Potential Therapeutic Effects of Psilocybin/Psilocin are Minimized While Possible Adverse Reactions are Overrated

Santos, Rafael G. dos

doi:10.1097/ftd.0000000000000028

Cited by 5 publications

(3 citation statements)

References 14 publications

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“…There is limited evidence on the role of Psilocybe cubensis in modulating mood in rodents. On the other hand, the therapeutic effects of psilocybin have been reported in several psychiatric disorders such as obsessive compulsive disorder, anxiety, and addiction (Bogenschutz & Pommy, 2012; dos Santos, 2014; Grob et al, 2011; Stebelska, 2013). Despite the evidence of how psilocybin alters cognition in humans, unfortunately, little is known about its effects on cognition in animals (Rambousek et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Psilocybe cubensis extract potently prevents fear memory recall and freezing behavior in short- but not long-term in a rat model of posttraumatic stress disorder.

Ghofrani-Jahromi,

Nouri-Darehno,

Rahimi-Danesh

et al. 2024

Behavioral Neuroscience

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Psilocybe cubensis is a species of psilocybin mushroom (magic mushroom) of moderate potency whose principal active compounds are psilocybin and psilocin. Recent studies have shown the significant procognitive and mood-enhancer effects of Psilocybe cubensis. However, evidence is so limited, especially in preclinical studies. We aimed to investigate the effect of Psilocybe cubensis extract on posttraumatic stress disorder (PTSD)-like behavior, pain perception, locomotor activity, and anxiety in a rat model of PTSD. Male rats were exposed to three consecutive shocks (0.8 mA, 3 s interval) paired with three sounds broadcasted 3 s before delivering shocks (75 dB, 3 s). After 1, 3, or 21 days, freezing rate was measured in the fear-conditioning apparatus. Open filed test and hot plate were used to assess locomotor activity and anxiety, and pain subthreshold, respectively. Psilocybe cubensis was injected intraperitoneal at the dose of 25 mg/kg (single administration) before (pretrain) or after (posttrain) shocks, or before the test (pretest). Results showed psilocybin potently alleviated PTSD symptom is short-but not long-term after the induction of PTSD. Psilocybe cubensis decreased locomotor activity only in a short period after administration. Psilocybe cubensis also increased pain subthreshold and decreased anxiety. In conclusion, Psilocybe cubensis effects on PTSD-like behavior and locomotor activity seem to be remained in short-term, while Psilocybe cubensis effects on pain subthreshold and anxiety remained long-term. This is the first study evaluating the effect of Psilocybe cubensis on PTSD-like behavior in rats in three different time protocols (1, 3, and 21 days after fear conditioning).

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Section: Discussionmentioning

confidence: 99%

Psilocybe cubensis extract potently prevents fear memory recall and freezing behavior in short- but not long-term in a rat model of posttraumatic stress disorder.

Ghofrani-Jahromi,

Nouri-Darehno,

Rahimi-Danesh

et al. 2024

Behavioral Neuroscience

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“…These longlasting positive changes lead to an exploration of the therapeutic potential of psychedelics as well as the mechanisms underlying this potential. Because of its general safety, intermediate duration of action, and therapeutic potential in several neuropsychiatric disorders, psilocybin is currently the most intensely studied psychedelic in clinical trials (Sewell et al, 2006;Grob et al, 2011;Stebelska, 2013;Dos Santos, 2014).…”

Section: Introductionmentioning

confidence: 99%

The Effects of Daytime Psilocybin Administration on Sleep: Implications for Antidepressant Action

