# Influence of Altitude on Phytochemical Composition of Hemp Inflorescence: A Metabolomic Approach
## 1 Introduction  
Hemp (cannabis, _Cannabis sativa_ L., family: Cannabaceae) was frequently cultivated in the past, but its agronomic expansion was interrupted in the beginning of the 1950s for many reasons, one of them being the presence of psychoactive substance \(\Delta\)-9-tetrahydrocannabinol (THC) that is produced by some hemp varieties. Nowadays, this has been partly obliterated and the European Union permits the cultivation of hemp with THC content of less than 0.20% [1]. For example, in Italy, regulation n\({}^{2}\)242/2017 [2], delineates the conditions for hemp production, its commercialization, and utilization for specific industrial purposes. Therefore, different genotypes have been registered, along withstandardized cultivation procedures [3]. Many ecologically, agronomically, and pharmaceutically positive properties qualify this multifunctional crop as an opportune raw material for various traditional (fiber, food, oil, medicine) or innovative industrial applications (new biomaterials and biofuels) [4; 5]. The European Union has regulated commercial production and distribution of more than 70 hep varieties [6], among which the Kompolti variety is one of the oldest. This hep variety is frequently cultivated in continental European countries. This well-known diocious variety was developed in Hungary as the first hybrid breed [7] in order to produce seeds for oil production, but also its stalks have been largely exploited. The particularity of this strain is its growing dynamics: it needs a whopping 6-month flowering period that usually finishes in October. Its macro/microscopical botanical aspects, geographical distribution, and agricultural status have been comprehensively studied, but surprisingly, no information is currently available on the content of the high added-value bioactive substances that are characteristic of its flowers. The _C. sativa_ inflorescence contains a number of chemically active compounds, such as cannabinoids, terpenoids, and flavonoids. The most important secondary metabolites are phytocannabinoids whose acidic forms are exclusively biosynthesized in the glandular trichomes, which are abundant on the surface of the female flowers [8]. Inflorescences of industrial hep varieties, Kompolti included, are particularly rich in cannabidiolic acid (CBDA) that is disposed to the spontaneous decarboxylation to cannabidiol (CBD) under favorable environmental/conservational circumstances such as warming and light [9]. CBD is responsible for a variety of pharmacological actions that may have some remarkable applications, but unlike THC, CBD does not possess any psychoactive effects [10]. CBD has been studied intensively over the past decade due to its biomedical relevance. Several studies suggest that CBD can be effective in treating epilepsy and other neuropsychiatric disorders, including anxiety and schizophrenia [11]. This is the reason why CBD dietary supplements obtained from different industrial _C. sativa_ chemotypes have become particularly widespread [12]. On the other hand, it is important to evaluate the main factors that determine CBD production in hemp inflorescence--if it depends on the genetic predisposition of hep chemovar, or its production is conditioned by the environment, in particularly the geographical position where plant is bred [13]. Although CBD and THC are the crucial phytocannabinoids, hemp trichomes themselves are capable of generating a whole series of acidic/decarboxylated phytocannabinoids: about 120 have been isolated to date [8]. Based on their appearance in the metabolic pathway that involves their formation, all phytocannabinoids are categorized into 11 subclasses [9], where the central position belongs to cannabigerolic acid that is synthesized from geranyl diphosphate and olivetolic acid [14]. CBGA further provides tetrahydrocannabinolic acid (THCA), CBDA, and cannabichromenic acid (CBCA). Cannabigerol (CBG), THC, CBD, and cannabichromene (CBC) are corresponding neutral equivalents.