Opinion of the National Council for Medicines Policy

National Council for Medicines Policy

SEEM

Date: 19 December 2017
Refa: CNPM - P#01
Subject: Opinion of the National Council for Medicines Policy of the Portuguese Medical Association on the scientific evidence supporting the use of cannabis for therapeutic purposes

Editors: Luís Castelo-Branco (main editor), Luís Frade and Roberto Pinto (correstors)

previous notes

1. 1- This opinion is issued following a request made to the National Council for Medicines Policy (CNPM) of the Portuguese Medical Association, by the Hon. Chairman of the Order of Physicians, Dr. Miguel Guimarães, on the scientific evidence supporting the use of cannabis for therapeutic purposes.
2. 2- For the realization of this document, the most relevant publications on the topic were considered (infrastructured in the bibliographic references) and public information on clinical trials registered on the website of the European Medicines Agency (EMA) and Clinicaltrials.gov. On the effectiveness of the clinical use of cannabis and cannabinoids

• – Several countries allow the use of cannabis derivatives and cannabinoids for therapeutic purposes, including Canada, the United States of America and several European countries, including Portugal.
• – There is strong evidence for the effectiveness of cannabis and cannabinoids in the treatment of chronic pain in adults (including neuropathic pain), as an anti-emetic associated with cancer treatment, in reducing multiple sclerosis spasticity and in the management of anxiety.Page 1 of 4

  Composition of the CNPM: Carlos Fontes Ribeiro, Frederico Teixeira, Luís Almeida (Pres.), Luís Castelo-Branco, Luís Frade, Manuel Caneira da Silva, Manuel Vaz Silva, Roberto Pinto, Serafim M. Guimarães

National Council for Medicines Policy

• – There is some/moderate evidence supporting the use of cannabinoids in improving sleep in people with obstructive sleep apnea, fibromyalgia, cancer anorexia, post-traumatic stress disorder and in the treatment of glioma.
• – There is NO evidence to support the efficacy of cannabis or cannabinoids in the treatment of cancer (other than the treatment of glioma*), cancer-induced cachexia, symptoms of irritable bowel syndrome, epilepsy, spinal cord injury spasticity, amyotrophic lateral sclerosis, Huntington's chorea, glaucoma, Parkinson's disease or schizophrenia, despite studies carried out in these areas.* In March 2016, ∂-9-tetrahydrocannabinol was approved as an orphan drug in the treatment of glioma, based on studies in experimental models, and subject to active surveillance for years to come.

  On the safety of clinical use of cannabis and cannabinoids

• – There is strong evidence of an association between cannabis use and the development of dependence, schizophrenia and other psychoses (increasing risk with increasing use), worsening of respiratory distress, chronic bronchitis and road accidents.
• – There is strong evidence for the association of maternal cannabis use and low neonatal weight.
• – There is moderate evidence of an association between cannabis use and suicidal ideation, manic and hypomanic attacks in individuals with bipolar disorder, impaired learning, memory and attention difficulties, or depressive symptoms.
• – There is limited evidence for the association of cannabis use and death from overdose, development of bipolar or generalized anxiety disorder, development of chronic obstructive pulmonary disease (COPD), hospitalizations for COPD, asthma attacks, liver fibrosis, changes in the immune system, academic failure, or unemployment.
• – There is limited evidence between the association of cannabis use and risk of solid or hematological malignancies, and it cannot be said that consumption can constitute a risk factor for any type of cancer.Page 2 of 4

  Composition of the CNPM: Carlos Fontes Ribeiro, Frederico Teixeira, Luís Almeida (Pres.), Luís Castelo-Branco, Luís Frade, Manuel Caneira da Silva, Manuel Vaz Silva, Roberto Pinto, Serafim M. Guimarães

