Cannabinoids are natural compounds found in the cannabis plant that have been extensively studied for their beneficial effects on health and well-being. In this comprehensive guide, we will explore the world of cannabinoids and their derivatives, providing detailed information on each of them.
From Discovery to Scientific Studies on CBD
Cannabinoids have very ancient origins and are intertwined with the history of medicine itself. The first record of their use dates back to China, where Emperor Shen Nung, in 2737 BC, wrote a pharmacology treatise that mentioned Ma — the Chinese term for cannabis — as a remedy for various ailments.
For centuries, the properties of this plant were exploited without understanding its chemical complexity. It was only in 1940 that cannabidiol (CBD) was isolated, marking the beginning of a new scientific chapter. Since then, the study of cannabinoids has revealed their central role in the human body, paving the way for multiple therapeutic applications.
What Are Cannabinoids: Definition, Origin, and Derivatives
Cannabinoids are natural chemical compounds found in the Cannabis sativa L. plant, isolated from the female flowers and studied for their effects on the endocannabinoid system, which is involved in functions such as inflammation, pain, and immunity.
In the Cannabis sativa L. plant, cannabinoids predominantly exist in acidic forms — such as CBGA (cannabigerolic acid) and CBDA (cannabidiolic acid) — which are the natural precursors present in the female flowers. During maturation, plant enzymes drive the biosynthesis process, converting CBGA into THCA, CBDA, and CBCA, making it the “mother” of the biosynthetic pathways of the main cannabinoids.
Subsequently, upon exposure to heat or light, these acidic forms lose a carboxyl group (decarboxylation) and convert into their active neutral counterparts: for example, CBDA becomes CBD and CBGA becomes CBG. The latter, often present in low concentrations, can emerge in selected strains, while CBD becomes one of the most abundant phytocannabinoids due to its non-psychoactive role and its modulation of inflammation, pain, and immune function.
This complex biochemical process ensures that the plant initially produces inert precursors that can later be transformed into active molecules studied for their therapeutic potential.
Difference Between Phytocannabinoids and Endocannabinoids
· Phytocannabinoids, such as CBD and CBG, are compounds naturally produced by Cannabis sativa L,
· Endocannabinoids, on the other hand, are cannabinoids naturally produced by the human body.
These two families of molecules share a remarkable structural similarity, which allows phytocannabinoids to interact with the receptors of our endocannabinoid system, a complex biological network that plays a crucial role in maintaining the body’s internal balance.
Endocannabinoids are produced on demand in response to specific stimuli and participate in regulating numerous vital functions, including mood, appetite, sleep, and inflammatory response.
It is precisely this affinity between plant-derived molecules and endogenous molecules that explains the growing scientific interest in phytocannabinoids and their therapeutic potential. Without giving too much away, it is enough to know that the interaction between cannabinoids and the endocannabinoid system represents a fascinating example of dialogue between the plant world and human physiology, which remains the subject of extensive research today.
Types of Cannabinoids and Their Functions
Cannabinoids represent a highly diverse family of chemical compounds with different characteristics and potential effects. Beyond the best-known ones like THC and CBD, there are many other cannabinoids attracting research interest due to their unique properties.
Cannabichromene (CBC)
Cannabichromene (CBC) is a cannabinoid found in the cannabis plant. It occurs in varying concentrations across different cannabis strains but is present only in trace amounts in CBD oil. CBC binds to the CB1 and CB2 receptors of the endocannabinoid system but does not have psychoactive effects.
CBC has been studied for its anti-inflammatory and analgesic effects, and it appears to have a preferential absorption compared to CBD and THC (tetrahydrocannabinol) when administered together. Additionally, CBC has been shown to act as an antidepressant and anxiolytic and may have benefits for mental health. It could also possess antitumor properties, as studies have demonstrated its ability to inhibit the growth of certain cancer cells. However, many of these findings involve the synergistic administration of CBC, THC, and CBD, so further research is needed to confirm these effects.
Cannabinol (CBN)
Cannabinol (CBN) develops through the non-enzymatic oxidation of tetrahydrocannabinol, or THC. This simply means that CBN is formed as a result of the natural degradation of THC, the psychoactive compound in cannabis. CBN is found in varying concentrations across different cannabis strains but is present only in trace amounts in CBD oil. CBN binds to the CB1 and CB2 receptors of the endocannabinoid system but has very weak psychoactive effects. CBN has been studied for its sedative and analgesic properties and appears to offer benefits in managing chronic pain and insomnia. It is particularly noted for its effectiveness in regulating the sleep-wake cycle, although further research is needed. Additionally, CBN has been shown to act as an anti-inflammatory and anticonvulsant and may offer mental health benefits.
