Franjo Grotenhermen. Journal of Drug Issues. Volume 32, Issue 2. April 2002.
Introduction
Interest in the therapeutic potential of cannabis strongly increased in the second half of the 1990s. Despite a long history, the medicinal use of the plant was nearly completely forgotten in the second half of the 20th century (Fankhauser, 2002). A common positive attitude towards medicinal plants and natural forms of treatment in the general public and among many physicians and scientists is supposed to be advantageous for a reintroduction of natural cannabis-based medicines in Germany. There is a broad consensus that herbal medicines have a place in modern medicine (Blumenthal, 1998; Gaedcke, 2000), and the government agreed that a natural cannabis preparation should be made available on the condition that “the legal pharmaceutical regulations are observed” (Flenker & Moeller, 2001a, p. 1105).
History
The medical use of cannabis has a long history in Germany (for a review, see Fankhauser, 1996, 2001). In her medical work, Physica (circa 1150), the German abbess Hildegard von Bingen said that hemp “reduces the bad juices and reinforces the strong ones” (p. 28), that cannabis may help against headache (and may also cause headache), and that it may be used externally to treat sores and wounds.
In the centuries that followed, hemp was identified in most herbal and medicinal books. The physician and philosopher Paracelsus (1493-1541) described cannabis in a number of his many works. In his book Das Neunte Buch in der Arznei [The ninth book of medicine], he mentioned cannabis as a component of the “Arcana compositum,” which he regarded to be the most important medicine. Other wellknown herbal books are the Contrafayt Kreueterbuch by Otto Brunfels (1488-1534), the Kreuetterbuch by Hieronymus Bock (1498-1554), the New Kreueterbuch by Leonard Fuchs (1501-1566), and the Neu vollkommen Kraeuterbuch by Jacobus Theodorus Tabernaemontanus (1520-1590).
Throughout the middle ages and until the 18th century, the seeds of local cannabis were used, in the form of an oil or emulsion. Hemp oil was applied as a cure against a number of illnesses, such as inflammations of the breast (De Fouquet, 1708), gonorrhea (Tode, 1790), cough, stitch, jaundice, and worms (Medizinisches Lexikon, 1755). The first book on pharmaceutics that appeared in Germany was the Apparatus medicaminum tam simplicium quam praeparatorum et compositorium (1776-1789) by John Andreae Murray, professor in Goettingen and director of the local botanical garden. This work is regarded as the most important and best of its time and included 12 pages on cannabis. Murray recommends hemp oil as an analgesic and anesthetic, as well as for the treatment of gonorrhea and jaundice. The founder of homeopathy Samuel Hahnemann wrote in 1797: “Although until now only the seeds are used, other parts of the plant seem to be more effective and deserve more attention” (p. 266). Cannabis sativa (indigenous European hemp) was one of the first homeopathic medicines.
In the 17th century, European travelers to Arab countries and Asia were exposed to cannabis with higher THC content. The term “Indischer Hanf” [Indian hemp] was first introduced by the distinguished 17th century naturalist Georg Eberhard Rumpf (or Georgius Everhardus Rumphius, 1627-1702). However, Indian hemp did not become widely used in medicine until the 19th century.
In 1823, an article on the successful use of Indian hemp for the treatment of whooping cough appeared in the renowned Hufeland-Journal (Fankhauser, 1996). In 1830, the first detailed description on the medical use of Indian hemp was published in Europe by Theodor Friedrich Ludwig Nees von Esenbeck, professor for pharmacy and botany, in Bonn (Nees & Ebermaier, 1830). He writes: “Many doctors, even Hahnemann, apply the extract in wine in the case of some nervous ailments where opium or Hyoscyamus would otherwise have been used, being more bitter and without heating so much” (pp. 338-339). In 1841, two years after the important publication by William B. O’Shaugnessy on the medical use of cannabis (O’Shaugnessy, 1838-1840), the doctoral dissertation on cannabis of the physician Georg Freudenstein was published at the University of Marburg. Basilus Beron, who wrote his doctoral dissertation on the use of cannabis in tetanus at the University of Wuerzburg stated, “I was so happy – we had tried all known anti-tetanic substances in vain but the Indian hemp showed that the patient assigned to me could be cured completely” (Beron, 1852, p. 5). Great attention was paid to the doctoral dissertation of Georg Martius on the pharmacology of hemp, completed at the University of Erlangen in 1856, and to the standard work of Ernst Freiherr von Bibra on the narcotic stimulants that was published in 1855. It comprised a 30-page treatise on hashish and stated: “The more recent tests and experiences concerning the effects of the hemp plant and its preparations have turned out very advantageous” (p. 290).
