Analysis of the Spanish Health Ministry’s Medical Cannabis Decree

Spain’s Ministry of Health publishes the draft Royal Decree on medical cannabis

Today the Spanish Agency of Medicines and Medical Devices (AEMPS) published the draft Royal Decree laying down the conditions for the preparation and dispensing of standardised magistral formulas of standardised cannabis preparations. The text is currently open to public consultation.

This Royal Decree had been eagerly awaited since, in the previous legislature, the Health Committee of Congress set up a specific subcommittee on medical cannabis. That subcommittee produced a report of conclusions, which was then opened for contributions. Six months after that period ended, the Agency has finally published the Royal Decree, also explaining why it did or did not include the conclusions in the light of contributions from individuals, companies and organisations. Together with the Royal Decree, the Agency has issued a protocol setting out the rules for submitting to the AEMPS the registration of the standardised cannabis preparations arising from the Royal Decree published today. Update: the final Royal Decree on medical cannabis was approved in October 2025.

Content of the Health Ministry’s medical cannabis decree

The Royal Decree regulates the conditions for preparing and dispensing standardised magistral formulas of standardised cannabis preparations in Spain, establishing a clear regulatory framework for the medical use of cannabis. The regulation fits within Spanish legislation and complies with the international drug control treaties to which Spain is party, such as the 1961 Single Convention on Narcotic Drugs. This means that cannabis may only be manufactured, distributed and used for medical and scientific purposes.

Cannabis contains several compounds, notably tetrahydrocannabinol (THC), its main psychoactive component, and cannabidiol (CBD), considered to have no psychotropic effect. According to current scientific evidence, the therapeutic indications for cannabis with the strongest support are spasticity due to multiple sclerosis, severe forms of refractory epilepsy, chemotherapy-induced nausea and vomiting, and chronic pain refractory to other treatments. There are authorised medicines containing THC and/or CBD for the first three indications, but not for chronic pain in Spain.

The Royal Decree responds to the recommendation of the Congress subcommittee set up in May 2021 to examine the regulation of medical cannabis. The subcommittee concluded that cannabis-derived preparations could benefit some patients when available treatments are ineffective. The decree establishes a legal framework for the availability of these preparations, ensuring a standardised and controlled composition, which is essential to guarantee their dosage and stability.

The standardised magistral formulas are included in the National Formulary, ensuring standardisation in their preparation, dispensing and use. This ensures that the formulas are prepared with ingredients of proven quality, under the supervision of pharmacists in hospital pharmacy services. Inclusion in the National Formulary means that the composition of these preparations is precisely defined, enabling safe and effective use in cases where other therapies have failed.

The decree also creates a register of standardised cannabis preparations at the Spanish Agency of Medicines and Medical Devices (AEMPS), making it possible to monitor the traceability of these products and ensure their quality. To register a preparation, pharmaceutical laboratories must submit detailed documentation and comply with the manufacturing and distribution rules in force in the European Union.

Scope of the medical cannabis Royal Decree

The decree applies only to standardised magistral formulas of cannabis preparations with a defined THC and/or CBD composition, excluding industrially manufactured medicines and synthetic cannabinoids. Preparations with a THC content of 0.2% by weight or more are considered psychotropic and will be subject to stricter controls under Spain’s specific rules on psychotropic substances.

Article 3 of the decree states that cannabis, whatever its cannabinoid content, is a narcotic drug under Law 17/1967 and the 1961 Single Convention, and is subject to the restrictions and control measures laid down there. Laboratories authorised to manufacture these preparations must comply with EU good manufacturing practice and ensure the quality of the ingredients. The supply chain must be audited regularly to ensure that materials come from legal sources and comply with the applicable rules. Laboratories may only supply these preparations to hospital pharmacy services or for export, and must obtain the relevant authorisation where the preparation contains THC at levels considered psychotropic.

Article 4 states that the National Formulary monograph will define the conditions of use and therapeutic indications of these magistral formulas. The AEMPS will publish this monograph, which will include the applicable preparation and quality control requirements. To prepare them, hospital pharmacies must have the necessary resources and follow good preparation practice.

Prescribing standardised cannabis preparations

The decree allows these formulas to be prescribed only by medical specialists treating patients with the indications set out in the National Formulary monograph and when available medicines do not adequately control the symptoms. The prescription must be justified in the patient’s medical record, and the prescribing doctor will be responsible for regularly assessing the therapeutic usefulness and safety of the treatment, stopping it if the benefit is insufficient or the benefit-risk balance is unfavourable.

The preparation of these magistral formulas is restricted to hospital pharmacy services that meet the established conditions. Preparations with high THC concentrations must be handled in accordance with the rules on psychotropic control. Dispensing to patients will take place exclusively through these pharmacy services, ensuring comprehensive pharmacotherapeutic follow-up in collaboration with the medical team.

