Medicinal cannabis: keeping up with the changes€¦ · Cannabis as a medicine 4 SAAPI Conference...

Medicinal cannabis:

keeping up with the

changes

Andy GrayDivision of Pharmacology

Discipline of Pharmaceutical Sciences

SAAPI Conference May 2019 1

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.


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


Cannabis as a medicine

SAAPI Conference May 20194

Royal Pharmaceutical

Society Museum exhibits

A racialised past


“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


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.


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.


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)


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.


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,”


In draft form, but not yet published


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"].


The preamble to S4

(somewhat contested)


Legal?


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.


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.



https://www.na

p.edu/resourc

e/24625/Cann

abis_committe

e_conclusions

.pdf

Local stance - evolving


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


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.....”


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 ….



e.g. 19 placebo-controlled clinical

trials of oromucosal nabiximols for

spasticity, pain, nausea and

vomiting


• 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


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.

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.


20 April 2018


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

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.


Thank you!


Medicinal cannabis: keeping up with the changes€¦ · Cannabis as a medicine 4 SAAPI Conference...

Documents

Transcript of Medicinal cannabis: keeping up with the changes€¦ · Cannabis as a medicine 4 SAAPI Conference...