Research on Indian hemp advanced in Germany throughout the 19th century. A comprehensive, often quoted study of this time is that of Bernhard Fronmueller, physician at the hospital in Fuerth, in 1869. His tests with cannabis as a part of his clinical studies on sleep-inducing effects of narcotics were conducted with 1,000 patients who suffered from sleep disturbances. He reported a cure effect in 53%, a partial cure in 21.5%, and none or a small effect in 25.5% of these patients. Many German pharmacologists of the time wrote treatises on cannabis, among them J.B. Henkel (1825-1871), professor of pharmaceutics in Tuebingen; Otto Carl Berg (1815-1866), professor of botany and pharmacology in Berlin; Hermann Nothnagel (1841-1905), professor of pharmacology in Freiburg, Jena, and Vienna; H.A.L Wiggers (1803-1880), professor of pharmaceutics in Goettingen; and Oscar Liebreich (1839-1908), founder of the Pharmacological Institute of Berlin.
The period between 1880 and 1900 can be regarded as the climax of the medicinal use of cannabis. Above all, the company E. Merck in Darmstadt was the leading manufacturer of cannabis preparations in Europe at that time, producing cannabis extracts in large quantities, among them “Cannabinum tannicum, which came on the market in 1882; “Cannabinon” (1884); and “Cannabin” (1889), used as hypnotic, analgesic, and aphrodisiac, and against neuralgias, rheumatism, hysteria, depression, delirium tremens, and psychosis. In a review on the pharmacology of cannabis, indications for its use and recent clinical applications appearing in four succeeding issues of the Deutsche Medizinische Wochenschrift [German Medical Weekly], the author described Cannabinin, Cannabinon, Cannaben and Haschischin as the most important constituents of the cannabis plant, whereas Cannabinum tannicum was regarded as being composed of several glycosides, among them Cannabin (See 1890).
Many other preparations came on the market in Germany, e.g., “Extractum cannabis indic. pingue” against gastritis and dyspepsia, ointments with cannabis for external pain therapy (“Stilus cannabis unguens”) and for the inhibition of lactation (“Oleum cannabis pingue”) and “Migraenin” by the Royal Bavarian Pharmacy against migraine.
With the beginning of the 20th century, the medicinal use of cannabis rapidly decreased. New cannabis preparations that came on the market were mostly combination preparations with two or more ingredients, such as “Asthma-Bronchial Zigarren” [asthma bronchial cigars] of 1903 in the treatment of asthma, “Cannabiscollodium” of 1901 for the treatment of corns, “Mutterperlen Enta” by Dr. Meier in Rosenheim (1913) to treat women’s diseases, “Gonakyl” (1920) against gonorrhea, “Indonal Buergi” by Dr. Fresnius in Frankfurt (1930), a hypnotic containing cannabis indica and a barbiturate, “Organin” by Homoia Gesellschaft in Karlsruhe (1933) to treat impotence, “Dysmenorrhan” by Lauxmann in Munich (1933) to treat dysmenorrhoe, and many others. Doctoral dissertations on cannabis were written until the 1930s, including one by Gottlieb Eckhard in 1933 and another by Hermann Foerster in 1939 (Fankhauser, 1996).
Very few new preparations containing cannabis came on the market after the Second World War. The medical use of the drug was negligible at the time, and it was actually prohibited in 1958. Only homeopathic uses of cannabis sativa and cannabis indica survived. Until 1974 (when even homeopathic uses of cannabis indica were prohibited), the pharmaceutical company “Weleda Heilmittel AG” in Schwaebisch Gmuend marketed an injectable homeopathic cannabis preparation (Gorter, 1996). Today, homeopathic preparations of cannabis sativa like that prepared from fiber hemp with low THC content by the small firm THC Pharm in Frankfurt, are available in Germany. The use of cannabis indica is illegal in Germany even in homeopathic doses, although sanctions against users are unheard of. These preparations are now usually imported from Switzerland or the Netherlands.
Revival
Two events occurred during the 1960s that caused a revival of interest in the clinical pharmacology of cannabinoids in Western societies: the exact determination of the chemical structure of THC by Gaoni and Mechoulam (1964), which resulted in a strong stimulation of research in the 1970s, and increased recreational use of cannabis by young people whereby many discovered that the drug was able to alleviate ailments caused by a number of diseases.
Until the second half of the 1990s, clinical research was rare in Germany, and the medical benefits of cannabis and the cannabinoids were nearly unknown to the broader public. Only a few German publications even mentioned its therapeutic potential (e.g., Quensel, 1989). In medical journals, there were only rare hints about the medicinal properties of cannabis. Heim (1982) published a short review on the history of cannabis in medicine and on cannabinoids, with some promising therapeutic potential in the treatment of nausea and vomiting, pain, glaucoma, epilepsy, spasticity, inflammation and loss of appetite. In a book on the pharmacology of cannabis containing a strong warning against its use, medical applications were mentioned in an amusing way, referring to these as strange practices in former times (Taeschner, 1986).
