### Incentive for Investigating Phytocannabinoids in C. sativa and Cannabis-Based Products  
Under the pressure of its criminal association, the chemical constitution, pharmacological effects, genetic structure, evolutionary and domestication history of remained poorly understood until the last decade of the 20 th century. Authorized investigations related to _C. sativa_ were either forensic studies to aid law enforcement or medical and social research specifically intended to document and reduce harmful effects [6]. Since the last decade of the 20 th century, a great urge for more thorough investigation of _C. sativa_appeared, mainly as a result of the resurrection of production of _C. sativa_ for non-narcotic and medical purposes and the growing tolerance of the extremely widespread recreational use. This increased attention _C. sativa_ and cannabis-based products gained due to their high pharmacological potential, updated legislation authorizing many different uses, and, thus, the emerging need to control their quality. This imposes a great challenge for academics, particularly in the field of natural products, from which a contribution to improve and standardize the extraction and characterization of the bioactive compounds from _C. sativa_ species is expected.  
Scientific and technological development in regards to C. _sativa_ began, highlighting the need of sensitive, specific and robust analytical methods for identification and quantification of the active constituents of _C. sativa_. Chemical profiling of the plant became extremely relevant, since the acquired knowledge further enhanced: (1) chemotaxonomic classification; (2) cultivation set-ups examination, and thus adjustment of cultivation conditions and breeding methodologies in order to produce _C. sativa_ varieties with fit-for-purpose physicochemical properties; (3) investigation of potency of seized samples, thus discovering sources of interconnected illegal production and trafficking; (4) association of medical and adverse health effects with potency and/or interplay of certain phytocannabinoids and other active _C. sativa_ constituents and (5) QC of medical cannabis and final medical cannabis-based products and potency examination [1,2].  
The multitude of cannabis-based products including cannabis extracts, oils, resins, pharmaceutical dosage forms, cannabis-infusedibles and beverages are obliged to comply with the national regulators' quality control regulations, especially in terms of phytocannabinoids content. Accurate qualitative and quantitative analyses of the phytocannabinoids content and chemical profile in cannabis plants are extremely relevant, in order to associate medicinal and possible adverse health effects with the potency of certain phytocannabinoids and other compounds, such as terpenoids [2]. One of the most relevant problems in analytical determinations for QC, especially when there are legal problems related with quantitation, such as for cannabis, relates to the proficiency of laboratories. Both qualitative and quantitative determinations require carrying out of standardized assays that meet the analytical criteria approved by the relevant control authorities.  
This review aims to capture the versatility of analytical methods for natural phytocannabinoids profiling in cannabis and cannabis-based products in the past four decades (1980-2021). As such, this thorough overview is first of its kind. Other most recent reviews cover either a shorter time period, i.e., 2002-2016 [1], 2010-2016 [2], 2009-2019 [39], focus on both plant materials and biological matrices [1,39], describe multiple [2] or single (GC) [39] instrumental analytical platforms, omit cannabis-based products [4] or, apart from phytocannabinoids, also include profiling of other bioactive _C. sativa_ constituents [1].