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Trillium Kids

David Sine, M.D.

Dr. David Sine received his Doctor of Medicine in 1993 and immediately pursued specialized credentialing in pediatric medicine, in which he became board certified in 1998. He received his board certification in 2002 from the American Board of Hospice and Palliative Medicine and began his career in providing compassionate care to the most critical of pediatric patients. He serves to guide both the patients, and their families, throughout their most difficult transition and has positively affected hundred of families in the most grim of situations.

Dr. Sine currently serves as the Medical Director of Pediatric Palliative Care for Central Valley Children’s Hospital, Hinds Hospice, and Tulare Hospice in Central California. He and his interdisciplinary care teams provide holistic care to children with life-threatening illnesses and those who are terminally ill. His program specializes in providing families with symptom management for chronically ill children and children at the end of life through communication, medical decision making, spiritual and psychosocial guidance. In addition to the clinical and administrative duties related to these palliative care programs, Dr. Sine is involved in Complementary Alternative Medicine and specializes in the use of medical cannabis in his pediatric patient populations. Dr. Sine also works closely with local regulators and law enforcement to help establish best practices for the use of cannabis in children.

Education 2002. American Board of

Hospice and Palliative Medicine

1998 American Board of Pediatrics 1993 Doctor of Medicine, McMaster University 1990. Bachelor of Science in

Nursing, McMaster University

Focused Training • Pediatric Hospice & Palliative Care • Pediatric Pain & Symptom Management. • Complementary & Alternative Medicine • Pediatric Medical Cannabis

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BioLife West

Don Anderson, Pharm.D.

Dr. Don Anderson received his Doctor of Pharmacy degree in 2002 and quickly began his career in pediatric pharmaceutical care with an emphasis on clinical pharmacotherapy management. He completed specialized training in neonatal and pediatric pharmacy, and has helped establish new care programs in multiple medical institutions in Central California. Don fills an integral role within his care management teams in driving holistic and alternative medication management.

Don began his work in medial cannabis in 2013 in Denver, Colorado, serving as a pharmacotherapy advisor to both academic and private sector organizations looking to bring innovative, high quality and consistent forms of cannabis to select populations. His extensive experience in pediatrics has led him to focus on specific formulations of cannabis for the most severely afflicted young patients. Focusing on two major treatment groups, those in hospice/palliative care programs and those designated as medically fragile. Dr. Anderson and his team are providing significant improvement to those most in need. In 2015 he formed the non-profit collective, BioLife West Solutions, based out of Central California in an effort to provide the highest quality customized cannabis blends to his patients. He has developed a repeatable, quality and quantity tested line of cannabis blends uniquely formulated for each of his patients. Don has successfully applied the art of custom compounding to cannabis-based medicines, which is demonstrating highly effective outcomes in each patient segment.

Education 2002 Doctor of Pharmacy, University of the Pacific School of Pharmacy and Health Sciences 1998 Bachelor of Science in Business Administration, Pacific Union College

Focused Training • Medication formulation and

compounding • Pediatric pharmacotherapy • Clinical management of

complex diseases in pediatrics • Specialized pharmacotherapy

in palliative care • Pediatric pain management

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Sean

Sean Hunt, BSN, RN, CPN

Sean Hunt completed an Associate Degree Nursing Program at the College of the Sequoias in Visalia, CA in 2006. After passing the Board of Registered Nursing state exam, he immediately started working as a staff RN on the inpatient pediatric unit at Kaweah Delta Medical Center in Visalia, CA. There he cared for children with various diagnosis and ailments for the next three years. During the final semester of his RN program Sean did a focused rotation on an adult oncology unit. This was an area of nursing that really spoke to his heart.   When the opportunity to work on the hematology/oncology at the local Valley Children’s Hospital became available, he jumped right in. Sean has worked on the heme/onc unit for the past eight years. After working on the oncology unit for a few years, his focus narrowed on palliation, pain, and symptom management of the oncology patient. Sean joined the palliative care team at Valley Children’s Hospital in 2015. He now serves as the palliative care unit champion on the heme/onc unit and is a part-time palliative care coordinator nurse. He also serves on the unit-based CLABSI taskforce committee. His other duties include relief charge nurse, clinical education, and mentor to new staff. Sean is currently enrolled in a Pediatric Nurse Practitioner program at CSU Fresno, which will be completed in spring 2017. He is excited about potentially working as a pediatric hospice and palliative care nurse practitioner.