An extensively illustrated 1982 book on the history, culture and politics of cannabis by Hans-Georg Behr contained a small section on medical uses, but this work was only noted by a limited public. Two other books attracted much more attention and provoked an increased interest in the hemp plant in the 1990s. This may be due to the fact that the emphasis in these books was on the contemporary benefits of the cannabis plant. In 1993, a book by Jack Herer on cannabis as a crop and medicine was translated from English into German (Herer, 1993). In 1994, a book was published by Lester Grinspoon and James Bakalar on the medical use of marijuana (Grinspoon & Bakalar, 1994). Both books appeared in co-authorship with German scientists: the book by Herer in cooperation with Matthias Broeckers and the Katalyse Institute (Michael Karus), the book by Grinspoon and Bakalar with a second part by Franjo Grotenhermen and Karus (Grotenhermen & Karus, 1994).
Beginning in 1995, the Institute for Oncological and Immunological Research in Berlin, under the guidance of Robert Gorter, prepared a three-pronged multicenter study with a standardized oral cannabis extract, dronabinol and placebo in AIDS and cancer patients. Due to several difficulties in obtaining required approvals and organizational problems based on the legal status of cannabis, the study had to be postponed several times, finally beginning in 1999. In cooperation with Gorter, Alexander Remmele, and other patients, a first self-help group of people who used cannabis for medicinal purposes was founded in Berlin in December 1995. Another early organization involved in the support of medical users was the ‘Gruene Hilfe’ [Green Help], a small network that assists people experiencing legal problems related to cannabis possession that also had a branch dedicated to the therapeutic use of the plant.
In March 1995, several lectures were presented on the medical use of cannabis at the Bioresource Hemp Symposium in Frankfurt. In October 1995, the Deutsche AIDS-Hilfe [German AIDS organization], in cooperation with the Medical Association of Berlin, organized a congress on cannabis as medicine. A survey by the Deutsche AIDS-Hilfe among AIDS patients presented at the meeting revealed that many patients used marijuana for the enhancement of general well-being and for the treatment of physical complaints (Barsch, 1996).
Among German users, natural cannabis products are usually bought in the Netherlands or are home-grown. Several German patients have contacted Dutch organizations dedicated to the medical use of cannabis, among them Maripharm in Rotterdam, the Stichting Patientenbelangen Medicinale Marihuana in Rotterdam, and the Stichting Institute of Medical Marijuana in Rotterdam.
Today, two German pharmaceutical companies are engaged in the development of natural cannabis preparations: THC Pharm and Binorica. THC Pharm that has been marketing dronabinol since 2000. In September 2001, the company received approval to import cannabis from Asia in order to develop a natural cannabis preparation. The phytopharmaceutical company Binorica announced in autumn 2001 its intention to develop a dronabinol and a natural cannabis preparation.
The Legal Situation
The second Opium Law of 1929 prohibited the recreational use of cannabis in Germany (Harrach & Eul, 1998). The cultivation of hemp for the production of fiber and medical use was still allowed, however. Medical use was prohibited in 1958. In 1972, the Narcotics Law (Betaeubungsmittelgesetz) replaced the Opium Law.
The German laws distinguish five groups of substances with regard to medical use. Three groups are regulated by the Narcotics Law and listed in Appendix A. Some changes occurred with regard to THC (dronabinol) during the last few years and are directed at cannabis.
- Substances belonging to Annex I are illegal. They are “not prescribable” and “not negotiable.” Heroin, psilocybin, cannabis, LSD, etc. belong to this group. Exemption from general prohibition may be obtained from the Federal Institute for Drugs and Medical Devices (subauthority of the Federal Ministry of Health) but “only exceptionally for scientific or other purposes of public interest,” thereby inhibiting clinical research with cannabis.
- Substances belonging to Annex II are not prescribable. They may be manufactured or bought by pharmacies. Many of the substances in Annex II are precursors of substances of Annex III, such as isomethadon and dihydromorphin. In 1994, dronabinol (THC) was rescheduled from Annex I to Annex II to ease research.
- Substances belonging to Annex III are restricted to medicinal use prescribed on a “Narcotics Prescription” [Betaeubungsmittelrezept]. Among these drugs are morphine, cocaine, opium, pethidin, methadone, etc. Since 1983, the synthetic dronabinol derivative nabilone has been listed in Annex III. In 1998, dronabinol was rescheduled from Annex II to Annex III and since then has been available by prescription.
The other two groups of drugs not regulated by the Narcotics Law are either available through a regular prescription (sedatives, non-opiate analgesics, antipsychotic medications, etc.) or as over-the-counter drugs that can be bought without prescription in pharmacies.
The ‘Deutscher Arzneimittelkodex’ (DAC, German Pharmaceutical Codex), which is responsible for the development of formulas for medicinal plants, intends to publish a monograph in late 2002 that will contain a formula for a cannabis extract. This formula will be based on a standard THC strength that pharmacists can use to produce tinctures or capsules. This unique cannabis extract is the only form of cannabis that the government intends to reschedule from Annex I to Annex III.
