Cialis and the Sense of Time: Does PDE5 Inhibition Alter Subjective Duration and Attention in Performance Anxiety?

Introduction: Performance Anxiety, “Time Pressure,” and Sexual Function

Performance Anxiety is a well-documented phenomenon that occurs in high-stakes, time-sensitive contexts, ranging from public speaking to athletic competition to sexual encounters. A common thread across these settings is the intrusive sense of “time pressure,” often described subjectively as time moving too fast, slipping away, or becoming fragmented. This altered perception of time is not merely poetic: it reflects measurable changes in temporal processing, attentional control, and cognitive load, particularly in individuals with elevated anxiety sensitivity.

In sexual performance anxiety, which is a subtype of social anxiety disorder, the sense of being watched or judged often leads to self-monitoring, attentional narrowing, and premature disengagement from sensory experience. These changes may interfere with sexual arousal and satisfaction, but they also highlight a deeper psychophysiological issue: how perceived time and cognitive presence are disrupted under pressure. Current treatment options focus on cognitive-behavioral interventions or SSRIs, but emerging interest surrounds whether certain pharmacological agents could modulate the temporal and attentional distortions seen in performance anxiety.

This article explores a novel hypothesis: that tadalafil, a long-acting PDE5 inhibitor used primarily to treat erectile dysfunction, may influence subjective time perception and sustained attention through central nervous system effects on NO–cGMP signaling.

Though originally developed for vascular smooth muscle relaxation, tadalafil’s partial blood-brain barrier penetration and interaction with corticostriatal circuits involved in timing and attention suggest a plausible mechanism of action worth exploring—particularly in performance contexts where time feels compressed, and attentional clarity is compromised.

Neurobiological Framework: cGMP in the Cortex, Striatum, and Cerebellum

While the vascular effects of PDE5 inhibition, particularly smooth muscle relaxation and vasodilation, are well characterized, a growing body of evidence supports the role of NO–cGMP pathways in the central nervous system, with implications for cognition, attentional control, and time perception.

PDE5 Inhibition has been identified in several brain regions involved in interval timing and attentional gating, including the prefrontal cortex, striatum, and cerebellum. The prefrontal cortex (PFC), critical for sustained attention and working memory, relies on finely tuned dopaminergic and glutamatergic activity, both of which intersect with NO–cGMP Signaling cascades. Similarly, the dorsal striatum, long implicated in motor timing and action sequencing, shows dynamic cGMP fluctuations during temporal processing tasks. The cerebellum, once considered primarily a motor structure, is increasingly recognized for its role in subsecond timing, prediction error detection, and sensorimotor integration, all of which are modulated by NO-dependent plasticity. Animal studies and ex vivo models have demonstrated that enhanced cGMP signaling can facilitate long-term potentiation (LTP) and improve performance on memory and attention paradigms. Tadalafil, though optimized for peripheral targets, has shown partial central bioavailability, particularly under conditions of increased BBB permeability or chronic low-dose exposure (França et al., 2020). Its long half-life (≈17.5 hours) allows for a sustained elevation in cGMP, making it a viable candidate for exploring cognitive and perceptual modulation over behaviorally relevant timescales.

Together, these findings support the theoretical plausibility that tadalafil could modulate subjective duration and attentional stability, particularly in anxiety-provoking contexts where these cognitive domains are disrupted.

Psychophysics of Time in Anxiety and Depression

Perception of time is not merely a reflection of clock-based duration but a neurocognitive construct shaped by emotional states, attention, and internal arousal.

In anxiety and depressive disorders, this construct is consistently altered, though in opposite directions. Individuals with anxiety often report time as racing or fragmented, especially in situations involving social scrutiny or performance pressure. In contrast, those with depression tend to perceive time as slowed, dragging, or emotionally detached from the present moment.

Experimental studies using temporal bisection tasks, which ask participants to classify durations as closer to “short” or “long” anchor intervals, have shown that anxiety typically compresses perceived duration, particularly in the subsecond to several-second range. This is thought to reflect a combination of attentional narrowing, increased arousal, and impaired working memory updating – all factors that interfere with the brain’s internal timing mechanisms (Mioni et al., 2020). These distortions are frequently modeled through scalar expectancy theory (SET), which posits an “internal clock” regulated by attention and arousal. In anxiety, the internal clock may “tick” faster, but attentional fragmentation leads to underestimation of elapsed time, particularly during performance stress. Neurobiologically, this involves disrupted connectivity between the prefrontal cortex, striatum, and cerebellum, regions linked to both time estimation and executive control.

This altered timing may be especially relevant in performance anxiety, where individuals often describe losing control over pacing, coordination, or rhythm, i.e., hallmarks of disrupted temporal processing. It sets the stage for pharmacological interventions that target cortico-striatal modulation, such as PDE5 inhibitors.

Concept Pilot: 5–10 mg Tadalafil vs. Placebo

To explore the hypothesis that tadalafil may modulate subjective time perception and attentional stability in individuals with performance anxiety, a proof-of-concept pilot study is proposed using a double-blind, placebo-controlled, within-subject crossover design.

