קנאביס רפואי - Cannabis

חלק הצמח | איכויות | רכיבים פעילים | פעילות רפואית | התוויות | מינונים | רגישות | תופעות לוואי | 

מינון יתר | אזהרות | התוויות נגד | רעילות | אינטראקציות | הריון | הנקה | מקורות

 

קנאביס רפואי הוא שם כללי לתכשירים שמופקים מצמח הקנאביס, ובעיקר מהמין Cannabis sativa. תכשירים אלו מכילים קנבינואידים ביחסים משתנים, בעיקר THC ו-CBD, לצד רכיבים פעילים נוספים כמו טרפנים ופלבנואידים.

שני הקנבינואידים המרכזיים בקנאביס הם THC ו-CBD.

THC ‏(Δ9-Tetrahydrocannabinol) הוא הרכיב הפסיכואקטיבי המרכזי בצמח, והוא אחראי בעיקר להשפעה המשכרת או משנה התודעה של הקנאביס. לצד זאת, הוא קשור גם להשפעות רפואיות שונות, כמו שיכוך כאב, הרפיית שרירים, השפעה על בחילות, תיאבון ושינה.

CBD ‏(Cannabidiol) הוא קנבינואיד שאינו נחשב משכר כמו THC, ואינו גורם לאותה תחושת “היי”. הוא נחקר בעיקר בהקשרים של פעילות נוגדת פרכוסים, השפעה מרגיעה, פעילות אנטי-דלקתית, והשפעות אפשריות על כאב, חרדה ושינה.

קנאביס רפואי אינו חומר אחיד. בשונה ממוצרים פרמצבטיים מבוססי קנבינואידים, אשר הינם בעלי הרכב קבוע ומדויק יותר, קנאביס רפואי הוא תערובת מורכבת שההרכב שלה יכול להשתנות מאוד כתלות בזן הגנטי של הצמח, מתנאי הגידול, משיטת ההפקה, מצורת ההכנה ומהמוצר הסופי.

כתוצאה מכך, ההשפעה של קנאביס רפואי עשויה להשתנות ממוצר למוצר ואינה תמיד צפויה באותה מידה. ההבדלים יכולים להתבטא ביחס בין THC ל-CBD, בכמות החומרים הפעילים שנספגים בגוף, במשך ההשפעה ובעוצמתה. מאחר שרוב מוצרי הקנאביס הרפואי אינם סטנדרטיים כמו תכשירים פרמצבטיים מבוקרים, קשה יותר להשליך ממחקרים שנעשו על מוצר מסוים לגבי מוצרים אחרים, וכן להעריך באופן חד-משמעי את היעילות והבטיחות של הקנאביס הרפואי ככלל.

גם מבחינת המחקר הקליני, הידע הקיים על קנאביס רפואי אינו אחיד, והוא משתנה בהתאם להתוויה הרפואית הנבדקת. נכון להיום, התמיכה המחקרית המבוססת ביותר קיימת בעיקר במצבים נוירולוגיים מסוימים, כגון ספסטיות על רקע טרשת נפוצה, ובחלק מהמקרים של אפילפסיה עמידה לטיפול, בעיקר כאשר מדובר בתכשירים מבוססי CBD.
לעומת זאת, בתחומים כמו כאב, חרדה, הפרעות שינה ומצבים פסיכיאטריים, הממצאים פחות עקביים, ולעיתים קשה לגזור מהם מסקנות חד-משמעיות בשל היקפי מחקר קטנים, שונות גדולה בין המוצרים שנבדקו ומגבלות מתודולוגיות נוספות.

לסיכום, ההשפעה של קנאביס רפואי תלויה בהרבה גורמים: הרכב הקנבינואידים, המינון, דרך הנטילה, צורת המוצר והמאפיינים האישיים של המטופל. לכן, קשה להתייחס לכל מוצרי הקנאביס הרפואי כאל קבוצה אחידה, וחשוב לבחון כל מוצר וכל מקרה לגופו.

 

חלק הצמח

פרחים ועלים

 

איכויות

טמפרטורה: חמה.
לחות: יבשה.
טעם: מתקתק במידה מסוימת, מריר.

 

רכיבים פעילים

קנאביס רפואי מכיל מגוון קנבינואידים בעלי פעילות ביולוגית. הרכיבים המרכזיים בו הם Δ9-טטרהידרוקנבינול (THC), קנבידיול (CBD) ו-קנבינול (CBN), לצד קנבינואידים משניים נוספים וטרפנים.

ריכוז הקנבינואידים בצמח הקנאביס משתנה באופן משמעותי בהתאם לזן ולתנאי הגידול:

(Δ9-tetrahydrocannabinol) THC - בתפרחת מיובשת ריכוזו נע בדרך כלל בין כ-5% ל-25%, כאשר בזנים בעלי עוצמה גבוהה הוא עשוי להיות אף גבוה יותר.

