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Basic Information of Cannabis Chatchada Bodhibukkana, Ph.D. R&D Institute, GPO Plant Type sativa indica ruderalis Ref : https://smoke.io/strains/@jwolf/the-clear-difference-between-cannabis-sativa-indica-and-ruderalis-or-simple-photos2 Plant Type - Origin Sativa Indica Ruderalis Tropical zone, which is The dry regions with little rainfall; The Asian parts of Russia. characterized by its warm and Afghanistan, Lebanon, and the Difference in daylengths. humid climate. Hindu Kush. (approx. 19 hours of daylight in It is located 23.5 degrees above Central Asia summer & 10.5 hours of daylight and below the equator. in winter) Small difference in daylengths. (approx. 13.5 hours of daylight in Short vegetative phase (growth summer & 10.5 hours of daylight phase). in winter) Automatically switches to the flowering phase (floral phase) regardless of the season. Ref : https://www.mallorca-seeds.com/difference-sativa-indica-ruderalis/ 3 Plant Type - Origin สายพันธ์ไทย-> sativa Ref : https://smoke.io/strains/@jwolf/the-clear-difference-between-cannabis-sativa-indica-and-ruderalis-or-simple-photos4 Sativa Vs Indica Ref: https://wisetoast.com/types-of-marijuana-and-effects Ref : https://www.cannaconnection.com/blog/11392-difference-indica-sativa-ruderalis-hybrid-plants 5 Ref : https://www.amazon.com/Periodic-Table-Cannabis-Poster-Print/dp/B00MBI4HVM Cannabis Plant Anatomy Sinsemilla “without seeds” Trichomes Ref : https://herbology.org/2019/08/14/cannabis-anatomy-the-parts-of-the-plant/ Male Female Hermaphroditic Pollen sac Stigma Pollen sac + Stigma Ref : https://www.amsterdamgenetics.com/spot-male-female-hermaphrodite-cannabis/ Non cannabinoids • Terpenes • Sugars • Flavonoids • Fats • Chlorophyll • Lignin • Pigments • Starches • Waxes • Celluloses • Pectins • Etc. Ref : https://www.royalqueenseeds.com/blog-what-are-cannabis-flavonoids-and-what- Ref : https://www.nature.com/articles/d42473-018-00066-4 do-they-do-n799 D 9-THC D 8-THC CBN CBC CBG CBD Chemical structures of compounds isolated from Cannabis sativa organized via family substructure. Ref : Husni et.al, 2014 Examples of Terpenes in Cannabis α-Pinene Δ3-Carene cis-Ocimene Humulene γ-Eudesmol β-Pinene α-Terpinene Terpinolene δ-Guaiene β-Eudesmol Myrcene β-Phellandrene β-Caryophyllene Elemene α-Phellandrene Limonene α-Guaiene Guaiol Ref : https://profofpot.com/terpene-content-cannabis/ Examples of Terpenes in Cannabis Ref : https://www.cannainsider.com/reviews/cannabis-terpenes/ Entourage Effect The Entourage effect is the synergistic benefit of whole- plant cannabis that contains a range of naturally occurring cannabinoids flavonoids and terpenes to maximize the potency, effectiveness, and therapeutic scope of cannabis. Ref : https://blog.funpot.ca/cbd-a-better-you-cbd-the-entourage-effect/ Ref : https://cannigma.com/treatment/what-is-the-entourage-effect/ เปรียบเทียบการปลูก 3 แบบ Outdoor Indoor Greenhouse 1.ต้นทุนต ่า 1.ต้นทุนสูงมาก 1.ต้นทุนต ่ากว่าระบบ Indoor 2.ผลผลิตไม่แน่นอนและไม่มีคุณภาพ 2.ผลผลิตมีคุณภาพสูง 2.ผลผลิตมีคุณภาพสูง 3.ปลูกได้ปีละรอบ 3.ปลูกได้ปีละสามรอบ 3.ปลูกได้ปีละสามรอบ 4.ใช้เกษตรกรทั วไป 4.ใช้บุคคลากรที มีความช่านาญ 4.ใช้เกษตรกรช่านาญการ 5.เสี ยงต่อโรคพืชและแมลง และอาจ เฉพาะมาก 5.อาจจะมีโรคพืชหรือแมลงได้ ปนเปื้อนโลหะหนัก 5.ไม่มีโรคพืช แมลง และโลหะหนัก 6.