bioRxiv (Cold Spring Harbor Laboratory)
December 12, 2023
Hanna Honcamp, Michael Schwartze, Maria Amorim et al.
preprint
Resting state brain activity is inherently non-stationary. Hidden Semi-Markov Models can characterize continuous resting state data as a sequence of recurring brain states. Previous research suggested that EEG brain state dynamics in the alpha frequency link to auditory hallucination proneness in non-clinical individuals. This study aimed to replicate those findings. Most brain states were reproducible across different data sets, confirming robust and generalizable EEG resting state dynamics. However, the association with hallucination proneness was not directly reproducible across data sets.
bioRxiv (Cold Spring Harbor Laboratory)
October 23, 2023
Ryan J. Rakoczy, Grace N. Runge, Abhishek K. Sen et al.
preprint
Naturally occurring tryptamines in psilocybin-containing mushrooms—baeocystin, norbaeocystin, and aeruginascin—were compared with psilocybin for pharmacological and behavioral effects. All compounds showed nearly identical rates of dephosphorylation and metabolism. Only dephosphorylated forms of baeocystin and norbaeocystin crossed a blood-brain barrier model similarly to psilocin (psilocybin's active form). In rats, only psilocybin triggered head twitch responses (a marker of hallucinogenic potential), but norbaeocystin, like psilocybin, improved outcomes in the forced swim test. All compounds showed minimal effects on renal and hepatic health markers. The findings suggest norbaeocystin may share psilocybin's therapeutic potential without causing hallucinations.
bioRxiv (Cold Spring Harbor Laboratory)
October 16, 2023
Xiaofei Jia, Rui Li, Changle Zhou
preprint
Leyi mental training, which combines relaxation, breathing, meditation, koan, and cognitive regulation, improved both emotion and cognition in practitioners. Electroencephalography and psychological scales showed significant enhancements after the intervention. The training may boost emotional regulation by increasing sensitivity to present experiences and strengthening cognitive control, allowing non-reactive attention to all stimuli regardless of emotional valence. It also helps allocate cognitive resources more effectively for current tasks.
bioRxiv (Cold Spring Harbor Laboratory)
August 28, 2023
Nicholas Kolbman, Tiecheng Liu, Peter R. Guzzo et al.
preprint
A single intravenous dose of psilocybin (1 mg/kg or 10 mg/kg) reduced mechanical hypersensitivity in rats for 28 days after formalin-induced chronic pain, but had only a limited effect on thermal hyperalgesia. Formalin injection caused thermal hyperalgesia and bilateral mechanical hypersensitivity in all rats. Psilocybin significantly attenuated the mechanical hypersensitivity throughout the 28-day testing period, while thermal hyperalgesia was reduced only on days 1, 3, 5, and 21. These results suggest psilocybin may have potential for treating chronic pain, though its effects on different pain types vary.
bioRxiv (Cold Spring Harbor Laboratory)
August 13, 2023
Oris Shenyan, Matteo Lisi, John A. Greenwood et al.
preprint
Hallucinatory experiences, defined as perception without external stimuli, occur in both pathological and non-pathological states and are divided into simple and complex types. Non-pathological visual hallucinations can be induced experimentally using different methods. This study compared two techniques: flicker and perceptual deprivation (Ganzfeld) in 20 participants, measuring hallucination frequency and complexity through button press, retrospective drawing, interviews, and questionnaires. Simple hallucinations were more common than complex hallucinations with both techniques. Flicker elicited more hallucinations on average, but Ganzfeld hallucinations lasted longer.
bioRxiv (Cold Spring Harbor Laboratory)
July 20, 2023
Rafael V Lima Da Cruz, Richardson N. Leão, Thiago C. Moulin
preprint
New neurons continue to be generated in the mammalian brain throughout life, a process linked to the HPA axis and mood disorders. Psychedelic compounds—including phenethylamines, tryptamines, cannabinoids, and others—have emerged as potential treatments for neuropsychiatric disorders, with evidence suggesting they increase adult neurogenesis. This systematic review examined 68 studies from a total of 205 articles, covering CB1 agonists, NMDA antagonists, harmala alkaloids, tryptamines, and entactogens. The findings describe how different psychedelics affect the birth of new neurons and brain plasticity, providing a comprehensive picture that may inform future therapeutic strategies for neuropsychiatric disorders.
bioRxiv (Cold Spring Harbor Laboratory)
June 5, 2023
Annie Da Costa Souza, Bryan Da Costa Souza, Arthur França et al.
preprint
The psychedelic 5-MeO-DMT increases delta power and decreases theta power in the hippocampus of freely moving rats, effects not explained by changes in locomotion. It also dose-dependently reduces slow and mid gamma power and theta phase modulation. The overall spectral profile of awake behavior after 5-MeO-DMT resembles electrophysiological states seen during slow-wave sleep and REM sleep. These findings suggest that classical psychedelics may integrate waking behaviors with sleep-like neural activity patterns.
