Modulating the Rate and Rhythmicity of Perceptual Rivalry Alternations with the Mixed 5-HT2A and 5-HT1A Agonist Psilocybin

Abstract

Binocular rivalry occurs when different images are presented simultaneously to corresponding points within the left and right eyes. Under these conditions, the observer's perception will alternate between the two perceptual alternatives. Motivated by the reported link between the rate of perceptual alternations, symptoms of psychosis and an incidental observation that the rhythmicity of perceptual alternations during binocular rivalry was greatly increased 10 h after the consumption of LSD, this study aimed to investigate the pharmacology underlying binocular rivalry and to explore the connection between the timing of perceptual switching and psychosis. Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine, PY) was chosen for the study because, like LSD, it is known to act as an agonist at serotonin (5-HT) 1A and 5-HT 2A receptors and to produce an altered state sometimes marked by psychosis-like symptoms. A total of 12 healthy human volunteers were tested under placebo, low-dose (115 mg/kg) and high-dose (250 mg/kg) PY conditions. In line with predictions, under both low-and high-dose conditions, the results show that at 90 min postadministration (the peak of drug action), rate and rhythmicity of perceptual alternations were significantly reduced from placebo levels. Following the 90 min testing period, the perceptual switch rate successively increased, with some individuals showing increases well beyond pretest levels at the final testing, 360 min postadministration. However, as some subjects had still not returned to pretest levels by this time, the mean phase duration at 360 min was not found to differ significantly from placebo. Reflecting the drug-induced changes in rivalry phase durations, subjects showed clear changes in psychological state as indexed by the 5D-ASC (altered states of consciousness) rating scales. This study suggests the involvement of serotonergic pathways in binocular rivalry and supports the previously proposed role of a brainstem oscillator in perceptual rivalry alternations and symptoms of psychosis.

Quantum formalism to describe binocular rivalry

“…More specifically, in Ref. (Carter et al, 2005), it was found that the response of subjects at the peak of the drug influence was found to be significantly slower; however, switches for all subjects became increasingly faster, such that six hours later some subjects were switching at intervals that were shorter, more regular and more rhythmic than their pretest levels. Therefore, this is also consistent with the results of Ref.…”

“…Therefore, we conclude that, within the context of our model, the hallucinogenic drug changes the burst frequency and the char-acteristic period T significantly, which places the observing conscious apparatus into a regime where oscillations are transparent. More recent studies on the influence of hallucinogenic drugs (Carter et al, 2007(Carter et al, , 2005 indicate that it might be in the "rebound-phase" (a phase reached several hours after the peak of the drug influence) that a state of the type indicated in Fig. 5 and in Ref.…”

The effect of particular active substances of hallucinogenic mushrooms

“…Jednakże, jak podaje w swojej pracy przeglądowej Stebelska (2013), niektóre efekty działania tych tryptamin nie zostają zniesione, a nawet ulegają nasileniu. Dotyczy to szczególnie osłabienia reakcji kognitywnych, wyrażanych trudnością w utrzymaniu uwagi oraz obniżeniem czujności (Carter et al 2005, Delgado & Moreno 1998, Stebelska 2013. Ta sama Autorka, podsumowując cytowane wyniki badań stwierdza, że system serotoninergiczny odpowiada za psychotyczne efekty działania tych substancji, zarówno przez wzbudzenie receptorów 5-HT 2A w obrębie obszarów kory mózgowej, ale także przez połączenie się z presynaptycznymi receptorami 5-HT 1A , które znajdują się w obrębie komórek serotoninergicznych grzbietowego jądra szwu.…”

“…Psilocin leads to deactivation of nerve cells within the DRN, which resembles that observed during REM sleep. Consequently, it leads to a reduction in serotonin release from terminals of ascending serotonergic projections to the cortex (Stebelska 2013, Carter et al 2005. This type of reduction in the concentration of serotonin in serotonergic projection target area, beginning in the DRN, may lead to the occurrence of hallucinations similar to those that occur among people suffering from schizophrenia (Aghajanian & Marek 1999, Gonzalez-Maeso & Sealfon 2009.…”

“…However, as Stebelska (2013) reported in her review article, some of the effects of these tryptamines shall not be removed, and would even undergo intensification. This is particularly the weakening of cognitive response, expressed as difficulty in maintaining attention and reduced vigilance (Carter et al 2005, Delgado & Moreno 1998, Stebelska 2013. The same author, summarizing the cited results, states that the serotonergic system is responsible for the psychotic effects of these substances, by the excitation of 5-HT 2A receptors within areas of the cerebral cortex, but also by the combination with the presynaptic 5-HT1A receptors, which are found in serotonergic cells within the dorsal raphe nucleus (DRN).…”