Cannabidiol (CBD), commonly abbreviated as CBD, is a phytocannabinoid derived from Cannabis sativa and, in contrast to Δ-9-tetrahydrocannabinol (THC), it is non-psychotropic. CBD exhibits diverse properties, including neuroprotective, cardioprotective, and anti-inflammatory effects [1]. Currently, CBD products are utilized without regulatory approval, relying on perceived health benefits, although scientific evidence supporting these claims often lacks controlled clinical trials. The recognition of CBD’s ability to influence numerous biological targets forms the basis of these assertions. Notably, Epidiolex^® is the sole product subjected to rigorous pharmacokinetic evaluation and clinical studies, receiving FDA approval as an over-the-counter drug for treating infantile-onset intractable seizures [1].

In this context, THC emerges as the primary psychoactive component of cannabis, responsible for the classic feeling of “high” or “euphoria”. Conversely, a substantial body of literature discusses CBD’s medical potential, particularly in addressing anxiolytic and antiepileptic effects. Popular sentiments also suggest additional therapeutic benefits, such as mitigating adverse side effects of THC, including intoxications, psychomotor dysfunctions, and psychotic manifestations [2].

Furthermore, the two main cannabinoid receptors, cannabinoid 1 (CB1) and cannabinoid 2 (CB2), are inhibitory G protein-coupled receptors consisting of a polypeptide chain with seven transmembrane segments that traverse the bilayer cell membrane lipid. CB1 receptors are predominantly found not only in the central nervous system [3] but also in various tissues, including the heart, lungs, intestines, kidneys, and liver [4]. On the other hand, CB2 receptors are localized in cells of the immune system [5], the gastrointestinal tract [6], and minimally in the central nervous system [7]. Specifically, CB2 receptors are identified in a particular type of the microglial cell in the human cerebellum, as confirmed by immunohistochemical analyses on tissue sections from the cerebellum’s white matter areas, demonstrating their presence in perivascular microglial cells [5].

THC functions as a partial agonist for both CBD receptors, while CBD inhibits metabolic enhancement by impeding the oxidation of THC to 11-OH THC. Acting as an inverse agonist of CB1, CBD limits its action. Additionally, CBD has the capacity to bind to CB2 as a low-affinity agonist and other non-cannabinoid receptors [8].

It is well established that THC primarily induces pharmacological effects such as analgesia, muscle relaxation, nausea reduction, appetite stimulation, and psychoactivity. In contrast, CBD has been demonstrated to possess neuroprotective, anticonvulsant, antipsychotic, muscle relaxant, anxiolytic, and antioxidant activities. Moreover, CBD diminishes both anxiety and the psychoactive effects of THC [9].

Preliminary pharmacological and behavioural activity tests affirm the similarity between endogenous anandamide, CB, and THC, all acting as partial agonists of the CB1 receptor. Conversely, CBD exhibits weak binding to CB1 and CB2 [9, 10]. However, CBD is portrayed as a neutral receptor antagonist, signifying its lack of direct activity on these receptors but its ability to reverse both agonist and inverse responses.

Moreover, CBD has demonstrated robust anti-inflammatory, immunomodulatory, and antioxidant properties in vitro [11]. Consequently, the therapeutic implications of CBD are multifaceted. Numerous studies detail its impact on neurological disorders, including Parkinson’s disease, Lennox-Gastaut syndrome, Huntington’s disease, and various forms of epilepsy [12, 13]. Research also extensively explores the effects of CBD on pain [14], inflammation [15], and the immune system [16].

In a noteworthy study, Palmieri et al. investigated the therapeutic effects of a CBD ointment administered on severe chronic skin diseases or resulting scars. The topical application of the CBD-enriched ointment significantly improved skin parameters, symptoms, and scores on specific questionnaires. Importantly, no irritant or allergic reactions were recorded during the treatment period. Consequently, the topical use of an ointment containing only CBD (without THC) has emerged as a safe and non-invasive alternative to enhance the quality of life for patients suffering from skin problems, particularly those associated with inflammation [17, 18].

In the context of dermatology, atopic dermatitis (or atopic eczema) stands out as a significant chronic inflammatory skin disease characterized by itching and skin manifestations, including erythema, desquamation, lichenification, and papulo-vesicular eruption. In some cases, it may be associated with asthma or allergic oculorhinitis. This condition predominantly affects children, adolescents, or adults and has multifactorial origins encompassing genetic, environmental, immunological, and psychological factors. Diagnosis primarily relies on clinical observations. Several reports have elucidated the involvement of T lymphocytes in the pathogenesis of atopic dermatitis [19].

For the treatment of mild forms, topical cortisone drugs and immunomodulatory topical drugs such as tacrolimus and pimecrolimus are commonly employed. Phototherapy is an option for extensive lesions, and antihistamines are widely used to control itching. In severe cases, systemic steroids and other immunosuppressants such as cyclosporine are utilized [20]. Recent therapeutic developments include monoclonal antibody-based therapies targeting interleukins pivotal in inflammation, such as dupilumab (anti IL-4 receptor α), tralokinumab (anti IL-13), or, in more resistant forms, Janus kinase inhibitors like baricitinib and upadacitinib.

Furthermore, CBD containing ointments represents a potential treatment option for atopic dermatitis. The increasing legalization of cannabis in numerous countries has opened up new research opportunities to explore the use of cannabinoids in topical formulations for therapeutic purposes.

Humans possess an endocannabinoid system that plays a pivotal role in regulating various physiological processes, encompassing the natural production of endocannabinoids and the proteins involved in their transport, synthesis, and degradation. The discovery of an endocannabinoid system in the skin, coupled with cannabinoids’ anti-inflammatory properties, has sparked interest in their application for treating inflammatory skin diseases [18].

Data compiled in the literature suggest that CBD functions as an immunomodulator, directly suppressing the activation of immune cells such as monocytes, macrophages, neutrophil granulocytes, dendritic cells, and T cells, inducing apoptosis, down-regulation, and promoting regulatory T cells instead [21]. Consequently, there is a significant suppression of production of inflammatory cytokines, including TNF-α, IFN-γ, IL-6, IL-1β, IL-2, IL-17A, and chemokines such as CCL-2.