Article 6 regulates the registration of standardised cannabis preparations in a specific register managed by the AEMPS. Registration requires laboratories to submit the relevant documentation and comply with all applicable rules. The Agency has six months to decide on registration applications, and failure to respond will mean that registration is refused.

Dispensing cannabis preparations

Dispensing will be limited to inpatients or outpatients requiring pharmaceutical care, ensuring thorough control of the use of these preparations. The rules also provide for a pharmacovigilance system, under which health professionals must report any suspected adverse reaction to the relevant regional centres.

Registering a standardised cannabis preparation with the Spanish Agency of Medicines and Medical Devices

How to register standardised cannabis preparations

The information submitted to the Spanish Agency of Medicines and Medical Devices to register standardised cannabis preparations must be accompanied by data and documentation meeting the following requirements:

When compiling the registration application file, applicants must also take into account the general chapters and monographs of the European Pharmacopoeia that apply to them, as well as the specific guidelines on herbal substances and preparations published by the European Medicines Agency. For the purposes of this annex, the term extract shall be considered equivalent to the term “herbal drug extracts“, as defined in the European Pharmacopoeia.

1. Module 1: Administrative information

• The name and address of the applicant, the name and address of the suppliers of the herbal substance, and the name and address of the manufacturers and the sites where the various stages of manufacture of the standardised extract(s) and the standardised cannabis preparation and their control take place.

1.1 The registration form shall include:

• Identification of the standardised cannabis preparation by its name, the name of the herbal substance (according to the European Pharmacopoeia) and the definition of the extract(s) (including the physical state and the extraction solvent(s); as these are standardised extracts, the THC and/or CBD content and any excipients must be stated; the equivalent quantity of genuine herbal preparation must also be stated, as a range, where applicable).

1.2 Additional documentation

The application shall be accompanied by the Manufacturing and Import Authorisation of the manufacturer(s) of the standardised cannabis preparation. The latest Good Manufacturing Practice (GMP) certificate or other proof of GMP compliance (reference number in the EudraGMDP database) shall also be attached.

1.3 Proposed labelling

The text of the proposed labelling for the immediate packaging of the container supplied to hospital pharmacy services must be provided.

The labelling of that container must contain at least the following information:

• Name of the standardised cannabis preparation, as well as the name of the herbal substance (according to the European Pharmacopoeia) and the definition of the extract(s) (including the physical state and the extraction solvent(s); as these are standardised extracts, the THC and/or CBD content and any excipients must be stated; the equivalent quantity of genuine herbal preparation must also be stated, as a range, where applicable).
• Expiry date.
• Storage conditions.

2. Module 2: Chemical and pharmaceutical information

2.1 Standardised cannabis extract

2.1.1 General information

• Herbal substance: It must comply with the European Pharmacopoeia monograph on Cannabis flos (3028). The chemotype must be stated.
• Extract: The extract’s nomenclature shall include the binomial scientific name of the plant (Cannabis sativa L.), its chemotype, the plant parts used, the definition of the extract, the ratio of herbal substance to extract and the extraction solvent(s). The physical form and the content of constituents with known therapeutic activity (THC and CBD) and other constituents shall be stated. Where applicable, the excipients used shall be stated.

2.1.2 Manufacture

2.1.2.1 Manufacturers

• Herbal substance: The name, address and responsibility of each supplier, including contractors, and each proposed site or facility for the production/harvesting and control of the herbal substance shall be stated. It must be confirmed that the herbal substance complies with good agricultural and collection practice for starting materials of herbal origin.
• Extract: The name, address and responsibility of each manufacturer, including contractors, and each proposed manufacturing site or facility for the manufacture and testing of the extract shall be stated.

2.1.2.2 Description of the manufacturing process and in-process controls

• Herbal substance: For each producer, information shall be provided to adequately describe the production and harvesting of the plants, including their geographical origin, growing conditions, pre- and post-harvest treatments, drying and storage conditions, and batch size.
• Extract: A detailed description of each stage of the manufacturing process shall be provided, including a flow chart. It shall be stated how the extract is standardised to the declared THC/CBD content and, if excipients are used for standardisation, the amount that may be added. The batch size shall be stated.

2.1.2.3 Control of starting materials

• Herbal substance: Not applicable.
• Extract: A list of all materials used in the manufacture of the extract (herbal substance, solvents and reagents, and excipients if used) shall be provided, identifying the stage of the process at which each is used. Information on the quality and control of these materials shall also be provided; they must meet the requirements of the applicable European Pharmacopoeia monographs.

2.1.2.4 Control of critical steps and intermediates

• Herbal substance: Not applicable.
• Extract: Information on critical steps shall be provided. Information on the quality and control of process intermediates, if any, shall be provided.

