Gamma irradiation is commonly used to decontaminate medicinal cannabis and meet strict microbial safety standards. The author evaluated the effects of gamma irradiation on four varieties of medicinal cannabis covering different cannabinoid compositions and plant types. Quantitative analysis found no changes in THC or CBD content after irradiation. Some terpenes were reduced but the overall terpene profile was maintained. Water content and microscopic structure were also unchanged. Gamma irradiation remains the recommended method for decontamination until better alternatives are developed and validated.
Natural Products: The Case for a Product Development Paradigm in Malaysian Na...Murray Hunter
The document discusses the need for a new paradigm in natural product research in Malaysia that focuses on development and commercialization, rather than just discovery and publication. It outlines a natural product development process involving biological and regulatory screening, market development, technical development, and commercialization strategies. This requires a shift from single discipline research to multidisciplinary collaboration with an emphasis on potential applications and economic viability.
This document provides an overview of pharmacovigilance and phytoresearch. It discusses the process of pharmacovigilance including adverse drug reaction reporting and its history and purpose. Key terms in pharmacovigilance like causation and stakeholders are defined. The document also covers the identification, extraction, and detection methods used in phytoresearch like chromatography, spectroscopy, and endophyte evaluation. Skills gained in pharmacovigilance like risk management and report writing and those in phytoresearch like instrumentation use and formulation development are summarized. The conclusion emphasizes the goals of ensuring drug safety and discovering bioactive plant compounds.
Biologist Louis Guillette found alligators at Lake Apopka, Florida with reproductive abnormalities. Research revealed that chemicals contaminating the lake were disrupting the alligators' reproductive hormones. The lake had been contaminated with pesticides that acted as endocrine disruptors.
Regulatory toxicologists provide science-based advice to governments, companies, health professionals, politicians, and the public on potential hazards and risks associated with chemical exposure. Their role is to identify health hazards and risks posed by substances to allow for appropriate risk management strategies to protect public health. However, regulatory toxicology does not operate as public relations, sales, advertising, lobbying, or spin doctoring. Rather, it is a scientific discipline that builds knowledge through testable hypotheses. Regulatory toxicologists must navigate complex social and political factors like risk perception, communication, and what constitutes an "acceptable risk." Their aim is to advocate for informed and balanced decision making regarding chemical risks.
Toxicology is the study of poisons and their effects on living organisms. It involves understanding the adverse health effects of chemicals and their mechanisms of action. Toxicology assimilates knowledge from various fields to study how chemicals are absorbed, distributed, metabolized and excreted by the body, and to characterize dose-response relationships. The response depends on factors like the chemical properties, route and duration of exposure, and individual susceptibility. Toxicity can range from reversible pharmacological effects to irreversible damage, and interactions between chemicals may result in additive, synergistic or antagonistic effects.
Introduction to toxicology gases and metalsNITISH SHAH
Toxicology is the study of the harmful effects of chemicals on living organisms, with toxicologists studying these effects and assessing the probability of their occurrence. The document outlines the key aspects of toxicology including what it entails, common toxic agents, how toxicity is classified and measured, diagnostic evaluation of potential poisoning, and general management approaches for poisoning patients. Toxicology plays an important role in various fields including public health, forensics, occupational safety and environmental protection.
Application of deuterium in drug discoveryRahul B S
Deuterium, a stable isotope of hydrogen, can be used in drug discovery to modify drugs' pharmacokinetic and pharmacodynamic properties. Replacing hydrogen with deuterium (deuteration) utilizes the kinetic isotope effect to slow metabolism and increase drug exposure. Several deuterated drugs have been clinically tested, including D1-halothane, fludalanine, D6-nifedipine, and deuterated nevirapine, which all showed improved properties over their non-deuterated counterparts. The deuterium chemical entity platform allows for more efficient drug development by building upon existing drugs and clinical compounds. Challenges include deuterium exchange and metabolic switching, but overall deuter
This presentation provides a knowledge about Toxicology, its types , definition, regulatory guidelines for conducting toxicological studies, OECD guidelines for GLP. This is an assignment in the subject, Pharmacological & Toxicological Screening Methods - II, 2nd Semester, M.Pharm (Pharmacology)
Natural Products: The Case for a Product Development Paradigm in Malaysian Na...Murray Hunter
The document discusses the need for a new paradigm in natural product research in Malaysia that focuses on development and commercialization, rather than just discovery and publication. It outlines a natural product development process involving biological and regulatory screening, market development, technical development, and commercialization strategies. This requires a shift from single discipline research to multidisciplinary collaboration with an emphasis on potential applications and economic viability.
This document provides an overview of pharmacovigilance and phytoresearch. It discusses the process of pharmacovigilance including adverse drug reaction reporting and its history and purpose. Key terms in pharmacovigilance like causation and stakeholders are defined. The document also covers the identification, extraction, and detection methods used in phytoresearch like chromatography, spectroscopy, and endophyte evaluation. Skills gained in pharmacovigilance like risk management and report writing and those in phytoresearch like instrumentation use and formulation development are summarized. The conclusion emphasizes the goals of ensuring drug safety and discovering bioactive plant compounds.
Biologist Louis Guillette found alligators at Lake Apopka, Florida with reproductive abnormalities. Research revealed that chemicals contaminating the lake were disrupting the alligators' reproductive hormones. The lake had been contaminated with pesticides that acted as endocrine disruptors.
Regulatory toxicologists provide science-based advice to governments, companies, health professionals, politicians, and the public on potential hazards and risks associated with chemical exposure. Their role is to identify health hazards and risks posed by substances to allow for appropriate risk management strategies to protect public health. However, regulatory toxicology does not operate as public relations, sales, advertising, lobbying, or spin doctoring. Rather, it is a scientific discipline that builds knowledge through testable hypotheses. Regulatory toxicologists must navigate complex social and political factors like risk perception, communication, and what constitutes an "acceptable risk." Their aim is to advocate for informed and balanced decision making regarding chemical risks.
Toxicology is the study of poisons and their effects on living organisms. It involves understanding the adverse health effects of chemicals and their mechanisms of action. Toxicology assimilates knowledge from various fields to study how chemicals are absorbed, distributed, metabolized and excreted by the body, and to characterize dose-response relationships. The response depends on factors like the chemical properties, route and duration of exposure, and individual susceptibility. Toxicity can range from reversible pharmacological effects to irreversible damage, and interactions between chemicals may result in additive, synergistic or antagonistic effects.
Introduction to toxicology gases and metalsNITISH SHAH
Toxicology is the study of the harmful effects of chemicals on living organisms, with toxicologists studying these effects and assessing the probability of their occurrence. The document outlines the key aspects of toxicology including what it entails, common toxic agents, how toxicity is classified and measured, diagnostic evaluation of potential poisoning, and general management approaches for poisoning patients. Toxicology plays an important role in various fields including public health, forensics, occupational safety and environmental protection.
