Cannabis Use in Epilepsy: Parent & Scientist Weighs In. Catherine Jacobson, PhD Director, Clinical Research

Transcription

1 Cannabis Use in Epilepsy: Parent & Scientist Weighs In Catherine Jacobson, PhD Director, Clinical Research

2 Professional Background PhD, Neuroscience, Oregon Health & Science University Post-doctoral Fellowship, Basic Science, Epilepsy, Stanford University Published first survey of parental use of cannabis preparations to treat intractable epilepsy (Epilepsy & Behavior, 2013) Post-doctoral Training, Clinical Research, UCSF Pediatric Epilepsy Center Assisted with first compassionate use IND for Epidiolex (2013) Director, Clinical Research, Tilray

3 Early Human Studies 1978 Mechoulam & Carlini 200 mg CBD daily in adult patients with temporal lobe epilepsy 2/4 patients receiving CBD became seizure free 1/4 patients receiving CBD saw a marked reduction in frequency None of the 4 patients receiving placebo reported any change 1980 Cunha et al. 400 mgs CBD daily in adult patients with temporal lobe epilepsy 4/8 patients receiving CBD became seizure free 3/8 patients receiving CBD saw a marked reduction in frequency 1/7 patients in placebo group saw a reduction in frequency 1986 Ames & Cridland 12 patients receiving 200 mg CBD daily saw no benefits

4 Professional Background PhD, Neuroscience, Oregon Health & Science University Post-doctoral Fellowship, Basic Science, Epilepsy, Stanford University Published first survey of parental use of cannabis preparations to treat intractable epilepsy (Epilepsy & Behavior, 2013) Post-doctoral Training, Clinical Research, UCSF Pediatric Epilepsy Center Assisted with first compassionate use IND for Epidiolex (2013) Director, Clinical Research, Tilray

5 Personal Experience with Epilepsy & Cannabis Ben

6 Personal Experience with Epilepsy & Cannabis May 7, 2009 August 18, 2009 Nov & Dec 2009 Ben was born, healthy pregnancy & birth First seizure (keppra, trileptal, phenytoin) High doses of oral steroids present Tegretol, lamictal, depakote, phenobarbital, topamax, onfi, clonazepam, ketogenic diet, VNS Implantation, felbatol, sabril May 2012 First heard about parental treatment with cannabis; tried artisanal preparation (later tested it and found it was sugar water) 2012 & 2013 Separated CBD and THC in my garage; 200mg CBD ~40% reduction in seizure frequency for Ben July 2014 Ben received access to Epidiolex via compassionate use IND; subsequently removed by his physician January 2015 Ben underwent resective brain surgery at Stanford; half of right parietal lobe removed

7 Chemical Structure of Cannabinoids 9 -Tetrahydrocannabinol (THC) Cannabidiol (CBD) Tetrahydrocannabinol (THC) Cannabidiol (CBD)

8 Column Chromatography

9 Personal Experience with Epilepsy & Cannabis May 7, 2009 August 18, 2009 Nov & Dec 2009 Ben was born, healthy pregnancy & birth First seizure (keppra, trileptal, phenytoin) High doses of oral steroids present Tegretol, lamictal, depakote, phenobarbital, topamax, onfi, clonazepam, ketogenic diet, VNS Implantation, felbatol, sabril May 2012 First heard about parental treatment with cannabis; tried artisanal preparation (later tested it and found it was sugar water) 2012 & 2013 Separated CBD and THC in my garage; 200mg CBD ~40% reduction in seizure frequency for Ben July 2014 Ben received access to Epidiolex via compassionate use IND; subsequently removed by his physician January 2015 Ben underwent resective brain surgery at Stanford; half of right parietal lobe removed

10 Issues relevant to the clinical discussion Artisanal cannabis preparations Data for informed treatment Patient-centered care Improving data collection efforts and outcomes

11 Epidiolex vs. Artisanal Cannabis Preparations Epidiolex = Pharmaceutical Preparation One active ingredient: Cannabidiol Manufactured in accordance with ICH guidelines - Stability - Analytical validation - Impurities - Good manufacturing practices Allows for precise dosing Artisanal Preparations Whole plant extracts contain dozens of compounds (cannabinoids & terpenes) Very little to no regulatory oversight in manufacturing standards - Dependent on state regulations of medical cannabis Precise dosing unlikely