‏(cannabidiol) CBD - בקנאביס עשיר ב-THC ריכוזו בדרך כלל נמוך מ-1%, אך בזנים עשירים ב-CBD או בזנים שמקורם בהמפ, הוא עשוי להגיע 15%-5%.

‏(cannabinol) CBN - נמצא לרוב בריכוזים נמוכים, בדרך כלל מתחת ל-1%, ונוצר בעיקר כתוצר פירוק של THC.

קנבינואידים נוספים-כגון CBG ו-CBC, נמצאים לרוב בריכוזים נמוכים, בדרך כלל מתחת ל-3%-1%.

 

פעילות רפואית

נוגד דלקת, נוגד בחילה, נוגד הקאה, נוגד עווית, נוגד כאב, נוגד פרכוסים, נוגד חרדה, מרגיע, מגביר תיאבון, מחזק/מזין מערכת העצבים.

 

התוויות

כאב כרוני, כאב נוירופתי, ספסטיות על רקע טרשת נפוצה, הפרעות שינה, הפרעת דחק פוסט-טראומטית, מחלת פרקינסון, מחלת אלצהיימר, טיפול פליאטיבי ותמיכה בתסמינים, בחילות, הקאות, תסמונת לנוקס-גסטו, תסמונת דרווה, אפילפסיה, קכקסיה, חרדה.

 

מינונים

שימוש יומי בקנאביס מדווח לעיתים קרובות בגרמים של תפרחת מיובשת.
בשימוש קליני, הטווח המקובל נע לרוב סביב 0.2-1 גרם ליום, כאשר במצבים מורכבים יותר, עמידים לטיפול או בעלי עצימות גבוהה, חלק מהמטופלים עשויים להשתמש גם בכמות של עד 2-3 גרם ליום.

המינון היעיל תלוי בהרכב הקנבינואידים במוצר, ובעיקר ביחס בין THC ל-CBD. מוצרים המכילים THC ניתנים לרוב בהתחלה במינונים נמוכים, למשל כמה מיליגרמים בודדים של THC בכל מנה, ולאחר מכן מעלים את המינון בהדרגה בהתאם לתגובה ולסבילות. לעומת זאת, מוצרים עשירים ב-CBD ניתנים בדרך כלל במינון יומי כולל גבוה יותר.

גם דרך המתן משפיעה מאוד על החשיפה לחומרים הפעילים. בשאיפה, ההשפעה מופיעה במהירות יחסית ונמשכת זמן קצר יותר. לעומת זאת, במתן פומי, כמו שמנים או תכשירים לבליעה, תחילת ההשפעה איטית יותר, והספיגה והפיזור בגוף משתנים יותר בין אדם לאדם.

בסך הכול, מינון קנאביס רפואי הוא אישי מאוד ותלוי במטופל, במוצר ובדרך השימוש. לכן, צריכה הנמדדת בגרמים אינה משקפת בהכרח את כמות הקנבינואידים שנספגת בפועל בגוף, משום שקיימת שונות גדולה בעוצמת המוצר, בזמינות הביולוגית ובצורת ההכנה.

 

רגישות

רגישות לקנאביס רפואי אינה נפוצה, אך קיימות התייחסויות לכך בספרות המקצועית _(252,384).

רגישות זו מיוחסת בעיקר לחלבונים שמקורם בצמח Cannabis sativa, ובפרט לחלבוני nsLTPs, חלבונים נשאי ליפידים לא ספציפיים  למידע השלם למנויים

 

תופעות לוואי

שימוש בקנאביס רפואי עשוי להיות מלווה בתופעות לוואי שונות  למידע השלם למנויים

 

מינון יתר

אין דיווחים בספרות אודות תופעות הקשורות לנטילה של מינוני יתר.

 

אזהרות

יש להשתמש בקנאביס רפואי בזהירות, בשל  למידע השלם למנויים

 

התוויות נגד

אין מידע.