Application of deuterium in drug discoveryRahul B S
Deuterium, a stable isotope of hydrogen, can be used in drug discovery to modify drugs' pharmacokinetic and pharmacodynamic properties. Replacing hydrogen with deuterium (deuteration) utilizes the kinetic isotope effect to slow metabolism and increase drug exposure. Several deuterated drugs have been clinically tested, including D1-halothane, fludalanine, D6-nifedipine, and deuterated nevirapine, which all showed improved properties over their non-deuterated counterparts. The deuterium chemical entity platform allows for more efficient drug development by building upon existing drugs and clinical compounds. Challenges include deuterium exchange and metabolic switching, but overall deuter
This presentation provides a knowledge about Toxicology, its types , definition, regulatory guidelines for conducting toxicological studies, OECD guidelines for GLP. This is an assignment in the subject, Pharmacological & Toxicological Screening Methods - II, 2nd Semester, M.Pharm (Pharmacology)
In tech natural-products_from_plants_as_potential_source_agents_for_controlli...Friska Aprianti
This document provides an overview of natural products from plants that have potential antifungal activity against Fusarium. It discusses Fusarium as an important plant pathogen, current chemical control methods and their drawbacks. It then reviews several plant-derived natural products that have shown antifungal effects against Fusarium in laboratory assays, suggesting they may provide more sustainable alternatives for controlling this fungus.
This document presents a study on the safety evaluation of microalgae in rodents. The study aims to evaluate the acute and sub-acute oral toxicity of various microalgae species, including Cladophora, Spirogyra, and Chlorella, in rats. The study will involve collecting algal biomass, selecting and housing laboratory animals, and administering single and repeated doses of the algal extracts to test groups of rats. The rats will be observed for toxicity and various physiological parameters will be measured over the course of the study period. The results will help determine if the algal species are safe enough to be used as nutritional supplements, pharmaceutical ingredients, or other applications.
This document discusses basic concepts in toxicology. It defines toxicology as the study of adverse effects of chemicals on living organisms. Toxic effects can occur through various routes of exposure and be seen immediately or long after exposure. The dose and duration of exposure determine the severity of response. Target organs are also discussed, where specific tissues are affected rather than the whole body. Factors like intrinsic toxicity, dose, exposure conditions, and individual susceptibility influence the adverse health effects of toxins.
The document discusses the management of biomedical waste from hospitals. It notes that hospital waste is classified as 85% non-hazardous and 15% hazardous, with the hazardous waste further divided into infectious (10%) and toxic (5%). The key aspects of management include proper segregation of waste based on category at the point of generation, use of colored containers, treatment and disposal options according to waste type, and compliance with the Bio-Medical Waste (Management and Handling) Rules 1998 which regulate waste disposal. Improper management can pose health risks like infections to patients, staff and the public.
This document provides an introduction to the field of pharmacology. It defines pharmacology and discusses the history and scope of the field. It describes different types of drugs sources including natural, semi-synthetic, synthetic and biosynthetic sources. It also outlines various routes of drug administration including local, oral, rectal, inhalation and parenteral routes. The document provides definitions of key terminologies and concepts in pharmacology including essential medicines.
Toxicology is the study of how poisons affect living organisms. Some key points:
- Toxicology has a long history dating back to the 15th century physician Paracelsus who said "the dose makes the poison."
- Toxicants can enter the body through various routes like skin contact, inhalation, or ingestion and cause local or systemic effects.
- Toxicants are classified into categories like heavy metals, solvents, radiation, pesticides, and plant/animal toxins. Each can have acute and chronic health effects depending on dose and route of exposure.
- Toxicokinetics refers to how the body absorbs, distributes, and eliminates toxins while
introduction toxicology, general information on some basic toxins used in day to day life and also unknown toxins we are always in contact with but little do we know about them
This document discusses herbs and natural products as a major source of drug discovery. It begins by explaining how natural products, including plants, animals, and minerals, have historically formed the basis of traditional medicine and modern drugs. The majority of new drugs are still generated from natural products or compounds derived from them. The document then discusses the history of using plant extracts in medicine before the 20th century and the later focus on isolating pure chemical compounds from extracts. It provides examples of important drugs discovered this way, like morphine, aspirin, antibiotics. The rest of the document outlines the process used today in natural product drug discovery, including techniques like high-throughput screening, dereplication, and lead optimization used to identify potential drug candidates from
Antimalarial activity gardenia lutea and sida rhombifolia ijrpppharmamailbox1
This study investigated the in vivo antimalarial activity of hydroalcoholic leaf extracts of Gardenia lutea and Sida rhombifolia against Plasmodium berghei in mice. The extracts were administered orally at doses of 200, 400, and 600 mg/kg to infected mice. The extracts showed significant antimalarial activity in a dose-dependent manner, reducing parasitemia compared to the negative control. The plant extracts also demonstrated an acceptable safety profile at test doses up to 2000 mg/kg. The results suggest that Gardenia lutea and Sida rhombifolia extracts have promising antimalarial properties worthy of further study.
Natural products are an important source for drug discovery. The drug discovery process involves several steps including target identification, validation, lead identification and optimization through screening compounds for activity against the target. Promising lead compounds then undergo preclinical testing in labs and animal models before progressing to human clinical trials. Computational tools also play an important role in drug design, such as identifying binding sites on target proteins and modeling molecular interactions to optimize lead compounds. Natural products, especially toxins from venom, continue to provide templates for rational drug design.
The document discusses the field of toxicology, including its definition, scope, history, and methods for evaluating toxicity. Toxicology is defined as the study of adverse effects of chemicals on living organisms. The scope of toxicology includes biomedical research, public health, regulation, and clinical applications. Historically, toxicology dates back to ancient uses of poisons and has evolved with scientific advancements. Modern methods for evaluating toxicity include analyzing case reports of poisonings, developing predictive models based on chemical structure, and conducting in vitro, in vivo, and environmental toxicity tests.
Toxicology is the scientific study of adverse effects that occur in living organisms due to chemicals. It involves observing and reporting symptoms that arise following exposure to toxic substances.
Toxicology is the branch of science that deals with nature, effects, and detection of poison. The degree to which a substance can harm an organism is called toxicity. The types of toxicity depending upon the time of exposure of the toxicant have been described.
This document provides an overview of herbal medicines. It discusses that herbal medicines are plant-based preparations used in traditional and modern medical practices. The World Health Organization defines herbal medicines and categorizes them. The document then covers the scientific and non-scientific reasons for using herbal medicines to treat diseases. It also discusses herbal medicine safety, efficacy, present market scenario, and potential future developments. In particular, it notes the growing interest in herbal medicines due to concerns about side effects of synthetic drugs, herbal medicines' potential as sources of new pharmaceuticals, and their widespread traditional use.
Final course module for may 2010 pharmacology-iii - copy - copypctebpharm
This document provides information on the Pharmacology-III course for 7th semester B.Pharm students. The 40-lecture course covers drugs acting on the gastrointestinal tract, endocrine system, chemotherapy, and toxicology principles. Assessment includes assignments, presentations, tests, and semester exams. Students must maintain 75% attendance and follow instructions for assignments, presentations, and practicals to be eligible to appear for exams. The course aims to provide in-depth knowledge of drug pharmacokinetics, pharmacodynamics, and therapeutic and toxic effects.
This document discusses environmental pharmacology and the impacts of pharmaceuticals on the environment. It begins by defining environmental pharmacology as dealing with chemicals and drugs that enter the environment after being eliminated from humans and animals. It then discusses how low levels of various drugs like beta-blockers, clofibric acid, and steroids have been detected in water supplies. The document outlines the origins of pharmaceuticals and personal care products in the environment from excretion and incomplete removal by sewage treatment. It details several impacts drugs can have on aquatic organisms and potential subtle effects. The document calls for improved waste and water treatment and controlling overuse to minimize environmental effects of pharmaceuticals.