Education 2015. Certified Pediatric

Nurse 2014. Bachelor’s of

Science In Nursing, CSU Fresno

2006. Associate’s of Science In Nursing, College of the Sequoias

Focused Training • Pediatric Chemo/

Biotherapy • Pediatric Oncology • Pediatric Hematology • Pediatric Endocrinology • Pediatric Nephrology • Pediatric Palliative,

Pain, and Symptom Mgmt

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Joint Programs and Works

Drs. Sine and Anderson have synchronized their efforts to provide both outcomes data and practical perspectives. With a rapidly growing patient population by which to monitor and track successful outcomes; they are uniquely qualified to share successful alternative therapy regimens applied with the highest of standards to fellow practitioners and regulatory bodies alike. They have created a network of partnerships and resources that combine to make their offering truly unique in the application of medicinal cannabis in this setting.

Publications and Presentations 2015, 2016 “Blending of CBD and THC In Pain and Symptom Management in Pediatric Palliative Care”

-presented at the International Children’s Palliative Care Network Annual Conference, Buenos Aires, Argentina May 2016

“The Use of CBD/THC Blends For Pediatric Palliative Care” -presented at California Compassionate Care Annual Symposium in Newport Beach, CA May 2016

“Cannabinoids: A New Hope For Pain and Symptom Management - Part 1” -due to publish in August by the National Hospice and Palliative Care Organization via ChiPPS E- Journal

“Cannabinoids: A New Hope For Pain and Symptom Management – Part 2” -due to publish in October by the National Hospice and Palliative Care Organization via ChiPPS E- Journal

“A Novel Three-Dimensional Chemical Characterization and Visualization Tool For Cannabis Varieties”

-presented at the 16th Annual Oxford International Conference on the Science of Botanicals in Oxford, MS 2016

“Cannabis Product Variations As A Result of Growing Conditions – A Medical Perspective” -presented at the 8th Annual Joint Natural Products Conference via the American Society of Pharmacognosy in Breckenridge, CO July 2015

Our ApproachOur primary goal in using medicinal cannabis therapy in pediatric patients is to improve quality of life. We recognize the value of an alternative medicinal product and believe that it can provide successful outcomes when traditional medicines have not. We whole heartedly agree that the manner in which cannabis is applied is heavily correlated with the success rate.

The model we use centers on a focused approach between the provider and the pharmacist, with an intensive follow-up regimen through our nursing team. Our fundamental requirement was that our patients have constant access to a pure, sustainable, high quality, organic product that is measurable, tested, and thoroughly documented.

Our outcomes are achieved through a concerted effort between: • Dedicated and willing parents • Supervising physician • Specialized pharmacist • Nursing follow-up This three arm approach allows information to be communicated fluidly between the parties and maintains a steady dialogue so that care and product can be individualized to each patient’s specific needs.

Focused Treatment Groups

Qualified patients are placed into one of three major treatment groups: 1. Pain management

a. Pain of chronic disease b. Acute pain crisis c. Terminally ill d. End of life

2. Refractory seizure a. Neurodegenerative disease b. Hypoxic encephalopathy c. Traumatic brain injury

3. Severe behavioral disorders a. Autism Spectrum Disorders (ASD) b. Pervasive Developmental Delay (PDD) c. Oppositional Defiant Disorder (ODD)

*Unique formulations are made in bulk and kept on hand for each of these three groups

Refractory SeizuresRefractory seizure patients exist in all shapes and sizes with highly variable etiologies. While the populations are mixed, there are common treatment threads within them. Approximately half of our seizure patients are of a life-threatening nature. We strive to find the common threads and use our knowledge of cannabis components to affect change.

