Hallucinogen Persistent Perception Disorder Induced by New Psychoactive Substituted Phenethylamines; A Review with Illustrative Case
Cornel N. Stanciu and Thomas M. Penders
Current Psychiatry Reviews, 2016, Vol. 12, No. 2, 1-3.
Hallucinogen Persistent Perception Disorder (HPPD) is considered an “uncommon” disorder described in association with use of hallucinogens such as LSD, mescaline and psilocybin. Despite multiple mentions of persistence of visual disturbances reported by users on online forums, clinicians may not be aware of this complication. There have been few descriptions of HPPD in association with use of new psychoactive substances (such as 2C-E). Increasing use of these designer stimulants places greater numbers at risk for psychiatric morbidities including HPPD. Here we report the first documented case of HPPD due to high dose 2C-E and blunting of symptoms with addition of lamotrigine.
Keywords : Stimulants, hallucinogen, psychoactive, phenylethylamines.
Hallucinogens are a group of substances that include both naturally occurring and synthetic agents. During intoxication hallucinogens induce a reversible and transient state characterized by a variety of perceptual disturbances including visual illusions and hallucinations. A rare phenomenon termed hallucinogen persistent perception disorder (HPPD) has been observed in users of hallucinogens Reports have been, most commonly associated with use of LSD. This diagnostic category has been included as a DSM diagnosis since DSM IV. There is a corresponding ICD-10 code for this diagnosis (Hallucinogen Use, unspecified with hallucinogen persisting perception disorder). The incidence of this disorder is uncertain. An online survey suggests that 0.12-4.1% of users may develop HPPD .
It is characterized by partial recurrence or persistence of visual disturbances previously experienced during intoxication following drug-free periods of varying lengths ranging from days to years. Such experiences have similarities to acute LSD intoxication and take the form of various geometrical shapes, peripheral visual field flickers, flashes of colors, halos and palinopsia (trailing phenomena). Unlike true psychosis, users are able to recognize these as hallucinatory experiences. Little is known about the long-term natural history of this disorder . Symptoms are recurrent and may be precipitated by stress, change in ambient light or use of alcohol, and cannabis. Precipitation after use of risperidone has also been reported to precipitate such phenomena [3-6]. Case reports of LSD [7, 8], MDMA  and psilocybin  have been extensively described.Rarely cases have been reported that are attributed to newer psychoactive substances.
Phenylethylamines are a class of substances with documented psychoactive stimulant effects that include
amphetamines, methamphetamines and MDMA. When manipulated chemically in research laboratories they produce ring-substituted compounds that result in enhanced effects and novel psychoactive properties. Since first synthesized and popularized in the 1970s by the biochemist Alexander Shulgin, prevalence of use of these substances have varied over time. Recently, there has been a somewhat dramatic increase in the availability and use of these designer substances. The United Nations Office on
Drugs and Crime (UNODC) on new psychoactive substances have reported the use of increasing numbers of such compounds.
Despite some identified phenylethylamines having been included as schedule-I substances, the number of reports made to UNDOC has quadrupled in recent years with approximately 20% attributed to phenylethylamines .
One such molecule is 4-ethyl-2,5-dimethoxy-phenethylamine (2C-E or “Europa”) . Ingested in pill form or powder as suggested by the drug information website, Erowid, a 10-20mg dose produces a rapid onset of perceptual changes with duration of effect from three hours to 24 hours [3, 13]. A dose-effect relationship is described by users with reports of changes with increasing dosages in the nature, duration and intensity of effects. Erowid users have reported normal thought processes without impaired judgment while experiencing visual and auditory perceptual disturbance giving, a property valued by some who use this agent.
Some perceptual disturbances are described as distortions in perception of time, distortion of sounds described as echoing, or shifting of pitch. Auditory hallucinations perceived as scraping or popping sounds are commonly experienced. Visual disturbances are similar to those associated with mescaline and LSD use. However more geometrically complex and more intense appreciation of color effects of hallucinations are commonly reported. These agents do not appear to induce euphoria.