Research
In 1950, an article on the active ingredients of cannabis and the pharmacology of cannabinoids by Walter Siegfried Loewe appeared in a German journal (Loewe 1950). He described attempts to isolate cannabinoids from cannabis extract by American and British researchers and in his own research on the structure activity relationship (SAR) of cannabinoids. He also discussed his pharmacological investigation of ‘Charas-THC’ and other cannabinoids in the 1930s and 1940s, where he noted the sedating, anticonvulsant and analgesic properties of Charas-THC and first synthetic derivatives (Parahexyl, Isohexyl, etc.). At that time, a few cannabinoids were already known: cannabinol (1939), cannabidiol (1940), and tetrahydrocannabinol (1942). However, researchers had failed to identify the exact chemical structure of charas-tetrahydrocannabinol (as it has been called since 1942) because it was not possible to locate a double bond in the terpene ring of the molecule. A clarification of this question was not obtained until the early 1960s when more sophisticated technical equipment was available, and Gaoni and Mechoulam identified the active principle of Cannabis sativa as tetrahydrocannabinol (Gaoni & Mechoulam, 1964). A German review, co-authored by the two Israeli researchers, appeared in 1965 (Budzikiewicz et al., 1965).
Clinical research in Germany was rare until the second half of the 1990s. There was no published clinical research on THC in Germany before its rescheduling into Annex III of the Narcotics Law in 1998. Several clinics were involved in the investigation of the synthetic THC analogue levonantradol, including the University of Heidelberg (Heim, Romer, & Queisser, 1981) and the Hospital A. Krupp von Bohlen und Halbach in Essen (Higi et al., 1982). Levonantradol was tested by Pfizer as an antiemetic in cancer chemotherapy and for some other indications but was never approved.
In 1989, Meinck, Schoenle, and Conrad investigated the effect of a smoked marijuana cigarette on the motor function of a multiple sclerosis patient at the Department of Clinical Neurophysiology of the University of Goettingen. The patient himself had observed an improvement of spasticity and tremors following the inhalation of cannabis. The quantitative assessment by means of clinical rating, electromyographic investigation of the leg flexor reflexes, and electromagnetic recording of the hand action tremors confirmed his experience. As with other indications and in other countries, clinical research was often stimulated by the personal experiences reported by patients.
This was also the case with the current studies of the Institute for Oncological and Immunological Research in Berlin and the clinical research in subjects suffering from Tourette-Syndrome at the Medical School of Hannover under the guidance of Kirsten Mueller-Vahl.
Since autumn of 1999, the multicenter study comparing the effect of an oral cannabis extract, dronabinol and placebo on appetite, weight, nausea, and wellbeing in cancer patients in Germany and Switzerland has been headed jointly by Thomas Cerny and Florian Strasser (both are Swiss) and Martin Schnelle (Institute for Oncological and Immunological Research, Berlin). Other studies initiated by the Berlin Institute are being conducted with multiple sclerosis patients at the ‘Hoehenklinik Montana’ in Bern (Switzerland) under the guidance of Claude Vaney, at the Derriford Hospital in Plymouth (UK) under the guidance of John Zajicek and at the Free University of Amsterdam (The Netherlands) under the guidance of Joep Killestein. The study by Killestein and his colleagues was completed in spring 2001 (Killestein, 2001). A study at the Charité Berlin with patients suffering from chronic zoster (herpes) pain is intended to start soon under the guidance of Gernot Ernst. The studies by the Institute for Oncological and Immunological Research aim at gaining pharmaceutical approval of the standardized cannabis extract under investigation.
Mueller-Vahl and colleagues noticed that some patients suffering from the Gilles de la Tourette Syndrome (Tourette-Syndrome, TS) reported symptom improvement following marijuana use. They interviewed 64 TS patients about their use of smoked cannabis and its influence on TS symptomatology. Of 17 patients reporting prior use of marijuana, 14 (82%) experienced a reduction or complete remission of symptoms (Mueller-Vahl, Kolbe, Schneider, & Emrich, 1998). These personal experiences were confirmed by an uncontrolled open clinical trial with 10 mg oral THC in a Tourette patient who showed marked improvement of both vocal and motor tics (Mueller-Vahl, Schneider, Kolbe, & Emrich, 1999). A randomized double-blind placebo-controlled crossover trial of THC (5, 7.5, or 10.0 mg THC) in 12 adults suffering from Tourette-Syndrome followed, demonstrating significant improvement of symptoms following administration of the cannabinoid (Mueller-Vahl, Kolbe, Schneider, & Emrich, 1999). Plasma concentrations of THC were correlated to symptom improvement. A six-week study in 24 patients demonstrated a significant improvement of tics with THC compared to placebo over a longer time period (Mueller-Vahl, et al., 2001).
