Cannabis na Medicina

Faculdade de Medicina de Ribeirão Preto

– Universidade de São Paulo

São Paulo, 30 de Agosto de 2023

Prof. Dr. José Alexandre S. Crippa

Departamento de Neurociências e Ciências do Comportamento – FMRP-USP
Departamento de Psiquiatria – FM-USP
 Disclosure and Potential Conflicts of Interest
• Co-inventor (Mechoulam R, Crippa JA, Guimaraes FS, Zuardi A, Hallak, JE, and Breuer A) of the
patent “Fluorinated CBD compounds, compositions and uses thereof. Pub. No.:
WO/2014/108899. International Application No.: PCT/IL2014/050023” Def. US no. Reg. 62193296;
July 29, 2015; INPI on August 19, 2015 (BR1120150164927).
• Universidade de São Paulo has licensed the patent to Phytecs Pharm (USP Resolution no.
15.1.130002.1.1). USP has an agreement with Prati-Donaduzzi (Toledo, Brazil) to “develop a
pharmaceutical product containing synthetic CBD and prove its safety and therapeutic efficacy in
the treatment of epilepsy, schizophrenia, Parkinson’s disease, and anxiety disorders.”
• I received speaking fees from Torrent, Green Care, DSM, ArtMed, EaseLabs, Mantecorp, Prati and
Janssen
• I received travel support and personal consultancy fees from BSPG-Pharm in the past, and I was a
scientific advisor of BSPG and PurMed Global in the past
• I had a grant from University Global Partnership Network (UGPN) – “Global priorities in
cannabinoid research excellence.”
• Member of the international advisory board of The Australian Centre for Cannabinoid Clinical and
Research Excellence (ACRE; funded by the National Health and Medical Research Council through
the Centre of Research Excellence).
• Participated as invited of the Uruguay’s Presidential Office to join an international committee for
the evaluation of documents regulating their legalization of marijuana
História da Maconha como Medicamento

3000 a.C 1000 a.C 1910-1930 1964 1989 1992 1995

Cannabis is Delta-9-THC and much, much more

+ 250 canabinoids CBD and THC: main

cannabinoids in Canabis
sativa with similar
structures

Delta9THC
Isolation, strucuture and
partial synthesis of an
active constituent of
hashish. Y. Gaoni, Raphael
Mechoulam. J. Am. Chem.
Soc. 86, 1964: 1646.

CBD

Prof. Raphael Mechoulam

University of Jerusalem
O Estudo do Suco de Laranja
1mg/Kg 1mg/Kg 0.5mg/Kg 10mg
0.5mg/Kg Farinha-Placebo

THC CBD

8 horas – avaliações de 30’

24h após
 Interação THC x CBD
20
Prof. Antonio Zuardi
18
Universidade de São Paulo
16
THC
14
THC + CBDmais
Maconha
12
Escore

10
segura?
8
6
4
2
0
Efeitos Maconha ANSIEDADE PSICOSE

Zuardi e col., 1982 - Psychopharmacology76 (3):245-250.

Prof Celia
Morgan
Paris Hilton was right!
“Socialite Paris Hilton (25) has launched a campaign to have the
Cannabidiol content of Marijuana increased.

A reduction in the amount of the Cannabidiol a non-psychoactive

cannabinoid which has antipsychotic properties has been
identified by Paris Hilton as a major factor contributing to the
psychotic breakdowns of Britney Spears”

“These findings raise concerns for the harms stemming from use
of varieties such as 'skunk', which lack any CBD but currently
Morgan et al, Psychol Med, dominate the supply of cannabis in many countries”.
Ahead of Prinf 29July2011
 THC/CBD ratios in Cannabis samples:
Less Neuroprotection; More Neurotoxicity

Neurotoxic Effect (2013) Psychosis (2016)

Anxiety (2015) Memory (2015)

ElSohly et al. Biological Psychiatry, 2016

 20
Interação THC x CBD
Prof. Antonio Zuardi
18 Universidade de São Paulo
16
THC
14
THC
THC + CBD
com menos
12
Escore

10
efeitos colaterais?
8
6
4
2
0
Efeitos Maconha ANSIEDADE PSICOSE

Zuardi e col., 1982 - Psychopharmacology76 (3):245-250.

