The neverending trip: associations between Hallucinogen Persisting Perception Disorder (HPPD) and non-visual perceptual disturbances

Abstract: Objective: Hallucinogen Persistent Perception Disorder (HPPD) is a condition where the effects of hallucinogenic drugs reoccur long after the acute effects have stopped. No established risk factors or mechanisms for HPPD have been identified. However, reports have suggested a risk phenotype for HPPD due to associations with other perceptual disturbances. With recent increases in therapeutic psychedelic drug use, it is essential to consider the existence of HPPD risk factors. Therefore, exploring potential links between HPPD and other perceptual disturbances, such as tinnitus and migraine with aura, is a necessary first step. This study aimed to investigate the association between HPPD and other perceptual disorders. Methods: One hundred thirty-eight individuals with HPPD and 116 controls participated in a survey assessing the prevalence of various perceptual disturbances: photosensitivity, phonosensitivity, tinnitus, migraine with aura, vertigo, paraesthesia, and synaesthesia. Results: The survey results showed a significant association between HPPD and photosensitivity (OR = 10.65), phonosensitivity (OR = 8.00), and the number of perceptual disturbances (OR = 1.59) in the HPPD group compared to the control group. The study also observed trends of dual prevalence between HPPD and tinnitus, migraine with aura, vertigo, paraesthesia, and synaesthesia. Participants with both HPPD and other perceptual disturbances were likelier to experience additional perceptual disturbances after the onset of HPPD. Conclusions: These findings suggest a common vulnerability or pathophysiological mechanism among these perceptual disturbances. Given the increasing therapeutic use of hallucinogens, the results of this study provide essential considerations for HPPD risk profiles. Moreover, they may guide future investigations into HPPD's pathophysiology and management options.