Here we show in a placebo-controlled, double-blind, randomised trial with healthy older adults that microdose LSD produces a tendency to over-reproduce suprasecond intervals on a temporal reproduction task. Dose analyses further suggest potential linear effects of dose on temporal reproduction although over-reproduction tended to be most pronounced with a 10 μg dose. Alterations in temporal reproduction were restricted to intervals exceeding 1600 ms, suggesting that this effect may be interval-specific and restricted to suprasecond interval timing. Participants displayed a weak tendency to report greater subjective drug effects in the LSD conditions, hinting that participants were able to detect their assigned condition. However, LSD was not reliably associated with alterations in different self-reported dimensions of consciousness and the differential temporal reproduction performance across conditions was independent of self-reported drug effects. These results expand upon previous research showing that LSD modulates the perception of time (Aronson et al. 1959; Boardman et al. 1957; DeShon et al. 1952; Liechti et al. 2016; Speth et al. 2016) by indicating that LSD-mediating distorted timing can be independent of an altered state of consciousness. Interval timing appears to be particularly sensitive to the effects of psychedelics and thus represents a valuable method for measuring the psychological effects of these drugs (Wackermann et al. 2008; Wittmann et al. 2007).

A notable result of the present study is that the modulation of interval timing by LSD was restricted to intervals between 2000 and 4000 ms. This effect partially converges with the previous observation that the impact of psilocybin on temporal reproduction was specific to 4000–5000 ms intervals (and not 1500–2500 ms), albeit in the converse direction (Wittmann et al. 2007). Taken together, these results suggest that interval timing is most easily influenced by psychedelic drugs when intervals exceed 1600–2500 ms in duration. Multiple lines of research suggest that interval timing of subsecond and suprasecond intervals is subserved by partially distinct psychological and neurophysiological mechanisms (Coull et al. 2012; Hayashi et al. 2014; Rammsayer 1999; Rammsayer and Troche 2014; Wiener et al. 2011), although the approximate interval breakpoint that distinguishes these systems is poorly understood (Grondin 2014; Lewis and Miall 2009). The present results arguably provide further evidence for a dissociation between these putative timing systems, with LSD influencing a suprasecond system potentially through more cognitive dimensions of timing, including attention and working memory, which are recruited to a greater extent for timing in this interval range (Lewis and Miall 2003; Matthews and Meck 2016; Wittmann et al. 2007).

The present results are at odds with previous research that examined the impact of psychedelic drugs, which primarily function as serotonin agonists, on behavioural indices of time perception. As is the case with two previous studies using LSD (Aronson et al. 1959) and psilocybin (Wittmann et al. 2007), we failed to replicate the finding that LSD enhances variability of interval timing (Boardman et al. 1957). However, our primary finding of temporal over-reproduction in the microdose LSD condition for stimulus intervals from 2000 to 4000 ms in this study is inconsistent with the previous observation that LSD produced under-reproduction of temporal intervals (Aronson et al. 1959). Nevertheless, the latter study used substantially longer intervals (> 15 min), only a single trial per interval, and verbal estimates of duration, rendering comparison with the present study difficult. Our results are also discrepant with those of a previous study that found that relative to baseline, psilocybin produced temporal under-reproduction in an interval range that overlapped with the present study (Wittmann et al. 2007). Moreover, hierarchical regression analyses suggested that the magnitude of temporal over-reproduction under LSD covaries partly with dosage. Divergences between our results (temporal over-reproduction) and those of these previous studies (temporal under-reproduction) are plausibly attributable to the use of microdoses and psychedelic doses, respectively. Psychedelic doses of LSD and psilocybin commonly produce pronounced changes in different dimensions of consciousness, such as hallucinatory percepts (Carhart-Harris et al. 2016a; Liechti 2017; Nichols 2016), which are likely to attract attention and divert it away from the passage of time (Buhusi and Meck 2009). Similarly, the experience of elation in response to psychedelics (Carhart-Harris et al. 2016a) might produce a tendency to underestimate or under-reproduce temporal intervals, as is typically observed during positive affective states (Lake et al. 2016). Finally, a decrease in self-related processing in response to psychedelics (Carhart-Harris et al. 2016b; Liechti 2017; Preller and Vollenweider 2016; Tagliazucchi et al. 2016) would also be expected to produce under-reproduction (Wittmann 2013, 2015; Yin et al. 2016). Thus, the observed direction of distorted timing in the present study is arguably consistent with the relative lack of canonical alterations in consciousness and inconsistent with what is typically observed with serotonin agonists (Wittmann et al. 2007).

Insofar as the cognitive, neurochemical, and neurophysiological effects of microdose LSD are largely unknown, the proposal of plausible mechanisms is necessarily speculative and the following proposals should be treated with caution. Interval timing is closely intertwined with attention and working memory (Buhusi and Meck 2009; Gu et al. 2015; Matthews and Meck 2016), and thus, the present results are plausibly driven by changes in these fundamental cognitive systems. It seems unlikely that the current results can be attributed to poorer working memory or selective attention, such as an increase in attentional lapses, as such effects would have been expected to produce temporal under-reproduction (Buhusi and Meck 2009; Terhune et al. 2017; Wittmann et al. 2007). An alternative explanation for our results is that microdose LSD enhanced selective attention to duration during the task, resulting in a tendency to over-reproduce temporal intervals (Buhusi and Meck 2009; Lake and Meck 2013). Indirect support for this hypothesis comes from a recent survey of microdose users that found that participants reported being more focused on the first day of microdosing (Polito and Stevenson 2018), although this effect declined on subsequent dosing days and it remains unclear whether the self-reported change in attentional focus in the latter study is attributable to a placebo response. Although we are unable to completely discount this interpretation, participants completed the temporal reproduction task on the fourth dosing day and did not report differential concentration under LSD and previous research shows that both phenomenological and behavioural indices of attentional state covary with individual differences in interval timing (Berry et al. 2014; Terhune et al. 2017).