National Council for Medicines Policy

• – There is limited evidence between the association of cannabis use and acute myocardial infarction, ischemic stroke, subarachnoid hemorrhage or diabetes.
• – There is little information about the side effects of chronic cannabis use. Particular challenges in the use of the cannabis plant and its derivatives
• – In addition to the use of cannabis derivatives subject to drug regulation for human use (with adequate control of product specifications, including active substances, doses, manufacturing process, etc.), regulation of direct consumption of the cannabis plant or of its derivatives is particularly challenging given the heterogeneity of the amounts, efficacy and safety of its active components (tetrahydrocannabinol, cannabidiol and others). The approval of its use in the therapeutic context is not compatible with the current regulatory requirements applicable to medicines for human use. No European country currently authorizes cannabis smoked for medical purposes.
• – The (de)penalization of its cultivation for (self) consumption, given its classic classification as a drug of abuse, its production and commercialization in adequate quantities for patients who intend to acquire it, aware of the scientific doubts and the consequences of the consumption of a phytotherapeutic product, may deserve the reflection of society. Any legal amendments that may facilitate the direct use of cannabis for medical purposes should not overlook potential public health risks, including abuse in its use as a recreational drug.Recommendations

1. The direct use of the cannabis plant or its derivatives for medicinal purposes involves particular challenges. Its eventual permission must be the subject of thoughtful and multidisciplinary reflection, integrating the legal issues of its production, commercialization, quality control of phytotherapeutics, the therapeutic benefit/risk in each clinical condition, and perhaps the will of society, duly clarified. It is important to reflect on whether or not their access may be allowed, and under what circumstances, with respect for the autonomy and informed decision of each citizen, but

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Composition of the CNPM: Carlos Fontes Ribeiro, Frederico Teixeira, Luís Almeida (Pres.), Luís Castelo-Branco, Luís Frade, Manuel Caneira da Silva, Manuel Vaz Silva, Roberto Pinto, Serafim M. Guimarães

National Council for Medicines Policy

taking into account their potential risks and necessary public health protection.

2. The use of cannabis or cannabinoids as a medicine for human use must be subject to approval by health regulatory bodies, namely EMA or INFARMED.
3. The best current level of evidence allows considering its potential use with strong evidence in the relief of chronic pain in adults (including neuropathic pain), as an anti-emetic in cancer treatment, in the reduction of spasticity due to multiple sclerosis and in the control of anxiety. With moderate evidence, it could be used to improve sleep in people with obstructive sleep apnea, fibromyalgia, cancer anorexia or post-traumatic stress disorder, and in glioma.
4. Due to the clinical effects and toxicity potential of cannabis and cannabinoids, their prescription must be exclusively medical, with special regulations, as done, for example, with morphine derivatives.
5. Recommendations on the use of cannabis or cannabinoids should be updated as more evidence is published, including clinical trials that are currently ongoing.Bibliography

• – Barnes MP, Barnes JC. 2016. Cannabis: The Evidence for Medical Use.
• – European Monitoring Center for Drugs and Drug Addiction (2017), Cannabis legislation in Europe: an overview, Publications Office of the European Union, Luxembourg. doi:10.2810/4682
• – Grotenhermen, F., & Müller-Vahl, K. (2012). The Therapeutic Potential of Cannabis and Cannabinoids. Deutsches Ärzteblatt International, 109(29-30), 495–501. http://doi.org/ 10.3238/arztebl.2012.0495
• – Madras BK. 2015. Update of Cannabis and its medical use. World Health Organization
• – National Academies of Sciences, Engineering, and Medicine. 2017. The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. Washington, DC: The National Academies Press. doi: 10.17226/24625
• – Wilkinson ST, Radhakrishnan R, D'Souza DC. 2016. A Systematic Review of the Evidence for Medical Marijuana in Psychiatric Indications. J Clin Psychiatry. 2016 Aug;77(8):1050-64. doi: 10.4088/JCP.15r10036.Page 4 of 4

  Composition of the CNPM: Carlos Fontes Ribeiro, Frederico Teixeira, Luís Almeida (Pres.), Luís Castelo-Branco, Luís Frade, Manuel Caneira da Silva, Manuel Vaz Silva, Roberto Pinto, Serafim M. Guimarães