General medicine health assistant syllabus 2010sarosem
The curriculum document outlines the course structure and requirements for a Certificate in General Medicine program over three years. The second year includes courses in Medicine I, Surgery I, Clinical Pathology, Obstetrics/Gynecology, Pharmacology, Environmental Health, and other subjects. For Medicine I specifically, the document details that the course involves an in-depth presentation on diagnostic processes, history taking, and physical examination. It then covers selected conditions and disorders of internal systems as well as common communicable diseases in Nepal. The course objectives are to enable students to perform examinations and analyses, identify conditions, describe management and counseling, and identify opportunities for prevention and referral.
Toxicity testing is a way to discover the toxic effects of a drug or chemical on experimental animals and assess their potential safety for the humans and environment.
In tech natural-products_from_plants_as_potential_source_agents_for_controlli...Friska Aprianti
This document provides an overview of natural products from plants that have potential antifungal activity against Fusarium. It discusses Fusarium as an important plant pathogen, current chemical control methods and their drawbacks. It then reviews several plant-derived natural products that have shown antifungal effects against Fusarium in laboratory assays, suggesting they may provide more sustainable alternatives for controlling this fungus.
This document presents a study on the safety evaluation of microalgae in rodents. The study aims to evaluate the acute and sub-acute oral toxicity of various microalgae species, including Cladophora, Spirogyra, and Chlorella, in rats. The study will involve collecting algal biomass, selecting and housing laboratory animals, and administering single and repeated doses of the algal extracts to test groups of rats. The rats will be observed for toxicity and various physiological parameters will be measured over the course of the study period. The results will help determine if the algal species are safe enough to be used as nutritional supplements, pharmaceutical ingredients, or other applications.
This document discusses basic concepts in toxicology. It defines toxicology as the study of adverse effects of chemicals on living organisms. Toxic effects can occur through various routes of exposure and be seen immediately or long after exposure. The dose and duration of exposure determine the severity of response. Target organs are also discussed, where specific tissues are affected rather than the whole body. Factors like intrinsic toxicity, dose, exposure conditions, and individual susceptibility influence the adverse health effects of toxins.
The document discusses the management of biomedical waste from hospitals. It notes that hospital waste is classified as 85% non-hazardous and 15% hazardous, with the hazardous waste further divided into infectious (10%) and toxic (5%). The key aspects of management include proper segregation of waste based on category at the point of generation, use of colored containers, treatment and disposal options according to waste type, and compliance with the Bio-Medical Waste (Management and Handling) Rules 1998 which regulate waste disposal. Improper management can pose health risks like infections to patients, staff and the public.
This document provides an introduction to the field of pharmacology. It defines pharmacology and discusses the history and scope of the field. It describes different types of drugs sources including natural, semi-synthetic, synthetic and biosynthetic sources. It also outlines various routes of drug administration including local, oral, rectal, inhalation and parenteral routes. The document provides definitions of key terminologies and concepts in pharmacology including essential medicines.
Toxicology is the study of how poisons affect living organisms. Some key points:
- Toxicology has a long history dating back to the 15th century physician Paracelsus who said "the dose makes the poison."
- Toxicants can enter the body through various routes like skin contact, inhalation, or ingestion and cause local or systemic effects.
- Toxicants are classified into categories like heavy metals, solvents, radiation, pesticides, and plant/animal toxins. Each can have acute and chronic health effects depending on dose and route of exposure.
- Toxicokinetics refers to how the body absorbs, distributes, and eliminates toxins while
introduction toxicology, general information on some basic toxins used in day to day life and also unknown toxins we are always in contact with but little do we know about them
This document discusses herbs and natural products as a major source of drug discovery. It begins by explaining how natural products, including plants, animals, and minerals, have historically formed the basis of traditional medicine and modern drugs. The majority of new drugs are still generated from natural products or compounds derived from them. The document then discusses the history of using plant extracts in medicine before the 20th century and the later focus on isolating pure chemical compounds from extracts. It provides examples of important drugs discovered this way, like morphine, aspirin, antibiotics. The rest of the document outlines the process used today in natural product drug discovery, including techniques like high-throughput screening, dereplication, and lead optimization used to identify potential drug candidates from
Antimalarial activity gardenia lutea and sida rhombifolia ijrpppharmamailbox1
This study investigated the in vivo antimalarial activity of hydroalcoholic leaf extracts of Gardenia lutea and Sida rhombifolia against Plasmodium berghei in mice. The extracts were administered orally at doses of 200, 400, and 600 mg/kg to infected mice. The extracts showed significant antimalarial activity in a dose-dependent manner, reducing parasitemia compared to the negative control. The plant extracts also demonstrated an acceptable safety profile at test doses up to 2000 mg/kg. The results suggest that Gardenia lutea and Sida rhombifolia extracts have promising antimalarial properties worthy of further study.
Natural products are an important source for drug discovery. The drug discovery process involves several steps including target identification, validation, lead identification and optimization through screening compounds for activity against the target. Promising lead compounds then undergo preclinical testing in labs and animal models before progressing to human clinical trials. Computational tools also play an important role in drug design, such as identifying binding sites on target proteins and modeling molecular interactions to optimize lead compounds. Natural products, especially toxins from venom, continue to provide templates for rational drug design.
The document discusses the field of toxicology, including its definition, scope, history, and methods for evaluating toxicity. Toxicology is defined as the study of adverse effects of chemicals on living organisms. The scope of toxicology includes biomedical research, public health, regulation, and clinical applications. Historically, toxicology dates back to ancient uses of poisons and has evolved with scientific advancements. Modern methods for evaluating toxicity include analyzing case reports of poisonings, developing predictive models based on chemical structure, and conducting in vitro, in vivo, and environmental toxicity tests.
Toxicology is the scientific study of adverse effects that occur in living organisms due to chemicals. It involves observing and reporting symptoms that arise following exposure to toxic substances.
Toxicology is the branch of science that deals with nature, effects, and detection of poison. The degree to which a substance can harm an organism is called toxicity. The types of toxicity depending upon the time of exposure of the toxicant have been described.
This document provides an overview of herbal medicines. It discusses that herbal medicines are plant-based preparations used in traditional and modern medical practices. The World Health Organization defines herbal medicines and categorizes them. The document then covers the scientific and non-scientific reasons for using herbal medicines to treat diseases. It also discusses herbal medicine safety, efficacy, present market scenario, and potential future developments. In particular, it notes the growing interest in herbal medicines due to concerns about side effects of synthetic drugs, herbal medicines' potential as sources of new pharmaceuticals, and their widespread traditional use.
Final course module for may 2010 pharmacology-iii - copy - copypctebpharm
This document provides information on the Pharmacology-III course for 7th semester B.Pharm students. The 40-lecture course covers drugs acting on the gastrointestinal tract, endocrine system, chemotherapy, and toxicology principles. Assessment includes assignments, presentations, tests, and semester exams. Students must maintain 75% attendance and follow instructions for assignments, presentations, and practicals to be eligible to appear for exams. The course aims to provide in-depth knowledge of drug pharmacokinetics, pharmacodynamics, and therapeutic and toxic effects.
This document discusses environmental pharmacology and the impacts of pharmaceuticals on the environment. It begins by defining environmental pharmacology as dealing with chemicals and drugs that enter the environment after being eliminated from humans and animals. It then discusses how low levels of various drugs like beta-blockers, clofibric acid, and steroids have been detected in water supplies. The document outlines the origins of pharmaceuticals and personal care products in the environment from excretion and incomplete removal by sewage treatment. It details several impacts drugs can have on aquatic organisms and potential subtle effects. The document calls for improved waste and water treatment and controlling overuse to minimize environmental effects of pharmaceuticals.
