Cannabis is an unconventional plant commonly known for its intoxicating effects. Alongside alcohol and tobacco, it represents one of the most widespread addictions worldwide [1]. This substance is derived from the Cannabis sativa plant, belonging to the Cannabaceae family, native to South Asia and Central Asia [2] and, nowadays, extensively cultivated in Africa, Canada, Europe, and the United States [3]. The cannabis plant is rich in phytochemicals, primarily present in resin, within small crystals known as trichomes, located on the surface of the blossoms of mature unfertilized female specimens [4]. Marijuana (MJ) is obtained by drying the leaves and blossoms of the plant, while hashish is produced by drying the resin that accumulates on the leaves. These products are typically smoked, vaporized, or chewed when used as illicit substances; however, they can also be incorporated into pharmaceutical formulations or controlled-dose foods and beverages for therapeutic purposes [5]. The primary compounds found in cannabis are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). The biological effects of phytocannabinoids are facilitated through the G-protein-coupled cannabinoid receptors, CB1 and CB2 [6]. CB1 receptors are predominantly located in the central and peripheral nervous systems and the liver and pancreatic islets [7], while CB2 receptors are more prominently expressed in immune cells [8]. These receptors bind endocannabinoids like anandamide (AEA) and 2-arachidonoylglycerol (2-AG), which play essential roles in regulating various physiological processes, including appetite, pain perception, mood, memory, and inflammation [9]. Regarding exogenous THC, it acts as a partial agonist for CB1 and CB2 receptors, with a higher affinity for the former, which appears responsible for its psychotropic effects [10]. Conversely, CBD exhibits a low affinity for both CB1 and CB2 receptors [11]. CBD is an encouraging cannabinoid, as it has shown promise as a therapeutic agent in preclinical models of central nervous system disorders, including epilepsy, neurodegenerative conditions, schizophrenia, multiple sclerosis, mood disorders, and the central regulation of feeding behavior [12]. Cannabis is the primary illicit substance associated with abuse and dependence development between 12 and 17 years [13,14]. The most common motivations leading adolescents to use the so-called “joint” are the need to connect with peers, self-improvement, and a desire to reduce anxiety related to social contexts [15]. European School Survey Project on Alcohol and Other Drugs (ESPAD) is a repeated cross-sectional multinational survey conducted every four years since 1995, designed to provide nationally representative and comparable data on substance use and other risk behaviors among 16-year-old students in Europe through an anonymous self-administered questionnaire. According to the 2019 ESPAD report [16], the mean lifetime prevalence of cannabis utilization among adolescents in participating nations stands at 16%, demonstrating significant cross-country variation. The nations with the highest cannabis usage rates were Czechia (28%), Italy (27%), and Latvia (26%). Conversely, Nordic countries (the Faroes, Iceland, Norway, and Sweden), Balkan states (Kosovo, North Macedonia, Serbia, Montenegro, and Romania), Cyprus, and Greece all reported rates below 10%. On average, 2.4% of ESPAD students reported initiating cannabis use at age 13 or earlier. Regarding high-risk cannabis use, as indicated by the Cannabis Abuse Screening Test (CAST) results, 4.0% of students across the ESPAD group are susceptible to developing cannabis-related disorders. Notably, the prevalence of cannabis use in the past 12 months was remarkably low in Kosovo, Cyprus, Montenegro, Serbia, and Sweden, despite a higher proportion of users at a high risk of developing cannabis-related issues. Conversely, several countries with the highest rates of past-year use (The Netherlands, Latvia, and Czechia) reported some of the lowest proportions of high-risk users. This implies no direct correlation between cannabis consumption and risky usage. Additional factors, such as the quantities consumed, genetic predispositions, and broader social and cultural determinants, could play a role. These determinants may encompass societal attitudes towards cannabis use, affecting self-assessment of excessive consumption, willingness to discontinue use, recommendations from external sources (e.g., parents or teachers) to cease use, and the emergence of conflicts related to consumption [17,18]. In 2017, the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) assessed cannabis regulations in Europe, with a particular focus on “recreational” use [19]. Within the European Union (EU), there is no standardized legal framework governing cannabis consumption. While the EU has established some regulations regarding cannabis trafficking offences, individual member states continue to hold primary responsibility for legislating against unauthorized cannabis use and minor possession [20]. Additionally, the legal treatment of cannabis varies across countries; some nations place cannabis in a legal category similar to other drugs, while, in others, penalties for cannabis-related activities are comparatively lower, often influenced by the perceived level of harm the substance may cause [21]. In Europe, no national government currently supports legalizing cannabis sales for recreational purposes. Each European country maintains legal provisions [22,23]. Over recent years, numerous legislative proposals have been introduced in various national parliaments, seeking to reform extant cannabis policies. Furthermore, specific regions and municipalities have initiated localized endeavors to decriminalize or regulate cannabis. In 2012, 11 states in the USA and the sovereign nations of Canada and Uruguay passed legislation that legalized the growth, processing, and use of cannabis for adults [24,25]. The relaxation of laws regarding recreational cannabis use in the USA has led to various outcomes, including a significant reduction in the retail cost of cannabis [24]. In some EU member states (e.g., Italy, Germany, Poland, UK, Finland, Norway, Sweden, etc.), allowances are made for medical use of cannabis. Cannabis can be prescribed as a support to conventional therapies when the latter have failed to achieve the intended outcomes, have resulted in intolerable adverse effects, or necessitate dose escalations that may result in side effects. The medical uses of cannabis and specific medications used in clinical practice are outlined in Table 1, although, in most cases, they refer to studies conducted on adults [19]. Delta-9-tetrahydrocannabinol (THC or Δ9-THC), the primary psychotropic compound in cannabis, acts on numerous neurotransmitter pathways, quickly leading to well-being, euphoria, relaxation, sedation, and motor relaxation [26]. However, chronic use is associated with significant short- and long-term side effects, affecting various biological systems and multiple brain areas [27].