 

רעילות

לקנאביס רפואי רעילות אקוטית נמוכה יחסית בהשוואה לתרופות רבות, ולא נקבע מינון קטלני בבני אדם בתנאי חשיפה רגילים.
עם זאת, למרות הסיכון הנמוך לרעילות קטלנית אקוטית  למידע השלם למנויים

חשיפה כרונית או חשיפה למינונים גבוהים נקשרה גם למידע השלם למנויים

בנוסף, נתונים פרה קליניים ₍₁₇₎ מצביעים על  למידע השלם למנויים

מדד רעילות LD50:  למידע השלם למנויים

 

אינטראקציות

השפעה על חילוף חומרים תרופתי | אופיואידים | תרופות לדיכוי מערכת החיסון | Warfarin נוגד קרישה | תרופות לכאב נוירופתי |  נוגדי דיכאון | תרופות אנטי פסיכוטיות | ברביטורטים | בנזודיאזפינים | תרופות שינה ממשפחת Z  | אנטיהיסטמינים | כימותרפיה

 

השפעה על חילוף חומרים תרופתי

קנאביס רפואי, המכיל יחסים משתנים של קנבידיול (CBD) ו-Δ9 טטרהידרוקנבינול (THC), עשוי להשפיע על אנזימים המעורבים בפירוק תרופות בגוף. יחד עם זאת  למידע השלם למנויים

 

אופיואידים

Bezitramide, Buprenorphine, Butorphanol, Codeine, Dextromoramide, Dextropropoxyphene, Dihydrocodeine, Fentanyl, Hydromorphone, Ketobemidone, Meperidine, Methadone, Morphine, Nalbuphine, Naloxone, Nicomorphine, Opium, Oxycodone, Oxymorphone, Pentazocine, Phenazocine, Piritramide

אין מניעה לשלב אך יש לנקוט זהירות.  למידע השלם למנויים

 

 

תרופות לדיכוי מערכת החיסון בקרב מושתלי איברים

Cyclosporine, Tacrolimus, Voclosporin

יש לנקוט זהירות.  למידע השלם למנויים

 

התרופה Warfarin

יש לנקוט זהירות.

האינטראקציה בין קנאביס רפואי לבין Warfarin נחשבת בעלת פוטנציאל קליני משמעותי  למידע השלם למנויים

 

תרופות לכאב נוירופתי

Gaּbapentin, Pregaּbalin

השילוב אפשרי אך יש לנקוט זהירות.  למידע השלם למנויים

 

 

נוגדי דיכאון

אין מניעה לשלב אך יש לנקוט זהירות למידע השלם למנויים

 

 

תרופות אנטי פסיכוטיות

יש לנקוט זהירות למידע השלם למנויים

 

 

 

ברביטורטים

Allobarbital, Amobarbital, Aprobarbital, Barbital, Butobarbital, Cyclobarbital, Heptabarbital, Hexobarbital, Methohexital, Pentobarbital, Phenobarbital, Proxibarbal, Reposal, Secobarbital, Talbutal, Thiopental, Vinbarbital, Vinylbital

יש לנקוט זהירות  למידע השלם למנויים

 

 

בנזודיאזפינים

בנזודיאזפינים קצרי טווח | בנזודיאזפינים בעלי משך פעולה בינוני | בנזודיאזפינים ארוכי טווח

אין מניעה לשלב אך יש לנקוט זהירות.  למידע השלם למנויים

 

 

תרופות שינה ממשפחת  Z

Eszopiclone, Zopiclone, Zolpidem, Zaleplon

אין מניעה לשלב אך יש לנקוט זהירות  למידע השלם למנויים

 

 

אנטיהיסטמינים

אנטיהיסטמינים מהדור הראשון | אנטיהיסטמינים מהדור השני

 

אנטיהיסטמינים מהדור הראשון

Alimemazine, Antazoline, Azatadine, Brompheniramine, Buclizine, Carbinoxamine, Chlorcyclizine, Chloropyramine, Chlorpheniramine, Clemastine, Cyclizine, Cyproheptadine, Dexbrompheniramine, Dexchlorpheniramine, Dimenhydrinate, Dimetindene, Diphenhydramine, Diphenylpyraline, Doxylamine, Hydroxyzine, Ketotifen, Meclizine, Mepyramine, Methdilazine, Oxatomide, Pheniramine, Phenyltoloxamine, Pizotifen, Promethazine, Tripelennamine, Triprolidine

אין מניעה לשלב אך יש לנקוט זהירות למידע השלם למנויים

 

אנטיהיסטמינים מהדור השני

Acrivastine, Astemizole, Bilastine, Cetirizine, Desloratadine, Ebastine, Fexofenadine, Levocetirizine, Loratadine, Mizolastine, Rupatadine, Terfenadine

אין מניעה לשלב אך יש לנקוט זהירות  למידע השלם למנויים

 

כימותרפיה

התרופה Docetaxel | התרופה Irinotecan | התרופה Oxaliplatin

למידע השלם למנויים

 

הריון

שימוש בקנאביס רפואי במהלך ההריון  למידע השלם למנויים

 

הנקה

שימוש בקנאביס רפואי בתקופת ההנקה אינו מומלץ  למידע השלם למנויים

 