General medicine health assistant syllabus 2010sarosem
The curriculum document outlines the course structure and requirements for a Certificate in General Medicine program over three years. The second year includes courses in Medicine I, Surgery I, Clinical Pathology, Obstetrics/Gynecology, Pharmacology, Environmental Health, and other subjects. For Medicine I specifically, the document details that the course involves an in-depth presentation on diagnostic processes, history taking, and physical examination. It then covers selected conditions and disorders of internal systems as well as common communicable diseases in Nepal. The course objectives are to enable students to perform examinations and analyses, identify conditions, describe management and counseling, and identify opportunities for prevention and referral.
Toxicity testing is a way to discover the toxic effects of a drug or chemical on experimental animals and assess their potential safety for the humans and environment.
Este documento describe los módulos de capacitación en TIC para personas en situación de vulnerabilidad, incluyendo personas con discapacidad. Los módulos cubren temas como alfabetización digital, e-gobierno, e-learning, uso de TIC en artesanía, turismo y agricultura. El documento también describe las estrategias para formar instructores, enfocándose en el "saber", "saber hacer" y "saber ser". Los instructores deben dominar los contenidos de los módulos y aplicarlos de manera efectiva para convert
El documento describe un caso de bronquiolitis aguda en niños menores de 2 años. Generalmente es causada por el virus sincitial respiratorio y causa obstrucción de las vías respiratorias pequeñas luego de una infección del tracto respiratorio superior, presentando síntomas como sibilancias, tos y dificultad respiratoria. El tratamiento incluye broncodilatadores, corticoides, nebulizaciones y oxigenoterapia, pudiendo requerir hospitalización en casos graves.
O documento discute a assistência de enfermagem ao paciente politraumatizado e queimado. Ele fornece orientações sobre o atendimento inicial a esses pacientes, incluindo a avaliação ABCDE, medidas de suporte vital, exames complementares e reavaliações constantes. Também aborda classificações e agentes causadores de queimaduras, além dos cuidados com pacientes nessa condição.
Priorização de Portfólio de Projetos com o MS EPMAllan Rocha
O documento discute a importância da priorização de portfólios de projetos para alinhar investimentos às estratégias de negócio e objetivos organizacionais. Ele explica que a priorização de portfólios envolve definir drivers de negócios, medir o impacto potencial de projetos nesses drivers, e selecionar projetos de acordo com sua contribuição aos drivers mais importantes e à estratégia geral da empresa.
A student named Bibi Cantu is in class 9B. They appear to be student number 2 in that class. The document provides minimal identifying information for a single student.
Este documento discute os benefícios do planejamento com ERP, incluindo funcionalidade, disciplina, consistência e integração. Ele também descreve os vários níveis de planejamento no ERP, como planejamento estratégico, S&OP, planejamento de vendas e operações, MPS e programação mestre da produção. O objetivo do workshop é conscientizar sobre a importância do planejamento e implementar melhores práticas com o uso do ERP.
The document promotes an evening event that is still ongoing. It is sponsored by Preferred Capital Funding, a company that likely provides financial services related to funding or capital. In short, the brief document advertises a continuing evening event and names its corporate sponsor.
Comunidade Zabbix Brasil - Zabbix Conference LatAM 2016André Déo
O documento descreve a Comunidade Zabbix Brasil, fundada em 2008 para apoiar profissionais de TI no Brasil com o monitoramento de rede Zabbix. A comunidade cresceu para mais de 3400 membros no Facebook e 1750 na lista de discussão, fornecendo suporte em português e compartilhando projetos como relatórios, geolocalização, implementações SNMP e vídeos tutoriais. O fundador incentiva a participação para ajudar iniciantes e melhorar a documentação.
This document discusses using demographic data to improve segmentation and targeting in direct marketing. It provides examples showing that males and certain age groups tend to be more valuable donors. Specifically, males on average give 46% higher gifts and are 50% more valuable donors. Donors ages 45-54 generate the highest revenue per donor of all age groups. The document recommends testing gender and age-based segmentation, list selection, and messaging to acquire and upgrade more valuable male and certain age range donors.
El documento habla sobre la antigua Roma en el siglo II a.C., incluyendo la esclavitud como nueva fuente de riqueza, el conflicto entre el campo y la ciudad, y los intentos de los Gracos por cambiar el orden social. Luego se enfoca en Julio César y Pompeyo entre los años 100-48 a.C., sus ejércitos sin patriotismo, la conquista de las Galias por César en 50 a.C., y la guerra definitiva y muerte de César en 44 a.C.
The document discusses how fintechs and changing regulations have challenged banks' ability to attract talent. Management consulting firms are proving to be important allies for fintechs and banks by providing services like scalability, advisory support on new technologies, and connecting banks to fintech solutions. Selecting the right strategic partner is important for banks to efficiently comply with regulations and gain competitive advantages in the evolving financial landscape.
The OPS Leader-Manager Competency GuideWayne Wonder
This document provides an overview of the Ontario Public Service (OPS) Leader-Manager Competency Model from 2010. It includes:
- Descriptions of the four competencies (Connects, Delivers, Inspires, Transforms) and two attributes (Integrity, Self-Awareness) that make up the model and how they apply at different leadership levels.
- Details on how the competencies can be used for talent management, recruitment, learning and development, and succession planning.
- Applications of the model within the OPS and guidance on issues like diversity, change management, and vision/strategy.
- Competency dictionaries that define the focus areas for each competency at different leadership
O documento discute conceitos geográficos como espaço geográfico, cartografia, geologia, formação do relevo, recursos hídricos, climatologia e formações vegetais no Brasil. Aborda temas como projeções cartográficas, placas tectônicas, bacias hidrográficas, classificação climática e domínios morfoclimáticos. Fornece detalhes sobre mapas, coordenadas, escala, biomas, desmatamento e impactos ambientais.
11.protective effect of phyllanthus niruri on dmba croton oil mediated carcin...Alexander Decker
1) The study investigated the protective effects of Phyllanthus niruri extract (PNE) on skin carcinogenesis and oxidative damage in mice induced by 7,12-dimethylbenz(a)anthracene (DMBA) and croton oil.
2) PNE significantly reduced tumor incidence, burden, volume and weight compared to the carcinogen control group. It also prolonged the latent period of tumor occurrence.
3) PNE protected against losses in antioxidant levels like glutathione, vitamin C and activities of catalase and superoxide dismutase in the liver and skin caused by DMBA/croton oil. It also reduced lipid peroxidation levels.
4) PNE administration
Protective effect of phyllanthus niruri on dmba croton oil mediated carcinoge...Alexander Decker
1. The study investigated the protective effects of Phyllanthus niruri extract (PNE) on skin carcinogenesis induced by DMBA/croton oil in mice.
2. PNE significantly reduced tumor incidence, burden, volume and weight compared to the carcinogen control group. It also prolonged the latent period of tumor occurrence.
3. PNE administration protected against losses in antioxidant levels like glutathione, Vitamin C and activities of catalase and superoxide dismutase caused by DMBA/croton oil. It also reduced lipid peroxidation levels. PNE reverted pathological changes in skin and liver.
This document discusses various natural anticancer drugs, including taxanes like paclitaxel and docetaxel derived from yew trees, and podophyllotoxins like etoposide and teniposide derived from podophyllum hexandrum. It explains their mechanisms of action involving microtubule stabilization or inhibition of topoisomerase enzymes, and their clinical applications in treating several cancer types. Over 60% of anticancer drugs originate from natural products, and natural products continue providing leads for developing novel and selective anticancer agents.
