Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats

Kiilerich, Kat F.; Lorenz, Joe; Scharff, Malthe B.; Speth, Nikolaj Raahauge; Xiong, Mengfei; Jessen, Naja Støckel; Casado-Sainz, Agata; Shalgunov, Vladimir; Kjaerby, Celia; Satała, Grzegorz; Bojarski, Andrzej J.; Jensen, Anders A.; Herth, Matthias M.; Cumming, Paul; Overgaard, Agnete; Palner, Mikael

doi:10.31219/osf.io/gy6m9

Cited by 2 publications

(1 citation statement)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Complementary to these efforts, our study focuses moreover on enhancing overall brain state and its readiness for learning, aiming to boost neuroplasticity to amplify NF's impact: the current approach therefore combines fm-theta NF with psilocybin. While previous research on psychedelics has largely focused on high-dose studies, including those that highlight acute neuroplasticity (as reviewed by 68), as well as sustained neuroplastic effects specifically of psilocybin (101; 102), recent preclinical evidence is also revealing neuroplasticity changes resulting from repeated microdoses of psilocybin (103) and LSD in humans (70). As we delve deeper into understanding the complex mechanisms of neuroplasticity and the varied effects of psychedelics, the next logical step emerges: skillfully utilizing these insights to improve therapeutic interventions.…”

Section: Discussionmentioning

confidence: 99%

Psilocybin-assisted neurofeedback for the improvement of executive functions: a randomised semi-naturalistic-lab feasibility study

Enriquez-Geppert,

Krc,

O'Higgins

et al. 2023

Preprint

View full text Add to dashboard Cite

Widespread executive function deficits impair daily functioning in psychiatric disorders. In this group, reduced frontal-midline-theta neurofeedback responsiveness may be related to impaired neural plasticity. In our pioneering study, we investigated the feasibility and practicality of integrating a neuroplasticity agent by psilocybin-assisted neurofeedback. Thirty-seven participants were divided into an experimental and a passive control group. The experimental group received three microdose sessions followed by three psilocybin-assisted neurofeedback sessions. Our results showed changes in self-regulatory frontal-midline theta from session-to-session approaching significance. Importantly, placebo ratings and expectations did not differ between the two groups. There were no immediate improvements in the experimental tasks assessing executive functions. However significant improvements were observed in self-reported executive functions in daily life. Participants reported improvements in working memory, shifting, monitoring and inhibition with high effect sizes. In addition, the experimental group reported positive changes in their priority areas, which included cognition, presence and mood. These results suggest that psilocybin-assisted neurofeedback shows promise for a potential transdiagnostic treatment. Future research should investigate the optimal timing and duration of this pharmacological and neuroscientific combination. Overall, our study highlights the feasibility and potential of this innovative approach, emphasizing the potential for enhanced neuroplasticity that may amplify the impact of neurofeedback.

show abstract

Section: Discussionmentioning

confidence: 99%

Psilocybin-assisted neurofeedback for the improvement of executive functions: a randomised semi-naturalistic-lab feasibility study

Enriquez-Geppert,

Krc,

O'Higgins

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Psilocybin reduces heroin seeking behavior and modulates inflammatory gene expression in the nucleus accumbens and prefrontal cortex of male rats

Floris,

Dabrowski,

Zanda

et al. 2024

Preprint

View full text Add to dashboard Cite

Preclinical and human studies indicate psilocybin may reduce perseverant maladaptive behaviors, including nicotine and alcohol seeking. Such studies in the opioid field are lacking, though opioids are involved in more >50% of overdose deaths. Psilocybin is an agonist at the serotonin 2A receptor (5-HT2AR), a well-documented target for modulation of drug seeking, and evidence suggests 5-HT2AR agonists may dampen motivation for opioids. We sought to investigate the therapeutic efficacy of psilocybin in mediating cessation of opioid use and maintenance of long-lasting abstinence from opioid seeking behavior in a rat model of heroin self-administration (SA). Psilocybin or 5-HT2AR antagonists ketanserin and volinanserin were administered systemically to rats prior to SA of 0.075 mg/kg/infusion of heroin, or relapse following forced abstinence. Psilocybin did not alter heroin taking, but a single exposure to 3.0 mg/kg psilocybin 4-24 hours prior to a relapse test blunted cue-induced heroin seeking. Conversely, 5-HT2AR antagonists exacerbated heroin relapse. To begin to elucidate mechanisms of psilocybin, drug-naïve rats received psilocybin and/or ketanserin, and tissue was collected from the prefrontal cortex (PFC), a region critical for drug seeking and responsive to psilocybin, 24 hours later for RNA-sequencing. 3.0 mg/kg psilocybin regulated ∼2-fold more genes in the PFC than 1.0 mg/kg, including genes involved in the cytoskeleton and cytokine signaling. Ketanserin blocked >90% of psilocybin-regulated genes, including the IL-17a cytokine receptor,Il17ra. Psychedelic compounds have reported anti-inflammatory properties, and therefore we performed a gene expression array to measure chemokine/cytokine molecules in the PFC of animals that displayed psilocybin-mediated inhibition of heroin seeking. Psilocybin regulated 4 genes, includingIl17a, and a subset of genes correlated with relapse behavior. Selective inhibition of PFC IL-17a was sufficient to reduce heroin relapse. We conclude that psilocybin reduces heroin relapse and highlight IL-17a signaling as a potential downstream pathway of psilocybin that also reduces heroin seeking.

show abstract

Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats

Abstract: Repeated low doses of psilocybin reduce compulsive actions and increase synaptic connections in the paraventricular thalamic nucleus of the rat

Cited by 2 publications

References 45 publications

Psilocybin-assisted neurofeedback for the improvement of executive functions: a randomised semi-naturalistic-lab feasibility study

Psilocybin-assisted neurofeedback for the improvement of executive functions: a randomised semi-naturalistic-lab feasibility study

Psilocybin reduces heroin seeking behavior and modulates inflammatory gene expression in the nucleus accumbens and prefrontal cortex of male rats

Contact Info

Product

Resources

About