[Cannabinoid Drugs in the Treatment of Psychiatric Disorders - Data from the German Federal Institute for Drugs and Medical Devices]. / Cannabisarzneimittel in der Behandlung psychischer Störungen ­ Befunde aus der Cannabis-Begleiterhebung des Bundesinstituts für Arzneimittel und Medizinprodukte.

BACKGROUND: Since 2017 physicians in Germany can prescribe cannabis based medicines or medical cannabis with subsequent funding by the statutory health insurance system. METHODS: Physicians prescribing cannabinoid drugs were legally required to take part in a survey conducted by the Federal Institute for Drugs and Medical Devices. This study analyses data from 16.809 case reports that were collected from 30.3.2017 to 31.12.2021. RESULTS: There were 5582 cases documenting the use of cannabinoid drugs in psychiatric disorders. More than half of the prescriptions were Dronabinol. 80% of the treatments concerned somatoform disorders. Most of the treatments for other psychiatric disorders also targeted pain. Doctors reported a positive effect on symptoms in at least 75% of the cases. DISCUSSION: Most patients with psychiatric disorders received cannabinoid drugs for pain. The evidence from randomized controlled clinical trials for the use of cannabinoid drugs in psychiatric indications is weak.

[Cannabis as Medicine: Safe Use of Special Regulations]. / Cannabis als Medizin: Sonderregelungen sicher anwenden.

In 2017, the legislator created a special regulation for medical cannabis in Germany. Medical cannabis can also be prescribed without marketing authorization at the expense of the statutory health insurance, if other forms of therapy are not sufficiently effective. Before starting therapy with a cannabis medicine outside of approved indications, an application for reimbursement must be submitted to the health insurance company. Cannabis medicines are mainly prescribed for the treatment of chronic pain. There are some rules to be observed when prescribing cannabis medicines: The information according to Section 9 of the Narcotic Drugs Prescription Ordinance must be complete and clear. Data on the therapeutic success and the safe use of the cannabis medicines are collected in a five-year follow-up survey. According to first interim results of this survey, many side effects have an influence on the vigilance of patients. The risk of falling is increased, especially in older patients. In the medium term, the special regulation described above should become dispensable due to the approval of cannabis-based finished medicinal products.

[Three years of cannabis as medicine-preliminary results of the survey accompanying the prescription of medical cannabis in Germany]. / 3 Jahre Cannabis als Medizin ­ Zwischenergebnisse der Cannabisbegleiterhebung.

In Germany, physicians who prescribe medical cannabis flowers or cannabis-based medicines (narcotic prescription) at the expense of the statutory health insurance are obliged to take part in a noninterventional accompanying survey that runs until 31 March 2022.At the time of this interim evaluation, 11 May 2020, there were 10,010 complete datasets collected. The most frequently treated symptoms were pain (73%), followed by spasticity (10%), and anorexia/wasting (6%). Dronabinol (i.e., prescription drug or Marinol®) was most frequently (65%) prescribed, followed by cannabis flowers (18%), Sativex® (13%), cannabis extract (4%, with increasing frequency), and nabilone (0.3%). The 6485 cases treated with dronabinol already allows a subgroup evaluation concerning efficacy. The typical cannabis side effects of tiredness, dizziness, dry mouth, and nausea occur with all cannabis medicines, and correspond to those already known from the product information of the cannabis-based medicinal products authorized under the pharmaceutical law. The potentially serious adverse effects of depression, suicidal ideation, delusions, hallucinations, dissociation, and misperceptions were each reported with a frequency higher than 0.1%. There were remarkable differences between patients treated with cannabis flowers and those with other cannabis medicines.Patients treated with cannabis flowers are significantly younger and predominantly male. They are treated more often by general practitioners and internists, their diagnosis differs more often from the typical diagnoses (pain, spasticity, anorexia/wasting), and they have more prior experience with cannabis. The underreporting in the accompanying survey is mainly in this patient group.

Key elements of legal environments for medical use of cannabis in different countries.

Worldwide, a highly dynamic development of regulatory strategies for cannabis flowers and cannabis-derived products for medical use can be observed. Conditions laid down in the Single Convention on Narcotic Drugs are basic, and implementation in countries is diverse.As early as 1998, the Netherlands was the first Member State of the European Union (EU) to establish a strategy to provide patient access to cannabis for medical use. Since then, more and more Member States of the European Union have facilitated access to cannabis for medical use. A comparable development has taken place outside Europe. This article describes the current situation in the Netherlands and presents selected highlights of developments within and outside Europe to demonstrate the broad spectrum of strategies. Key parameters are identified that should be considered when changing or amending regulatory frameworks on cannabis for medical use. In addition to the establishment of adequate regulatory frameworks, there is a substantial need to generate adequate scientific data.

[Cannabis for medical purposes : Impact of the law of 6 March 2017 on physicians]. / Cannabis als Medizin : Auswirkungen des Gesetzes vom 6. März 2017 auf die Ärzteschaft.