The document discusses ecopharmacovigilance (EPV), which concerns adverse effects of pharmaceuticals in the environment. It notes that active pharmaceutical ingredients are emerging environmental contaminants consumed worldwide at over 100,000 tons annually. Even in trace amounts, they are a concern due to continuous introduction and impact on ecosystems and human/veterinary health. The document outlines sources of pharmaceuticals in the environment like patient excretion, manufacturing waste, and improper disposal. It discusses spread in water and effects of long-term exposure like antimicrobial resistance. Examples given include diclofenac poisoning vultures in South Asia and estrogenic effects on fish. The document advocates approaches like green drug design, minimizing emissions, and improved
Chemical carcinogens are substances capable of causing cancer through repeated or long-term exposure. They cause damage over time rather than immediately. Carcinogens are classified and their effects are studied through animal experiments and epidemiological studies. Proper handling of carcinogens involves engineering controls, personal protective equipment, labeling, storage, disposal, monitoring, training and standard operating procedures.
A investigatory project on carcinogens.
A very fatal disease causing bacteria tht can develop cancer cells in body. So as to get rod of cancer cells bacteria there are many therapy that can actually a boon to the patient of the india..
Two research articles on pesticides in cambodia 2011 02 28 vs 07 2011Scheewe
Brief discussion of the implication of two articles concerning pesticide use in vegetable production in Cambodia and effects on pesticide resiues in market vegetables.
Analytical method development of anticancer drugs by UV visible spectroscopySudip Khan
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This study evaluated 22 formulations of four essential drugs (paracetamol, acetylsalicylic acid, chloroquine, and sulphadoxine/pyrimethamine) marketed in Tanzania to analyze their drug content, in vitro availability through dissolution testing, and stability under simulated tropical storage conditions. While all formulations met requirements for drug content, seven failed dissolution testing requirements and five additional formulations failed dissolution testing after 6 months of accelerated stability testing. The results demonstrate that some essential drug formulations on the Tanzanian market meet potency standards but have unsatisfactory in vitro availability, failing to withstand typical tropical storage conditions.
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Irradiation does not affect medicinal cannabis
1. ORIGINAL RESEARCH
published: 27 April 2016
doi: 10.3389/fphar.2016.00108
Frontiers in Pharmacology | www.frontiersin.org 1 April 2016 | Volume 7 | Article 108
Edited by:
Adolfo Andrade-Cetto,
Universidad Nacional Autónoma de
México, Mexico
Reviewed by:
Jürg Gertsch,
University of Bern, Switzerland
Ashwell Rungano Ndhlala,
Agricultural Research Council,
South Africa
Ildikó Rácz,
University of Bonn, Germany
*Correspondence:
Arno Hazekamp
a.hazekamp@bedrocan.nl
Specialty section:
This article was submitted to
Ethnopharmacology,
a section of the journal
Frontiers in Pharmacology
Received: 25 January 2016
Accepted: 11 April 2016
Published: 27 April 2016
Citation:
Hazekamp A (2016) Evaluating the
Effects of Gamma-Irradiation for
Decontamination of Medicinal
Cannabis. Front. Pharmacol. 7:108.
doi: 10.3389/fphar.2016.00108
Evaluating the Effects of
Gamma-Irradiation for
Decontamination of Medicinal
Cannabis
Arno Hazekamp*
Head of Research and Education, Bedrocan International BV, Veendam, Netherlands
In several countries with a National medicinal cannabis program, pharmaceutical
regulations specify that herbal cannabis products must adhere to strict safety standards
regarding microbial contamination. Treatment by gamma irradiation currently seems the
only method available to meet these requirements. We evaluated the effects of irradiation
treatment of four different cannabis varieties covering different chemical compositions.
Samples were compared before and after standard gamma-irradiation treatment by
performing quantitative UPLC analysis of major cannabinoids, as well as qualitative
GC analysis of full cannabinoid and terpene profiles. In addition, water content and
microscopic appearance of the cannabis flowers was evaluated. This study found that
treatment did not cause changes in the content of THC and CBD, generally considered as
the most important therapeutically active components of medicinal cannabis. Likewise,
the water content and the microscopic structure of the dried cannabis flowers were not
altered by standard irradiation protocol in the cannabis varieties studied. The effect of
gamma-irradiation was limited to a reduction of some terpenes present in the cannabis,
but keeping the terpene profile qualitatively the same. Based on the results presented
in this report, gamma irradiation of herbal cannabis remains the recommended method
of decontamination, at least until other more generally accepted methods have been
developed and validated.
Keywords: medicinal cannabis, cannabinoids, terpenes, gamma-irradiation, quality control
INTRODUCTION
Because medicinal cannabis is often used by chronically ill patients affected by a weakened immune
system, pharmaceutical regulations in countries such as The Netherlands and Canada specify that
these products must adhere to strict safety standards regarding microbial contamination. When
harmful microbes or fungal spores are inhaled during e.g., vaporizing or smoking, they may directly
enter the bloodstream and cause opportunistic infections. Such contamination risks are not merely
hypothetical: cases of chronic pulmonary aspergillosis associated with smoking unsafe cannabis are
well established in the scientific literature (Llamas et al., 1978; Sutton et al., 1986; Marks et al., 1996;
Szyper-Kravitz et al., 2001; Kouevidjin et al., 2003; Cescon et al., 2008; Bal et al., 2010; Ruchlemer
et al., 2015). For those with compromised immune systems, such lung diseases could be even fatal
(Hamadeh et al., 1988).
2. Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
To minimize contamination risks to patients, Dutch
regulations demand that medicinal cannabis contains no more
than 100 colony-forming units (CFUs) per gram of final product,
which is close to sterility1. Under the Canadian program, limits
are somewhat higher with a maximum of 1.000 CFUs per gram2.
Following European or US Pharmacopoeia standards for inhaled
preparations, certain specific pathogens must be completely
absent, i.e., Staphylococcus aureus, Pseudomonas aeruginosa,
and any bile-tolerant Gram-negative bacteria such as E. coli
(EP, 2015; USP, 2015). Furthermore, the absence of fungal
mycotoxins must be confirmed by additional quality control
testing.
Decontamination of medicinal (herbal) cannabis is a
necessity, as it has yet not been possible to grow cannabis plants
under sufficiently sterile conditions to keep contamination
levels below the required safety limits. Even if this were feasible,
the multiple steps involved in harvesting, drying, processing
and packaging cannabis buds would make it extremely hard
to maintain near-sterile conditions throughout the entire
production procedure. As a result, medicinal cannabis in The
Netherlands as well as in Canada is treated by gamma irradiation
before it becomes available to patients1,2.
Methods of Decontamination
Reduction of microbes can be achieved by various treatments, as
listed in Table 1. The optimal choice of decontamination depends
on the nature of the product to be treated. For herbal materials
such as cannabis, the only currently viable option for treatment is
the use of ionizing radiation. Any of the other decontamination
treatments would either affect chemical content or texture (i.e.,
heat, chemicals, pressure, steam; Ruchlemer et al., 2015) or would
not penetrate beyond the surface of the dense cannabis flowers
(i.e., UV-light).
Gamma irradiation involves exposing the target material to
packets of light (photons) that are so highly energetic (gamma
rays) that they damage the DNA strands present in microbes. As
a result, the affected microbes cannot multiply, and consequently
they will perish3 . Because medicinal cannabis is a harvested and
dried (i.e., non-living) product, this effect is not relevant for the
condition of the cannabis plant cells.
