Effects on Time Perception

One of the common subjectively perceived effects of psychedelics is a strongly altered experience of time (reviewed in Heimann, 1994). Brief periods, sometimes

a few minutes of clock time, may be perceived as having been hours. Time may also be compressed. For example, one LSD user indicated that he had watched the big bang and the evolution of the universe all in the space of only a few minutes. Animal studies of effects of psyche- delics on time perception have been reported, a few of which will be briefly discussed here. Two studies of time perception after psilocybin administration to humans have also been reported and are also reviewed here.

To study the effect of DOI on the ability of rats to discriminate time intervals, Asgari et al. (2006a) trained 20 female rats in a discrete-trials psychophys- ical procedure to assess temporal discrimination. It had been previously shown that stimulation of 5-HT2recep- tors disrupted temporal differentiation in the free- operant psychophysical procedure. In this report, 50-second trials were carried out, with a light presented fortseconds, after which two levers were presented. A response on lever“A”was reinforced with a 45-mg food pellet when trials weret,25 seconds, and a response on lever “B” was reinforced if t . 25 seconds, with a series of different times t. DOI (various doses) and ketanserin (2 mg/kg) were given subcutaneously, and M100907 (0.5 and 1.0 mg/kg) was given by i.p. injection. DOI (0.25 mg/kg) produced a significant increase in %B 12.5 seconds after trial onset and significant decreases in %B at 32.5, 37.5, 42.5, and 47.5 seconds after trial onset. DOI thus disrupted the rats’ability to discrim- inate durations of exteroceptive stimuli (temporal discrimination). The 5-HT2A–selective antagonist ketanserin had no effect by itself but completely antagonized the effect of DOI. Likewise, 0.5 mg/kg M100907 had no effect by itself but completely antag- onized the effect of DOI, but only at the 47.5-second time point. At 1.0 mg/kg, M100907 blocked the effect of DOI at all time points .22.5 seconds, except 37.5 seconds after trial onset. Thus, DOI produced a dose-dependent disruption of temporal discrimination that was most evident at longer stimulus durations. The authors point out that it is not clear whether the effect of DOI is specific to the temporal dimension or whether it may reflect a more general breakdown of stimulus control. They also suggest the possibility that stimulus control is relatively weak and may be more vulnerable to disrup- tion at longer stimulus durations. These results are similar to those of Body et al. (2003), who found that DOI also altered temporal differentiation in the free- operant psychophysical procedure in rats, an effect that was similarly blocked by ketanserin.

Asgari et al. (2006b) examined the effect of (2)-DOI (0.25 mg/kg, s.c.) on the fixed-interval peak procedure in 18 female rats. In fixed-interval trials (16 per session), reinforcement (45-mg food pellets) was delivered after the first response emitted after 30 seconds since the start of the trial. In probe trials (16 per session), there was no reinforcement and the response lever remained in the chamber for 120 seconds. Fixed-interval and

probe trials were scheduled in a pseudo-random se- quence. In probe trials, the response rate in trained vehicle-treated rats reaches a peak time (tpeak, the peak of the Gaussian component of the function) close to the 30-second designated time of reinforcer availability and then subsequently declines. After vehicle treatment,

tpeak (33.2 6 1.3 seconds) was close to the scheduled reinforcement time of 30 seconds. DOI significantly decreasedtpeakto 29.761.1 seconds and also reduced peak response rate compared with controls, and the effect was significantly antagonized by ketanserin tartrate (2 mg/kg, s.c.).

Hampson et al. (2010) reported that in an ongoing series of experiments, DOI had qualitatively different effects on temporal differentiation and temporal dis- crimination. They note that previous investigators (Asgari et al., 2006a) suggested that the disruptive effect of DOI on temporal discrimination might reflect a general breakdown of stimulus control rather than a specific interaction with timing processes. That is, disruption of temporal discrimination by DOI might reflect a global impairment of animals’ ability to perform discriminative tasks. Therefore, one might expect that DOI would also disrupt stimulus control exerted by exteroceptive stimuli lacking temporal di- mensions. These investigators tested this prediction by comparing the effects of DOI on two dimensions of a light stimulus: duration and intensity. Twelve female Wistar rats were used for DOI experiments [the authors also compared the effects of (+)-amphetamine] main- tained at 80% of their free-feeding body weight. They used a two-lever paradigm with apertures 5 cm above and 2.5 cm on either side of a recess where 45-mg food pellets were provided. A light-emitting diode was located 2.5 cm above the food pellet delivery device whose intensity (luminance in cd/m2) was varied by computer control. Trials began with illumination of the light-emitting diode above the central reinforcer recess at an intensity of 22 cd/m2. For the temporal discrim- ination procedure, after a predetermined timet, the two levers were inserted into the chamber. A single re- sponse on either lever resulted in withdrawal of both levers, extinguishing of the light, and the chamber remained dark until the start of the next trial. The duration of stimulus presentation,t, in each trial varied between 2.5 and 47.5 seconds. Iftwas shorter than 25 seconds (the mean duration), a response on lever A resulted in reinforcer delivery, whereas a response on lever B had no consequence. Conversely, iftwas longer than 25 seconds, a response on lever B resulted in reinforcer delivery, whereas a response on lever A had no consequence. For the light-intensity discrimination procedure, stimulus durationtwas kept at 25 seconds for each trial, but the intensity of the lightivaried in 10 distinct values between 3.6 and 128.5 cd/m2. If