Participants would be adults reporting situational performance anxiety, particularly in sexual or social contexts, but without generalized anxiety or mood disorders. Each subject would complete two testing sessions (tadalafil vs. placebo), spaced one week apart, randomized in order. Assessments would be conducted approximately 2.5 to 3 hours post-dose, corresponding to the known Tmax of tadalafil (Forgue et al., 2006).

Primary outcome measures would include:

• Temporal bisection task, presenting auditory or visual stimuli of varying durations (e.g., 400–1600 ms) and requiring participants to classify each as closer to a “short” or “long” anchor duration. Shift in the bisection point would reflect changes in subjective time estimation.
• Sustained Attention to Response Task (SART), measuring attentional lapses via go/no-go stimuli over a 10-minute block.
• Subjective time perception, captured via a visual analog scale asking, “How fast did time seem to pass during this task?” (0 = very slow, 100 = very fast).

Secondary measures would assess mood, arousal…(truncated 702 characters)…

Clinical Implications and Ethical Boundaries

If tadalafil is found to influence subjective time perception and sustained attention in performance-anxious individuals, even subtly, it could suggest a broader therapeutic role for PDE5 inhibitors beyond vasodilation.

In performance settings where cognitive overload, hypervigilance, and distorted temporal experience undermine functioning, such as sexual performance anxiety, stage fright, or test-taking, modulation of corticostriatal timing networks may enhance not just physical readiness but also cognitive composure.

Clinically, this would raise important questions. Could tadalafil serve as an adjunct to behavioral therapies for performance-related anxiety? Might low-dose PDE5 inhibitors offer dual-action benefits, improving both hemodynamic function and time-based attention under stress? These possibilities echo prior speculation about off-label cognitive effects of PDE inhibitors in neurodegenerative disease and age-related cognitive decline (Puzzo et al., 2009).

However, ethical boundaries must be acknowledged. Tadalafil is not currently indicated for cognitive enhancement, and any such use would be considered experimental. There is a risk that findings could lead to non-therapeutic use among individuals seeking competitive or sexual performance advantages. The question of intent (restoring impaired functioning versus enhancing normative performance) is ethically fraught, particularly when applied to young, healthy populations. Furthermore, informed consent must be carefully structured in any experimental trial. Participants must understand that the drug may produce subjective changes in perception, mood, or alertness, some of which may not be directly therapeutic or desired. Long-term implications are unknown, and transient modulation of cognitive-emotional state should not be confused with treatment.

While the potential to subtly recalibrate attention and temporal awareness is intriguing, it underscores the need for rigorous empirical validation, ethical oversight, and clear boundary-setting between clinical exploration and enhancement-oriented use.

Limitations and Design of the Full-Length RCT

While a concept pilot can offer initial insight into the cognitive-perceptual effects of tadalafil, it comes with several limitations that constrain interpretation and generalizability.

First, the sample size in a proof-of-concept study is necessarily small, which limits statistical power and increases susceptibility to type I and II errors. Secondly, without an induced performance anxiety condition, participants may not be experiencing the cognitive state in which temporal distortion is most pronounced, thereby reducing ecological validity.

Moreover, expectancy effects, particularly when using subjective outcome measures such as perceived time flow, can introduce bias, even in a double-blind design. The physical sensations commonly associated with PDE5 inhibitors (e.g., flushing, nasal congestion, mild headache) could inadvertently unblind participants. Additionally, the short-term, single-dose nature of the pilot cannot assess chronic or cumulative effects, which may differ from acute changes in attentional or perceptual function.

To address these limitations, a fully powered randomized controlled trial (RCT) would need to include the following design elements:

• Larger sample size (n > 100) with stratification by baseline anxiety severity, gender, and prior PDE5 exposure.
• Three-arm crossover design: low-dose tadalafil (5 mg), moderate-dose (10 mg), and placebo.
• Anxiety induction paradigm (e.g., performance under observation, video recording, or a speech task) to mimic real-world stressors and heighten ecological relevance.
• Objective cognitive and physiological markers, such as:
• EEG (P300 latency and amplitude) to index attentional engagement and stimulus evaluation.
• Pupillometry as a proxy for cognitive load.
• Heart rate variability (HRV) to track autonomic arousal during task performance.

Furthermore, subjective measures should be complemented by behavioral metrics such as reaction time variability, omission/commission error rates, and performance persistence during sustained attention tasks. A longitudinal follow-up assessing tolerability, carry-over effects, and self-reported situational confidence would allow exploration of whether effects persist, fade, or sensitize with repeated dosing.

Crucially, ethical protocols must be embedded in all phases, including strict exclusion criteria (e.g., cardiovascular instability, concurrent anxiolytic use), active monitoring for side effects, and transparent communication regarding off-label use.

This RCT would help determine whether tadalafil’s influence on time perception and attention is a statistical curiosity or a clinically actionable phenomenon.

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