From April 1998 to April 1999, the Association for Cannabis as Medicine (Cologne), in cooperation with the Institute for Oncological and Immunological Research, conducted an anonymous standardized survey on the medical use of cannabis and cannabis products by patients in Germany, Austria and Switzerland (Schnelle, Grotenhermen, Reif, & Gorter, 1999). Throughout about one year, 170 subjects participated in this survey; questionnaires administered to 128 of these patients were included in the evaluation. The most frequently mentioned indications for medicinal cannabis use were depression (12%), multiple sclerosis (11%), HIV infection (9%), migraine (7%), asthma (6%), back pain (5%), hepatitis C (5%), sleeping disorders (5%), epilepsy, spasticity, headache, alcoholism, glaucoma, nausea, disk prolapse, and spinal cord injury. The majority of patients used natural cannabis products.
Of the patients surveyed, 72% stated the symptoms of their illness were “much improved” after cannabis ingestion, 23% noted a slight improvement, 5% experienced “no change,” and 2% reported their symptoms had worsened; 61% stated they were “very satisfied” with their therapeutic use of cannabis, 24% were satisfied, 11% were partly satisfied, and 4% were not satisfied. An extended survey was administered by the ACM and the Institute in Berlin, beginning in July 2001 and continued through December 2001. This survey covered questions about the comparison of THC and cannabis with regard to benefits and side effects. It was also concerned with the attitudes of physicians and the behavior of health insurance providers with regard to reimbursement for dronabinol treatment.
Mass Media and Medical Journals
The mass media began to show interest in this subject in 1994. Among others, the weeklies Der Spiegel, Stern, and Die Woche, featuring the reprint of the book by Behr, the book by Grinspoon and Bakalar, a German physician who recommended cannabis to his AIDS-patients, the history of the U.S. glaucoma patient Robert Randall, the first demonstration for the legalization of cannabis in Germany on April 2, 1994, in Kiel and the difficulties in conducting clinical research with cannabis (Der Spiegel, 1994; Bergmann, 1994; Meyer-Thompson, 1994). Hans-Michael Meinck who conducted the small study cited above (Meinck et al., 1989), now professor at the University of Heidelberg, regretted that “studies with cannabis are politically not enforceable in Germany” (Bergmann, 1994, p. 203). Several monthly or bi-monthly cannabis journals appeared (Hanfblatt in 1994, Hanf! in 1995, Grow!) that are still available today.
In the years that followed, even conservative newspapers reported on the topic and showed sympathy for patients who had profited from their use of the drug. The Frankfurter Allgemeine Zeitung headlined an article, “Soft drugs against pain,” reporting about a workshop on cannabis that took place at the annual meeting of pain therapists (Wandtner, 1998). There were many detailed articles featuring descriptions of the situations and experiences of single cannabis users (e.g., Dee, 1998), stories that covered up to two newspaper pages (Albrecht, 2000).
Medical journals also joined in the debate. A first short review on the medical use of cannabis and the cannabinoids appeared in the medical journal of Westphalia in 1998 (Grotenhermen, 1998), and an extensive overview appeared in a journal on internal medicine in 1999 (Grotenhermen, 1999a). Medical journals that deal with medicinal plants became interested in the subject (Grotenhermen, 1999b), and a Medline-listed journal for nurses presented a review as well (Fischer, 1999). A supplement of Research in Complementary Medicine printed lectures presented at two congresses in Cologne and Frankfurt in December 1998, with contributions by Reinhard Saller (1999), Roger Pertwee (1999), Franjo Grotenhermen (1999c, 1999d), Martin Schnelle (Schnelle et al., 1999), Robert Gorter (1999), Lester Grinspoon (1999), Raphael Mechoulam (1999) and Kirsten Mueller-Vahl (MuellerVahl, Kolbe et al., 1999).
The media usually supported facilitation of cannabis research and legal changes with headlines such as “Beneficent Herb” (Boecker, 1999). Skepticism and warnings were mainly expressed in medical journals, indicating a reserved attitude by many health care professionals (Keup, 1998; Rommelspacher, 2000). There were also some articles that differentiated between the ‘good’ dronabinol or cannabis preparations standardized on THC and the ‘bad’ crude drug (Vetter, 1999; Flenker & Moeller, 2001a).
The divided opinion about cannabis among German medical professionals was manifested by two articles in the Journal of the German Medical Association (Deutsches Aerzteblatt) in 2000. One stated that prohibition was a “collective wrong way” since harms were “subtle, infrequent and transient” (Nedelmann, 2000, p. 2833, p. 2837); the other, published three months later, stated that cannabis has little medical value but a considerable potential for serious side effects such as cancer, decreased lung function, infertility, decreased cognitive function, and dependency (Rommelspacher, 2000).
