Yuval Landschaft, Director of the Israeli Medical Cannabis Agency, outlines Israel’s regulatory approach to cannabis-based medical treatment.
In recent years, there has been an increase in the medical use of cannabis in many countries around the world, including in the State of Israel. Concurrently there has been significant progress in scientific research on the cannabis plant and the endocannabinoid system, which has shown to contain compounds that have beneficial medical effects on a variety of symptoms and conditions.
Cannabis is considered a ‘narcotic drug’ as defined by law, but many medical authorities around the world do recognise that cannabis also has potential medical applications which may benefit patients with specific indications. The use of cannabis for medical purposes is a dynamic and developing field; and its regulation for medical use remains an ongoing process in many countries around the world.
While cannabis is not currently officially registered as a medicine, the Ministry of Health of Israel believes that it can be beneficial in the treatment of certain medical conditions. Although it contains substances defined as narcotic drugs, which require control and regulation in order to ensure the health and safety of the public, cannabis should be treated as far as possible in the same manner as a registered medicine or medicinal product.
Legislation and regulation
In any programme pertaining to the use of cannabis for medical purposes, the State of Israel is bound to observe the provisions of the international Single Convention on Narcotic Drugs 1961 and the Israeli Dangerous Drugs Ordinance (New Version) of 1973. The Israeli Medical Cannabis Agency (IMCA), within the Ministry of Health, serves as a ‘governmental agency’ in accordance with the provisions of the Convention in all matters relating to the control and regulation of cannabis treatment for medical and research applications.
The State of Israel is one of the leading countries in the world in the sphere of cannabis for medical use. In June 2016, the government’s Resolution 1587 adopted a definition of ‘cannabis for medical and research purposes’, which ensures access to and supply of medical grade cannabis on the one hand and control of cannabis products which are still defined as ‘narcotic drugs’ on the other. The state is obligated to safeguard public health, wellbeing and safety; to prevent the misuse of the drug; and to regulate a new market with stringent quality control standards which are aligned with the laws of the State of Israel. It also needs to afford patients an appropriate source and supply of cannabis for medical purposes, and to allow research.
The regulation outline is intended to determine appropriate standards of cannabis for medical and research purposes, by defining the process of medicalisation. The issues of legalisation or decriminalisation of cannabis are not within the scope of this process: instead, they lie within the responsibility of the Israeli parliament and its legislative process, and must therefore be addressed by the parliament and not by medical professionals.
Setting and meeting quality standards
The concept of medicalisation of cannabis is based on the following principles:
Regulated supply chain, standardisation of medical grade cannabis products and quality assurance
In order to ensure high quality standardised medical grade products, all components of practice and workers in the supply chain of medical grade cannabis products, from the stage of raw plant material to the final cannabis product which is dispensed at the pharmacy, are to be controlled by stringent criteria and quality control in accordance with the IMCA’s Good Practices Procedures.
Medical cannabis products which are approved for commercialisation in Israel must be at a level of quality that is suitable for medical use and are to be marked ‘IMC – Medical Grade’. In order to reach a high level of standardisation and to ensure a high level of reproducibility and uniformity, as appropriate for a medicinal product, the entire process will be closely controlled and supervised in the form of good practices, in accordance with the IMCA’s quality directives: IMC-GAP, which outlines standards for growing and cultivating cannabis; IMC-GMP, which refers to manufacturing; IMC-GDP, which covers distribution and storage of cannabis products; and IMC-GSP, which sets standards for security under appropriate conditions. IMC-GMP implements EU-GMP Annex 7 alongside specific requirements pertaining to cannabis whole plant extract, based on current knowledge and expertise.1
Throughout the cultivation and production process, from the breeding material stage to the final medical grade cannabis product, optimal and uniform environmental conditions must be adhered to; work processes must be similarly uniform and based around standard operating procedures (SOPs).
Regular and periodic analytical checks will be required at each stage, in order to maintain and document the compliance of stem lines, reproduction batches, growing plants, growing batches and production batches of cannabis with the requisite standards and levels of quality, as prescribed for each stage of the process. The generic medical grade cannabis products which will be available at pharmacies will be defined by consistent margins of concentration, as laid out in the standards for industry.
