THE HISTORY OF CANNABIS IN MEDICINE

With the entry into force of the “Cannabis as Medicine” Act on 10 March 2017, the possibilities for prescribing cannabis medicines were expanded. This means that medicinal cannabis flowers have become reimbursable by the statutory health insurance funds under certain preconditions.[1] Medical cannabis has since then increasingly become the focus of public interest. How can patients benefit from cannabis-based medicines for various diseases? How and where can one get a prescription? What advice should one follow? This article provides answers to these and other questions and offers an up-to-date overview.

A historical review of the therapeutic use of the cannabis plant

The positive properties of cannabis plants have been known for a long time. For thousands of years, people have used stems, leaves or flowers to make not only ropes, clothes, shoes, paper but also food and medicine. The medicinal properties of cannabis were already known at least 2500 years ago, as a study by a team of Chinese scientists led by Hongen Jiang proves. They examined burial sites in Central Asia in which remains of hemp stalks and leaves were found among household objects.

The history of the widespread use of cannabis as a remedy began even before our era. This is confirmed by numerous historical sources:

• The Chinese emperor Fu Hsi mentioned medical cannabis in his records around 2900 BC.
• According to folk legend, the father of Chinese medicine, Shen Nung, found real evidence of the healing properties of cannabis around 2700 BC.
• The first descriptions of the use of cannabis in the treatment of glaucoma and inflammation date back to 1213 BC, when traces of this plant were found in the burial chamber of Ramses II.
• A specific anesthetic drink called bhang, which consisted of hemp and milk, was already produced in India around 1000 BC.
• Similarly, the ancient Greeks also used cannabis in around 200 BC, as a narcotic and anti-inflammatory substance.
• The works of the Roman historian Pliny the Elder mention the healing properties of boiled hemp roots against pain, cramps and gout.
• In the Middle Ages, cannabis-based medicines became widespread in Europe, North America and Great Britain.

In the second half of the 20th century, cannabis began gaining an ambivalent reputation. Some experts saw the plant as a promising drug for innovative therapeutic treatments. For others, cannabis was seen as a dangerous drug that promoted aggression, a propensity for violence and ultimately crime rates, while at the same time impairing people’s cognitive abilities. Views like these were widespread, although meaningful evidence was lacking.

For an objective and well-founded assessment of the effect of cannabis on the human body, findings and evidence from proper scientific research are important.

Medical cannabis: insight into the biological mechanism of action

Throughout history, scientists have gradually unravelled the importance and potential of cannabis in medicine. Among the most groundbreaking is the discovery of the so-called endocannabinoid system, which provided the first important evidence on the mechanism of action of cannabis in the human body.

The origins of endocannabinoid research date back to 1942, when the American scientist Roger Adams identified the first cannabinoid, cannabidiol (CBD). A few years later, in 1964, a team of Israeli researchers led by Raphael Mechoulam discovered what is now probably the best-known cannabinoid, tetrahydrocannabinol (THC). The fundamental difference between these two substances is the euphoric effect: while tetrahydrocannabinol has a psychotropic effect, cannabidiol is not psychoactive. At the time, no medical value was attached to these discoveries by experts. It was not until 1990 that Raphael Mechoulam, together with other researchers, confirmed that the human body itself produces substances similar to the plant cannabinoids. These so-called endocannabinoids belong to the body’s neurotransmitters, the messenger substances of our nervous system.

This discovery was decisive for defining the endocannabinoid system (ECS). The ECS has since been described as a signaling system that is crucially involved in the control of numerous physiological functions of the human body: in particular, the regulation of the nervous and immune systems, energy metabolism, reproduction, growth and differentiation of cells. The ECS consists of three main components: the cannabinoid receptors CB1 and CB2, endogenous cannabinoids and enzymes responsible for their synthesis and degradation.

