Comments and Observations on the Clinical Use of …2017.canntencon.com/wp-content/uploads/2017/06/1230_grunfeld.pdf · Comments and Observations on the Clinical Use of Cannabis Clinical

Comments and Observations on the Clinical Use of Cannabis

Clinical Use of Cannabis

Jonathan Grunfeld, M.D. Charged with Palliative Care in Dept. of Oncology,

Assaf HaRofeh Medical Center

Be’er Ya’akov, ISRAEL

Comments and Observations on the Clinical Use of Cannabis

Jonathan Grunfeld, M.D.

Disclosures: Niamedic healthcare and research clinics

Presentations sponsored by Tikun Olam, Better, Elixinol









The Discrepancy

Between

Anecdotal Observations and Institutional Medicine


The Discrepancy

Between


Clinical trial results INCOMPATIBLE with clinical observations


The Discrepancy

Between


EXAMPLE









Rigorous Institutional Standards or Anecdotal Evidence

APPROACH

• Available supportive preliminary data



APPROACH


Cannabinoids reputedly stimulate appetite, both historically and in

recent studies of human volunteers and AIDS patients.

…Data from four dose-finding and phase II studies of 161 patients with

cancer-related anorexia-cachexia syndrome (CACS) suggest cannabinoids’

potential at fixed doses of 2.5 mg of THC twice to three times daily.



APPROACH




Randomized Controlled Trial designed

APPROACH


To evaluate the hypothesis that THC or Cannabis extract improve QoL / appetite compared with placebo




Included patients with

• Incurable advanced cancer

• Involuntary weight loss over 5% of their total body weight over the last 6 months

• estimated life expectancy of less than 3 months

• ECOG performance status of equal or less than 2 (Ambulatory

and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours)




The Intervention

• Random, double blind, placebo controlled

• Two daily doses of cannabis extract containing 2.5mg THC, or 2.5mg THC + 1.0mg CBD, or Placebo

• Treatment was continued for 6 weeks




The Outcome Measures

• Appetite assessed by Visual Analogue Scale

• Quality of Life assessed by a composite of scores on questions 29 (overall assessment of health) and 30 (overall assessment of Quality of Life) from the EORTC QLQ-C30








• RCT designed and executed

Results

• The trial was stopped after the first interim analysis because data indicated insufficient differences between the study groups.

!


A LETTER from a PATIENT

Two months ago I started feeling pain in the side of my body. The pain was accompanied by loss of appetite and severe nausea. Just about every attempt to eat resulted in vomiting.

A comprehensive workup discovered a malignant tumour in the liver and at the moment I am being treated with pills for the pain. The pills also cause severe nausea and constipation, for which I am receiving an anti-nausea pill and a laxative which unfortunately are not helping and all I feel is fatigue and poor concentration and lack of interest, a strong urge to sleep all the time and low mood

I wish to point out that until now the only thing the made me feel much better was the use of cannabis. Physically the body is less tense and less painful. The appetite increases and I can eat anything without feeling full and choked up and I do not vomit at all the mood and general feeling are much better, without nausea or side effects.

The way I see it the difference between the feelings with cannabis and without it is the “difference between heaven and earth”.



How do we proceed in bridging the gap

between PLANT and PATIENT?

Clinical Trial Results INCOMPATIBLE with Clinical Observations


Clinical Trial Results INCOMPATIBLE with Clinical Observations

• The failure of the clinical trial is apparent.

• The reports from patients are reliable and consistent.

Clinical Observations

Quest

Clinical Trial

Hypothesis Driven


Clinical Trial

Endpoint

Fixed Outcome



Endpoint

Narrative

Evaluation

Clinical Trial

Strict Protocol

fixed dose

few specified preparations



Clinical Trial



Time Scale of Adjustment to Outcomes


i hly

d vi a i e

I t v n i n

Clinical Trial

No Individual Adaptation


• Cannabis is a plant with an extensive history of use for multiple medical purposes.

• Cannabis was introduced to “western medicine” in the early 19th century.

• Reports by clinicians who were dependent on skills of observation supported the medical use of cannabis.

Cannabis for Medical Purposes Clinical Experience

Essentials

Clinical Trial

Fixed Outcome

Strict Protocol

(fixed dose, few specified preparations)

Time Scale of Adjustment to Outcomes Prolonged

No Individual Adaptation


Narrative Evaluation

Flexible Regimen

(loosely defined dose, broad range of preparations)

Time Scale of Adjustment to Outcomes Short

Highly Individualized Intervention




How to bring Reliability and Efficacy Closer to Each Other?

Simply put:

How do I practice?

I engage with the patients on a narrative level

Provide them with access to a broad range of cannabis

species in various modes of use

Emphasize the importance of adherence and follow

closely remaining as accessible as possible

Clinical Trial



The Chef Perspective Not

The Engineer


The Discrepancy

Between

Institutional Medicine and Anecdotal Observations

Clinical trial results INCOMPATIBLE with clinical observations

Institutional medicine emphasis on single molecule pharmacological

intervention for single primary outcome

Cannabis success attributable to multiple molecule intervention

attaining multiple clinical objectives

The Chef Perspective Not

The Engineer

Clinical Trial



Relative Failure

Clinical Trial



Relative Failure

(failure?) Idiosyncratic (success?)

Clinical Trial



Relative Failure

Loosely Controlled

Clinical Trial



Study Success and Import into Reproducible Patterns of Practice

And then Re-evaluate

Clinical Trial



Study Success and Import into Reproducible Patterns of Practice

And then Re-evaluate

NO! THIS is NOT BEING DONE

Clinical Trial




Clinical Trial





How do we proceed as clinicians?


When to Consider Cannabis? Theoretical

Reaching out beyond the limits of standard medicine

Contributing to improved clinical management within the confines of standard medicine

Standard Medicine

No more effective relief

No more effective therapy Incompatible

Values


When to Consider Cannabis?

Concrete - Practical

Confrontation with management of refractory symptoms

Confrontation with management of complex patient

Confrontation with management of complex patient

• Cannabis is a plant with an extensive history of use for multiple medical purposes.

• Cannabis was introduced to “western medicine” in the early 19th century.

• Reports by clinicians who were dependent on skills of observation supported the medical use of cannabis.

Cannabis for Medical Purposes Clinical Experience

Essentials

Documents

Comments and Observations on the Clinical Use of …2017.canntencon.com/wp-content/uploads/2017/06/1230_grunfeld.pdf · Comments and Observations on the Clinical Use of Cannabis Clinical