Radio and television broadcasts usually criticize the current legal situation and show sympathy for patients who are being threatened by criminal procedures. On December 14, 1999, the issue was featured for the first time in the report of a complaint brought before the Federal Constitutional Court by eight patients with severe chronic illnesses who were demanding legal access to cannabis.
Legal Actions
Until this time, no prosecuted patient who had taken cannabis medicinally has ever been acquitted by a German court, although first offenders had a good chance that the prosecuting attorney would refrain from prosecution because of “low guiltiness” if the confiscated amount of cannabis was low. Several patients received large fines or were sentenced to prison in cases involving large amounts of marijuana. The Narcotics Law states that the district attorney “can refrain from prosecution if the guiltiness of the committer is low, if there is no public interest in prosecution and the committer cultivates, produces, imports, exports, transits, purchases, obtains in other ways, or possesses narcotics only in low amounts for personal use” (Betaeubungsmittelgesetz, 1981/2000, § 31a).
In 1994, the Federal Constitutional Court summoned the states of Germany to find a common definition of this “low amount” (Bundesverfassungsgericht, 1994). At that time, the low amount definition in different states still varied between about 3 and 30 grams. During recent years the legal authorities have developed an increasing sensitivity towards the medical use of cannabis. Patients have received lower penalties than recreational users and low guiltiness was often assumed even if the low amount had been exceeded somewhat. There have been some suggestions that “low guiltiness” should generally be assumed with medical use of cannabis and that the corresponding paragraph in the Narcotics Law should be rewritten.
Many German lawyers regard the denial of legal access to cannabis by patients with severe diseases as unjust. Juergen Schwabe, professor of law at the University of Hamburg, stated in the Juristenzeitung (German Lawyer’s Journal): “Even if the general public interest justifies governmental restrictions, exemptions are certainly mandated in cases where this interest is irrelevant or where it is far outweighed by benefits to an individual, otherwise subject to such restrictions. It is a scandal that, according to press reports, even cancer and AIDS patients are denied an exemption for cannabis treatment, even though this would clearly alleviate their suffering. It is inexplicable that, so far, no one has yet promptly and forcibly brought any legal action against such evident unlawfulness” (Schwabe, 1998).
On December 14, 1999, eight clients of Lorenz Böllinger, professor of law at the University of Bremen, and Robert Wenzel, attorney in Hamburg, submitted a complaint to the Federal Constitutional Court against the prohibition of cannabis for people with severe diseases. The patients in the case suffered from multiple sclerosis, HIV infection, hepatitis C, migraine, Tourette’s syndrome, and epilepsy. On January 20, 2000, the court decided on formal grounds not to accept the complaint. The judges argued that the patients should have tried other legal means before applications to the Federal Institute for Drugs and Medical Devices and before the provincial high courts for “preventive legal protection” against prosecution and investigations by the police.
The Narcotics Act allows the use of cannabis only for “scientific and other purposes of public interest,” and the Federal Constitutional Court ascertained: “The medical supply of the population is a public purpose that may justify an approval in individual cases” (Bundesverfassungsgericht, 2000). Thus, a corresponding application would “not be hopeless from the start.”
About 150 patients applied for an exemption from the general prohibition at the Federal Institute for Drugs and Medical Devices, but all of these applications were quickly rejected. With support of the ACM, some of these patients sued for such approval before the administrative courts.
According to the expert opinion of a senior public prosecutor, the medical use of cannabis may be allowed in Germany. Hans-Harald Koerner, head of the Center for the Combat against Narcotics Criminality at the Chief State Council of Hessen in Frankfurt, investigated the constitutionality of cannabis prohibition for medicinal purposes and the question whether the distribution of cannabis to patients is in accordance with the international treaties on narcotics (Koerner, 2000). He proposed models of how to supply individuals suffering from severe diseases with cannabis, among them the distribution by local health authorities or by municipal hospitals.
In summer 2001, another group of patients petitioned the administrative courts to sanction health insurance policies that deny reimbursement of treatment with dronabinol. Dronabinol/Marinol is rather expensive in Germany, and the health insurance companies usually only pay for the two indications for which Marinol is approved in the U.S.: nausea and vomiting caused by cancer chemotherapy and anorexia and cachexia in HIV/AIDS. Five milligrams of THC/Dronabinol costs about $25 in the form of a Marinol capsule imported from the U.S., about $6 as a dronabinol capsule by THC Pharm, and 40 cents as 0.1 gram of crude marijuana of medium quality containing 5 mg THC.
It is assumed that the position of the health insurance providers will be similar with regard to a standardized cannabis extract as it is towards dronabinol. This extract is to be introduced by the federal government within about one year. The outcome of the patients’ actions in seeking reimbursement for dronabinol will be influential on the health insurance companies’ future dealings with natural cannabis preparations.