เป็นระบบที คุ้มค่าและเหมาะส่าหรับ ภูมิอากาศประเทศไทย 14 Cannabis sativa L. subsp. indica . • Glandular trichomes เป็นส่วนที่ ผลิต Cannabinoids และ terpenes • Glandular trichomes พบได้ทั่วทั้ง ต้น แต่จะมีปริมาณหนาแน่นที่สุด บริเวณช่อดอก • ช่อดอก จึงเป็นส่วนส าคัญที่ให้ สารส าคัญ Cannabinoids (THC, CBD) 4 5 3 QC of Finished Product 2 Formulation • Appearance QC of Extract • Identification 1 • Capsules 9 • • Content of -THC • Appearance Sublingual drops • Extraction • Content of CBD • Identification Oromucosal spray • Microbial limit tests QC of Raw Material 9 • Suppositories • Solvent extraction • Content of -THC • Other parameters •Appearance • Content of CBD • Topicals • Supercritical fluid • depend on dosage •Identification • Loss on drying Transdermal patches form extraction (CO2) • Inhalers •Foreign material • Short path • Microbial limit tests •Moisture content distillation •Microbial limit tests •Metal limits •Pesticide limits 1 Ethanol Extraction ( - 50 °C ) Cannabis flos 2 3 Medical Cannabis Extracts (Cannabinoids + Terpenoids + Flavonoids) Separation by Evaporation 17 18 SOLVENT EXTRACTION • PROS: SOLVENT Evaporating solvent • Inexpensive- This method doesn’t require any fancy machinery. • Simple • High yield • CONS: • Have to evaporate solvent as much as possible • Aware - overheated or overmixed Solvent/extract and also flammable solvent. mixture Ref : https://www.powerblanket.com/blog/cbd-extraction-methods/ CO2 EXTRACTION • PROS: • Safe when done by professionals- CO2 is used in countless food products and is perfectly safe for consumption • Yields high-quality • CONS: • Very expensive- setup costs start at approximately $40,000 • Not suitable for industry scale production Ref : https://www.powerblanket.com/blog/cbd-extraction-methods/ Oil Extraction • Pros: • Easy- This is by far the easiest extraction method and is a popular home option. OIL • Cons: • Low Yields- This method produces low yields of heavily diluted CBD. • Aware – toxicity of oils (ex. Naphtha) using in the extraction method Ref : https://www.powerblanket.com/blog/cbd-extraction-methods/ Physical and Chemical properties Chemical formula C21H30O2 C21H30O2 Molecular weight 314.46 314.46 Solubility in water 0.0126 mg/mL 0.0028 mg/mL Solubility in ethanol 23.6 mg/mL Soluble (1:1) log P 6.1 6.93 Physical and Chemical properties Instability • Oxidation products derived from fatty acid degradation during the storage period of macerated oils are critical for overall formulation stability. • Exposure to light was shown to be the greatest single factors in loss of cannabinoids especially in solutions. Pharmacokinetics of Cannabis preparations • นอกจากข้อมูลด้านเภสัชวิทยา การจัดตั้งสูตรต่ารับสารสกัดกัญชา (Cannabis oil) ต้องพิจารณาถึง Physical & chemical properties รวมทั้ง Pharmacokinetic ของสารสกัดเพื อพัฒนาสูตรต่ารับที เหมาะสม มีคุณภาพ ประสิทธิภาพ ความปลอดภัย และตรงตามความต้องการของผู้ป่วย • เนื องจากการการได้รับ Cannabinoids รูปแบบรับประทาน ให้ค่าชีวปริมาณออกฤทธิ์ (bioavailability) ต ่า จากการผ่าน First-pass metabolism ดังนั้นเพื อเพิ มการน่าส่งยาเข้าร่างกาย จึงมีการพัฒนาสูตรต่ารับในรูปแบบอื นในการน่าส่งยา เช่น Sublingual, Vaporization of product and inhalation และ Rectal administration Cannabis preparations • Pharmaceutical preparations • CBD • THC • THC/CBD • Synthetic cannabinoids • Other preparations • Food supplements/ Cosmetics Pet products Cannabis oil - THC Cosmetics - CBD Drugs Cannabis - THC/CBD products Synthetic cannabinoids - Nabilone Supplements Foods/ Drinks - Dronabinol Ref : https://bedrocan.com/wp-content/uploads/a-primer-to-medicinal-cannabis_lr.pdf Approved Drugs Pharmaceutical preparations (Phytocannabinoids) EPIDIOLEX ® : Oral solutions USFDA approve : 2018 รักษาโรคลมชักในผู้ป่วยอายุ 2 ปีขึ้นไป Contains : CBD 100 mg/mL Dosage : เริ มให้ที 2.5 mg/kg วันละ 2 ครั้ง (5 mg/kg/day) หลังจากได้รับยา 1 สัปดาห์สามาถเพิ มได้ถึง 5 mg/kg วันละ 2 ครั้ง (10 mg/kg/day) Indication : seizures associated with Lennox-Gastaut syndrome or Dravet syndrome ในผู้ป่วยอายุ 2 ปีขึ้นไป Common side effects : sleepiness, decreased appetite, diarrhea, increase in liver enzymes, feeling very tired and weak, rash, sleep problems, and infections. • In an August 2018 call with investors, GW Pharmaceuticals revealed the price of Epidiolex would cost roughly $32,500 per patient, per year. Pharmaceutical preparations (Phytocannabinoids) SATIVEX® : Oromucosal spays UK Approve : 2010 รักษาภาวะกล้ามเนื้อหดเกร็ง