bioRxiv (Cold Spring Harbor Laboratory)
March 21, 2023
Adrien Martel, Nicolás Bruno, Ian H. Robertson et al.
preprint
Intentional and unintentional mind-wandering have distinct brain signatures measurable by scalp EEG. Theta-frequency activity best distinguishes on-task from off-task states, while alpha-frequency activity characterizes intentional task-unrelated thought compared to unintentional. These findings support the intentionality dimension of mind-wandering and suggest potential for real-time detection of maladaptive mind-wandering.
bioRxiv (Cold Spring Harbor Laboratory)
February 6, 2023
G Pradeep Kumar, Kanishka Sharma, A Adarsh et al.
preprint
Long-term Brahmakumaris Rajyoga meditators practicing with open eyes show distinct changes in brain functional connectivity compared to controls listening to music. Using two measures—magnitude squared coherence (MSC) and imaginary part of coherency (ICoh)—the study finds that meditators have higher baseline MSC in frontocentral and centroparietal regions and higher |ICoh| globally in higher beta and gamma bands. During meditation, MSC increases in higher theta and alpha bands in frontal and parietal regions, while |ICoh| decreases across most regions and bands except alpha. Controls show no such changes during music. Increased frontal MSC and decreased |ICoh| suggest enhanced self-awareness; lower occipital MSC in meditators at baseline implies altered visual processing from long-term open-eye practice.
bioRxiv (Cold Spring Harbor Laboratory)
May 22, 2022
Leonard Lerer, Eric Reynolds, Jeet Varia et al.
preprint
A sustainable source of 5-MeO-DMT, a promising compound for psychiatric treatment, has been developed using a cell line from the parotoid gland of the endangered Incilius alvarius toad. This innovative approach demonstrated successful biosynthesis of 5-MeO-DMT through chemical processes in vitro. Given that natural populations are under ecological threat due to habitat loss and demand, this method offers a cruelty-free alternative for producing 5-MeO-DMT, potentially supporting future psychedelics and drug studies while preserving biodiversity.
bioRxiv (Cold Spring Harbor Laboratory)
January 21, 2022
Konstantin A. Demin, Olga V. Kupriyanova, Вадим А. Шевырин et al.
preprint
Certain synthetic N-Benzyl-2-phenylethylamine (NBPEA) derivatives, related to hallucinogens like mescaline and MDMA, produce distinct behavioral and neurochemical effects in adult zebrafish. Substitutions on the N-benzyl fragment primarily affected locomotion, while those on the phenethylamine moiety influenced anxiety-like behavior. The compounds also modulated brain serotonin and/or dopamine turnover. Several behavioral clusters emerged: anxiogenic/hypolocomotor, behaviorally inert, anxiogenic/hallucinogenic-like, and anxiolytic/hallucinogenic-like. Two compounds reduced despair-like behavior. Artificial intelligence-driven phenotyping linked multiple compounds to NMDA antagonists and/or MDMA, suggesting hallucinogenic-like properties. In silico modeling indicated similarities between these NBPEAs, MDMA, and ketamine, implicating serotonin release, calcium channel activity, and serotonin receptor involvement.
bioRxiv (Cold Spring Harbor Laboratory)
November 3, 2021
Brandon Gunasekera, Cathy Davies, Grace Blest‐hopley et al.
preprint
A single dose of delta-9-tetrahydrocannabinol (THC) alters brain activation signals in a widespread network of regions, with some areas showing increased and others decreased activity. The magnitude of these changes is directly related to the local expression of the cannabinoid type-1 (CB1) receptor, but not the type-2 (CB2) receptor. THC increased activation in the anterior cingulate, superior frontal cortices, middle temporal and occipital gyri, striatum, amygdala, thalamus, and cerebellum crus II, while decreasing it in the middle temporal gyrus, superior temporal gyrus, angular gyrus, precuneus, cuneus, inferior parietal lobule, and cerebellum lobule IV/V. A dose-response relationship was observed in certain brain regions.
bioRxiv (Cold Spring Harbor Laboratory)
September 17, 2021
Tammi R. A. Kral, Regina C Lapate, Ted Imhoff‐Smith et al.
preprint
Long-term mindfulness meditation is associated with stronger resting-state functional connectivity between the posterior cingulate cortex and rostrolateral prefrontal cortex, lower connector hub strength of the default mode network relative to other networks, and better attention to task. In a sample of 40 long-term meditators (average 3,759 hours of practice) compared to 124 meditation-naïve controls, orienting attention positively correlated with posterior cingulate–rostrolateral prefrontal connectivity and negatively correlated with default mode network connector hub strength. These findings suggest that posterior cingulate–rostrolateral prefrontal connectivity may support attention orienting, consistent with a role for rostrolateral prefrontal cortex in meta-cognitive background awareness, a core component of mindfulness training.