Overall, numerous scientific studies provide results that show that the endocannabinoid system plays a decisive role in human body functions. The decisive factor here is the realization that the human body is naturally equipped with this system. This is exploited when taking products with synthetic or herbal cannabinoids, as these can bind onto the receptors in this system. These externally supplied cannabinoids are recognized by the body’s own structures and can trigger various reactions through their interaction with the CB1 and CB2 receptors.

Possible applications for medical cannabis

Medical cannabis is being studied in depth by many research groups around the world. Scientists from the USA, the Netherlands, Israel and other countries have succeeded in showing the effectiveness of cannabis-based medicines for various diseases.

Germany is also collecting information on the use and application for different diseases or symptoms through the so-called companion survey.

Important distinctions between different cannabis varieties

The distinction between medical cannabis and so-called industrial or commercial hemp is primarily based on the tetrahydrocannabinol (THC) content. The latter is characterized by a THC content of less than 0.2%. In contrast to THC, the cannabinoid CBD does not have any psychoactive effect, so no maximum limits are set here for industrial hemp.

Side effects and habituation

On the package inserts of cannabis-based preparations, reference is often made to the addictive potential as a possible side effect.

The most common side effects so far include reduced concentration and increased fatigue. Mood swings, muscle weakness, dry mouth, rapid heartbeat and increased appetite are also considered likely. No scientific study has yet shown that cannabis can cause life-threatening complications.

It is known that a habituation effect can often be observed with long-term use of cannabis, regardless of frequency and dosage. This should definitely be taken into account in cannabis-based

therapies in order to maintain therapeutic success in the patient. Due to this habituation effect, a dose adjustment in the sense of a moderate increase might become necessary.

Summary: Key effects of medical cannabis

The use of medicinal cannabis can have a wide range of effects, especially for certain diseases. Information can be found in the companion survey, which precisely examines these effects.

Medical cannabis in Germany: prescription rules

In the past, to receive a medical cannabis therapy, a narcotics licence had to be applied for at the Federal Opium Agency in order to be able to buy cannabis in the pharmacy as a patient in the context of a doctor-assisted therapy. This was changed by the passing of a corresponding law in 2017: since then, all licensed physicians in Germany are entitled to prescribe cannabis-based medicines to patients as primary or secondary treatment. However, the prescription requires an extensive medical history and detailed examination of the patient’s health condition and treatment prognosis. Dentists and veterinarians are not allowed to prescribe cannabis-based medicines.

In the case of the following initial conditions, a prescription of medicinal cannabis by the physician is considered likely:

• the patient is suffering from a serious illness;
• conventional treatment is ineffective or has unacceptable side effects;
• if there is a prospect that a cannabis-containing medicine could have a positive influence on the course of the disease.

After considering all the information about the disease and the patient’s condition, the doctor may issue a prescription. The costs of the treatment are covered by the health insurance under certain conditions. For this purpose, it is necessary to obtain detailed information from the health insurance company before the initial authorization and to submit a corresponding application for cost coverage.

It is important to understand that when prescribing medical cannabis, the doctor must take many factors into account and, above all, weigh the potential benefits of taking it against the possible risks and side effects.

Forms of cannabis as medicine available in Germany

Currently, different dosage forms and active ingredient compositions are offered in pharmacies in Germany. These can be prescribed by the doctor on a narcotic prescription. The following medicines can be used:

• Ready-to-use medicines with nabiximol and nabilone; these are offered as sprays or capsules;
• Medicines containing dronabinol; these are prepared in the pharmacy on the basis of the individual prescription for final delivery to the patient; they are usually prescribed as oil-based drops;
• dried cannabis flowers; these are prepared in simple steps prior to ingestion by the patient and then usually consumed with a vaporiser. By heating in this device; the active ingredients of the cannabis plant are activated. However, the doctor can also specify that the flowers should already be ground in the pharmacy and the patient only takes the amount specified by the doctor at home;
• Cannabis extracts, these are solutions in which the active substances are already activated;

[1] Horlemann, J. (2018). DGS Praxisleitlinien. Abgerufen 10. Juni 2020, von https://dgs-praxisleitlinien.de/cannabis/