The law on the amendment of the narcotics law and other regulations, which was accepted by consensus by the German Parliament, significantly expanded the options for the use of cannabis-based medicinal products. In individual cases, already approved cannabis-based medicinal products can also be prescribed outside the approved indication at the expense of the statutory health insurance funds (GKV). The cost of treatment with cannabis flowers and extracts as well as dronabinol, which are not approved under the drug law, will also be covered by the GKV upon application. Physicians must advise their patients on the options of treatment with cannabis-based medicinal products and support them in applying for reimbursement. The prescription of unauthorized medical cannabis products poses particular challenges, as there is no summary of product characteristics that is mandatory for authorized finished products. In addition, physicians are obliged to participate in an accompanying survey. To this end, they must send data to the Federal Institute for Drugs and Medical Devices providing information about treatment with cannabis-based medicinal products. When prescribing medical cannabis products as defined in the Act of 6 March 2017 amending the law on narcotic drugs and other regulations, physicians assume a special responsibility that goes far beyond the responsibility for the use of authorized finished medicinal products.

[Cannabis for medical purposes-the law of March 2017 and its history]. / Cannabis zu medizinischen Zwecken ­ Das Gesetz vom März 2017 und seine Vorgeschichte.

Since March 2017, the law amending narcotic and other regulations has expanded the options for prescribing cannabis-derived medicines by doctors. Under certain conditions, patients can be treated with cannabis-derived medicines at the expense of the statutory health insurance. With a prescription, cannabis-derived medicines may be available that are not approved as a finished medicinal product. The reasons for this lie in particular in court decisions from the years 2005 and 2016.The decisive legal regulation increases the responsibility of doctors and pharmacists in supplying their patients with cannabis-derived medicines. A five-year monitoring survey is being conducted by the Federal Institute for Drugs and Medical Devices (BfArM) to evaluate the effects on patient care. In order to ensure the supply of cannabis-derived medicines in the future, the cultivation of cannabis in Germany is planned under the conditions of the 1961 Single Convention on Narcotic Drugs under the control of a cannabis agency.

[Interim analysis of the survey accompanying insurance-covered prescriptions of cannabis-based medicines in Germany]. / Begleiterhebung zur Anwendung von Cannabisarzneimitteln in Deutschland ­ Zwischenauswertung.

In Germany, medical doctors who prescribe cannabis medicines at the expense of the statutory health insurance are obliged to take part in a noninterventional survey on the use of these cannabis medicines. The survey collects and evaluates anonymized treatment data and runs until 31 March 2022. Amongst other things, the results of the accompanying survey are the basis on which the Joint Federal Committee (G-BA) regulates the future assumption of treatment costs in the context of a therapy with cannabis medicines in accordance with the Social Code (SGB) V. The transmission of the data for the survey takes place via an online portal operated by the Federal Institute for Drugs and Medical Devices (BfArM). The first data transmission takes place after a treatment period of one year or, if the treatment discontinued before the end of one year, directly after discontinuation of therapy.At the time of the interim evaluation, 01 February 2019, there were 4153 complete datasets collected. Most frequently, the symptom "pain" was treated (69%), followed by spasticity (11%), and anorexia/wasting (8%). The observed adverse reactions correspond with those listed in the product information for the two cannabis-based proprietary medicinal products, Sativex® (GW Pharma Ltd, Salisbury, Wiltshire, UK) and Canemes® (AOP Orphan Pharmaceuticals AG, Vienna, Austria). Most often, insufficient effect was the reason for a discontinuation of treatment. The main indication of pain was already apparent in the licensing procedure for the acquisition of cannabis for medical purposes between the years 2005 and 2016. Further evaluations and subgroup analysis will be carried out when higher case numbers are available.

Estimation of the Number of People With Opioid Addiction in Germany.

BACKGROUND: Opioid addiction is one of the most common substance-related disorders worldwide, and morbidity and mortality due to opioid addiction place a heavy burden on society. Knowing the size of the population that is addicted to opioids is a prerequisite for the development and implementation of appropriate health-policy measures. METHODS: Our estimate for Germany for 2016 is based on an enumeration of opioid-addicted persons who were entered in a registry of persons receiving substitution therapy, an enumeration of persons receiving outpatient and inpatient care for addiction without substitution therapy, an extrapolation to all addiction care facilities, and an estimation of the number of opioid-addicted persons who were not accounted for either in the substitution registry or in addiction care. RESULTS: The overall estimate of the number of opioid-addicted persons in Germany in 2016 was 166 294 persons (lower and upper bounds: 164 794 and 167 794), including 123 988 men (122 968 to 125 007) and 42 307 women (41 826 to 42 787). The estimates for each German federal state per 1000 inhabitants ranged from 0.1 in Brandenburg to 3.0 in North Rhine-Westphalia and 5.5 in Bremen. The average value across Germany was 3.1 per 1000 inhabitants. CONCLUSION: Comparisons with earlier estimates suggest that the number of persons addicted to opioids in Germany has hardly changed over the past 20 years. Despite methodological limitations, this estimate can be considered highly valid. Nearly all persons who are addicted to opioids are in contact with the addiction care system.