เนื องมากจากโรค Each 100 microliter spray contains: ปลอกประสาทเสื อมแข็ง (MS) 2.7 mg delta-9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD). Dosage : ค่อยๆ เพิ มปริมาณสเปรย์ 1 สเปรย์ต่อวัน มากสูงสุดถึง 12 สเปรย์ต่อวัน Indication : Add-on treatment, for symptom improvement in patients with moderate to severe spasticity due to multiple sclerosis (MS). Common side effects : palpitations (1.2%), tooth discolouration (2.1%), oral mucosal disorder (2.2% ) Pharmaceutical preparations (Synthetic cannabinoids) CESAMET® : Capsules USFDA Approve : 1985 รักษาอาการคลื นไส้อาเจียนจากการใช้เคมีบ่าบัดใน Contains : 1 mg (2.7 µmol) Nabilone per cap การรักษามะเร็ง และไม่ตอบสนองต่อยาต้านอาการ คลื นไส้อาเจียนตัวอื น Dosage : ในผู้ใหญ่รับประมาณครั้งละ 1 หรือ 2 mg วันละ 2 ครั้ง สูงสุดไม่เกิน 6 mg แบ่งให้วันละ 3 ครั้ง Indication : for the treatment of the nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments Common side effects : drowsiness, vertigo, dry mouth, euphoria (feeling “high”), ataxia, headache, and concentration difficulties. Pharmaceutical preparations (Synthetic cannabinoids) MARINOL® : Capsules USFDA Approve : 1985 1. การเบื ออาหาร น้่าหนักลดในผู้ป่วยเอดส์ Contains : 2.5 mg, 5 mg, 10 mg Dronabinol per cap 2. รักษาอาการคลื นไส้อาเจียนจากการใช้เคมี Dosage : บ่าบัดในการรักษามะเร็ง ขนาดแนะน่าเริ มให้รับประทานครั้งละ 2.5 mg วันละ 2 ครั้ง ก่อนอาหารกลางวัน และอาหารเย็น 1 ชั วโมง Indication : 1. Anorexia associated with weight loss in patients with AIDS. 2. Nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments. Common side effects : abdominal pain, dizziness, euphoria, nausea, paranoid reaction, somnolence, thinking abnormal and vomiting. Unapproved Drugs Cannabis preparations • Pharmaceutical
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  • Pharmacodynamics of Cannabinoids

    Pharmacodynamics of Cannabinoids

    Open Access Archives of Pharmacy and Pharmaceutical Sciences Review Article Pharmacodynamics of cannabinoids Alexandra Sulcova* ISSN ICCI - International Cannabis and Cannabinoids Institute, Jachymova 26/2, 110 00 Praha, 2639-992X Czech Republic “Pharmacodynamics of cannabinoids “(i.e. a set of biological effects elicited in the *Address for Correspondence: Alexandra Sulcova, M.D, Ph.D, Professor of Pharmacology, living organism by interaction with its biochemical and biophysical functions up to the FCMA, FECNP, FCINP, ICCI - International cellular level) is studied for a long time during both, physiological and pathological Cannabis and Cannabinoids Institute, Jachymova conditions. Cannabinoids received their names according to their natural occurrence 26/2, 110 00 Praha, Czech Republic, Tel: 420 732167678; Email: [email protected] as constituents of Cannabis sativa L. (marijuana). The species was classiied in the “Linnaeus’s Species Plantarum (1753)”, the word “sativa” means things that are Submitted: 12 April 2019 Approved: 07 May 2019 cultivated [1]. For ages, people have used cannabis-based preparations for healing and Published: 08 May 2019 pain suppression until the discovery (in 1897) of aspirin (acetylsalicylic acid) which contemporary medicine uses until today. Chemical investigation of marijuana conirmed Copyright: © 2019 Sulcova A. This is an open access article distributed under the Creative various cannabinoid-type components called cannabinoids (presently estimated at Commons Attribution License, which permits about 150). Regarding their possible pharmacodynamic effects, tetrahydrocannabinol unrestricted use, distribution, and reproduction (THC) and cannabidiol (CBD) are the most explored. The determination of THC structure in any medium, provided the original work is properly cited by means of nuclear magnetic resonance imaging increased sharply the number of professional scientiic reports dealing with the studies of THC pharmacodynamic mechanisms of action [2].
