How does Concerta interact with marijuana

CBD hype sense or nonsense?

Transcript

1 CBD hype sense or nonsense? Cannabidiol in Psychiatry and Pediatrics Claudia Klier Assoc Prof PD Dr med. Pediatric Psychosomatics, University Clinic for Pediatrics, MedUniWien 1

2 Topics today Basics and questions Indications Pharmacology Risks of cannabinoids Endocannabinoid system Medical cannabis Approval status Cannabidiol (CBD) Psychosis Prodrome Anxiety Epilepsy ADHD Autism Case reports Decision-making support for prescription Outlook 2

3 Cannabis, marijuana Synthetic cannabinoids Cannabinoids act on the endocannabinoid system 11 major cannabinoids: cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), cannabigerol (CBG), cannabidiol (CBD), tetrahydrocannabivarin (THCV), cannabinol (CBN), Δ trans-tetrahydrocannabinol (Δ9-THC), Δ8-trans-tetrahydrocannabinol (Δ8-THC), cannabicyclol (CBL), cannabichromene (CBC), and Δ9-tetrahydrocannabinolic acid-a (THCAA) Gul W et al., 2015; Aizpurua-Olaizola et al., Terpenes 3

4 Tetrahydrocannabinol THC: changes in cannabis potency in the last 2 decades psychoactive: intoxicating and addictive ElSohly et al., 2016 Biol Psych 4

5 Cannabidiol (CBD) concentration in the last 2 decades Anxiolytic, neuroprotective, anti-inflammatory, non-addictive 5

6 Dramatic change in the THC-CBD ratio increases in favor of THC from 15 to 80 6

7 7

8 Daily cannabis 3-fold risk Daily + high potency 5-fold risk Risk highest with early start 15a DiForti et al., Lancet

9 Mental Health in a Cannabis Nation Hasin DS 2019 APA San Francisco (Interview in Medscape) In the USA 25% of the population have access to medical cannabis or cannabis as a recreational drug Cannabis use disorder DSM V CUD men (3.5%) women (1.7%) Kerridge BT 2018, Addict Behav Time to CUD 5.8years, men; 4.7years women, the younger the shorter comorbidity SUD, PTSD, ASPD, borderline and schizotypal PDs withdrawal (CWS) is similar to depression, leads to continued use, Livne O, 2019, Drug Alcohol Depend Self-medication for depression, sleep problems, ADHD, social anxiety, Pain of driving ability? In the US, cannabis in adolescents before nicoti 9

10 Comparative study Austria Czech Republic Klier, Felnhofer, Kothgassner, Stoll, Eden

11 1990 Start of research on the modulatory effects of the endocannabinoid system in the human body 11

12 Overview of cannabinoids Freeman TP et al., BMJ

13 Decision of the National Council to liberalize medical cannabis (in D 2017) 13

14 Evidence for the use of cannabinoids Freeman TP et al., BMJ

15 cannabindiol (CBD) for psychiatric disorders? CBD available everywhere, internet 15

16 Interactions of CBD and THC Rong C et al., 2017 Cannabidiol substrate of CYP450 isoenzyme and corresponding drug interactions are possible: CYP3A4 analgesics CYP2D6 opioids, ß-blockers CYP2C9 Ibu, diclophenac, warfarin CYP2C19 diazepam, venoplafaxine, Cital Increase drug levels 16

17 17

18 18

19 19

20 Anxiety as Target Patel et al.,

21 Potential anti-anxiolytics 21

22

23 Social anxiety therapy with CBD vs placebo: Bergamaschi MM et al., 2011 Title of the presentation OR of the lecturer's organizational unit 23

24 24

25 Role of the endocannabinoid system in the pathophysiology of schizophrenia Endocannabinoid anandamide and cannabinoid CB 1 receptor linked to the disease process Cannabidiol CBD has improved psychotic symptoms, associated with an increase in anandamide serum levels Leweke FM et al., 2012 Mechanism is inhibition of the anandamide module Deactivation CBD is a negative allosteric module of CB1R and thereby attenuates the effect of THC (partial agonist of CB1R) Candidate for an effective antipsychotic treatment with few side effects Leweke FM et al., 2018 CNS Drugs, Koethe D et al., World J Biol Psychiatry

26 Title of the presentation OR the lecturer's organizational unit 26

27 Title of the presentation OR the lecturer's organizational unit 27

28 28

29 Dravet syndrome CBD (120 children) CBD greater reduction in convulsive-seizure frequency & higher rates of adverse events Title of the presentation OR of the lecturer Organizational unit 29

30 Analysis of the substances classified as effective (3/4): only 6% contained> 10mg CBD! most THC 30

31 Safety of CBD discontinuation in 11.1% and 2.6% in CBD patients and placebo RR 3.54 RRs for CBD dose 10 and 20 mg / kg / day were 1.66 (95% CI; p = 0.626) and 6.89 (95% CI; p = 0.001). Side effects in 87.9% and 72.2% in CBD patients and placebo (RR 1.22, 95% CI; p <0.001). AEs somnolence, decreased appetite, diarrhea, increased serum aminotransferase GPT (ALT) Lattanzi S 1, et al., Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis. Drugs Nov 3rd doi: / s