Short-term effects include altered perception of time, mood changes, difficulty with thinking and problem-solving, altered senses, impaired movement, short-term memory alterations, and, when taken in high doses, hallucinations, illusions, and psychosis.

One of the primary short-term effects of cannabis consumption is acute intoxication. Per the DSM-5 diagnostic criteria, symptoms should manifest within two hours of cannabis consumption, with no other medical conditions or substance intoxication as the underlying cause. These symptoms include clinically significant problematic behaviors and psychological alterations, such as impaired motor co-ordination, feelings of euphoria, anxiety, a distorted sense of time, compromised critical thinking, and social isolation. These effects tend to arise during or shortly after cannabis use. Additionally, the diagnostic criteria require two or more of the following signs or symptoms within two hours of cannabis use: conjunctival injection, increased appetite, dry mouth (xerostomia), and tachycardia. Notably, a percentage ranging from 2% to 16% of the general population reports experiencing lifetime psychosis-like intoxication effects, such as hallucinations, delusions, or depersonalization. Typically, these effects are of a transient or attenuated nature [37]. Furthermore, several studies have established that simultaneous use of alcohol and marijuana (co-use), prevalent among young adult drinkers, leads to a phenomenon known as “Cross-Fading”, resulting from the combined impact of the two substances on absorption and blood concentration [38]. This cross-fading effect differs from using either substance alone and enhances the sensation of intoxication.

According to the DSM-5, marijuana use is associated with a significant impact on mental disorders, which can be categorized as “Cannabis Use Disorders”, such as abuse and dependence, and “Cannabis-Induced Disorders”, such as acute intoxication, delirium, psychotic disorder with hallucinations or illusions, anxiety disorder, and other unspecified cannabis-related disorders [39]. The most commonly acute symptoms linked to the use of cannabis are anxiety responses, panic attacks, and agoraphobia [40]. It is important to distinguish these from organically rooted psychiatric disorders such as major depression, bipolar disorder, or paranoid schizophrenia. In particular, cannabis use during adolescence has been identified as one of the main modifiable risk factors for anxiety disorders in adulthood [41]. The likelihood of diagnosing anxiety or mood disorders, whether within the last month or over a person’s lifetime, is roughly twofold higher in individuals with cannabis dependency. Thus, subjects with cannabis dependence have a higher comorbidity with anxiety disorders, between 6.9 and 29%, depending on the disorder [40]. While a direct causal connection between cannabis use and the emergence of anxiety remains uncertain, regular cannabis users tend to display a higher occurrence of anxiety disorders. Additionally, individuals with anxiety disorders demonstrate relatively higher levels of cannabis consumption. “Cannabis-induced delusional disorder” is a syndrome that manifests shortly after cannabis use and is sometimes misdiagnosed as schizophrenia. Typical manifestations include persecutory hallucinations, which can be accompanied by depersonalization, emotional lability with panic attacks, and occasional subsequent amnesia [39].

An important aspect of marijuana use on public health is its potential impact on the human mind, particularly in triggering suicidal thoughts. Licanin et al. (2003) [42] discovered that suicidal thoughts were more prevalent among individuals who abused cannabis (50.0%) and those who abused alcohol (36.6%), irrespective of gender or socio-economic status, in comparison to non-abusers. Another study conducted in Bosnia and Herzegovina confirmed this correlation, particularly among those reporting suicidal ideation, where 36.2% were using cannabis [43].

Allergic reactions have been described following exposure to cannabis pollen, marijuana smoke, ingestion of hemp seeds, and direct contact with cannabis plants. Sensitization and allergy to cannabis can result from exposure to allergens specific to Cannabis sativa and cross-reactivity with structurally similar foods. Only a limited number of documented IgE-dependent allergic reactions have been reported among illicit drug abusers, making it challenging to establish the actual frequency of this allergy [44,45]. Since cannabis is a plant, individuals sensitized to specific cannabis proteins can experience adverse reactions after consuming various fruits and vegetables due to cross-reactivity. This phenomenon is known as the “cannabis-fruit-vegetable syndrome” [46]. Potential clinical manifestations associated with cannabis pollen exposure include rhinitis, conjunctivitis, contact urticaria, angioedema, and exacerbation of asthma [46,47,48]. Ingestion of hemp seeds and extracts has been associated with gastrointestinal symptoms, such as abdominal cramps, and sporadic cases of anaphylactic shock have been reported [49]. Diagnosis of Cannabis sativa allergy relies on patient history and allergen testing. Gathering a history of cannabis consumption can be challenging due to the illegal nature of its use. A recent cross-sectional questionnaire-based study revealed that most asthma and allergic disease patients prefer not to discuss their cannabis use with their doctors and, simultaneously, doctors often fail to inquire about marijuana consumption [50]. Currently, no standardized allergen tests are commercially available. Treatment does not differ from that of common respiratory or food allergies. Prevention through abstinence from consumption represents the optimal management approach. If symptoms occur, they should be treated based on their expression phenotype with second-generation antihistamines, inhaled or oral corticosteroids, antihistamine eye drops, or mast cell stabilizers [51]. A case of successful anaphylaxis treatment using subcutaneous omalizumab administration has been reported in the literature [52]. Several studies investigate allergen-specific immunotherapy with Cannabis sativa via intramuscular or subcutaneous routes.