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Understanding the Basics of Medical Cannabis

Medical cannabis refers to the use of the cannabis plant, or any of its components, as a therapy to manage certain conditions and their associated symptoms. The cannabis plant contains over 500 chemical compounds, many of which have been shown to act on the endocannabinoid system within the body and so have various medicinal properties.

We take pride in extracting the most efficacious active pharmaceutical ingredients (API’s)
in the cannabis plant and formulating them to provide targeted relief and help advance patient care. our goal is to develop novel cannabis-based products that are currently
lacking in the European market.

Medical cannabis is typically manufactured from the cannabis flower tops, which has the highest concentration of cannabinoids. Unlike recreational cannabis, medicinal cannabis is highly regulated to safeguard patient safety and ensure there is consistency in product formulation. Here at SOMAÍ, all our products are manufactured under the most stringent regulatory requirements and meet the highest standards of reproducibility and accuracy.

What is the story behind medical cannabis?

Cannabis has actually been used for medicinal purposes since ancient times. In fact, the first record of its application in medicine comes from Pen-ts’ao ching, the world’s oldest pharmacopoeia, around 2700 BC.  Although cannabis was illegalised in most countries and its therapeutic use in mainstream medicine ceased in the first half of the 20th century, a renewed global interest in its medicinal applications has been dramatically increasing over the past 20 years following the discovery of the active component tetrahydrocannabinol (THC), as well as naturally occurring cannabinoids and the endocannabinoid system.  This fuelled investigations that demonstrated that cannabis does, in fact, have a direct effect on the body, with over 3,000 cannabis-related scientific articles published in 2021 alone.

All this research has advanced our understanding of the cannabis plant and encouraged the identification of many more active components that have prospective therapeutic effects across a range of conditions.

What are the key components in medical cannabis?

Cannabis contains 545 chemical compounds, including over 100 different cannabinoids.

Clinical evidence has illustrated that many cannabinoids interact with the body’s cannabinoid receptors to influence a range of physiological processes. To-date, the most widely studied cannabinoids have been THC and cannabidiol (CBD) which have very different pharmacological profiles and tremendous therapeutic potential.

THC is a cannabinoid molecule produced by the cannabis plant.  It is the main psychoactive agent, which means it affects a person’s mental state, causing the ‘high’ sensation.  THC works by stimulating cell receptors in the brain called cannabinoid receptors, of which there are two subtypes that have been studied: CB1 and CB2. By acting on these receptors, THC can induce a range of effects associated with reducing chronic pain, anxiety, spasticity, and nausea.

CBD is a non-psychoactive cannabinoid compound, which means it does not alter a person’s mental state or induce a ‘high’ sensation. Whilst CBD’s mode of action is currently less clear, evidence has suggested that it does not directly interact with the endocannabinoid system and acts on a range of other molecular targets.  It has been shown to have several therapeutic effects in epilepsy, inflammation, anxiety, chronic pain and insomnia.

Compounds other than THC and CBD may contribute to the broad beneficial effects of the plant, including minor cannabinoids such as cannabinol (CBN), cannabigerol (CBG) and cannabichromene (CBC).

THCA is the precursor to THC.1 THCA is considered to be non-psychoactive and has been shown to have anti-inflammatory and neuroprotective properties.  It’s also been shown to reduce nausea and vomiting.

CBN is a metabolite of THC.  CBN preferentially binds to cannabinoid CB2 receptors, which are mainly expressed on immune cells. It has been suggested to have immunosuppressive and anti-inflammatory activities.

CBG is a member of the class of resorcinols.
It enhances appetite and has anti-inflammatory, neuroprotective, and antioxidant benefits.

CBC is a non-psychoactive cannabinoid compound that has been shown to have anti-inflammatory, analgesic, and antidepressant-like activity.

Our extensive knowledge of the pharmacological activities and intrinsic medicinal properties of key cannabis-derived compounds means we are adept at blending the most suitable and effective ratios into formulations that:

  • Provide targeted, appropriate therapeutic relief
  • Interact uniquely with each patient’s endocannabinoid system and biochemistry
  • Are substantiated by ongoing clinical trials

What does the medical cannabis landscape look like today?

