Toward Mapping Neurobehavioral Heterogeneity of Psychedelic Neurobiology in Humans

Moujaes, Flora; Preller, Katrin H.; Ji, Jie Lisa; Murray, John D.; Berkovitch, Lucie; Vollenweider, Franz X.; Antičević, Alan

doi:10.1016/j.biopsych.2022.10.021

Cited by 30 publications

(21 citation statements)

References 117 publications

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“…Notably, this framework may prove fruitful in future pharmacological neuroimaging studies. Overall, our study chimes in with the trending call (Moujaes et al, 2022) for a stronger research focus on idiosyncratic rather than merely generalisable brain-activity patterns, paving the way for more effective, personalised medical approaches.…”

Section: Discussionmentioning

confidence: 56%

“…Notably, a stronger research focus on idiosyncratic rather than generalisable features may be key to the advancement of personalised medical approaches. Arguably, it is especially important in the context of psychedelic neuroimaging studies, as psychedelic drugs hold great therapeutic promise while at the same time they are known to induce highly variable responses in individuals (Moujaes et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

“…While network-based analyses of neuroimaging data have advanced our understanding of the group-level effect of psychedelics on the functional network organisation of the brain, it is less clear how each individual’s neural response to a psychedelic compound maps onto the various aspects of their unique subjective drug experience. In fact, the subjective effects of psychedelics are multifaceted and highly variable, both within and between subjects (Moujaes et al, 2022). Crucially, several lines of evidence suggest that the long-term benefits of psilocybin are influenced by the subjective acute drug experience (Bogenschutz et al, 2015; Griffiths et al, 2016; Johnson et al, 2017; Roseman et al, 2018; Ross et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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The Unique Neural Signature of Your Trip: Functional Connectome Fingerprints of Subjective Psilocybin Experience

Tolle

Farah

Mallaroni

et al. 2023

Preprint

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The emerging neuroscientific frontier of brain fingerprinting has recently established that human functional connectomes (FCs) exhibit fingerprint like idiosyncratic features, which map onto heterogeneously distributed behavioural traits. Here we harness brain fingerprinting tools to extract FC features that predict subjective drug experience induced by the psychedelic psilocybin. Specifically, in neuroimaging data of healthy volunteers under the acute influence of psilocybin or a placebo, we show that, post-psilocybin administration, FCs become more idiosyncratic due to greater inter-subject dissimilarity. Moreover, whereas in placebo subjects idiosyncratic features are primarily found in the frontoparietal network, in psilocybin subjects they concentrate in the default-mode network (DMN). Crucially, isolating the latter revealed an FC pattern that predicts subjective psilocybin experience and is characterised by reduced within-DMN and DMN-limbic connectivity, as well as increased connectivity between the DMN and attentional systems. Overall, these results contribute to bridging the gap between psilocybin-mediated effects on brain and behaviour, while demonstrating the value of a brain-fingerprinting approach to pharmacological neuroimaging.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Unique Neural Signature of Your Trip: Functional Connectome Fingerprints of Subjective Psilocybin Experience

Tolle

Farah

Mallaroni

et al. 2023

Preprint

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“…In the future, an approach tailored to the PK characteristics of the individual may thus be highly valuable to induce acute subjective effects that have been found to predict improvements in mental health outcomes in psychedelic experiences (Yaden and Griffiths, 2020). In this way, infusion parameters can be tailored to the specific characteristics of patient populations, treatment outcomes, and individual variables that bear relevance in psychedelic medicine e.g., personality traits (Aday et al, 2021), genetics, and brain function (Moujaes et al, 2022). Importantly, personalized infusion parameters can be leveraged beyond attaining a stable plateau of effects.…”

Section: Discussionmentioning

confidence: 99%

Psychological and physiological effects of extended DMT

Luan¹,

Eckernäs²,

Ashton³

et al. 2023

Preprint

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Background: N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic that when injected as a bolus intravenous injection induces a rapid and transient altered state of consciousness. Its marked and novel subjective effects make DMT a powerful tool for the neuroscientific study of consciousness and preliminary results show its potential role in treating mental health conditions. Aims: In a within-subjects, placebo-controlled study, we investigated a novel method of DMT administration involving a bolus injection paired with a constant-rate infusion, with the goal of extending the DMT experience. Methods: Pharmacokinetic parameters of DMT estimated from plasma data of a previous study of bolus intravenous DMT were used to derive dose regimens necessary to keep subjects in steady levels of immersion into the DMT experience over an extended period of 30 minutes, and four dose regimens were tested. Results: The present method is effective for extending the DMT experience in a stable and tolerable fashion. While subjective effects were maintained over the period of active infusion, anxiety ratings remained low and heart rate habituated within 15 minutes, indicating psychological and physiological safety of extended DMT. Plasma DMT concentrations increased consistently starting ten minutes into DMT administration, whereas psychological effects plateaued into the desired steady state, suggesting the development of acute psychological tolerance to DMT. Conclusion: Taken together, these findings demonstrate the safety and effectiveness of continuous IV DMT administration, laying the groundwork for the further development of this method of administration for basic and clinical research.

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“…Psychedelics, or hallucinogens, are members of a class of drugs known for their ability to cause significant alterations in perception, mood, and cognitive processes. , Despite historical and ongoing stigmatization, psychedelics have demonstrated potential in the treatment of a range of mental health disorders, including anxiety, cluster headaches, obsessive–compulsive disorder, and depression . This potential is primarily attributed to their interaction with the serotonergic system, with individual responses varying greatly due to genetic differences …”

Section: Current State Of Psychedelic Researchmentioning

confidence: 99%

Unraveling Psychedelic Responses: Targeted Protein Degradation and Genetic Diversity

Kargbo

2023

ACS Med. Chem. Lett.

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This Viewpoint discusses the intersection of targeted protein degradation (TPD) technologies and psychedelic research. The resurgence in interest in psychedelics for treating mental disorders and the known genetic variability in responses require new strategies. TPD technologies might address this variability, modulating protein expressions based on genetic profiles. The discussion includes potential challenges in implementing TPD technologies in psychedelic research and potential strategies to address these issues. It considers lessons from COVID-19 research on genetic variability, proposing integration of TPD technologies into psychedelic research as a promising field despite these challenges, possibly leading to personalized treatments and improved patient outcomes.

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Toward Mapping Neurobehavioral Heterogeneity of Psychedelic Neurobiology in Humans

Cited by 30 publications

References 117 publications

The Unique Neural Signature of Your Trip: Functional Connectome Fingerprints of Subjective Psilocybin Experience

The Unique Neural Signature of Your Trip: Functional Connectome Fingerprints of Subjective Psilocybin Experience

Psychological and physiological effects of extended DMT

Unraveling Psychedelic Responses: Targeted Protein Degradation and Genetic Diversity

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