 20
Interação THC x CBD
Prof. Antonio Zuardi
18 Universidade de São Paulo
16
THC
14
THC +pode
O CBD CBD ser
12
Escore

10
Ansiolítico ou
8
Antipsicótico
6
isoladamente?
4
2
0
Efeitos Maconha ANSIEDADE PSICOSE

Zuardi e col., 1982 - Psychopharmacology76 (3):245-250.

CBD and Social Anxiety
Prof Dr Geraldo Busatto
Opposite Effects of CBD and THC

Prof Dr Philip McGuire,

Oxford
Cannabidiol and Autism
 CBD and Epilepsy
Prof Isaak Prof Elisaldo
Karniol Carlini

Very first evidence of a CBD effect!

 2009

“Ninguém mais fez outro

trabalho clínico com o
Canabidiol na Epilepsia e eu
gostaria de saber o por quê”
Stages of Clinical Trials
Cannabidiol and Epilepsy

Elizabeth A Thiele
First, do no Harm (Primum non nocere)
Cannabidiol is NOT Cannabis or ‘Medical Cannabis’
O que as pessoas
veem
“Canabis
Medicinal”

Canabinoides
296
O que as pessoas
NÃO veem Terpenos 174

Terpenoides
220

Flavonoides 19

Glicosideo
Flavonoides 63

Polifenois 46

Esteroides 92

Outras subst
1092

TOTAL 2024
Les Demoiselles d'Avignon

Pablo Picasso, 1907 - Museum of Modern Art, New York

First, do no Harm (Primum non nocere)
GMP/GLP vs Non-labeled
Cannabis Sativa Extracts X Pure Grade CBD

“Full Spectrum” “Broad Spectrum” “Isolated” GM P Pharmaceutical

Grade

Degree of Acceptance as a Medication by the Regulatory Agencies;

Achievement of Pharmaceutical Standards
Uso Médico de Fármacos
•Medicamento registrado
•OffLabel
•Uso Compassivo
O que é Seguro?
First, do no Harm (Primum non nocere)
Pharmaceutical Potency Matters!
“A potência é a medida da atividade da
droga expressada em termos de quantidade
necessária para produzir um efeito de uma Antipsicóticos*
determinada intensidade”

The difference between

‘potency’ and ‘activity’

Haloperidol Clorpromazine
5mg 300 mg

*Pharmacologic Considerations in the Treatment of Schizophrenia and Psychosis

First, do no Harm (Primum non nocere)
Pharmaceutical Potency Matters!

Sample/Brand % CBD %THC

1 (A) 97,3 1,6

2 (A) 93,6 5,1 300mg/CBD = 15,5mg/THC
3 (A) 93,7 3,6
4 (A) 92,2 2,3
5 (A) 98,2 0,6
6 (B) 95,3 1,1
7 (B) 96,8 0,8 1000mg/CBD = 51,6mg/THC
8 (C) 94,7 3,2
9 (C) 95,5 0,5
10-years-old, refractory epilepsy, 210mg/day
“CBD”

4,1% THC (Extract); 3,1% THC (Hair)

CBD Purified 400mg/dia

First, do no Harm (Primum non nocere)
CBD is ‘Natural’, but may NOT be inoquous – Adverse Effects

Crippa, Souza et al, JAMA 2021;

Souza et al, Front Pharmacol 2022
First, do no Harm (Primum non nocere)
Drug-drug interactions
 Conclusões
• CBD, THC e ‘Cannabis Medicinal’ não são a mesma coisa
• O CBD pode ser um candidato para diversas indicações
terapêuticas, mas só tem dose estabelecida e indicação de
bula para epilepsias
• As doses para cada paciente variam muito
• Extrato rico em canabidiol (CBD) com THC, não deve ser dado
para crianças, adolescentes, pessoas com história de psicose e
em gestantes
• Pesquisa clínica e ciência aliadas à produtos de altíssima
qualidade e ética são sempre necessários e oportunos
Sam Bartram (1914-81) vs a Névoa (1937)
Prof Dr Antonio Waldo Zuardi
‘Buda Sensei’
Prof Dr Raphael Mehoulam
Prefácio – ‘O Canabidiol e a
Pesquisa no Brasil para o
mundo’
 University of São Paulo
Ribeirão Preto-São Paulo-Brazil