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Ditta Zobor, Andre Messias, Soenke Wimmers, Vladimir Milenkovic, Olaf Strauss, Eberhart Zrenner; Hallucinogen Persisting Perception Disorder (HPPD) After Marijuana Consumption: Clinical And In-vitro Evidence Of Cannabinoid (CB) Receptors In RPE Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3523.
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To present detailed electrophysiological data of a young male patient, who suffered from HPPD after a long period of marihuana abstinence, and new in-vitro evidences for the presence of CB receptors in RPE cells. A possible mechanism of long-term changes in the retina will be provided.
A complete ophthalmological examination was carried out, including psychophysical and electrophysiological examinations. Ganzfeld ERG, multifocal ERG and EOG were recorded including additional stimulation paradigms to improve retinal function evaluation. Furthermore, electrically evoked phosphene thresholds (EPTs) were measured to test retinal sensitivity.We also isolated mRNA from human neuronal retina and RPE for PCR examinations to study the expression of CB1 and CB2 receptors. In order to detect further interaction partners of cannabinoid-dependent signalling RT-PCR was performed using primers against TRPV1 and TRPV2 Ca2+-conducting ion channels.
Ganzfeld ERG responses and intensity-response function were within normal ranges in both eyes, so as multifocal ERG responses. The EOG showed a slightly reduced fast oscillation ratio (max = 11.9 / 12.8 µV/deg and min = 11.0 / 11.1 µV/deg: ratio = 1.08 and 1.15 on right and left eyes respectively), and the slow oscillation showed diminished standing potentials (6.0 and 6.45 µV/deg) and a light peak within the normal range (23.79 and 19.16 µV/deg) with Arden ratios of 3.967 and 2.97, respectively. The EPTs were considerably reduced in both eyes, in particular for pulses with long durations (50 ms) where the subject reported visual sensations even at the lowest possible currents of the neurostimulator.In our in-vitro studies CB1 and CB2 receptors were identified in both, human retina and RPE cDNA, furthermore, TRPV1 and TRPV2 Ca2+-conducting ion channels could also be detected, which are known to be linked to the cannabinoid-dependent signalling.
Our findings strongly suggest the presence of functional CB1 and CB2 receptors in both human retina and RPE. The observations presented here in relation to electrophysiological events in our patient as well as in relation to Cl- channel may contribute to the elucidation of the detailed mechanism. Furhermore, EOG and EPT measurements may be used to demonstrate long-term retinal alterations in cannabis-induced HPPD in patients.
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