12 Importance of Regulating Products Vandrey et al. JAMA 2016 The Globe and Mail Report products tested 83% were inaccurately labeled for THC content 44 products had detectable levels of CBD 13 of these products were labeled for CBD content 9 unregulated dispensary products tested Products were contaminated: 1 yeast & mold 2 microorganism count exceeded limits 3 potentially harmful bacteria 100% were inaccurately labeled for CBD content

13 Cannabis Preparations *Strain names do NOT equal different species *Chemical composition of strains are not the same from seller to seller

14 Cannabis Preparations Chemical composition of the extract or oil depends on: 1. Species of starting raw plant material 2. Extraction methodology a. Solvents b. Heat settings c. Vacuum pressure settings d. Time of extraction

15 Issues relevant to the clinical discussion Artisanal cannabis preparations Data for informed treatment Patient-centered care Improving data collection efforts and outcomes

16 Data for informed treatment Data to inform treatment does NOT equal trials required for FDA approval

17 Data for informed treatment Data to inform treatment does NOT equal trials required for FDA approval Epidiolex provided to 100s of children via compassionate use INDs information gathered: starting dose titration schedule response signal side effects drug-drug interactions adverse events

18 What we don t know What we do know Safe & efficacious dosing of artisanal preparations

19 What we don t know What we do know Safe & efficacious dosing of artisanal preparations Which pediatric syndromes are most likely to respond to artisanal preparations

20 What we don t know What we do know Safe & efficacious dosing of artisanal preparations Which pediatric syndromes are most likely to respond to artisanal preparations Efficacy data (responder rates; seizure frequency reduction vs. placebo)

21 What we don t know What we do know Safe & efficacious dosing of artisanal preparations Which pediatric syndromes are most likely to respond to artisanal preparations Efficacy data (responder rates; seizure frequency reduction vs. placebo) Risks of adverse events of THC in a seizure-prone brain

22 What we don t know What we do know Safe & efficacious dosing of artisanal preparations Which pediatric syndromes are most likely to respond to artisanal preparations Efficacy data (responder rates; seizure frequency reduction vs. placebo) Risks of adverse events of THC in a seizure-prone brain Long-term cognitive side effects of CBD & THC use in a developing brain

23 What we don t know Safe & efficacious dosing of artisanal preparations What we do know Safe & efficacious CBD Dosing: 5-25mg/kg Which pediatric syndromes are most likely to respond to artisanal preparations Efficacy data (responder rates; seizure frequency reduction vs. placebo) Risks of adverse events of THC in a seizure-prone brain Long-term cognitive side effects of CBD & THC use in a developing brain

24 What we don t know Safe & efficacious dosing of artisanal preparations Which pediatric syndromes are most likely to respond to artisanal preparations What we do know Safe & efficacious CBD Dosing: 5-25mg/kg Efficacy of CBD in two specific pediatric epilepsy syndromes Efficacy data (responder rates; seizure frequency reduction vs. placebo) Risks of adverse events of THC in a seizure-prone brain Long-term cognitive side effects of CBD & THC use in a developing brain

25 What we don t know Safe & efficacious dosing of artisanal preparations Which pediatric syndromes are most likely to respond to artisanal preparations Efficacy data (responder rates; seizure frequency reduction vs. placebo) What we do know Safe & efficacious CBD Dosing: 5-25mg/kg Efficacy of CBD in two specific pediatric epilepsy syndromes Side effects of CBD in healthy adults and pediatric patient population Risks of adverse events of THC in a seizure-prone brain Long-term cognitive side effects of CBD & THC use in a developing brain

26 What we don t know Safe & efficacious dosing of artisanal preparations Which pediatric syndromes are most likely to respond to artisanal preparations Efficacy data (responder rates; seizure frequency reduction vs. placebo) What we do know Safe & efficacious CBD Dosing: 5-25mg/kg Efficacy of CBD in two specific pediatric epilepsy syndromes Side effects of CBD in healthy adults and pediatric patient population Risks of adverse events of THC in a seizure-prone brain Side effects of THC in healthy adults and adult patient population Long-term cognitive side effects of CBD & THC use in a developing brain