Methodology for indication-based clinical practice and training of physicians
The use of medical grade cannabis should be comparable to the use of any other registered medicine or medicinal product, as far as possible. A fundamental clinical methodology for treatment using medical grade cannabis products is required, in order to ensure the appropriate treatment can be administered based on the medical indication.
The attending physician is required to determine the appropriate product type and adjust the potency, administration route, monthly quantity, daily dosage and consumption. The increasing number of potential patients further necessitates the need for a definitive clinical guideline in order to provide existing relevant information and scientific background; authorised indications for treatment; and a clinical method for the administration of treatment with cannabis products. In order to ensure physicians are appropriately equipped to deliver such treatment, therefore, the necessity has arisen for a training programme for physicians based on these guidelines, in order to equip them with the tools necessary to build a treatment plan using medical grade cannabis products and create an ongoing, constantly improving medical cannabis ecosystem.
Research and development
The current availability of scientific data regarding the mechanisms and effects of cannabis and its constituents in the human body is lacking. There is little wholly evidence-based medicine in the field, as academic research into cannabis is prohibited or severely restricted in many countries around the world due to its legal status. The Ministry of Health of Israel acknowledges the necessity for more research and for evidence-based medicine in the field of cannabis; and is therefore in favour of promoting research and advancing scientific knowledge at all levels, from plant science to clinical trials.
Supervision and compliance with the legal status of cannabis
Under the provisions of the International Single Convention on Narcotic Drugs and the Dangerous Drugs Ordinance (New Version), the State of Israel is responsible for and committed to protecting public safety and health; and is entrusted with the prevention of misuse and criminal use related to narcotic drugs, including cannabis. The primary target of the Ministry of Health is to make treatment with medical grade cannabis accessible to patients who need it, while ensuring safety and quality. The process of medicalisation is intended to ensure correct medical practice and to implement measures at each stage of the medical cannabis supply chain – including growing, production, distribution and dispensing of medical grade cannabis products – will be of the highest quality.
With the assistance of Professor Rafael Mechoulam, a world renowned expert in cannabis research who pioneered the characterisation of the endocannabinoid pathway, the IMCA has prepared ‘The medical grade cannabis Cannacopoeia’, a manual for prescribing physicians after the fashion of a pharmacopoeia. The document is based on the IMCA’s Good Clinical Practices guidelines; and provides an initial base of information concerning all stages of the cannabis chain:
• IMC-GAP, for medical grade cannabis growers;
• IMC-GMP, for medical grade cannabis products manufacturers;
• IMC-GDP, for distributors and pharmacies;
• IMC-GSP, for security across the supply chain; and most importantly,
• IMC-GCP: Good Clinical Practices.2
The information covered in the clinical guide is based on data which has been collated from studies published in scientific literature, as well as the accumulated practical experience of professionals operating in the field. The guide covers information regarding the cannabis plant and its constituents, the endocannabinoid system, pharmacology, side effects, main drug interactions and more.
The cannabis research on offer includes a comprehensive meta-analysis of multiple sources dealing with cannabis in the fields of botany, pharmacology, chemistry and biochemistry. This has enabled the determination of a ‘therapeutic methodology’. The guide also shows the approved indications for receiving a cannabis usage licence, as well as guidelines and recommendations for developing an effective treatment plan.
The combination of the clinical guide (affectionately nicknamed ‘The Green Book’) and the quality procedures in place governing the supply chain of medical grade cannabis products constitute the Israeli pharmacopeia for medical grade cannabis. Accordingly, the combination of coherent, well defined medical practice with products which fulfil quality standards, constitutes the first step to regulated, research-based medical use.
There remains a paucity of evidence-based medicine in the field of medical grade cannabis. With this guide, we hope to encourage the creation of an expert community that will be part of the ongoing research effort. In order to expand our evidence-based knowledge, a concerted effort must be made to advance research. In the future, as more studies and knowledge based on empirical facts and medical opinions evolve, modifications may be made to this clinical guide to improve and upgrade the medical guidelines for treatment with medical grade cannabis; thereby benefiting the wellbeing and health of the public.
1 https://www.health.gov.il/hozer/mmk152_2016.pdf (regulations and guidelines are in Hebrew, in process of translation).
2 ‘Medical Grade Cannabis – A Clinical Guide’. https://www.health.gov.il/hozer/mmk154_2016.pdf
Israeli Medical Cannabis Agency