medicinal cannabis: keeping up with the changes€¦ · cannabis as a medicine 4 saapi conference...
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Medicinal cannabis:
keeping up with the
changes
Andy GrayDivision of Pharmacology
Discipline of Pharmaceutical Sciences
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Disclaimer
◼ I am the chair of SAHPRA’s Names and
Scheduling Advisory Committee, and a member
of its Legal Advisory Committee and Regulatory
Advisory Committee.
◼ I am the chair of SAHPRA’s Cannabis Working
Group.
◼ I am speaking here as an academic, and not on
behalf of the Authority or any of its advisory
committees or task teams.
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Outline
◼ Legal and policy background – fitting in with the
global regulatory system (as that changes)
◼ Implementing the ConCourt decision
◼ Current and envisaged provisions for legal
access in South Africa for medicinal purposes
◼ Evidence for the therapeutic value of
cannabinoids
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Cannabis as a medicine
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Royal Pharmaceutical
Society Museum exhibits
A racialised past
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“Dr. White replied that in western countries it might be assumed that the use of a drug was
legitimate if it was prescribed by a doctor, but in such a country as India it was necessary to
define, not merely legitimate use, but also the doctor. He had known native practitioners in
India who used opium. very skilfully in the treatment of disease, but according to western
standards their use of the drug would be regarded as illegitimate. He agreed that there was
much greater tolerance for narcotic drugs amongst the Indian native population than
amongst Europeans.”
International regulation
United Nations
International Narcotic Control Board
WHO Expert Committee on Drug Dependence
Commission on Narcotic Drugs
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UN Organization on
Drugs and Crime
Current status
◼ Cannabis and cannabis resin are currently
listed in Schedules I and IV in terms of the
Single Convention on Narcotic Drugs (1961), so
are prohibited substances, considered to
have no therapeutic uses.
◼ This status was “inherited” from the 1923 Opium
Commission, which specifically included
cannabis on the request of the South African
government.
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A slow review process
◼ The 38th ECDD in November 2016 considered a “pre-
review” document on cannabis and cannabis resin.
◼ The 39th ECDD in November 2017 considered a “pre-
review” on cannabidiol.
◼ The 40th ECDD in June 2018 was a special session
looking only at cannabis and cannabis resin, extracts
and tinctures of cannabis, THC and isomers of THC.
◼ The 41st ECDD in November 2018 made a series of
recommendations, which were to be considered by the
62nd Session of the CND in March 2019, but were
deferred to December 2019.
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Overlapping jurisdictions
Minister of Health/SAHPRA/
Names and Scheduling
Advisory Committee
• Medicines and Related Substances Act (Act 101 of 1965)
Minister of Social
Development/ Central
Drug Authority
• Prevention of and Treatment for Substance Abuse Act (Act 70 of 2008)
Minister of Justice/National
Prosecuting Authority/
Police
• Drugs and Drug Trafficking Act (Act 140 of 1992)
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South African Constitutional Court judgment 2018
◼ In a unanimous judgment written by Zondo ACJ, as he then was, the
Constitutional Court declared that—
(a) section 4(b) of the Drugs Act was unconstitutional and, therefore,
invalid to the extent that it prohibits the use or possession of cannabis
by an adult in private for that adult’s personal consumption in private;
(b) section 5(b) of the Drugs Act was constitutionally invalid to the
extent that it prohibits the cultivation of cannabis by an adult in a private
place for that adult’s personal consumption in private; and
(c) section 22A(9)(a)(i) of the Medicines Act was constitutionally invalid
to the extent that it renders the use or possession of cannabis by an
adult in private for that adult’s personal consumption in private a
criminal offence.
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Consequences
◼ Parliament has 24 months to revise the 2
Acts, BUT in the interim, the following is
“read in” “(c)the following words and commas are to be read
into the provisions of section 22A(9)(a)(i) of the
Medicines and Related Substances Control Act 101
of 1965 after the word “unless”:
“, in the case of cannabis, he or she, being an adult,
uses it or is in possession thereof in private for his or
her personal consumption in private or, in any other
case,”
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In draft form, but not yet published
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Current scheduling (about to change)◼ S4
Cannabidiol, when intended for therapeutic purposes. (S7)
◼ S6
Dronabinol ((-)-transdelta-9-tetrahydrocannabinol), when intended for therapeutic
purposes. (S7)
◼ S7
Cannabidiol, except when intended for therapeutic purposes. (S4)
Cannabis (dagga), the whole plant or any portion or product thereof, except:
a. when separately specified in the Schedules; (S6) or
b. processed hemp fibre containing 0,1 percent or less of tetrahydrocannabinol
and products manufactured from such fibre, provided that the product does not
contain whole cannabis seeds and is in a form not suitable for ingestion, smoking
or inhaling purposes; or
c. processed product made from cannabis seeds containing not more than 10
milligrams per kilogram (0,001 percent) of tetrahydrocannabinol and does not
contain whole cannabis seeds.
