Hallucinogen Persisting Perception Disorder (HPPD) is a rare, and therefore, poorly understood condition linked to hallucinogenic drugs consumption. The prevalence of this disorder is low; the condition is more often diagnosed in individuals with a history of previous psychological issues or substance misuse, but it can arise in anyone, even after a single exposure to triggering drugs. The aims of the present study are to review all the original studies about HPPD in order to evaluate the following: (1) the possible suggested etiologies; (2) the possible hallucinogens involved in HPPD induction; (3) the clinical features of both HPPD I and II; (4) the possible psychiatric comorbidities; and (5) the available and potential therapeutic strategies. We searched PubMed to identify original studies about psychedelics and Hallucinogen Persisting Perception Disorder (HPPD). Our research yielded a total of 45 papers, which have been analyzed and tabled to provide readers with the most updated and comprehensive literature review about the clinical features and treatment options for HPPD.

Hallucinogen persisting perception disorder (HPPD) is rarely encountered in clinical settings. It is described as a re-experiencing of some perceptual distortions induced while intoxicated and suggested to subsequently cause functional impairment or anxiety. Two forms exist: Type 1, which are brief "flashbacks," and Type 2 claimed to be chronic, waxing, and waning over months to years. A review of HPPD is presented. In addition, data from a comprehensive survey of 20 subjects reporting Type-2 HPPD-like symptoms are presented and evaluated. Dissociative Symptoms are consistently associated with HPPD. Results of the survey suggest that HPPD is in most cases due to a subtle over-activation of predominantly neural visual pathways that worsens anxiety after ingestion of arousal-altering drugs, including non-hallucinogenic substances. Individual or family histories of anxiety and pre-drug use complaints of tinnitus, eye floaters, and concentration problems may predict vulnerability for HPPD. Future research should take a broader outlook as many perceptual symptoms reported were not first experienced while intoxicated and are partially associated with pre-existing psychiatric comorbidity.

Dopamine receptor antagonism is a common mechanism underlying the therapeutic efficacy of all classical antipsychotic drugs. It is also thought to underlie the propensity of these agents to induce the movement disorder, tardive dyskinesia (TD), in one fifth of chronically exposed schizophrenia patients. We examined the polymorphic serine to glycine substitution in the first exon of the gene encoding the dopamine D3 receptor (DRD3) inn 53 schizophrenia patients with TD, 63 matched patients with similar antipsychotic exposure but no TD and 117 normal controls. There was a difference in allele frequency that was of borderline significance (P = 0.055), due to an excess of the DRD3 gly allele (allele 2) in the schizophrenia patients with TD. The difference in genotype distribution among the groups was highly significant ( The dopamine D3 receptor gene (DRD3) has been a focus of intense interest in psychiatric genetics for a number of years, primarily in relation to schizophrenia. This interest has not waned in spite of a discouraging disparity in the results obtained. The human DRD3 gene was localized to 3q13.3 by in situ hybridization.1 A polymorphic site in exon 1 of DRD3 gives rise to a serine to glycine substitution in the N terminal extracellular domain of the receptor protein. This creates a BalI (MscI) restriction enzyme site.2 Numerous groups have examined linkage and association of schizophrenia with DRD3. Linkage studies have been uniformly negative. Over 30 studies (mostly population-but also family-based) were included by Williams et al 3 in a meta-analysis that yielded evidence for a modest association with homozygosity for either Correspondence: Professor B Lerer,