CBN may also have antibacterial and antifungal properties, as it has been shown to inhibit the growth of certain microorganisms. However, further studies are required to confirm these effects.
Cannabidivarin (CBDV)
Cannabidivarin (CBDV) is a non-psychoactive cannabinoid found in varying concentrations across different cannabis strains, particularly those with low THC content, such as hemp. CBDV does not have a strong affinity for the CB1 or CB2 cannabinoid receptors, which is why it does not produce the psychotropic effects typically associated with cannabis.
CBDV has been studied for its anticonvulsant and antipsychotic properties and appears to have beneficial effects in managing epilepsy and schizophrenia. Additionally, it has been shown to act as an anti-inflammatory and antinausea agent and may offer mental health benefits.
Cannabidiolic Acid (CBDA)
Cannabidiolic acid (CBDA) is a precursor to the much better-known cannabidiol (CBD), and it forms during the growth of the cannabis plant. CBDA originates from cannabigerolic acid (CBGA), which is the source of the active compounds found in cannabis. CBDA is present in varying concentrations across different cannabis strains but appears only in small traces in CBD oil.
CBDA does not interact directly with the CB1 and CB2 receptors of the endocannabinoid system; it inhibits the enzyme cyclooxygenase-2 (COX-2), which is associated with inflammation. Inhibiting COX-2 interrupts the inflammatory cascade, thereby reducing inflammation and pain.
For this reason, CBDA has been studied for its anti-inflammatory and anti-tumor effects and appears to offer benefits in managing chronic pain and inflammation. Additionally, CBDA has been shown to act as an antinausea and antioxidant agent and may also provide mental health benefits.
Cannabigerolic Acid (CBGA)
Cannabigerolic acid (CBGA) is a precursor of cannabigerol (CBG), which forms during the growth of the cannabis plant. CBGA is produced in the plant’s trichomes and triggers cellular necrosis that facilitates the natural pruning of the plant’s leaves, thereby allowing the plant to maximize the energy directed toward the flower. CBGA is a fundamental compound in the cannabis flower and is at the top of the cascade reaction that produces the three main types of cannabinoids:
· THCA (tetrahydrocannabinolic acid), from which THC (tetrahydrocannabinol) is formed
· CBDA (cannabidiolic acid), from which CBD (cannabidiol) is formed
· CBCA (cannabichromenic acid), from which CBC (cannabichromene) is formed
CBGA can also convert into CBG, but in most strains, CBGA ultimately converts into other cannabinoids such as THC or CBD. CBGA is found in varying concentrations in different cannabis varieties but is present only in trace amounts in CBD oil. CBGA binds to the CB1 and CB2 receptors of the endocannabinoid system but has no psychotropic effects.
CBGA has been studied for its anti-inflammatory and analgesic effects and appears to have beneficial effects in managing chronic pain and inflammation. Furthermore, it has been shown that CBGA acts as an anti-nausea and antioxidant agent and could have beneficial effects on mental health.
How Cannabinoids Act in the Body
As we’ve seen, both phytocannabinoids and endocannabinoids interact with the endocannabinoid system, a complex biological system within the body that plays a key role in maintaining internal balance. But how do cannabinoids act in the body?
Interaction with CB1 and CB2 Receptors
Cannabinoids exert their effects by binding to CB1 and CB2 receptors in the endocannabinoid system, which are membrane proteins linked to intracellular G-protein mechanisms. Specifically:
· CB1 receptors, found in large quantities in the brain (cortex, hippocampus, cerebellum) as well as in peripheral nerve structures, modulate the release of neurotransmitters, influencing memory, pain, mood, and motor coordination.
· CB2 receptors, located mainly in immune system cells and peripheral tissues, regulate inflammation and the immune response.
Physiological Mechanisms of Action
When cannabinoids bind to CB1 and CB2 receptors, they trigger a series of physiological responses that modulate various body systems.
· This is precisely why interaction with CB1 receptors can alter the release of neurotransmitters such as serotonin, dopamine, or glutamate, thereby influencing mood, pain perception, appetite, and the sleep–wake cycle.