et al. 2020

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Serotonergic agonist psilocybin is a psychedelic with antidepressant potential. Sleep may interact with psilocybin’s antidepressant properties like other antidepressant drugs via induction of neuroplasticity. The main aim of the study was to evaluate the effect of psilocybin on sleep architecture on the night after psilocybin administration. Regarding the potential antidepressant properties, we hypothesized that psilocybin, similar to other classical antidepressants, would reduce rapid eye movement (REM) sleep and prolong REM sleep latency. Moreover, we also hypothesized that psilocybin would promote slow-wave activity (SWA) expression in the first sleep cycle, a marker of sleep-related neuroplasticity. Twenty healthy volunteers (10 women, age 28–53) underwent two drug administration sessions, psilocybin or placebo, in a randomized, double-blinded design. Changes in sleep macrostructure, SWA during the first sleep cycle, whole night EEG spectral power across frequencies in non-rapid eye movement (NREM) and REM sleep, and changes in subjective sleep measures were analyzed. The results revealed prolonged REM sleep latency after psilocybin administration and a trend toward a decrease in overall REM sleep duration. No changes in NREM sleep were observed. Psilocybin did not affect EEG power spectra in NREM or REM sleep when examined across the whole night. However, psilocybin suppressed SWA in the first sleep cycle. No evidence was found for sleep-related neuroplasticity, however, a different dosage, timing, effect on homeostatic regulation of sleep, or other mechanisms related to antidepressant effects may play a role. Overall, this study suggests that potential antidepressant properties of psilocybin might be related to changes in sleep.

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“…Due to this phenomenological resemblance of acute intoxication with psychosis and its long history of safe clinical use (including psychiatric treatment) it is, nowadays, the most frequently used serotonergic model of psychosis in humans (Tyls et al, 2013). Furthermore, the therapeutic potential of psilocin/psilocybin has been recently investigated in several psychiatric disorders such as obsessive–compulsive disorder, anxiety, and addiction (Moreno et al, 2006; Grob et al, 2011; Bogenschutz and Pommy, 2012; Stebelska, 2013; dos Santos, 2014). Despite the evidence of how psilocybin changes cognitive performance in humans, little is known about its effects on cognition in animals.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Psilocin on Memory Acquisition, Retrieval, and Consolidation in the Rat

Rambousek

Páleníček²,

Valeš

et al. 2014

Front. Behav. Neurosci.

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The involvement of the serotonin system in the pathophysiology of schizophrenia has been elucidated by experiments with hallucinogens. Application of a hallucinogen to humans leads to changes in perception, cognition, emotions, and induction of psychotic-like symptoms that resemble symptoms of schizophrenia. In rodent studies, their acute administration affects sensorimotor gating, locomotor activity, social behavior, and cognition including working memory, the phenotypes are considered as an animal model of schizophrenia. The complexity and singularity of human cognition raises questions about the validity of animal models utilizing agonists of 5-HT2A receptors. The present study thus investigated the effect of psilocin on memory acquisition, reinforced retrieval, and memory consolidation in rats. Psilocin is a main metabolite of psilocybin acting as an agonist at 5-HT2A receptors with a contribution of 5-HT2C and 5-HT1A receptors. First, we tested the effect of psilocin on the acquisition of a Carousel maze, a spatial task requiring navigation using distal cues, attention, and cognitive coordination. Psilocin significantly impaired the acquisition of the Carousel maze at both doses (1 and 4 mg/kg). The higher dose of psilocin blocked the learning processes even in an additional session when the rats received only saline. Next, we examined the effect of psilocin on reinforced retrieval and consolidation in the Morris water maze (MWM). The dose of 4 mg/kg disrupted reinforced retrieval in the MWM. However, the application of a lower dose was without any significant effect. Finally, neither the low nor high dose of psilocin injected post-training caused a deficit in memory consolidation in the MWM. Taken together, the psilocin dose dependently impaired the acquisition of the Carousel maze and reinforced retrieval in MWM; however, it had no effect on memory consolidation.

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Potential Therapeutic Effects of Psilocybin/Psilocin are Minimized While Possible Adverse Reactions are Overrated

Cited by 5 publications

References 14 publications

Psilocybe cubensis extract potently prevents fear memory recall and freezing behavior in short- but not long-term in a rat model of posttraumatic stress disorder.

Psilocybe cubensis extract potently prevents fear memory recall and freezing behavior in short- but not long-term in a rat model of posttraumatic stress disorder.

The Effects of Daytime Psilocybin Administration on Sleep: Implications for Antidepressant Action

The Effect of Psilocin on Memory Acquisition, Retrieval, and Consolidation in the Rat

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