Political Developments
In 1995, the Federal Government had to answer a parliamentary interpellation of Barbara Hoell, a member of the German Bundestag (first and representational chamber of parliament) and the Socialist Party (PDS) regarding the medical use of cannabis. The Federal Institute for Drugs and Medical Devices was asked to prepare a confidential expert opinion on the subject. In November 1995, the authority presented its expert opinion to the Federal Health Ministry, stating that “an uncritical euphoria with regard to the therapeutic potential of cannabis and THC lacks a basis as much as does their general rejection based on the assertion that there are superior therapeutic alternatives in every area” (Goedecke & Karkos, 1996, p. 208). In 1996, the expert opinion was published in the official journal of the federal health institutes (Goedecke & Karkos).
In its written response to the parliamentary interpellation of December 5, 1995, the government said:
Accordingly, the medical use of cannabis and cannabinoids is conceivable for treatment of nausea and vomiting in a therapy with cytostatic agents, to increase appetite in the therapy of AIDS patients, for the treatment of muscle spasms in spinal cord injury, for the lowering of intraocular pressure in glaucoma patients, and as an analgesic.
The therapeutic effects in these indications are primarily based on the main psychoactive constituent of cannabis, delta-9-THC. Thus, for the achievement of a therapeutic effect it is not necessary to smoke cannabis or marijuana. Rather, the question is whether in addition to already approved drugs for a certain indication the use of a drug containing THC and standardized to its content is required.
It was stated that “individual uncounted inquiries of citizens on the possibilities of a medical use of cannabis and cannabinoids” were received by the Health Ministry. These inquiries had been “dismissed due to the legal situation.” In January 1996, the responsible expert committee on narcotics recommended the change of the narcotics law to make THC available on prescription, and this finally took place in 1998.
In April 1997, the Association for Cannabis as Medicine (ACM) was founded by physicians, patients, and others interested in the medical use of cannabis. Participants were from Austria, Switzerland, and Germany, initiating several activities to improve the legal situation of patients who profit from cannabis products, to inform the public and health care professionals about the pharmacology and toxicology of cannabis and the cannabinoids, and to increase the available knowledge of cannabis effects by supporting research and collecting experiences of patients. The ACM is an important contact for patients who are using cannabis, for physicians and medical associations, for journalists, and for politicians. In March 2000, the International Association for Cannabis as Medicine (IACM), a scientific society, was founded, mainly by members of the ACM; the German and the Austrian ACM were the first regional sections of the IACM. The electronic newsletter of the ACM, later followed by the IACM-Bulletin, has become an important information source on the subject (IACM-Bulletin, 1997-2001).
At the congress, “Medical Marijuana,” held in Frankfurt in December 1998, the following Frankfurt Resolution was passed:
In the belief that all available humane medical means ought to be utilized for the cure of the ill and the alleviation of their suffering we request that the German Parliament: (1) Allow the medical use of marijuana, (2) permit the smoking of natural marijuana for therapeutic purposes, (3) provide fiscal support to scientific research of the medical uses of marijuana.
Among the first to sign the resolution were well-known actors and other artists, journalists and other persons from the media, university professors and scientists, and politicians from the Social Democratic Party (SPD), the Socialist Party (PDS), and the Greens. The resolution was prepared by the metropolitan AIDS support centers in Cologne, Frankfurt/Main, Duesseldorf, and Munich, by the Hessian Society for Democracy and Ecology, and by the ACM.
In March 1999, 11,000 signatures in support of the Frankfurt Resolution were handed over to the Federal Drugs Commissioner, Christa Nickels (member of Parliament representing the Greens). It was also signed by the German Association for Epilepsy, the German Society for Algesiology, the German Society for Addiction Medicine, the German Working Group for Therapists of the HIV Infected (DAGNAE), the Federal Union for Poliomyelitis and the Schmerztherapeutisches Kolloquium (STK, Society of Pain Therapists). Nickels showed much sympathy for a legal access to cannabis for patients and said that she wants to ask the ‘Deutscher Arzneimittelkodex’ (DAC, German Pharmaceutical Codex) to develop a formula for a natural cannabis preparation in cooperation with the ACM, so that pharmacists can prepare medicaments from cannabis.
In March 2000, a discussion among experts on legal aspects of the medical use of cannabis and THC took place in Berlin on invitation of the Working Group on Health of the parliamentary parties of the Social Democrats (SPD) and the Greens, the two governmental parties. Representatives of both governmental parties made it clear that they take the topic of cannabis as medicine seriously and they want to make cannabis available on prescription. At the same time, they oppose the idea of exempting individual patients from cannabis prohibition with regard to personal use of cannabis or cultivation of cannabis, as is found in Canada or several states of the U.S.A.
In April 2000, the German company THC Pharm received the approval to make THC (dronabinol) available to pharmacies. Pharmacists are allowed to prepare tinctures or capsules from this dronabinol, which, while much cheaper than Marinol, is still very expensive.