bioRxiv (Cold Spring Harbor Laboratory)
July 24, 2020
Timo Torsten Schmidt, Simon Reiche, Caroline L. C. Hage et al.
preprint
Kambô, the secretion of the Giant Leaf Frog (Phyllomedusa bicolor), is ritually used by Amazonian ethnicities against bad luck in hunting and has spread to Western urban centers, often alongside ayahuasca. A retrospective study of 22 anonymous users (mean age 39 years, 45.5% female) assessed acute and subacute psychological effects with standardized questionnaires. Acutely, participants reported mild to moderate psychological effects without psychedelic-type perceptual or thinking distortions. Persisting effects were predominantly positive and pleasant, with surprisingly high personal and spiritual significance. Subacute and long-term effects overlapped with the 'afterglow' phenomena following serotonergic psychedelics.
bioRxiv (Cold Spring Harbor Laboratory)
January 23, 2020
Ca Hales, Jm Bartlett, R Arban et al.
preprint
Ketamine and other rapid-acting antidepressants (RAADs) like CP-101,606 and scopolamine produce a positive bias in decision-making in rodents, shifting choices toward more optimistic outcomes. This effect is localized to the medial prefrontal cortex (mPFC), as targeted infusions into this brain region replicate the bias. In contrast, other NMDA receptor antagonists that lack rapid antidepressant effects do not induce this positive bias. Temporary inactivation of the mPFC with muscimol caused general behavioral disruptions rather than the specific positive bias seen with RAADs. These findings suggest that ketamine and similar RAADs act through a distinct mechanism involving the mPFC to alter affective biases, which may underlie their therapeutic action in major depressive disorder.
bioRxiv (Cold Spring Harbor Laboratory)
June 17, 2019
Tetiana Kardash, Dmitry Rodin, Michael Kirby et al.
preprint
Mice bred for stress resilience (socially dominant) or stress sensitivity (socially submissive) responded differently to delta-9-tetrahydrocannabinol (THC). At a high dose (15 mg/kg), submissive mice developed a place aversion, while dominant mice showed no preference or aversion. After a six-week washout, the low dose (1.5 mg/kg) reduced depressive-like behavior in submissive mice, but the high dose increased it in dominant mice. High-dose THC raised serum corticosterone in both groups. The findings suggest that individual differences in stress vulnerability and dominance influence cannabis responses and should be considered when prescribing THC-containing medications.
bioRxiv (Cold Spring Harbor Laboratory)
February 13, 2017
Vanja Dakic, Juliana Nascimento, Rafaela Sartore et al.
preprint
5-MeO-DMT, a hallucinogenic molecule found in traditional Amerindian medicine, alters the proteome of human cerebral organoids. Of 6,728 identified proteins, 934 were differentially expressed after treatment. Systems biology analyses indicate anti-inflammatory effects and modulation of proteins linked to long-term potentiation, dendritic spine formation, cellular protrusion, microtubule dynamics, and cytoskeletal reorganization. These findings provide mechanistic insights into the neuropsychological changes associated with dimethyltryptamine ingestion.
bioRxiv (Cold Spring Harbor Laboratory)
Scott A. Ford, Rob W. Ness, Moonhyuk Kwon et al.
preprint
A chromosome-level genome assembly of the diviners sage plant, which produces the hallucinogen salvinorin A, has been produced. The genome is about 541 million base pairs, diploid, and comparable to other sage species. Two gene clusters involved in diterpene biosynthesis were identified, including a gene that forms the dihydrofuran ring early in the salvinorin A pathway. Other enzyme classes likely involved in later steps are scattered across the genome. Most of these genes are not activated by methyl jasmonate treatment. This high-quality genome sequence will help uncover the remaining steps in salvinorin A biosynthesis and support exploration of its medical potential for chronic pain, addiction, and post-traumatic stress disorder.
bioRxiv (Cold Spring Harbor Laboratory)
M. A. Taffe
preprint
Sustained physical activity worsens the hyperthermic (overheating) response to MDMA (Ecstasy) and increases the risk of death, according to experiments with rats. Male Wistar rats given MDMA (1.0, 5.6, or 10.0 mg/kg) were monitored with radiotelemetry in low (23-25°C) or high (27°C) ambient temperatures, with or without access to an activity wheel. The highest dose (10 mg/kg) combined with high temperature and wheel access produced the greatest rise in body temperature and more deaths than the no-wheel condition. This provides direct experimental evidence that physical activity is a risk factor for severe reactions to MDMA in humans.