["Processed" means treated by mechanical, chemical or other artificial means but
does not include - (a) harvesting; or (b) the natural process of decay"].
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The preamble to S4
(somewhat contested)
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Legal?
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Cannabinoid receptors
◼ Cannabinoid receptors are widely distributed,
not only in the CNS, but also in the GIT, liver,
adipocytes, skeletal muscle, macrophages,
osteoclasts and osteoblasts. They also have
complex and poorly understood immunological
effects.
◼ Cannabinoid receptors bind both to endogenous
endocannabinoids (neurotransmitters) and,
variably, to exogenous cannabinoids.
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Exogenous cannabinoids
◼ Herbal cannabis has at least 489 chemical constituents,
at least 70 of which are cannabinoids.
◼ The main psychoactive ingredient is
delta‐9‐tetrahydrocannabinol (THC), which interacts with
a number of cannabinoid receptors (CBRs). THC has
also been named as dronabinol, when registered as a
medicine. A synthetic variant, nabilone, has also been
available in the past. They are basically equivalent.
◼ The other major cannabinoid of interest is cannabidiol
(CBD), which is not psychoactive.
◼ A 50:50 THC:CBD mixture has been registered by GW
Pharmaceuticals as nabiximols in some jurisdictions.
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https://www.na
p.edu/resourc
e/24625/Cann
abis_committe
e_conclusions
Local stance - evolving
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The Minister of Social Development has failed to issue an updated National Drug
Master Plan (though the Cabinet has accepted a report on the 2013-2018 version
and indicated that the next version should be called the “Anti-Drug Master Plan“)
Local “right-to-try” legislation
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Legal basis - Medicines Act
◼ Section 22C(1)(b): “the Council may - on application in the
prescribed manner and on payment of the prescribed fee, issue to a
manufacturer....of a medicine, ...or scheduled substance a licence to
manufacture....such medicine, .....or scheduled substance, upon
such conditions as to the application of such acceptable quality
assurance principles and good manufacturing and distribution
practices as the council may determine.”
◼ Section 22A(9)(a)(i): “No person shall - acquire, use, possess,
manufacture, or supply any Schedule 7....substance, or manufacture
any .....Schedule 6 substance unless he or she has been issued with
a permit by the Director-General for such acquisition, use,
possession, manufacture, or supply.....”
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Key developments to date
◼ By February 2019, there had been 56 section 21
approvals, for importation from Canada and The
Netherlands
◼ On 16 April 2019, SAHPRA announced that 3 licence to
cultivate medicinal cannabis would be issued – evidence
of a “developmental approach”
◼ NO legal, locally-produced medicinal products as yet
◼ BUT ….
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e.g. 19 placebo-controlled clinical
trials of oromucosal nabiximols for
spasticity, pain, nausea and
vomiting
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• Started with 726
abstracts
• Selected 65 papers
for full text review
• Eliminated all but 7,
but could only do a
qualitative review, as
disparate outcomes
did not allow meta-
analysis
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Adverse Effects
Dry mouth, sedation, orthostatic hypotension, ataxia, and dizziness occur
frequently with medical use of both cannabis and synthetic cannabinoids.
Anxiety, tachycardia, agitation, and confusion are also common, especially in
older patients, and driving may be impaired. Cannabinoids can cause sedation,
motor dysfunction, altered perception, cognitive dysfunction, and dose-related
psychosis. Pure CBD, however, does not have psychoactive effects. Death from
an acute overdose of cannabis used alone has not been reported.
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Findings – 4 studies (n=48)Implications for practice
No reliable conclusions can be drawn at present regarding the efficacy
of cannabinoids as a treatment for epilepsy. There is an insufficient
body of evidence to recommend using marijuana to treat epilepsy. The
dose of 200 to 300 mg daily of cannabidiol was safely administered to
small numbers of patients, for generally short periods of time, and so
no conclusions can be drawn about the safety of long term cannabidiol
treatment.
Implications for research
There is a body of animal research that suggests that it might be useful
to evaluate the efficacy of cannabinoids for treatment of epilepsy in
humans. None of the existing clinical research is of sufficient quality or
size to answer this question. If the question were to be addressed,
there would need to be a series of properly designed, high quality, and
adequately powered trials.
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20 April 2018
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https://www.nytimes.com/2018/04/19/health/epidiolex-fda-cannabis-marajuana.html
Indication limited to
two rare and difficult to
treat paediatric
epilepsy syndromes:
• Lennox-Gastaut
syndrome
• Dravet syndrome
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Conclusion◼ Societal views on the prohibition of cannabis for recreational
purposes are changing. Parliament needs to address the
existing law within 24 months, as ordered by the ConCourt.
◼ Many patients desire access to cannabis/cannabinoid
products for medicinal purposes, despite the paucity of
evidence.
◼ Although some legal provisions are in place, there is still a
lack of access to standardised, regulated products (unless
imported under s21).
◼ The widespread marketing of unregulated medicinal products,
some making unsubstantiated claims, demands regulatory
intervention, but also a pragmatic and reasonable approach.
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Thank you!
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