Background and objective: Changes in cannabis legalization regimes in several countries have influenced the diversification of cannabis use. There is an ever-increasing number of cannabis forms available, which are gaining popularity for both recreational and therapeutic use. From a therapeutic perspective, oral cannabis containing Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is a promising route of administration but there is still little information about its pharmacokinetics (PK) effects in humans. The purpose of this systematic review is to provide a general overview of the available PK data on cannabis and THC after oral administration. Materials and Methods: A search of the published literature was conducted using the PubMed database to collect available articles describing the PK data of THC after oral administration in humans. Results: The literature search yielded 363 results, 26 of which met our inclusion criteria. The PK of oral THC has been studied using capsules (including oil content), tablets, baked goods (brownies and cookies), and oil and tea (decoctions). Capsules and tablets, which mainly correspond to pharmaceutical forms, were found to be the oral formulations most commonly studied. Overall, the results reflect the high variability in the THC absorption of oral formulations, with delayed peak plasma concentrations compared to other routes of administration. Conclusions: Oral THC has a highly variable PK profile that differs between formulations, with seemingly higher variability in baked goods and oil forms. Overall, there is limited information available in this field. Therefore, further investigations are required to unravel the unpredictability of oral THC administration to increase the effectiveness and safety of oral formulations in medicinal use.

In recent years, the consumption of energy drinks (EDs) has become increasingly popular, especially among adolescents. Caffeine, a psychostimulant, is the main compound of EDs which also contain other substances with pharmacological effects. This review aims to compile current evidence concerning the potential interactions between EDs, medicines, and drugs of abuse as they are frequently consumed in combination. The substances involved are mainly substrates, inductors or inhibitors of CYP1A2, psychostimulants, alcohol and other depressant drugs. Furthermore, intoxications reported with EDs and other substances have also been screened to describe acute toxicity. The results of our review show that the consumption of both EDs alone and in combination is not as safe as previously thought. Health professionals and consumers need to be aware of the potential interactions of these drinks as well as the absence of long-term safety data.

Inhalation by vaporization is a useful application mode for medical cannabis. In this study, we present the disposition of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, and their metabolites in serum, oral fluid, and urine together with the acute pharmacological effects in 14 healthy individuals treated with vaporized medical cannabis. THC and CBD peaked firstly in serum and then in oral fluid, with higher concentrations in the first biological matrices and consequent higher area under the curve AUCs. Acidic precursors Δ-9-tetrahydrocannabinolic acid A (THCA) and cannabidiolic acid (CBDA) showed a similar time course profile but lower concentrations due to the fact that vaporization partly decarboxylated these compounds. All THC and CBD metabolites showed a later onset with respect to the parent compounds in the absorption phase and a slower decrease to baseline. In agreement with serum kinetics, THC-COOH-GLUC and 7-COOH-CBD were the significantly most excreted THC and CBD metabolites. The administration of vaporized medical cannabis induced prototypical effects associated with the administration of cannabis or THC in humans, with a kinetic trend overlapping that of parent compounds and metabolites in serum. The pharmacokinetics of cannabinoids, their precursors, and their metabolites in biological fluids of individuals treated with vaporized medical cannabis preparations showed a high interindividual variability as in the case of oral medical cannabis decoction and oil. Inhaled medical cannabis was absorbed into the organism earlier than decoction and oil. Cannabinoids reached higher systemic concentrations, also due to the fact that the acid precursors decarboxylated to parent cannabinoids at high temperatures, and consequently, the physiological and subjective effects occurred earlier and resulted with higher intensity. No serious adverse effects were observed.