32 Cannabis and ADHD and ASA? THC acts on dopamine and could have a positive effect on ADHD BUT new understanding of ADHD as a brain network dysfunction AND no studies on children and adolescents so far Many risks and unanswered questions, self-medication? Studies on ADHD and cannabidiol CBD ongoing numerous studies on ASA ongoing Poleg et al., 2019, Barchel et al., 2019, Premoli et al.,

33 Case report 1 Cystic fibrosis, ADHD, cannabis addiction Patient 19a Diagnosis ADHD since 13LJ at that time no drug ADHD therapy due to risk of weight loss with methylphenidate Repeated admissions for i.v. Germ remediation for 10 days Can't last the 10 days because of cannabis addiction (inhalation !!) with comorbidity ADHD Reported that she relaxes cannabis and helps with ADHD Always interrupting the recordings by offering dronabinol per os daily h.o. She gladly accepts, but no ADHD medication. The patient feels no effect at a maximum dose of 20gtt and, as always, leaves the ward too early, incomplete germ removal, resistances? 33

34 Anti-inflammatory Effects of CBD? Inhibits the release of proinflammatory mediators (IL-1ß, TNF, nitric oxide) This has been confirmed in numerous animal models (Izzo, 2009) Study in humans 2017 Low-Dose Cannabidiol Is Safe but Not Effective in the Treatment for Crohn's Disease, a Randomized Controlled Trial. Naftali 2017 Low dose 10mg, no Nw 34

35 Case report 2 Patient 14a M Crohn's anxiety disorder: needle phobia, social fears, rejection of many medical interventions; ongoing psychological care, 2nd psychosomatic stay because of colonoscopy attempt with benzodiazepines: ineffective SSRI would be the next step: KM rejects, but also gastrointestinal Nw alternative CBD 4 months 400 mg (50kg: 8mg / kg), then 600mg, increasingly good effect in relation on anxiety and mood no change in the level of calprotectin (4800), transaminase elevation passager 35

36 Dynamics of CBD, FC values ​​and Crohn's symptoms Klier et al., 2019 J Clin Psychopharmacology accepted 36

37 Case report 3 patient M. Crohn, neurofibromatosis, opticus glioma, cafe au lait flecken, patient 18 years old poor appetite, weight loss, BMI 13, mood depressed, hospitalized, sleep only 3-4 hours adjustment disorder with depressive symptoms F43.2 Dronabinol 12gtt as medication ? Recommendation Antidepressant Fluctine and psychotherapy at home. Change to CBD if there is no sufficient improvement under Fluctine? No dronabinol indication 37

38 Case report 4 patient 16a insatiable vomiting, tic disorder transfer from peripheral children's hospital to pediatric general hospital in the case of therapy resistance Hypothesis there: cannabis-associated vomiting (21 d) before cannabis consumption No organic cause can be found, up to 10 times spontaneous vomiting, and even the smallest amounts of fluids vomited (CVC under discussion ) Therapy attempts beforehand with Zofran and other antiemetics, Haldol and Temesta (best effect so far) Tic diagnosis will be made Therapy attempt Dronabinol was considered by the peripheral hospital 38

39 Course case report 4 Increasing the dose of dronabinol on gtt, thus improving vomiting Referral ad psychosomatic to the KJP with recommendation of Intuniv (retarded guanfacine) or Catapressan for the tic disorder Hypothesis Cannabis use as self-medication for tic disorder External anamnesis: KV has always reported that it has been in stressful situations for years vomited, last twice a month, KM died a few years ago Diagnoses Tic disorder (motor) somatization disorder 39

40 Title of the presentation OR the lecturer's organizational unit 40

41 Is hemp the solution? Pieper S, Bergstrasse E. Univ. Children's Hospital Zurich 41

42 Advice on cannabis treatment request Freeman BMJ 2019 Check whether the indication is given by RCTs Which cannabinoid profile is requested? (CBD, THC, or combination) Is this product prescribable and who can prescribe it? Does the product interact with other prescribed drugs? Particular caution with vulnerable patient groups: children, babies, old people, patients with psychiatric disorders, pregnant and breastfeeding women. Consider whether patients then resort to unsafe products if they refuse, choose the keyword Internet or more harmful variants such as inhaled cannabis ... 42

43 Which indications? Chronic pain, chemotherapy nausea and spasticity are well documented. In psychiatric diagnoses, large RCTs are currently underway Cannabis withdrawal, opiate withdrawal Schizophrenia: prodromal phase, first episode and chronic illness Anxiety disorders Autism Tourette Review Bonnacorso S et al., Neurotoxicology 2019 Title of the presentation OR des Presenting organizational unit 43

44 Outlook Cannabis cave high potency of THC Cannabidiol (CBD): interesting substance does not yet have the status of a medical product, but can be obtained from the pharmacy High-quality product necessary (oils widespread with unclear dose, cave toxicity) Dose? Effectiveness? Safety? The study situation should be improved quickly 44