  • Cannabis-Related Pharmaceutical Drugs

    Cannabis-Related Pharmaceutical Drugs

    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 31 August 2020 Type of the Paper (Review) Cannabis-related pharmaceutical drugs Dvora Namdar1, Omer Anis2, Patrick Poulin3, Hinanit Koltai1,* 1 Institute of Plant Science, Agriculture Research Organization, Volcani Center, Rishon LeZion 7528809, Israel; [email protected]; [email protected] 2 Department of Urology, Sheba Medical Center; [email protected] 3 Consultant Patrick Poulin Inc., Québec City, Québec, Canada; School of Public Health, Université de Montréal, Montréal, Canada; [email protected] * Correspondence: [email protected]; Tel.: +972‐3‐9683039 (H.K.) Abstract: Despite the surge in the research of cannabis chemistry and its biological and medical activity, only a few cannabis‐based pharmaceutical‐grade drugs have been developed and marketed to date. Not many of these drugs are Food and Drug Administration (FDA)‐approved and some are still going through regulation processes. Active compounds including cannabinergic compounds (i.e., molecules targeted to modulate the endocannabinoid system) or analogs of phytocannabinoids (cannabinoids produced by the plant) may be developed into single‐molecule drugs. However, since in many cases treatment with whole plant extract is preferred over treatment with a single purified molecule, some more recently developed cannabis‐derived drugs contain several molecules. Different combinations of active plant ingredients (API) from cannabis with proven synergy may be identified and developed as drugs to treat different medical conditions. However, possible negative effects between cannabis compounds should also be considered, as well as the effect of the cannabis treatment on the endocannabinoid system. FDA registration of single, few or multiple molecules as drugs is a challenging process and certain considerations that should be reviewed in this process, including issues of drug‐drug interactions, are also discussed here.
  • Factors Affecting the Regulatory Context of Marijuana and Cannabinoids in the Workplace Technical Letter Report

    Factors Affecting the Regulatory Context of Marijuana and Cannabinoids in the Workplace Technical Letter Report

    PNNL-27050 Factors Affecting the Regulatory Context of Marijuana and Cannabinoids in the Workplace Technical Letter Report November 2017 KM Branch EP Kennedy ME Lerchen* AC Dalton *Corresponding author Prepared for the U.S. Nuclear Regulatory Commission under an Interagency Agreement with the U.S. Department of Energy Contract DE-AC05-76RL01830 PNNL-27050 Factors Affecting the Regulatory Context of Marijuana and Cannabinoids in the Workplace Technical Letter Report KM Branch EP Kennedy ME Lerchen* AC Dalton *Corresponding author November 2017 Prepared for the U.S. Nuclear Regulatory Commission under an Interagency Agreement with the U.S. Department of Energy Contract DE-AC05-76RL01830 Pacific Northwest National Laboratory Richland, Washington 99352 PNNL-27050 ABSTRACT Studies clearly demonstrate that the use of marijuana (Cannabis sativa and other related Cannabis species and hybrids) and cannabinoids from other sources have negative impacts on an individual’s fitness to perform safety- or security-sensitive functions. The discovery of the endocannabinoid system (i.e., cannabinoid receptors, their location, and function within the human body) in the 1980s, and the subsequent characterization of that system provided a framework for examining the role and function of cannabinoids. That framework prompted an increase in research on the effects of substances that activate or inhibit the endocannabinoid system, including marijuana and synthetic cannabinoids, which led to a greater understanding of the potential benefits and adverse effects of such substances. This new understanding has heightened interest in the potential medical uses of cannabinoids, development of pharmaceutical cannabinoids, and re-examination of previous research on cannabinoid metabolism, elimination, and the relationship of effects to dose and time.