In June 2000, the Petition Committee of the German Bundestag, consisting of 29 members of the parliament, supported the petition of the Self-Help Group Cannabis as Medicine in Berlin and the ACM to allow a medical use of cannabis (German Bundestag, 2001). In July, the German Bundestag followed the recommendation of the Petition Committee and referred it to the Federal Government “for consideration.”
In September 2000, the Federal Drug Commissioner informed the President of the Bundestag that the Health Ministry “advocates the use of medicines based on cannabis” but opposes the use of hashish and marijuana since they do not “fulfill the requirements of the Pharmaceuticals Law” (Nickels, 2000).
In February 2001, in the daily Physician’s Journal (Aerzte Zeitung, 2001), the President of the Berlin Medical Association, Guenter Jonitz, called for a general legalization of cannabis. The International Association for Cannabis as Medicine held its first international congress in Berlin in October 2001 in cooperation with the Medical Association of Berlin and the Charité medical faculty of the Humboldt University of Berlin (IACM, 2001).
The official position of the German Medical Association was presented in an article by Ingo Flenker, President of the Medical Association of Westphalia and Chairman of the Committee for Addiction and Addictive Drugs of the German Medical Association, and Horst Moeller, official of the Narcotics Department of the Federal Health Ministry, in the German Medical Journal (Flenker & Moeller, 2001a, p. 1105) and the German Pharmacists Journal (Flenker & Moeller, 2001b, p. 47):
Supplying the general population with cannabis medicines is only possible properly, if the legal pharmaceutical regulations are observed…. So far, this has been the case for the active cannabis agents nabilone and dronabinol, based upon clinical tests. Naturally occurring mixtures (e.g., cannabis extract) could also be included in Annex III if the necessary presuppositions are fulfilled. With hashish, marijuana, and other illegal hemp preparations, this is not the case. Thus, neither their content of active agents nor kind and extent of harmful additives (solvents, heavy metals, insecticides, etc.) are known…. The provision of a standardized cannabis extract is currently being prepared by the ‘Deutscher Arzneimittelkodex’ in cooperation with various companies. Such extract is expected to be available before long. In this context the listing of a cannabis extract in the Annex III of the Narcotics Act will be prepared.
Critics have pointed out that unknown THC content and possible contamination are consequences of the current system of prohibition and thus are weak arguments in support of continuing prohibition of the medical use of cannabis (Grotenhermen, 2002).
Summary
The request for legal access to cannabis products for medicinal purposes has gained increasing support in recent years, resulting in growing attention by the media, in several political activities, in legal actions, and in the formation of groups that advocate the improvement of the legal situation for patients who benefit from cannabinoids. Clinical research into the therapeutic potential of THC and a cannabis extract is being conducted at the Medical School of Hannover with patients suffering from Tourette’s Syndrome and at several centers in the Netherlands, Switzerland, the UK, and Germany. This research was initiated by the Institute for Oncological and Immunological Research in Berlin with patients suffering from cancer, multiple sclerosis and pain. The studies by the Berlin Institute seek pharmaceutical approval of a standardized oral cannabis extract.
The availability of medical cannabis products has improved. Since 1998 dronabinol (THC) has been available on a narcotics prescription, and a move by the federal legislator to make a natural cannabis extract legally available is expected in 2002 or 2003. It is unknown when the clinical research conducted by the Institute for Oncological and Immunological Research will result in a pharmaceutically approved cannabis preparation. Dronabinol is at least ten times more expensive than illegal marijuana, and since the health insurance providers do not reimburse the costs for many of the patients seeking treatment with cannabinoids, the use of illegal crude cannabis products provides a more economical option. It is unclear whether this situation will change fundamentally with the availability of a cannabis extract on a narcotics prescription. Physicians avoid prescribing a medicament on this special prescription, especially when it is expensive and health insurance companies are not willing to provide reimbursement for the treatment.
There are several legal strategies aimed at attaining an exemption from the general prohibition against cannabis for patients and to getting treatment with dronabinol and later natural cannabis paid for by the health insurance providers, among them a complaint before the Federal Constitutional Court. The media have generally shown sympathy for patients who are threatened by criminal sanctions. The discussion of these issues within the medical profession is comparatively recent. There is much divisiveness, and sometimes the discussion is confounded with the debate on recreational use. Judges often show sympathy and administer low penalties, although no patient charged with using cannabis illegally has ever been acquitted.
The discussion has reached the political agenda with much support from the Petition Committee of the German Bundestag and several politicians. The federal government opposes both an exemption from the general prohibition and the medical use of the crude drug. In agreement with the German Medical Association, it favors the development of a monograph on cannabis, and one is currently being prepared by the Deutscher Arzneimittelkodex that allows pharmacists to prepare cannabisbased medicines.
Further developments will depend on whether the legal access to a cannabis extract advocated by the Federal Government will be regarded as a sufficient supply by patients, physicians, politicians, lawyers and others involved in the debate.