Over the last couple of decades, there has been a gradual, widespread endorsement of using cannabis for its medicinal properties. In fact, the United Nations (UN) Commission on Narcotic Drugs reclassified cannabis to acknowledge its therapeutic uses in 2020.  Cannabis is increasingly being legalised for medical purposes across Europe and the rest of the world. However, the individual regulations for cannabis-based medical products vary considerably between countries.

Safety of medical cannabis and its side effects

As with all medicines, medical cannabis is not without potential side effects. These vary depending on the person, the type of product and the way in which medical cannabis is used. Side effects are typically mild, well tolerated, and temporary.  Some of the most common side effects include:

Disorientation

Dizziness

Euphoria

Confusion

Drowsiness

Dry mouth

Somnolence
(sleepiness or drowsiness)

It is worth noting that formulations that have a high THC concentration tend to have more psychoactive side effects.  However, since THC and CBD work synergistically, it is understood that CBD can to some extent counteract the side effects associated with THC.  Since the ratios of THC and CBD are carefully prepared for each of our formulations, the side effect profile can vary in patients.

The endocannabinoid system

Over the last twenty-five years, the endocannabinoid system (ECS) has emerged as an important neurotransmitter system within the body.  This complex cell-signalling system plays a key role in regulating homeostasis within the body, and so plays a key role in a range of functions and processes including, but not limited to:

  • Energy balance
  • Appetite stimulation
  • Blood pressure
  • Pain relief
  • Nausea control
  • Learning and memory
  • Immune response
  • Sleep
  • Anxiety and depression
  • Motor control
  • Neuroprotection
  • Liver function
  • Fertility regulation
  • Cardiac function

The ECS is present and is active in your body even if you do not use cannabis.

How does the endocannabinoid system work?

The ECS is made up of three core components:

1 Endocannabinoids, also referred to as endogenous cannabinoids, that are molecules made by your body

2 Cannabinoid
receptors

3 Enzymes that synthesise
and degrade
endocannabinoids

1 Endocannabinoids

Endocannabinoids are chemical messengers that bind to cannabinoid receptors to signal that the ECS needs to take action.  They are similar to cannabinoids, except that they are produced by your body.

There are two key endocannabinoids that have been identified:

  • Anandamide (AEA)
  • 2-arachidonoyglyerol (2-AG)

These chemical messengers keep internal functions running smoothly and are produced by your body as and when they are needed.

2 Cannabinoid receptors

Cannabinoid receptors can be found throughout your body. To-date, two cannabinoid receptors that have been studied: CB1 and CB2. CB1 receptors can be found in abundance in the central and peripheral nervous system, as well as the gastrointestinal tract and skeletal system.  CB2 receptors, on the other hand, are mostly located in the peripheral nervous system, particularly immune cells.  Endocannabinoids can bind to either receptor. The influence that this has depends on where the receptor is located, and which endocannabinoid binds to it.

CB1 receptors influence pain, sleep, appetite, and memory, and mediate most psychoactive effects of cannabinoids.  On the other hand, CB2 receptors are primarily involved in anti-inflammatory and immunosuppressive actions.

 

3 Enzymes

Enzymes are responsible for synthesising and breaking down endocannabinoids once they have carried out their function.

There are two main enzymes that are responsible for the degradation of endocannabinoids:

  • Fatty acid amid hydrolase, which breaks down endocannabinoid AEA
  • Monoacylglycerol lipase, which typically breaks down 2-AG

Cannabinoids and the endocannabinoid system

Cannabinoids, such as THC, fit like a lock and key into the cannabinoid receptors that are present in the body – just like endocannabinoids. Therefore, cannabinoids work by ‘mimicking’ the effects of the human endocannabinoid system.  Given that each receptor serves a distinct function in human health and well-being, specific external cannabinoids can be used to activate this system to achieve a desired therapeutic effect for individual conditions.