· CB2 receptors, on the other hand, are mainly involved in the regulation of inflammation and in the modulation of the immune response. Depending on the type of cannabinoid, its affinity with the receptors, and the individual physiological context, these responses can be stimulated or inhibited. The endocannabinoid system, in fact, acts as a true “balance sensor,” intervening when the organism is under stress or out of balance, in order to restore homeostasis, that is, the internal stability necessary for general well-being.
Metabolism of Cannabinoids and Duration of Effects
As with many cannabinoids, the metabolism and duration of effects depend on various individual factors and the method of administration.
For example, once introduced into the body, CBD is mainly metabolized by the liver, and its presence in the body can vary from a few hours to several days.
The duration of perceivable effects depends on the route of administration: if taken sublingually, the action generally begins within 30 minutes and can last up to 6 hours; in oral form (such as capsules or food), absorption is slower, but the effects can be more prolonged, reaching up to 8 hours or more.
Furthermore, frequency of use, dosage, and individual physiological characteristics significantly influence the speed of elimination of the compound and its perceived effectiveness.
What Are the Potential Benefits of Cannabinoids
Cannabinoids can produce beneficial effects on the body precisely because they act in synergy with the endocannabinoid system. This interaction allows for the natural modulation of numerous physiological functions.
Among the benefits most frequently associated with the use of cannabinoids are:
- possible reduction of chronic pain,
- mitigation of inflammation,
- improvement of mental health,
- potential reduction of cardiovascular risk,
- potential reduction of issues related to diabetes,
- benefits for the skin.
Scientific Studies and Clinical Evidence
In recent years, scientific interest in cannabinoids has grown exponentially, and with it, the number of clinical studies exploring their potential benefits.
CBD, for example, has been the subject of research for its possible positive impact on skin health. A study published in Pharmaceuticals highlighted how CBD can help regulate sebum production and counteract inflammatory skin conditions. It thus appears promising in the treatment of disorders such as acne and dermatitis. But its benefits do not stop at the skin. Another study, conducted in 2022, examined the use of CBD against insomnia: the results showed improvements in sleep quality and duration, particularly among subjects with anxiety or chronic disorders.
Also interesting is the emerging role of CBG, another non-psychoactive phytocannabinoid: a 2022 review examined its potential in the treatment of neurodegenerative diseases, intestinal inflammations, and even metabolic dysfunctions.
And these are just some of the studies conducted in recent years. Although further studies are necessary, the evidence collected so far strongly suggests that cannabinoids can represent a concrete support in various areas of human health.
How to Use Cannabinoids and Their Derivatives
Cannabinoids can be taken in different forms, each suited to specific needs and goals. The chosen method affects both the speed of onset and the duration of the effect. Cannabinoids can be used in the form of:
- CBD oil: CBD oil can be taken orally or applied to the skin to reduce chronic pain, inflammation, and improve skin health.
- Cannabis extracts: Cannabis extracts can be used to prepare teas or to vaporize cannabis to reduce chronic pain and inflammation.
- Creams and ointments: Cannabinoid-based creams and ointments can be applied to the skin to reduce pain and inflammation.
· Capsules: Cannabinoid capsules can be taken orally to reduce chronic pain and improve mental health.
Possible Side Effects of Cannabinoids
Despite the benefits, the use of cannabinoids can also cause some side effects that vary in intensity from person to person.
Among the most common are:
· Dry mouth,
· Drowsiness,
· Nausea,
· dizziness,
· Anxiety.
These disturbances are generally temporary and diminish as the body adapts or the dosage is adjusted. However, prolonged use can lead to more significant effects, such as tolerance, dependence, and difficulties with memory and motor coordination.
For this reason, it is essential to use cannabinoids carefully and preferably under medical supervision, to balance the benefits with the potential risks.
Possible Interactions Between Cannabinoids and Other Medications
Cannabinoids, and in particular CBD, can interact with some common medications and affect their effectiveness or metabolism.
CBD, for example, acts on liver enzymes such as those of the cytochrome P450 system, which are involved in the metabolism of numerous drugs. For this reason, it can alter the response to antibiotics, anti-inflammatories, antiepileptics, psychiatric medications, and anticoagulants.
It should be noted, however, that these possible interactions do not automatically mean that CBD is contraindicated when such therapies are present. It is often possible to adjust the dosage or choose methods of intake that minimize the risk of interference.
Guidelines for Conscious Use
For safe and effective use of cannabinoids, such as CBD, it is essential to adopt a conscious approach.
Each person has unique characteristics that influence the response to these substances, and the reasons for using them can vary significantly. For this reason, it is always advisable to consult a doctor before starting any cannabinoid-based treatment. Only a professional can properly assess the individual situation, suggest the most appropriate dosages, and minimize potential risks.
