In total, 13 publications between 1974 and 2023 reporting PK data of DMT were included (see Fig. 1) [13,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35], [13,27,28,29,30,31,32,33,34,35], covering eight distinct clinical datasets. One study was preprinted at the time of inclusion and subsequently published in October 2023 [13]. Individual concentration over time data were available in four studies [14], [15], [30], [31], mean data in ten studies [13,14,15], [26], [27], [29], [32,33,34,35], and median data in one study [30]. An overview of the included reports and data is presented in Fig. 1 and Table 1.

PRISMA flowchart for selection of included literature. PK: pharmacokinetic

All studies were performed in healthy volunteers, in group sizes ranging from 5 to 27 subjects per dose level. DMT was administered as a single dose in six studies [15], [28,29,30,31], [35], a four-way crossover in six studies [13], [14], [27], [13,33,34], and a single dose in crossover with ketamine in one study [26]. The washout period in repeat-dose studies included 7 days [14], [27], [33], [34], 14 days [13], and 2–4 weeks [26] as well as 29 min 15 s in a tolerability study [32]. DMT was administered intravenously in all studies, except for one intramuscular administration of approximately 30.3 mg in 11 subjects [35].

DMT hemifumarate was administered in four studies [14], [14,30,31], DMT fumarate was administered in six studies [13], [15], [26], [13,33,34], and two studies did not report the DMT form used [27], [35]. However, one of these studies [27] was based on the same clinical dataset used by Vogt et al. [14], so we assumed that DMT hemifumarate was administered in both studies. For Kaplan et al. [35], we assumed the DMT fumarate form.

Intravenous infusion schemes included 30-s bolus [29,30,31,32], [34], 90-min infusion [14], [27], 5-min bolus followed by 84-min infusion [26], two consecutive 5-min boluses [15], 30-s bolus followed by 30-min infusion [13] and a 45-s bolus followed by 90-min infusion [14]. Intravenous bolus doses ranged from 2.6 to 20.3 mg, and infusion doses ranged from 3 mg over 5 min to 68.8 mg over 90 min. Gouzoulis-Mayfrank et al. [26] administered various doses that were recalculated to average values of 7.7 mg bolus + 48.5 mg infusion and 11.1 mg bolus + 64.7 mg infusion.

Reported demographics included gender (n = 12) [13,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34], [13,27,28,29,30,