A final explanation for the present results is that temporal over-reproduction was driven by the activation of D 2 receptors, as suggested by non-human animal research indicating that LSD functions as a dopamine agonist at a late phase (Marona-Lewicka and Nichols 2007; Marona-Lewicka et al. 2005) (see also De Gregorio et al. 2016; Giacomelli et al. 1998; Rickli et al. 2016). This interpretation is consistent with a wealth of evidence implicating dopamine in interval timing (for reviews, see Coull et al. 2011; Matell and Meck 2004) and in particular that dopamine agonists produce overestimation or over-reproduction of temporal intervals (Buhusi and Meck 2007; Lake and Meck 2013; Maricq et al. 1981). Nevertheless, this interpretation remains controversial because these putative biphasic pharmacological effects have not yet been observed in humans with microdoses or psychoactive doses to our knowledge. Non-human animal research does not always translate to humans (Ioannidis 2012), and thus, this interpretation should be treated with caution until corroborative evidence for biphasic effects is observed in humans.

Future research on the effects of micro- and psychoactive doses of psychedelic drugs on interval timing will benefit from more systematically exploring the mediators of these effects, their interval specificity, their time course, and their neurochemical specificity. Further study of the seemingly differential impact of micro- and psychoactive doses on interval timing tasks is necessary to determine whether the apparent converse effects of these doses on timing are replicable and not attributable to an as of yet unknown confound. Such an orientation will also be valuable in understanding how distorted timing relates to broader alterations in affect, cognition, and perception in response to psychedelic doses of LSD (Carhart-Harris et al. 2016a; Liechti 2017; Terhune et al. 2016a). Concurrent measurement of different psychological and physiological parameters that might mediate distorted timing, such as attention, arousal, memory, working memory, and affect (Lake et al. 2016; Matthews and Meck 2016), will enable a more precise understanding of the psychological variables that underlie changes in interval timing in response to LSD and other psychedelics. The latter approach will be especially beneficial when coupled with the measurement of a wide interval range in order to establish the cognitive and perceptual bases for the repeated observation that distorted timing under psychedelics is restricted to suprasecond intervals (Wittmann et al. 2007). The aim to understand distorted timing in response to psychedelics will further benefit from integrating research on psychedelics with that on germane phenomena known to modulate awareness and time perception (Berkovich-Ohana and Wittmann 2017; Lemercier and Terhune 2018; Noreika et al. 2014; Yin et al. 2016). Repeated measurement of interval timing at multiple time points post-dosage will allow for greater insights into whether and how timing changes during different hypothesised phases of LSD (Marona-Lewicka and Nichols 2007; Marona-Lewicka et al. 2005). Similarly, the use of serotonin and dopamine antagonists at different time points post-dose (Preller et al. 2017) will enable a more robust assessment of the role of these neurochemicals in LSD-mediated distorted timing.

Interpretation of the present results must also consider the limitations of our design. Given the methodological challenges of conducting LSD research, this study, like many other human studies in this domain (Liechti 2017), included a small sample size. The analyses were plausibly underpowered, particularly those pertaining to dosage effects, and we observed multiple suggestive, convergent effects with strong effect sizes that may have met our thresholds for statistical significance with a larger sample size. For example, the lack of clear linear dosage effects in the ANOVAs is potentially due to low statistical power, particularly since evidence for linear dosage effects were observed in the hierarchical regression analyses. Indeed, temporal over-reproduction was observed in multiple dosage conditions relative to placebo at trend levels (.05 < ps < .10) and thus would have plausibly achieved statistical significance with larger sample sizes in each dose condition. This limitation is perhaps compounded by the use of a between-group design as a within-group design would have afforded greater internal validity and increased the likelihood that the observed effects are attributable to the drug conditions. For this reason, the non-significant dosage effects should be interpreted with caution. Participants in the different conditions did not significantly differ in the self-report measures, but there was a weak tendency for those in the LSD condition to report greater subjective drug effects, but not other subjective effects, than those in the placebo condition. This effect was not observed across drug doses but it is possible that our small sample sizes attenuated our ability to detect such effects. A further limitation of the study is the absence of a baseline condition for the temporal reproduction task. Although the use of random assignment mitigates the negative impact of the absence of baseline data on the internal validity of the study, such data would allow for stronger inferences regarding the effect of LSD on interval timing. A final limitation of this study is that the sample was comprised entirely of older adults. Older adults display temporal contraction on interval timing tasks (Lustig and Meck 2011; Turgeon and Wing 2012) with some constraints (for a review see Turgeon et al. 2016), potentially due to reduced striatal dopamine receptor availability (Allard and Marcusson 1989; Shingai et al. 2014; Zelnik et al. 1986). Accordingly, the observed changes in interval timing are potentially restricted to this population and not generalizable to younger populations.

The present results suggest that microdose LSD produces a tendency to over-reproduce suprasecond temporal intervals in older adults. Additional evidence from self-report measures suggests that the observed effects are unlikely to be attributable to altered states of consciousness. In particular, although there was a tendency for those in the LSD condition to report greater drug effects, the observed temporal over-reproduction effect was independent of self-report drug effects. Further research is required to replicate these results, including their interval specificity, and identify the neurochemical and cognitive mediators of distorted timing under micro- and psychoactive doses of LSD.