (p < 0.001). CONCLUSIONS: Cannabis education needs to consider attitudes about cannabis, especially among those who might benefit from medical cannabis.

Cannabis: An Emerging Occupational Allergen?

Cannabis is the most commonly used psychoactive drug. In recent years, Cannabis access has expanded for both medicinal and non-medicinal has grown. This is also marked with an increasing number of individuals gaining employment in this emerging industry. In this article, we briefly discuss the health hazards associated with Cannabis exposure with an emphasis on the potential for allergic reactions in workers who handle and process Cannabis plant.

Occupational Allergies to Cannabis.

Within the last decade there has been a significant expansion in access to cannabis for medicinal and adult nonmedical use in the United States and abroad. This has resulted in a rapidly growing and diverse workforce that is involved with the growth, cultivation, handling, and dispensing of the cannabis plant and its products. The objective of this review was to educate physicians on the complexities associated with the health effects of cannabis exposure, the nature of these exposures, and the future practical challenges of managing these in the context of allergic disease. We will detail the biological hazards related to typical modern cannabis industry operations that may potentially drive allergic sensitization in workers. We will highlight the limitations that have hindered the development of objective diagnostic measures that are essential in separating "true" cannabis allergies from nonspecific reactions/irritations that "mimic" allergy-like symptoms. Finally, we will discuss recent advances in the basic and translational scientific research that will aid the development of diagnostic tools and therapeutic standards to serve optimal management of cannabis allergies across the occupational spectrum.