INTER-AMERICAN DRUG ABUSECONTROL COMMISSION

C I C A DSecretariat for Multidimensional Security

THE CHALLENGE OF MEDICAL CANNABIS: NATIONAL PROGRAM

SIXTY-FIFTH REGULAR SESSION OF CICADMay 8 - 10, 2019 Buenos Aires, Argentina

OEA/Ser.L/XIV.1.65CICAD/doc.2476/198 May 2019Original: English

The challenge of

medical cannabis:

National Program

Dr. Diego SarasolaMedical Specialist in Psychiatry and Medical Psychology.

Research Coordinator on Medical Cannabis MS and DS.Director, Alexander Luria Neurosciences Institute

Physician, Cognitive Neurology Service, FLENI

ACTIVE INGREDIENT

The genus of plants with cannabis flowers primarily includes two species: Sativa (made up of more than 500 compounds) and Indica

The three major neuroactive components of cannabis are

• D9-tetrahydrocannabinol (D9-THC) (psychoactive substance),

• Cannabidiol (CBD) (non-psychoactive substance). CBD, in turn, reduces the psychotropic activity of D9-THC, increasing its tolerability.

• Cannabinol (CBN) (mildly psychoactive) .

THC and CANNABIDIOL

PRESENT

FUTURE

PHARMACOKINETICS

Distribution (32 L/Kg): Highly fat-soluble, with rapid entry to the CNS, adipose tissue and other organs. Protein binding of 90%

Metabolism and excretion: Metabolizes in the liver through hydroxylation to 7-OH-CBD via the P450 cytochrome system.

Half-life of CBD is 18-32 hours

Drug interactions:

• Inhibitor of P450 cytochrome enzymes (CYP2C and CYP3A isoenzymes (acts on the metabolism of CBZ and DFH)

• In chronic administration, inductive effect on the isoenzyme CYP 2B 1/6 (acts on the metabolism of VALP and Clobazam)

“A BUNCH OF ANECDOTES DOES NOT CONSTITUTE EVIDENCE”

THE ARDUOUS PROBLEM OF THE SEARCH FOR EVIDENCE

1. The sources of evidence are not uniform.

2. Even in qualified sources, some evidence remains controversial.

3. When an illness has low frequency, the level of evidence usually

declines.

4. Without STANDARDIZED MOLECULES it is difficult to obtain evidence.

Some examples of contradictory evidence

Meta-analysis

JAMA. 2015;313(24):2456-2473.

Conclusions and relevance:

Moderate quality evidence to support the use of cannabinoids in the

treatment of chronic pain and spasticity.

There was low quality evidence suggesting that cannabinoids were

associated with improvements in nausea and vomiting due to

chemotherapy, increased appetite and weight in HIV/AIDS patients, sleep

disorders and Tourette syndrome.

Cannabinoids were associated with greater short-term risk of adverse

effects.

Meta-analysis

JAMA. 2015;313(24):2456-2473. Copyright 2015 American Medical Association. All rights reserved.

CONCLUSION OF THE AMERICAN EPILEPSY SOCIETY

CONCLUSION:

The most conclusive evidence is with Dravet syndrome.

By extension, although with a lower level of evidence, it is generally used for infantile refractory epilepsy, always as an add-

on .

MORE RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED STUDIES NEED TO BE COMPLETED

CONCLUSION OF THE AMERICAN TOURETTE ASSOCIATION

There is not enough evidence to support or refute the efficacy of THC in reducing the severity of tics in patients with Tourette syndrome.

Superior to placebofor nausea and vomitingdue to chemotherapy.

Superior to placebo for reducing pain

Increased weight and improvedsleep in HIV/AIDS patients

Reduced severity of ticsin Tourette syndrome.

“ THE REAL WORLD ”

J Clin Psychiatry 2016;77(8):1050-1064

Substantial evidence in:

Neuropathic pain in adults.

Nausea and vomiting in chemotherapy.

Spasticity in multiple sclerosis.

Moderate evidence in:

Infantile refractory epilepsy

Secondary sleep disorders in neurological diseases

Insufficient or low-quality evidence in:

PTSD

Tourette.

Irritable colon

Neurodegenerative diseases.

CLASS “A”

EVIDENCE !!

THE RISKS OF DICHOTOMOUS THINKING

Scientific evidence

Clinical experience

Patient values and preferences

Oh my goodness

Have you heard?

The required steps in research

I DON’T CARE ABOUT YOUR MICE!!!!

Time in science, time in health

GENTILEZA: Dr. Allegri

The problem of biases and fallacies.

1. “It’s published in English so it must be serious.”

2. “I look at (and I measure) what I want.”

European Journal of Internal Medicine 49 (2018) 44–50

How do we get beyond the crossroads?

ENSURE QUALITY MOLECULES IN CURRENT TREATMENT

RESEARCH MEDICAL TRAINING

Conclusions I

For now, cannabis derivatives represent a limited treatment option, with little evidence. However, they offer potential applications in diverse pathologies.

The cannabinoid system neuromodulates multiple actions with cortical repercussions but also with systemic effects.

Their use in medicine is increasingly being investigated, with potential properties affecting prevalent symptoms and diseases (pain, epilepsy, spasticity, and others).

Medicinal use must be differentiated from recreational use.

Conclusions II

The systematic study of cannabis represents a challenge in terms of:

- Neurochemical, neurobiological, and psychopharmacological research.

- Prevention and psychoeducation in the community.

- Ongoing medical education.

- Scientific information confirmed to regulatory authorities.

Conclusions III

As in few situations, the debate regarding medical cannabis brings us face to face with own biases, both for and against.

We should try to bring the scientific-academic debate on cannabis into the usual settings so as to be sure it reaches the entire health community.

The National Program for Study and Research on the Medicinal Use of the Cannabis Plant represents an important step that seeks to provide a regulatory framework and promote development in research on future applications.

THANK YOU VERY MUCH

“We know very little, and yet it is astonishing that

we know so much.”

Bertrand Russell (1872-1970)