2.1.2.5 Process validation and/or evaluation

Herbal substance: Not applicable.

Extract: Validation data for the manufacturing procedure shall be provided.

2.1.2.6 Manufacturing process development

A brief summary shall be provided.

2.1.3 Characterisation

2.1.3.1 Elucidation of structure and other characteristics

• Herbal substance: Information on botanical, macroscopic, microscopic and phytochemical characterisation shall be provided.
• Extract: Information on phytochemical and physicochemical characterisation shall be provided.

2.1.3.2 Impurities

• Herbal substance: Potential contaminants/impurities arising from the cultivation of the herbal substance and from post-harvest treatments (pesticide and fumigant residues, toxic metals, aflatoxins, etc.) shall be stated and their origin described.
• Extract: Potential contaminants/impurities in the extract shall be stated and their origin described.

2.1.4 Control of the active substance

2.1.4.1 Specifications

• Herbal substance: Detailed information on the specifications used to control the herbal substance shall be provided; they must comply with the European Pharmacopoeia monograph on Cannabis flos (3028) and with the applicable general monograph (Herbal drugs, 1433).
• Extract: Detailed information on the specifications used to control the extract shall be provided. These specifications shall follow the applicable European guidelines or the specific European Pharmacopoeia monograph, if any.

2.1.4.2 Analytical procedures

The analytical procedures used to control both the herbal substance and the extract must be described in sufficient detail to be reproduced in tests carried out at the request of the competent authority. For test procedures included in the European Pharmacopoeia, this description may be replaced by the relevant reference to the monograph(s) and general chapter(s).

2.1.4.3 Validation of analytical procedures

The validation results of the analytical procedures used to control the herbal substance and the extract shall be provided, where appropriate.

2.1.4.4 Batch analyses

Results of analyses of representative batches shall be provided for both the herbal substance and the extract.

2.1.4.5 Justification of specifications

The specifications of the herbal substance, where relevant, and those of the extract shall be justified.

2.1.4.6 Reference standards or materials

The reference standards and materials used to control both the herbal substance and the extract shall be identified and described in detail. Where available, European Pharmacopoeia reference standards shall be used.

2.1.4.7 Container closure system

For both the herbal substance and the extract, a description of the container closure system and its specifications shall be provided. They must comply with EU legislation on plastic materials and articles intended to come into contact with food or with the applicable general chapters of the European Pharmacopoeia.

2.1.5 Stability

Information on the stability studies carried out and their conclusions (retest period or shelf life and storage conditions) shall be provided. In the absence of such studies, and therefore where no retest period or shelf life has been established for the herbal substance and/or the extract, they must meet the specifications immediately before use.

2.2 Standardised cannabis preparation

If the standardised cannabis preparation contains more than one standardised extract, the above information shall be provided for each of them.

2.2.1 Description and composition of the mixture of standardised extracts and/or their dilutions

The full composition of the preparation shall be detailed, including all standardised extracts and dilutions used.

2.2.2 Manufacture of the mixture of standardised extracts and/or their dilutions

• Manufacturers involved in the process: Information on all manufacturers involved in the process shall be provided.
• Batch formula: The detailed batch formula for the proposed batch size shall be provided.
• Description of the manufacturing process and in-process controls: The manufacturing process and the controls carried out during it shall be described in detail.

2.2.3 Control of excipients

Information on the quality and control of excipients must be provided, where necessary.

2.2.4 Control of the mixture of standardised extracts and/or their dilutions

Where the manufacturing process of the standardised cannabis preparation includes mixing different standardised extracts and/or their dilutions, the following information must also be provided:

2.2.4.1 Specifications

Detailed information on the specifications used for its control shall be provided.

2.2.4.2 Analytical procedures

The analytical procedures used for control must be described in sufficient detail to be reproduced in tests carried out at the request of the competent authority. For test procedures included in the European Pharmacopoeia, this description may be replaced by the relevant reference to the monograph(s) and general chapter(s).

2.2.4.3 Validation of analytical procedures

The validation results of the analytical procedures used for its control shall be provided.

2.2.4.4 Batch analyses

Results of analyses of representative batches shall be provided.

2.2.4.5 Justification of specifications

The proposed specifications shall be justified.

2.2.5 Reference standards or materials

The reference standards and materials used for its control shall be identified and described in detail, if they differ from those used to control the extract.

2.2.6 Packaging material

A description of the container closure system and its specifications shall be provided. They must comply with EU legislation on plastic materials and articles intended to come into contact with food or with the applicable general chapters of the European Pharmacopoeia.

2.2.7 Stability

Information on the studies carried out and their conclusions (shelf life and storage conditions) must be included.