Irradiation Safety and Concerns
Most commonly, the radioactive element cobalt-60 (60Co) is
used as the source for gamma irradiation. If administered at
appropriate levels, irradiation can be used for the removal of
decay-causing bacteria from many foods and herbs, and can
prevent sprouting of fruit and vegetables to maintain freshness
and flavor (EFSA Panel on Food Contact Materials Enzymes
Flavourings Processing Aids-CEF, 2011; Arvanitoyannis et al.,
2009). Decontamination or sterilization by gamma irradiation
is also widely applied to medical instruments and medicines
(Hasanain et al., 2014).
1https://www.cannabisbureau.nl/english/specication-sheets
2http://www.hc-sc.gc.ca/dhp-mps/marihuana/info/techni-eng.php
3http://www.cdc.gov/nczved/divisions/dfbmd/diseases/irradiation_food/#affect_
foods
TABLE 1 | List of current main methods available for decontamination or
sterilization of (food) products.
Type of decontamination Main treatments
Heat: Dry heat
Steam (autoclave)
Chemicals: Gas (ethylene oxide, ozone, nitrogen dioxide)
Liquid (hydrogen peroxide, formaldehyde)
High pressure: Pascalization
Filtration: Micropore filter (NB: for liquids only)
Radiation: Non-ionizing (UV-light)
Ionizing (gamma-irradiation, X-rays, electron beam)
Over the years, the safety of irradiated foods has been
confirmed in various animal as well as human studies. These
include animal feeding studies lasting for several generations
in several different species, including mice, rats and dogs
(WHO, 1999; EFSA Panel on Food Contact Materials Enzymes
Flavourings Processing Aids-CEF, 2011). NASA astronauts have
been eating irradiated foods when they fly in space since the
1970s (Perchonok and Bourland, 2002). Irradiation-induced
changes in food components are generally small and not
significantly different from those reported in other conventional
preservation processes, especially those based on thermal
treatment (EFSA Panel on Food Contact Materials Enzymes
Flavourings Processing Aids-CEF, 2011; Shahbaz et al., 2015).
The changes in some components that are sensitive to irradiation,
like some vitamins or micronutrients (Caulfield et al., 2008) may
be minimized by using proper treatment conditions (Kilcast,
1994; WHO, 1999).
The safety of irradiated foods has been endorsed by the
World Health Organization (WHO), the Food and Agriculture
Organization of the United Nations (FAO), the U.S. Department
of Agriculture (USDA), Health Canada (HC), the European
Union (EU), and the Food and Drug Administration (FDA).
Gamma irradiation is now permitted by over 60 countries with
at least 400,000 metric tons of foodstuffs annually processed
worldwide (EFSA Panel on Food Contact Materials Enzymes
Flavourings Processing Aids-CEF, 2011). The regulations that
dictate how food is to be irradiated, as well as which foods
are allowed to be treated, may vary greatly from country to
country4.
Despite these developments, irradiation remains a somewhat
controversial decontamination technique that can spark
emotional debates among the general public. One specific
concern with irradiation treatment is the formation of radiolytic
compounds, in particular 2-alkylcyclobutanones (2-ACBs).
These chemicals are formed in minute quantities when high
fat containing foods (such as sesame seeds, pork meat, cheese,
eggs, fish) are subjected to gamma irradiation, and their content
increases with irradiation dose (Zanardi et al., 2007; Lee et al.,
2008). Although some contradictory in vitro findings exist on
the safety of these compounds, overall scientific consensus is that
2-ACBs are not an immediate cause for concern (EFSA Panel
4https://nucleus.iaea.org/ifa/
Frontiers in Pharmacology | www.frontiersin.org 2 April 2016 | Volume 7 | Article 108
3. Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
on Food Contact Materials Enzymes Flavourings Processing
Aids-CEF, 2011).
Of course, consumers may also be concerned about the
indirect effects of irradiation, such as the way it changes
the way we relate to food or herbal medicine, or how the
use of radioactive materials affect the environment during
their mining, shipping and use. Furthermore, irradiation,
like any form of treatment, adds to the final cost of a
food product or medicine. All these concerns should be
taken into consideration when determining whether gamma
irradiation is the proper choice for decontamination of a
product.
Evaluating the Effects of Gamma
Irradiation on Medicinal Cannabis
Patients have occasionally expressed their concerns about the
effects of irradiation treatment on medicinal cannabis. Some
have claimed a change of taste or effect, while others worry
about changes in the chemical composition or the quality of
their medicine5. In response to such concerns, some Canadian
licensed producers of medicinal cannabis initially pledged not
to apply irradiation, but were forced to reconsider when their
products could not meet microbial safety requirements. To
cushion the impact on their customers, the obscuring term “cold
pasteurization” was introduced when in fact gamma irradiation
treatment was applied6.
In fresh Cilantro leaves, gamma irradiation was shown to
reduce the content of terpenes such as myrcene and linalool (Fan
and Sokorai, 2002). Likewise, irradiation may perhaps have an
effect on cannabis terpenes, which seem to play an important
role in the synergistic effect and bioavailability of cannabinoids
(Russo, 2011). Although an early study by our group on
the effect of cannabis irradiation did not indicate changes in
the cannabinoid profile (unpublished data), chromatographic
analysis of cannabinoids has significantly improved over the
years meaning that more detailed changes in the cannabinoid
profile may now be visualized. The occurrence of 2-ACBs
seems of limited relevance in the case of cannabis, because
average daily cannabis consumption is very small compared to
other irradiated products such as meats, fruits of vegetables.
Also, cannabis flowers do not contain significant amounts
of fat needed to form these radiolytic compounds in the
first place.
To address the concerns that may exist around gamma
irradiation of medicinal cannabis, we evaluated the effects of
irradiation treatment of four different cannabis varieties covering
different compositions (THC vs. CBD dominant types, Sativa
vs. Indica types). Samples were compared before and right
after standard gamma-irradiation treatment, by performing
quantitative analysis of major cannabinoids, as well as qualitative
analysis of full cannabinoid and terpene profiles. In addition,
water content and microscopic appearance of the cannabis
flowers was evaluated.
5http://www.hc-sc.gc.ca/fn-an/securit/irridation/cyclobutanone-eng.php
6http://www.leafscience.com/2014/05/01/tweeds-first-marijuana-orders-
delayed-irradiated/
MATERIALS AND METHODS
Solvents and Chemicals
All organic solvents were HPLC or analytical grade. Acetonitrile
was obtained from Boom labs BV (Meppel, The Netherlands).
Ethanol and phosphorus pentoxide (P4O10) was purchased from
VWR (Amsterdam, The Netherlands).
Cannabis Samples
Pharmaceutical-grade cannabis was obtained from the licensed
Dutch cultivator, Bedrocan BV (Veendam, the Netherlands).
Plants were grown from genetically identical clones under
standardized indoor conditions. Flower tops were harvested
and air-dried for 1 week under controlled temperature and
humidity. Four different standardized varieties available in
Dutch pharmacies were used for this study i.e., Bedrocan R
,
Bediol R
, Bedica R
, and Bedrolite R
. Batch information
and chemical composition of these products is listed in
Table 2.
All cannabis batches used for this study were harvested in the
period of late 2014–early 2015. Following standard procedure,
each batch was packaged in portions of 250 grams in triple
laminate foil bags with zip-lock closure (type Lamizip aluminum;
Daklapack, The Netherlands) for gamma irradiation treatment
at Synergy Health (Etten-Leur, The Netherlands). Each batch
received an irradiation dose of (minimum) 10 kGy produced with
a Cobalt-60 radiation source.