Overview: • Infantile Spasms, Dravets, cryptic seizures are all various forms of severe seizure

disorders that may not be well controlled with anti-epileptic drugs (AED’s). • Patients are assessed for current seizure activity and a review of current and past

AEDs are reviewed. • Initial blend therapy is initiated based on the particular patient type and the

experience with patients with similar seizure types etc.  Clinical Pearls: • Chasing seizure thresholds is not always weight-based CBD success. • There is a sometimes a need for a maintenance blend CBD/THC with a emergency or

crisis blend to be used in rescue fashion. • After ~90 days of seizure control a collaborative discussion between the team and

outside specialists will determine what drug regimen adjustments are appropriate.

Pain ManagementThis patient group is mixed with moderate-to-severe chronic pain as well as more severe end of life pain. Many of these patients come to us on multiple narcotics and suffer the side effects of those medications, as well as the symptoms of their progressing disease. Our treatment path focuses on displacing opiate analgesics with equal or greater pain control.

Overview: • P atients are assessed in the usual manner for location, type and source of pain.   • A detailed history of previous therapies is reviewed (including both traditional and CAM

therapy). • Initial dosing is then determined for that patient based on all of the symptoms cohorted.  Clinical Pearls: • THC is the more effective ingredient for both visceral and somatic pain, though varying

doses of CBD are important for some types of pain. • Side effect profile is minimal to absent with the cannabis blend allowing decreased use

of traditional narcotics (all with more extensive side effects, tolerance, and much greater cost).

• Even the most potent narcotic regimens seems eligible for cannabis replacement if transitioned appropriately.

Severe Behavioral Disorders

These patients demonstrate a wide variety of behavioral issues, the worst being self-mutilation and physical harm to family members and care givers. They are frequently misdiagnosed and on multiple medications to control their behaviors. Medication side effects are numerous and results tend to be limited.

Diagnoses include: • Autism Spectrum Disorders (ASD) • Reactive Affective Disorder • Pervasive Developmental Delay • Severe Anxiety • Tourette’s • Conduct Disorder

Clinical Pearls: Initial approach was heavily CBD oriented with little improvement being noted in primary symptoms. Reports of increasing hyperactivity were noted among several patients. Revised formula contained lesser amounts of CBD, increased amounts of CBN and moderate doses of THC. • Significant decrease in number and severity of outbursts • Marked improvement in following directions and responding to behavior modifications • Improved sleep

Product SourcingFor families of Medical Marijuana (MMJ) therapy, finding and maintaining a consistent source of medicinal grade product is a challenge. Our decision to enter the supply provision was driven by our patients repeated lack of ability to source high quality product in a repeatable manner. In addition, product suspicions started after multiple reports of patient regression or relapse into pre-treatment states were shared with the team. Parents were asked to render a small sample of product for analysis which was sent for testing. Results were compiled and discussed with the care team and families.

Pre-existing supply challenges include: • Product contaminants • Supply restrictions • Cost of therapy • Product formulation • Accurate dosing • Product consistency • Product contaminants • Product availability • Location

Contaminant testing confirmed presence or excessive amounts of inorganic compounds: • Lead • Arsenic • Cyanide • Mercury Residual Solvent Testing (RST) identified unrecovered reaction compounds: • Cyclohexane • Benzene • n-Butane • n-Hexane

Product Philosophy

Available products quickly became of concern as families brought them to follow- up appointments, and began asking questions. It was also at that time that we realized that there was no true pharmacologic expertise available to them. We found that there was no ability to individualize therapy, not even slightly, which became a major concern because we know that one size does not fit all! These issues quickly became our primary drivers for creating a product that could address the key issues facing our patients. These drivers were addressed by several key decisions: • Dosing could not be based on the plant strain, but rather needed to be at the

individual ingredient level for each substance included (THC, THCΔ, CBD, etc) • Extraction method of choice needed to retain the highest level of terpenes possible