Legal Cannabinoids in Italy and Regulatory Context
The regulatory history of cannabinoids reflects a complex and constantly evolving path. For a long time, cannabinoids were considered exclusively within the framework of cannabis regulation. Only in recent decades, thanks to advances in research, have many European legislations, including the Italian one, begun to distinguish between medical use and recreational use, and between psychoactive cannabinoids and non-psychoactive cannabinoids, recognizing the therapeutic potential of compounds such as CBD and regulating their production, distribution, and prescription.
This is a regulatory context that remains dynamic and evolving, with increasing attention to safety and quality standards.
Regulation of Cannabinoids in Italy and Europe
The regulation of cannabinoids in Europe and in Italy has undergone significant transformations in recent years.
In Italy, a key milestone is represented by the ministerial decree of 2015, which defined the methods for the prescription, production, and distribution of cannabinoids for medical use, in order to ensure a clear and safe framework for patients and healthcare professionals.
At the European level, regulatory developments have followed the recommendations of the World Health Organization, which has promoted the revision of international classifications, distinguishing CBD from substances with psychoactive effects and facilitating its access for medical use. It should be noted, however, that despite this progress, regulations still differ among the various Member States.
Cannabinoids: Which and How to Choose Them
Cannabinoid-based products are now easily available in physical stores and online shops. However, it is essential to opt for high-quality solutions to ensure safety and effectiveness.
Before purchasing, it is useful to learn how to read labels carefully, as well as to know the certifications and quality controls carried out by the manufacturing company.
It should also be noted that consulting a doctor remains an important step to assess individual suitability for use.
How to Read the Label of a Cannabinoid-Based Product
Another key aspect when choosing a cannabinoid-based product is learning how to correctly read the label. It contains valuable information that helps you understand what you are purchasing and evaluate its effectiveness and safety. In the case of CBD products, it is especially important to check a few key elements, including:
· The type of CBD present (oil, cream, capsules, etc.)
· The full composition and any additional ingredients,
· The presence and percentage of THC, which must comply with legal limits,
· An indication of whether the product has been tested by independent laboratories, ensuring quality and purity.
Relying on certified manufacturers is an essential step to avoid risks and choose high-quality cannabinoids.
FAQ – Answers to the Most Frequently Asked Questions About Cannabinoids
After exploring the main aspects related to cannabinoids, this section answers the most frequently asked questions to clarify doubts and provide practical and reliable information.
Are cannabinoids legal in Italy?
Yes, cannabinoids such as CBD are legal in Italy as long as the THC content is below 0.6%, according to current regulations.
Which cannabinoids do not have psychoactive effect?
CBD, CBG, and CBC are examples of non-psychoactive cannabinoids that do not alter perception or mental state.
What Is the Difference Between Medical, Recreational, and Supplemental Use?
Cannabinoids can be used in very different ways, depending on the goals and methods of use:
· Medical use involves the use of specific cannabinoids, such as CBD or THC, in controlled dosages prescribed by a doctor to treat clinical conditions like chronic pain, epilepsy, or chemotherapy-induced nausea.
· Recreational use refers to the consumption of cannabinoids, often in the form of cannabis or extracts, for psychoactive and leisure effects, without therapeutic purposes. It remains regulated or prohibited in many countries.
· Supplemental use refers to the intake of cannabinoid-based products, such as dietary supplements, intended to support everyday well-being, for example to improve relaxation or sleep, without replacing medical treatments.
Can I Take Cannabinoids If I’m on Other Medications?
CBD can interact with certain medications, but it does not necessarily need to be avoided; it is important to evaluate each case individually.
Are Cannabinoids Suitable for Animals?
Yes, cannabinoids can also be used for animals, but always with specific products and under veterinary advice.
Where Can I Buy Certified Cannabinoids?
Eusphera offers various CBD-based products (such as CBD oils, CBD creams, and supplements), listing all ingredients. Additionally, the company holds all legally required certifications, and the products are tested in independent and accredited laboratories.
What Certifications Must Cannabinoids Have to Be Considered Safe?
When purchasing cannabinoid-based products, especially online, it is essential to ensure that the manufacturing company holds the necessary quality certifications.
Among the most important are ISO certifications, which attest to compliance with international standards concerning quality management, food safety, and production processes. These certifications ensure that the product has been made under strict controls, guaranteeing purity, safety, and transparency.