i,22 cd/m2(the geometric mean of the intensity range), a response on lever A resulted in reinforcer delivery,

whereas a response on lever B had no consequence. Conversely, ifiwas greater than 22 cd/m2, a response on lever B led to reinforcer delivery, whereas a response on lever A did not. Doses of DOI were 0.0625, 0.125, and 0.25 mg/kg and were given 15 minutes prior to test sessions.

In this temporal discrimination task, Hampson et al. (2010) found that selection of lever B (%B) increased progressively as a function of stimulus durationt. The value of the indifference point T50, was close to the midpoint of the range of durations (25 seconds). In the light-intensity discrimination task, %B increased progressively as a function of light intensityi. The value of the indifference pointI50 was close to the geometric mean of the range of the light intensities (22 cd/m2).

DOI was found to flatten the psychometric function, tending to displace it rightward, and increased the Weber fraction, but only for temporal discrimination. DOI at 0.25 mg produced a significant reduction of %B on temporal discrimination but had no effect on in- tensity discrimination. The authors present a detailed statistical analysis that included slope « and Weber fraction, but they conclude that that the impairment of the precision with which the rats discriminated the durations of the stimulus was not due to a general disruption of stimulus control. Their results strongly suggest that DOI has a greater effect on temporal discrimination than on light-intensity discrimination.

Wittmann et al. (2007) carried out a study to elucidate the role of the serotonin system in time perception and temporal behavior. Theirs was the first study to sys- tematically assess the effect of psilocybin on timing performance on standardized measures of temporal processing. They used a placebo-controlled, double- blind design in 12 healthy volunteers, administering placebo, a medium psilocybin dose of 115 mg/kg, or a high psilocybin dose of 250 mg/kg. The standardized measures of temporal processing included the temporal reproduction, sensorimotor synchronization, and tap- ping speed (personal and maximal). They tested spatial working memory span using the spatial span test. Psychometric measures included the 5D-ASC scale and the AMRS.

Wittmann et al. (2007) reported that high-dose psilocybin led to significant under-reproduction of time intervals 4 seconds and longer. Psilocybin significantly impaired the subject’s ability to reproduce interval durations longer than 2.5 seconds, and it impaired the ability to synchronize to interbeat interval durations longer than 2 seconds. High-dose psilocybin also slowed the personal preferred tapping rate to 949 milliseconds from a baseline of 692 milliseconds but had no effect on the maximum tapping rate. No effect at the medium dose of psilocybin was observed. At the time of peak of effects, high-dose psilocybin (but not the medium dose) impaired spatial span task performance as indexed by span length. The investigators indicate that the

disturbed timing abilities for sensorimotor synchroni- zation and duration reproduction observed could reflect impairments of short-term memory, attention, or decision-making mechanisms. Given the selective effect of psilocybin on longer-duration intervals in both the temporal reproduction and sensory synchronization tasks, it was suggested that the observed temporal disturbance is induced through interference with cog- nitive processes like attention and working memory.

In a subsequent study, Wackermann et al. (2008) reanalyzed the data from the Wittmann et al. (2007) study and added an additional group of nine subjects that was administered a very low dose of psilocybin (12 mg/kg). Their new analysis employed a “dual klepsydra”model of duration reproduction. They mea- sured changes in a dual klepsydra parameter desig- natedk, which proved to be a sensitive measure of the effect of a psychoactive substance on the internal representation of time. The results were similar to those from Wittmann et al. (2007), and the estimate ofkwas significantly increased by psilocybin 90 minutes after the drug was administered, which was interpreted to mean that psilocybin led to a higher loss rate of the internal duration representation.