Of each cannabis variety a 10 gram sample was collected
before (non-irradiated control) as well as after (irradiated
sample) gamma irradiation, resulting in a total of 8 samples for
this study [4 varieties × 2 treatments (before/after irradiation)].
Samples were homogenized by grinding in a blender until the
material was about 5 mm in diameter. Ground samples were
finally used for determination of water content, and for sample
extraction for GC/UPLC analysis. Of variety Bedrocan, the
most popular variety used by Dutch patients (Hazekamp and
Heerdink, 2013), some non-homogenized samples were kept for
microscopic analysis.
All samples were handled and stored under equivalent
conditions. For each variety, irradiated and control samples
were extracted and analyzed on the same day, so that any
changes in chemical composition could only be attributed
to the irradiation treatment. This study was carried out
under a cannabis research license issued by the Dutch Health
Department.
TABLE 2 | Cannabis type and batch information of the cannabis varieties
used in this study.
Variety name Batch # THC/CBD
type
Sativa/Indica
type
Harvest date
Bedrocan A1.01.45 THC Sativa 11-12-2014
Bediol A2.05.15 THC +
CBD
Sativa 25-12-2014
Bedrolite A2.08.13 CBD Sativa 08-01-2015
Bedica A2.07.20 THC Indica 22-01-2015
Frontiers in Pharmacology | www.frontiersin.org 3 April 2016 | Volume 7 | Article 108
4. Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
FIGURE 1 | Structures of the cannabinoids quantitatively analyzed by UPLC.
Water Content Determination
Water content of each homogenized sample was determined
by using the Loss on Drying (LOD) method according
to EP monograph 2.3.32 (method C). In short, 500 mg of
each sample (in duplicate) was accurately weighed in small
plastic containers, and dried for 24 h at 40◦C under vacuum
inside a desiccator containing the potent desiccant phosphorus
pentoxide. Subsequently, all samples were weighed again. Water
content (in percentage of initial weight) was determined by
comparing weight before and after the procedure.
Sample Extraction
Ground cannabis samples were extracted for Gas
Chromatography (GC) and Ultra-Performance Liquid
Chromatography (UPLC) analysis as described in the
Dutch Analvtical Monograph for release testing of Cannabis
Flos, version 7.1 (OMC, 2015)7. In short, 1000 mg of each
7https://www.cannabisbureau.nl/medicinale-cannabis-artsen-en-apothekers-
specificaties-en-analysevoorschriften
homogenized sample (in duplicate) was extracted with 40 mL
of absolute ethanol in plastic serum tubes (maximum content
50 mL) while mechanically shaking for 15 min at 300 rpm.
Tubes were then centrifuged at 3000 rpm and clear supernatant
was transferred to a 100 mL volumetric flask. For exhaustive
extraction, the procedure was repeated twice more with 25 mL
of ethanol, and supernatants were combined. Volumes were
adjusted to 100 mL with ethanol, mixed well, and filtered through
a 0.45 µm PTFE syringe filter to remove small particles. Filtrated
extracts were used directly for GC analysis, or further diluted
with acetonitrile/water (70:30, v/v) for analysis by UPLC.
Quantitative UPLC Analysis of Major
Cannabinoids
The UPLC profiles were acquired on a Waters (Milford, MA)
Acquity UPLC system consisting of a gradient pump, an
autosampler, a column oven and a diode array detector (DAD).
The device was controlled by Waters Empower software. Full
spectra were recorded in the range of 200–400 nm. The analytical
Frontiers in Pharmacology | www.frontiersin.org 4 April 2016 | Volume 7 | Article 108
5. Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
FIGURE 2 | Total THC and total CBD content (in % of dry weight) as determined by UPLC analysis, as well as water content (in % of total weight) as
determined by Loss on Drying method (LOD) in all studied varieties before (gray bars) and after (black bars) irradiation treatment.
column was a Waters Aquity C18 (1.7 µm, 2.1 × 150 mm)
equipped with a matching guard column. The mobile phase
consisted of a gradient of acetonitrile (A) and water (B), both
containing 0.1% formic acid. The gradient was programmed as
follows: 0–6 min (hold at 70% A); 6–10.5 min (linear increase to
100% A); 10.5–11 min (hold at 100% A). The column was then
re-equilibrated under initial conditions for 1.5 min, resulting in a
total runtime was 12.5 min. Flow-rate was 0.4 mL/min. Injection
volume was 10 µL. Chromatographic peaks were recorded at
228 nm. All determinations were carried out at 30◦C. All samples
were analyzed in duplicate.
Applying the standard protocol for release testing of medicinal
cannabis (OMC, 2015)7, the following cannabinoids were
quantitatively determined: THC, THCA, CBD, CBDA, delta-8-
THC, CBN. The structures of these compounds, including their
full chemical names, are shown in Figure 1.
Qualitative GC Analysis of Cannabinoid
and Terpene Profiles
Gas chromatography was used for the simultaneous qualitative
analysis of monoterpenes, sesquiterpenes, and cannabinoids
as previously reported (Hazekamp and Fischedick, 2012). An
Agilent GC 6890 series (Agilent Technologies Inc., Santa Clara,
CA, USA) equipped with a 7683 autosampler and a flame
ionization detector (FID) was used. The instrument was equipped
with a DB5 capillary column (30 m length, 0.25 mm internal
diameter, film thickness 0.25 µm; J&W Scientific Inc., Folsom,
CA, USA). The injector temperature was 230◦C, with an injection
volume of 1 µl, a split ratio of 1:20 and a carrier gas (N2) flow
rate of 1.2 ml/min. The temperature gradient started at 60◦C and
linearly increased at a rate of 3◦C/min until the final temperature
of 240◦C which was held for 5 min resulting in a total run time of
65 min/sample. The FID detector temperature was set to 250◦C.
The device was controlled by Agilent GC Chemstation software
version B.04.01.
Microscopic Visualization of Glandular
Hairs
In order to visualize potential morphological changes in
the glandular hairs (where cannabinoids and terpenes are
produced) present in the cannabis flowers, microscopic
analysis of cannabis variety Bedrocan was performed before
and after gamma-irradiation treatment. Whole cannabis
flowers were used, without homogenizing. A Leica (type
MZ16FA) stereo-microscope was used. Images were captured
at a magnification factor ranging from 20 to 120 times
with a Leica (type DFC420C) camera, controlled by LAS
software.
Frontiers in Pharmacology | www.frontiersin.org 5 April 2016 | Volume 7 | Article 108
6. Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
FIGURE 3 | Continued
RESULTS
Loss on Drying
Inhalation, either by smoking or vaporizing, is currently the main
mode of administration used by patients (Hazekamp et al., 2013).
Water content (humidity) seems to have significant impact on
how consumers appreciate medicinal cannabis products during
inhalation (Ware et al., 2006). Although gamma irradiation does
not significantly heat up the treated product, water may be lost
during the procedure either as a result of the irradiation itself
(Yu and Wang, 2007) or because of shipping and handling
of the product during the treatment. Release specifications for
Bedrocan products require the water content to be no more
than 10%. As shown in Figure 2, the actual water content of the
analyzed varieties ranged between 5 and 8%, with no differences
between treated and control samples.
UPLC Analysis
Six major cannabinoids were quantitatively analyzed by applying
a validated UPLC methodology that is used as standard
procedure for release testing of medicinal cannabis in The
Netherlands. As customary, the sum of THC and its acidic
precursor THCA is reported as “total THC content.” Similarly,
the sum of CBD and CBDA is reported as “total CBD content.”