– solvent recovery had to be 100% • No ingredient would be utilized until all batch testing had been reviewed • Final product must work in both oral and non-oral routes of administration

– could not compromise the feeding tubes • Product had to be homogenized and stable for a minimum of 120 days

Administration Challenges

Administration Challanges

Best Practice Dosing

Initiating Therapy • Each treatment group has a standard formula applied to every new start

– Irrespective of previous cannabis therapy or other medications on board – Initial dose is always conservative to assess tolerance of the primary ingredients

as THC and CBD both has cross reaction and allergy potentials • Dosing volume is based on bodyweight and other patient specific parameters • Titration to effect governs the entire dosing process

Ongoing adjustments • Feedback from each patient drives volumetric dosing modifications • Formula adjustments are made as needed at each refill interval • Detailed patient records drive overall dose and formula, and weigh heavily into the

overall success of each blend • As new challenges arise adjustments can be made, where appropriate, to address

– Menses, physical illness, etc.

Medication Therapy Management

As patients progress over time, during which the ideal blend and dose are established, traditional medicines will be re-evaluated for continued use. In many cases these traditional medicines can be significantly reduced or eliminated altogether as patients stabilize. It is not uncommon to completely displace narcotics, anti-inflammatory agents and antiepileptic drugs (AED’s) in the 3 treatment groups. This approach to medication reduction/elimination is performed carefully and collaboratively within the team and external specialists as appropriate. Coordination with external providers exposes them to cannabis success and establishes the basis for gaining acceptance in the medical community.

Why a pharmacist? • Uniquely qualified to make dosing and formula adjustments in accordance with diagnosis

and traditional medication considerations • Highly trained to identify drug interactions and minimize/manage side effects

– Many patients are on complex medication regimens from multiple specialized providers, our pharmacist maintains “the big picture” and intervenes as needed

• Product formulation requires an in-depth knowledge of chemistry, laboratory abilities and analytical methods

• Compounding pharmacy concepts and techniques are essential in developing appropriate products

Follow-Up Upon initial meeting with the team, patient and family goals of therapy are identified • Reduction of symptoms • Reduction of side effects from current medication regimen • Reduction in total number of necessary medications • Overall improved quality of life Routine assessment from the pharmacist and nurses document tracking metrics • Following up with patient/family on a monthly basis and more often as needed • Measure success of therapy through historical comparison or recorded information from family

– Embrace “journaling”! • Identify opportunities for therapeutic improvements and inform Pharmacist Persistent Symptoms • Initial dosing is conservative, increases are based on persistence of symptoms • Notifying Pharmacist of other medications allows team to investigate interactions and side

effects • May advise family to use adjunct medications to reduce symptoms while adjusting blend

composition or dosing • Collaboration with affiliates and colleagues can identify other opportunities for increased

symptom control

Outcomes Case 1 – 14 years old Diagnosis: Acute Lymphocytic Leukemia with previous bone marrow transplant x 2, repeat graft-versus-host disease and relapse

Prognosis: Grim - honeymoon phase and comfort care measures Intake: Referred to palliative care in Nov of 2015 with estimated life expectancy 30-60 days Weighed 48lb and was wheelchair bound Taking Vicodin, Methadone, Fentanyl, Ativan, Neurontin and Lidocaine for pain Using steroid pulses therapy to achieve “honeymoon” periods Multiple ER admissions for pain crisis

Progress: Started MMJ in Nov, 2015 No ER visits in 2016 (none) Has gained over 20lbs and is completely ambulatory (no wheelchair or assist) CBC and bone marrow are clean, though we believe she has leukemic infiltrate in her tibia which may be the source of relapse and intense pain Candidate for salvage amputation, currently in evaluation

Outcomes Case 2 - 2 years old

Diagnosis: Hypoxic Ischemic Encephalopathy, Complex Seizures, Tracheostomy, G-tube, vocal cord paralysis