Epidemiology of hepatitis C virus infection among people receiving opioid substitution therapy (ECHO): study protocol.

BACKGROUND: Hepatitis C virus infection is highly prevalent among people who inject drugs. Opioid substitution therapy, the standard treatment for opioid dependence, provides an excellent opportunity for the treatment of hepatitis C virus infection due to the close and regular contact between patients and clinicians. However, there is little research on the impact of opioid substitution therapy on the prevalence of the hepatitis C virus at a national level. This paper describes the protocol for the Epidemiology of Hepatitis C Virus Infection among People Receiving Opioid Substitution Therapy (ECHO) study. The aim of this study is to estimate the national prevalence and incidence of hepatitis C virus infection among people receiving opioid substitution therapy in Germany and to describe factors associated with hepatitis C treatment uptake and seroconversion. METHODS/DESIGN: An observational, longitudinal, multicentre study is being conducted between 2014 and 2016 in a representative sample of approximately 2500 people receiving opioid substitution therapy from about 100 clinicians providing opioid substitution therapy in Germany. Data will be collected during routine patient care and by means of patient and clinician questionnaires at baseline and 12-month follow-up. Stratified sampling will be performed to obtain a representative sample of clinicians providing opioid substitution therapy. The strata will be constructed based on the distribution of the total sample of clinicians providing opioid substitution therapy in Germany according to German Federal State and the number of patients per clinician. DISCUSSION: Opioid substitution therapy may be an important strategy to prevent the spread of hepatitis C virus in opioid dependent populations, but its effectiveness may be diminished by our limited understanding of factors associated with treatment uptake and seroconversion. The present study will provide important information for developing strategies to address hepatitis C virus-related disease burden in people receiving opioid substitution therapy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02395198.

Topical review on the abuse and misuse potential of tramadol and tilidine in Germany.

BACKGROUND: Tramadol and tilidine (in combination with naloxone) are used as weak opioid analgesics in Germany. Tramadol is not scheduled in the German Narcotic Drugs Act. Tilidine is scheduled, whereas Tilidine in fixed combinations with naloxone is exempt from some of the provisions of the Narcotic Drugs Act. Recent reports on misuse of both substances led to an evaluation of their potential for misuse, abuse, and dependency by the expert advisory committee established by the German Federal Government, resident at the Federal Institute for Drugs and Medical Devices. METHODS: A subcommittee formulated key questions and identified available data sources for each of these questions. Additional information was solicited where necessary, including a survey among a panel of pharmacists, a survey in an addiction clinic, analysis of prescription patterns, and information from the boards of pharmacists of the federal states and the Federal Bureau of Criminal Investigation. RESULTS: Analgesic efficiency in the treatment of acute and chronic pain has been proven for both tramadol and tilidine/naloxone. For tramadol, high evidence has been confirmed in systematic reviews, and tramadol is listed in national and international guidelines on acute and chronic pain management. Animal and human studies found a low potential for misuse, abuse, and dependency for both substances. Information from 2 tramadol safety databases allowed calculation of the incidence of abuse or dependency as 0.21 and 0.12 cases per million defined daily dosages (DDDs), with lower incidences in recent years. For tilidine/naloxone, the incidence was calculated as 0.43 cases per million DDDs for oral solution and 0.18 for slow-release tablets. In an online survey among German pharmacies as well as in the reports from state pharmacy boards, fraud attempts were repeated more frequently with tilidine/naloxone than with tramadol in the last 2 years. The Federal Bureau of Criminal Investigations reported prescription fraud only with tilidine/naloxone and predominantly in the region of Berlin. Dependency on tramadol or tilidine/naloxone is reported only rarely from addiction counseling centers. One third of the patients surveyed in an addiction clinic reported experiences with tramadol or tilidine/naloxone, but mostly with duration of less than 4 weeks and with a medical prescription based on a reasonable indication. Also, occasional illegal use of opioid analgesics as a substitute of heroin was reported. An evaluation of pooled data from statutory health insurance companies found 2.5% of persons receiving at least 1 prescription of tramadol or the combination of tilidine and naloxone in 2009 (1.6% with tramadol and 1.0% with tilidine/naloxone). High usage with more than 180 DDDs per year was found in 8.6% of patients treated with tramadol and 17.2% of patients with tilidine/naloxone. CONCLUSIONS: In conclusion, the subcommittee of the expert advisory committee found a low potential for misuse, abuse, and dependency for tramadol, and a low prevalence in clinical practice. Considerable less information is available for the combination of tilidine and naloxone. However, the cumulation of evidence indicated a higher risk of misuse, abuse, and dependency for tilidine/naloxone solution, but not for slow-release tablets.