We are focused on formulating optimal cannabinoid mixtures that provide targeted therapeutic benefit for individual conditions and associated symptoms.

Cannabis-Based Products for Medicinal Use – An evolving Regulatory Landscape

The regulations for cannabis-containing medicinal products vary considerably between European countries.  Some countries allow the use of medicinal cannabinoids, while others allow the medical use of unauthorised products or preparations. In terms of manufacture and import, some countries allow cannabis product manufacture; others allow import but do not allow manufacture, and some countries allow manufacture and import.

Clearly, there is no common regulatory pathway to European markets, which makes marketing cannabis products across Europe challenging. Ideally, there should be clear and consistent policies and regulations across countries.

In the UK, only clinicians listed on the Specialist Register of the General Medical Council can prescribe cannabis-based products for medicinal use if exceptional clinical needs cannot be met by licensed or off-label medicine.

In Germany, every doctor is permitted to prescribe medical cannabis to those with serious illness.

As of August 2022, three three broad legal frameworks exist among European countries:

  1. Established medical cannabis legislation
    For example the UK, the Netherlands, Poland, Portugal, Greece, Germany, Italy, Switzerland, Czechia, Malta and Luxembourg. In these countries the use of medical cannabis is legally permitted and comes with the usual pharmacovigilance regulations as for other medicinal products, ensuring patient safety measures are implemented. However, the specific access scheme for medicinal cannabis is variable between countries and typically limited to a restricted set of medical conditions.
  2. Supply of specific cannabis products permitted under specific conditions
    This includes countries with ongoing trial periods or pilot schemes investigating the potential benefit/risk of medical cannabis, for example France, Ireland, Denmark, and Finland. Often, the importation and/or use of medical cannabis is allowed at the discretion of physicians, usually for a specific treatment for a named patient.
  3. Medical cannabis is strictly prohibited
    For example countries such as Sweden, Latvia, Belgium, and Albania. It is illegal to use, buy or sell cannabis in these countries, including medical cannabis.

Here at SomaÍ, we have real-world experience on how to navigate the evolving regulatory landscape, staying ahead of the legislative curve to ensure products can successfully be brought to market.

Evolving legislature

There is little consistency across Europe relating to when cannabis-based products may be used for medicinal purposes, and for which conditions. Clinical trials are showing good results in several therapeutic areas, but there are currently only four pharmaceutical cannabis formulations approved in Europe, of which only Epidiolex® (cannabidiol) has received Europe-wide approval for the treatment of Dravet syndrome and Lennox-Gastaut syndrome – rare and severe forms of epilepsy.

Pharmaceutical cannabis formulations currently approved in Europe

Brand name Cannabinoid component Indication European counties approved
Epidiolex® Cannabidiol Lennox-Gastaut syndrome and Dravet syndrome All 27 countries of the EU, alongside Norway, Iceland and Liechtenstein
Sativex® Nabiximols (plant-derived Δ9-THC and CBD at a ratio of 1:1) Spasticity associated with multiple sclerosis 22 countries, including France, Germany, Italy, Poland, Spain, and the UK
Cesamet® Nabilone (Δ9-THC analogue) Nausea and vomiting associated with chemotherapy 11 countries, including Germany, Ireland, Norway, Poland, Spain, and the UK
Marinol® Dronabinol Nausea and appetite loss due to chemotherapy, HIV or AIDS 13 countries, including France, Germany, Poland, Spain, Sweden, and Switzerland

It is a complex market which is growing fast, so there is likely to be rapid parallel evolution in the regulatory environment for medicinal cannabinoid products.

Administration options

To date, a handful of cannabis-based products have been authorised for marketing in Europe, of which the primary routes of administration include:

  • Oral capsules
  • Oral tablets
  • Oral solutions
  • Oromucosal spray
  • Dried cannabis flower
  • Extracts of standardised quality

At SOMAÍ, we are determined to increase accessibility to medical cannabis by providing patients with products formulated in a breadth of delivery systems.

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