27 What we don t know Safe & efficacious dosing of artisanal preparations Which pediatric syndromes are most likely to respond to artisanal preparations Efficacy data (responder rates; seizure frequency reduction vs. placebo) What we do know Safe & efficacious CBD Dosing: 5-25mg/kg Efficacy of CBD in two specific pediatric epilepsy syndromes Side effects of CBD in healthy adults and pediatric patient population Risks of adverse events of THC in a seizure-prone brain Side effects of THC in healthy adults and adult patient population Long-term cognitive side effects of CBD & THC use in a developing brain Artisanal CBD preparations contain THC: 100mg dose of CBD also contains 3-5mg THC

28 What we don t know Safe & efficacious dosing of artisanal preparations Which pediatric syndromes are most likely to respond to artisanal preparations Efficacy data (responder rates; seizure frequency reduction vs. placebo) What we do know Safe & efficacious CBD Dosing: 5-25mg/kg Efficacy of CBD in two specific pediatric epilepsy syndromes Side effects of CBD in healthy adults and pediatric patient population Risks of adverse events of THC in a seizure-prone brain Side effects of THC in healthy adults and adult patient population Long-term cognitive side effects of CBD & THC use in a developing brain Artisanal CBD preparations contain THC: 100mg dose of CBD also contains 3-5mg THC Preclinical evidence supports anticonvulsant properties of THC

29 What we don t know Safe & efficacious dosing of artisanal preparations Which pediatric syndromes are most likely to respond to artisanal preparations Efficacy data (responder rates; seizure frequency reduction vs. placebo) What we do know Safe & efficacious CBD Dosing: 5-25mg/kg Efficacy of CBD in two specific pediatric epilepsy syndromes Side effects of CBD in healthy adults and pediatric patient population Risks of adverse events of THC in a seizure-prone brain Side effects of THC in healthy adults and adult patient population Long-term cognitive side effects of CBD & THC use in a developing brain Artisanal CBD preparations contain THC: 100mg dose of CBD also contains 3-5mg THC Preclinical evidence supports anticonvulsant properties of THC Epidemiological studies cannabis use results in fewer hospital admissions of patients

30 What we don t know Safe & efficacious dosing of artisanal preparations Which pediatric syndromes are most likely to respond to artisanal preparations Efficacy data (responder rates; seizure frequency reduction vs. placebo) What we do know Safe & efficacious CBD Dosing: 5-25mg/kg Efficacy of CBD in two specific pediatric epilepsy syndromes Side effects of CBD in healthy adults and pediatric patient population Risks of adverse events of THC in a seizure-prone brain Side effects of THC in healthy adults and adult patient population Long-term cognitive side effects of CBD & THC use in a developing brain Artisanal CBD preparations contain THC: 100mg dose of CBD also contains 3-5mg THC Preclinical evidence supports anticonvulsant properties of THC Epidemiological studies cannabis use results in fewer hospital admissions of patients Uncontrolled seizures very poor outcome

31 Issues relevant to the clinical discussion Artisanal cannabis preparations Data for informed treatment Patient-centered care Improving data collection efforts and outcomes

32 When you treat the patient, you treat the family

33 Patient-centered Care Goal: Provide Best Possible Care to Each Patient Each patient is an individual case Relevance of 50% responder rate or seizure frequency reduction in a given patient population Quality of life improvement cannot be overestimated Seizure frequency Seizure severity Cognitive improvements Behavioral improvements Sleep quality Patient/caregiver empowerment What is the role of the physician in treating the patient?

34 Issues relevant to the clinical discussion Artisanal cannabis preparations Data for informed treatment Patient-centered care Improving data collection efforts and outcomes

35 Improving Data Collection & Outcomes Elephant in the room: How will we, as a community, collect data to inform treatment and thereby increase the chances of better outcomes? Push for legislation that regulates the manufacturing of artisanal cannabis products Hold manufacturers accountable for their manufacturing practices and their products Company-sponsored clinical trials are very unlikely; therefore, NINDS, patient advocacy groups, physicians must collaborate on data collection efforts

36 Thank You Catherine Jacobson, PhD Director, Clinical Research