It should be noted that delta-8-THC and CBN are not originally
Frontiers in Pharmacology | www.frontiersin.org 6 April 2016 | Volume 7 | Article 108
7. Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
FIGURE 3 | Continued
produced by the cannabis plant, but are formed as degradation
products of THC by exposure to heat or light, or by prolonged
storage (Hazekamp et al., 2010).
Results of cannabinoid testing are shown in Figure 2,
indicating that levels of total THC and/or CBD were not altered
by irradiation treatment in any of the varieties studied. No delta-
8-THC or CBN was detected in any of the samples (before or
after irradiation) at levels over 0.1% (which equals 1 mg/gram of
cannabis flower).
GC Analysis
Components visualized by GC analysis were not individually
quantified because of the multitude of chromatographic peaks
of interest (>50). Instead, the entire profiles of all visible
peaks are presented in Figure 3. Because of the complexity of
these profiles, the sections of the profile where monoterpenes,
sesquiterpenes, and cannabinoids elute are displayed separately.
For each variety, control (non-irradiated) samples, and treated
(irradiated) samples are shown side by side, using the same
vertical scale to allow direct comparison. The main peaks in
each variety were identified based on previously published data
(Hazekamp and Fischedick, 2012).
While the overall qualitative composition of the samples
was unaltered, differences in several terpene components could
be detected after irradiation in the cannabis varieties studied.
Components that showed a clear reduction after irradiation
Frontiers in Pharmacology | www.frontiersin.org 7 April 2016 | Volume 7 | Article 108
8. Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
FIGURE 3 | Continued
treatment are indicated in Figure 3 by showing the relative
change (in %) compared to untreated sample. Because a small
variability of terpene content between samples is to be expected,
and is also observed between replicates of non-treated samples,
changes that are smaller than +/– 5% are not indicated. The
main components affected were the monoterpenes myrcene,
cis-ocimene and terpinolene, and the sesquiterpenes gamma-
selinene, eudesma-3,7(11)-diene and gamma-selinene. No new
terpene peaks were formed as a result of treatment. No
cannabinoids were altered or formed as a result of irradiation.
Microscopy
Multiple microscopic images were obtained of variety
Bedrocan on flowers collected before and after treatment
with gamma-irradiation, at a magnification of about 20–120
times. The trichomes (glandular hairs) where cannabinoid and
terpenes are excreted by the cannabis plant are clearly visible, as
shown in Figure 4. No clear differences in trichome structure,
color, density, or shape could be observed between the control
(non-irradiated) samples and treated (irradiated) samples.
DISCUSSION AND CONCLUSION
Gamma irradiation treatment of cannabis has become standard
practice in the government-supported medicinal cannabis
programs of The Netherlands as well as Canada. In the study
presented here such treatment, at a radiation dose (10 kGy)
sufficient to reduce microbial contamination (bioburden) to
pharmaceutically acceptable levels, did not cause any changes
in the content of THC and CBD, generally considered as the
most important therapeutically active components of medicinal
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9. Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
FIGURE 3 | GC profiles of four studied varieties showing monoterpenes, sesquiterpenes, and cannabinoids in separate sections. C, control
(non-irradiated); T, treated (irradiated); *: artifact. Numbers indicate percentage of change in treated samples compared to non-treated controls.
cannabis (Grotenhermen and Müller-Vahl, 2012). Likewise, the
water content and the microscopic structure of the dried cannabis
flowers were not altered by standard irradiation protocol in four
different cannabis varieties. The study included representative
varieties of THC and CBD dominant types, as well as Sativa and
Indica types.
In our study, irradiation had a measurable effect on the
content of multiple cannabis terpenes, mainly on the more
volatile monoterpenes. Reduction of affected terpenes was in
general between 10 and 20%, but for some components this
may be as much as 38%. In a previous study evaluating
the effect of gamma irradiation on fresh Cilantro, a decrease
in terpene content was also described (Fan and Sokorai,
2002). However, the authors concluded that the observed loss
of terpenes such as myrcene and linalool was insignificant
compared to the losses that occurred by evaporation during
refrigerated storage of Cilantro. Also in orange juice the effect
of irradiation on terpenes was found to be non-significant
in comparison to changes induced by refrigerated storage
(Fan and Gates, 2001). Likewise, the slight terpene reduction
observed in the current study is comparable to the effect
that short term storage in a paper bag had on cannabis
samples, in a study performed by (Ross and ElSohly, 1996).
A likely explanation therefore seems that gamma irradiation
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10. Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
FIGURE 4 | Microscopic images of trichomes (glandular hairs) before and after treatment with gamma-irradiation. Cannabis variety Bedrocan was used.
Magnification ± 20–120 times.
slightly accelerates the evaporation of some of the more volatile
terpenes. This idea is supported by the fact that no degradation
products or additional chromatographic peaks were found to
account for the lost terpenes, with the exception of some
beta-caryophyllene oxide formed in the irradiated sample of
variety Bedica. Interestingly, terpenes were not affected to the
Frontiers in Pharmacology | www.frontiersin.org 10 April 2016 | Volume 7 | Article 108
11. Hazekamp Effects of Gamma-Irradiation on Medicinal Cannabis
same degree in all varieties, e.g., myrcene content was clearly
reduced in varieties Bedica and Bedrolite but not in variety
Bediol. Perhaps this indicates a protective effect that cannabis
components may have on each other when present in specific
proportions.
Some cannabis users have claimed that irradiation changes
the taste and/or smell of cannabis during smoking or vaporizing
(personal observation by the author). Unfortunately, such
opinions may be hard to substantiate because the same cannabis
is usually not available to consumers in both its irradiated and
non-irradiated form to allow direct comparison, meaning there is
no “base-line” product to quantify the magnitude of the change.
Nevertheless, the taste and smell of cannabis mainly depends
on its terpene (essential oil) content (Russo, 2011). While the
current study indicated quantitative changes in some of the
terpenes upon irradiation, a subtle change in smell or taste may
indeed be possible as a result of such treatment. Despite these
changes, the overall terpene profile of each variety remained
clearly recognizable.
Gamma irradiation remains controversial among some
consumers of medicinal cannabis. However, weighing the risks
vs. the benefits currently keeps pointing toward the use of this
decontamination procedure. After all, cannabis plants cannot
(yet) be grown and processed under conditions aseptic enough
to meet pharmaceutical standards, while infection risks are well
documented in the medical literature and can be harmful or
even fatal to seriously ill patients. Meanwhile, the main harm of
gamma-irradiation seems to be limited to a reduction of some
terpenes present in the cannabis, leading to a small quantitative
effect, but keeping the terpene profile qualitatively essentially
intact.
Based on the results presented in this report, gamma
irradiation of herbal cannabis remains the recommended method
of decontamination, at least until other more generally accepted
methods have been developed and validated. This is especially
important when cannabis is prescribed to seriously ill and
possibly immune-deprived patients, with an increased risk of
suffering from microbial infection. Meanwhile, the development
of improved hygienic standards for cultivation and processing
of medicinal cannabis may ensure that irradiation doses can be
reduced to an absolute minimum. In time, gamma-irradiation
may eventually be replaced with other, more generally accepted,
forms of reliable decontamination.
AUTHOR CONTRIBUTIONS
The author confirms being the sole contributor of this work and
approved it for publication.
ACKNOWLEDGMENTS
The Dutch Office of Medicinal Cannabis (OMC) and
pharmaceutical quality control laboratory Proxy Labs (Leiden,
The Netherlands) are gratefully acknowledged for their support
in performing this study. A big thanks to Gerda Lamers (Leiden
University) for preparing the microscopic images.
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