The use of cannabis flowering tops with standardized amounts of active phytocannabinoids was recently authorized in several countries to treat several painful pathological conditions. The acute pharmacological effects and disposition of Δ-9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors and THC metabolites after oil and decoction administration have been already described. In this study, the disposition of CBD metabolites: 7-carboxy-cannabidiol (7-COOH-CBD), 7-hydroxycannabidiol (7-OH-CBD), 6-α-hydroxycannabidiol (6-α-OH-CBD), and 6-β-hydroxycannabidiol (6-β-OH-CBD) in the serum and urine of healthy volunteers was presented. Thirteen healthy volunteers were administered 100 mL of cannabis decoction in the first experimental session and, after 15 days of washout, 0.45 mL of oil. Serum and urine samples were collected at different time points, and the CBD metabolites were quantified by ultra-high-performance liquid chromatography–tandem mass spectrometry. The most abundant serum metabolite was 7-COOH-CBD, followed by 7-OH-CBD, 6-β-OH-CBD, and6-α-OH-CBD, after decoction and oil. Both 7-OH-CBD and the 6-α-OH-CBD showed similar pharmacokinetic properties following administration of both cannabis preparations, whereas 7-COOH and 6-α-OH-CBD displayed a significant higher bioavailability after decoction consumption. All CBD metabolites were similarly excreted after oil and decoction intake apart from 6-α-OH-CBD, which had a significantly lower excretion after oil administration. The pharmacokinetic characterization of CBD metabolites is crucial for clinical practice since the cannabis herbal preparations are increasingly used for several pathological conditions.

Background: Synthetic cathinones (SCs) are the second most representative class of New Psychoactive Substances, with more than 100 analogues identified in the illicit drug market up to 2024. According to the United Nations Office on Drugs and Crimes, N-ethylhexedrone (NEH) and N-ethyl-nor-pentedrone (NEP) were identified among the most frequently seized SCs worldwide. However, still, little is known with regard to their pharmacological effects in humans. Methods: For the first time, we conducted a naturalistic, prospective observational study in 16 participants (7 women and 9 men) with a previous history of psychostimulant recreational use. They intranasally self-administered a single dose of NEP (n = 8, 20–40 mg) or NEH (n = 8, 20–40 mg). The physiological effects (systolic and diastolic blood pressure, heart rate, and temperature) and subjective effects (visual analogue scales, Addiction Research Center Inventory questionnaire and Evaluation of Subjective Effects of Substances with Abuse Potential questionnaire) were assessed up to 4 h after the self-administration at different time points (0, 20 and 40 min and 1, 1.5, 2, 3 and 4 h). Results: Despite several differences, both NEP and NEH produced significant effects within 20 min, with a return to baseline 3–4 h after self-administration. In general, NEP showed a faster onset and a more rapid disappearance of subjective effects than NEH. Moreover, intranasal self-administration of NEH and NEP in experienced recreational drug users, within a non-controlled setting, induces a constellation of psychostimulant-like effects. Conclusion: NEH and NEP showed similar pharmacological properties after insufflation, with typical effects of SCs

Synthetic cathinones represent the second most frequently reported group of new psychoactive substances identified annually, according to the United Nations. It remains unknown whether specific derivatives differ in the onset of effects related to absorption kinetics. Clephedrone (4-chloromethcathinone, 4-CMC) has been among the most frequently seized cathinones in recent years; however, available data on its pharmacology and abuse potential remain scarce. A non-controlled, prospective, observational study was conducted involving eight healthy volunteers (six women) who self-administered a single oral dose of clephedrone (100 or 150 mg). Study variables were assessed at baseline and over a 5-h period following administration, including vital signs and subjective effects. Oral fluid concentrations of clephedrone and cortisol were determined. For comparison, this article also presents previously unpublished data from a pilot study in which 12 healthy male participants received 150 or 200 mg of methylone under comparable conditions to evaluate effects. Results indicated that both clephedrone and methylone produced stimulant-like subjective effects. However, clephedrone exhibited a delayed onset and peak of effects compared with methylone, indicating a clinically relevant pharmacokinetic difference. Both substances were detected in oral fluid, with peak concentrations occurring later following clephedrone administration, consistent with its delayed pharmacodynamic profile.