מקורות

1. Udomuksorn W, Saowaneepitak N, Dolthammasiri P, Ruanglertboon W, Limsuwanchote S, Wiriyapongsukit S, Tungsukruthai S. Unveiling the impact of water-boiled cannabis on warfarin: A case report of atrial fibrillation patients after cannabis legalization in Thailand. Toxicol Rep. 2024;13:101838. https://pubmed.ncbi.nlm.nih.gov/39703766/
2. Nachnani R, Knehans A, Neighbors JD, Kocis PT, Lee T, Tegeler K, Trite T, Raup-Konsavage WM, Vrana KE. Systematic review of drug-drug interactions of delta-9-tetrahydrocannabinol, cannabidiol, and Cannabis. Front Pharmacol. 2024;15:1282831. https://pubmed.ncbi.nlm.nih.gov/38868665/
3. Ho JJY, Goh C, Leong CSA, Ng KY, Bakhtiar A. Evaluation of potential drug-drug interactions with medical cannabis. Clin Transl Sci. 2024;17₍₅₎:e13812. https://pubmed.ncbi.nlm.nih.gov/38720531/
4. Smythe MA, Wu W, Garwood CL. Anticoagulant drug-drug interactions with cannabinoids: A systematic review. Pharmacotherapy. 2023;43₍₁₂₎:1327-1338. https://pubmed.ncbi.nlm.nih.gov/37740600/
5. Haider M, Acevedo-Cajigas C, Ortiz D, Zorrilla CA, Perez J. Persistent Coagulopathy After Synthetic Cannabinoid Use. Cureus. 2023;15₍₃₎:e36156. https://pubmed.ncbi.nlm.nih.gov/37065401/
6. Torian SC, Hayes L, Negrete A. Factor-guided diagnosis of coagulopathy associated with coumarin-contaminated synthetic cannabinoids. Am J Emerg Med. 2022;58:350.e5-350.e6. https://pubmed.ncbi.nlm.nih.gov/35577625/
7. Lopera V, Rodríguez A, Amariles P. Clinical Relevance of Drug Interactions with Cannabis: A Systematic Review. J Clin Med. 2022;11₍₅₎:1154. https://pubmed.ncbi.nlm.nih.gov/35268245/
8. Das S, Dubey S, Pandit A, Ray BK. Bilateral thalamic lesion presenting as Broca's type subcortical aphasia in cerebral venous thrombosis: index case report. BMJ Case Rep. 2021;14₍₃₎:e240196. https://pubmed.ncbi.nlm.nih.gov/33653859/
9. Cortopassi J. Warfarin dose adjustment required after cannabidiol initiation and titration. Am J Health Syst Pharm. 2020;77₍₂₂₎:1846-1851. https://pubmed.ncbi.nlm.nih.gov/33016308/
10. Brown GW, Bellnier TJ, Janda M, Miskowitz K. Δ-9-tetrahydrocannabinol dose increase leads to warfarin drug interaction and elevated INR. J Am Pharm Assoc ₍₂₀₀₃₎. 2021;61₍₁₎:e57-e60. https://pubmed.ncbi.nlm.nih.gov/32828704/
11. Tan CSS, Lee SWH. Warfarin and food, herbal or dietary supplement interactions: A systematic review. Br J Clin Pharmacol. 2021;87₍₂₎:352-374. https://pubmed.ncbi.nlm.nih.gov/32478963/
12. Hsu A, Painter NA. Probable Interaction Between Warfarin and Inhaled and Oral Administration of Cannabis. J Pharm Pract. 2020;33₍₆₎:915-918. https://pubmed.ncbi.nlm.nih.gov/31319733/
13. Ross CH, Singh P, Simon EL. Hemorrhagic Soft Tissue Upper Airway Obstruction From Brodifacoum-Contaminated Synthetic Cannabinoid. J Emerg Med. 2019;57₍₁₎:47-50. https://pubmed.ncbi.nlm.nih.gov/31078349/
14. Damkier P, Lassen D, Christensen MMH, Madsen KG, Hellfritzsch M, Pottegård A. Interaction between warfarin and cannabis. Basic Clin Pharmacol Toxicol. 2019;124₍₁₎:28-31. https://pubmed.ncbi.nlm.nih.gov/30326170/
15. Grayson L, Vines B, Nichol K, Szaflarski JP. An interaction between warfarin and cannabidiol, a case report. Epilepsy Behav Case Rep. 2017;9:10-11. https://pubmed.ncbi.nlm.nih.gov/29387536/
16. Elikowski W, Małek M, Kurosz J, Podkowińska A, Lukowiak-Głębocka M, Zawilska K. [Severe pulmonary embolism in a young marijuana smoker]. Kardiol Pol. 2011;69₍₁₁₎:1168-70. https://pubmed.ncbi.nlm.nih.gov/22090230/
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