Prognosis: Grim – life threatening

Intake: Frequent complex seizures started at 5mo Contracted Human Metapneuovirus resulting in complete respiratory failure resulting in Extracorporal Membranous Oxygenation (ECMO) Progress: Started on Oct, 2015 (seizure free 4 days after moderate dosing CBD/THC) Viral infection caused severe pulmonary collapse, admitted to PICU and started ECMO Care team and parents decided to maintain CBD/THC therapy during PICU stay Improved and returned home sooner than expected Increased THC component to help drive neuroregeneration and improve lung development Bronchoscopy revealed his vocal cords no longer paralyzed Passed swallow study and will likely move toward de-cannulation and oral feeding Now able to ambulate in a walker

Outcomes Case 3 - 12 years old

Diagnosis: Autism Spectrum Disorder, Oppositional Defiant Disorder, Reactive Affective Disorder

Prognosis: Poor; institutional placement was being recommended due to self-harm and extreme instability

Intake: Taking Abilify, Depakote, Prozac, Gained 60lbs; developed fatty liver disease and hypertension from medications Missed, or was sent home, half of last school year for behavioral issues and outbursts

Progress: Started ASD blend on 2/1/2016 Has lost 15lbs, liver enzymes reverting to normal status, no longer needs blood pressure meds Abilify has been discontinued, Depakote discontinued as well Has not missed any days of summer school to date, expect similar ongoing Increasing rationalization and ability to self-regulate (stop,start)

Outcomes

Case 4 - 9 years old

Diagnosis: Cerebral Palsy, Recurrent Seizures, Sympathetic Storming

Prognosis: Poor; progressive storming and seizure severity

Intake: 9 y/o with history of ‘near SIDS’ requiring full CPR, later determined to be a stroke Developed seizures early on that became resistant to as many as 4 AED’s and a vagal nerve stimulator (VNS) implant Developed autonomic storming which trigger his seizures Hemiplegic and globally hypotonic, wheelchair bound and non verbal Progress: Started therapy Nov 2015, seizures minimized within 4 weeks Continues to improve; now vocalizing and ambulating on his own Tolerating oral feeds, gastric tube to be removed this Fall

The Bigger PictureHow does our program work into other programs • Our program is stand alone therapy but is often used by patients who are either enrolled in a

chronic care management program through their primary care clinic • Other programs such as concurrent care and hospice utilize our program to offer alternative

means • Specialties such as neurology, oncology and psychiatry look to our team for aid in symptom

management Alternative medicine approach and acceptance is rapidly changing • The growth of new medications for seizures, pain, and … have stalled in the last two decades • The number of patients outgrowing their medication’s efficacy is staggering • Patients are frustrated and looking for new therapies • Physicians are increasingly recommend patients to seek help from alternative medicine providers • Testimonies being shared through social media, news reports, and documentaries What does this mean for providers? • Medical cannabis is not for everyone, it is not a magic bullet • Decide where you personally stand on the use of medical cannabis, do you feel it is safe? • Regardless of your stance, be open to having a discussion about it, your patient may ask • Provide support, guide with useful information to help patient/family make a safer informed

choice

PartnershipsThe provider of the ultimate chemical fingerprint for phytochemicals, CannaPrint provides the tool by which we authenticate each ingredient before use. CannaPrint is truly unique in its ability to render a 3-dimensional image of complex molecules for authentication purposes and analyses.

Sweet Nectar Society’s mission is to provide comfort and love to families of children who are affected by serious illness, disability or injury through its photography and community outreach programs. They focus on raising awareness of childhood illness and disabilities while providing lasting memories for families through the art of photography.

The University of Ohio Department of Chemistry and Biochemistry is a prestigious participant in the DEA Class 1 testing program, and an integral part of our quality and purity standards. They use High Performance Liquid Chromatography, Ion Mobility Spectrometry and Mass Spectrometry to support an extensive drug identification program in both cannabis-based initiatives and others.

Thank you