Bartosz Jakubowski ⟠

Yesterday we announced Cryptio's $45M Series B. Here’s what we’re going to do with the money.

ASSET MANAGER APOLLO, WHICH MANAGES $900B, ENTERS AGREEMENT TO PURCHASE UP TO 90M MORPHO OVER 4 YEAR PERIOD; WILL WORK TOGETHER FOR ONCHAIN LENDING: BLOG

Thank you Poland for all these awesome food.

Predicting cell state in previously unseen conditions such as disease or in response to a drug has typically required retraining for each new biological context. Today, Arc is releasing Stack, a foundation model that learns to simulate cell state under novel conditions directly at inference time, no fine-tuning required.

First mushroom trip data is out: my brain activity. Dose: 5 g dried Psilocybe cubensis (B+ strain) Containing 24.9 mg psilocybin Psilocybin longevity experiment. What we see in the brain: + brain activity data mirror my subjective experience + strong decrease in my brain’s control center (prefrontal + premotor cortex) + strong increase in sensory, auditory and speech integration + higher entropic brain patterns: open, flexible, less predictable, exploratory + brain network patterns resembling a youthful state vs aged and rigid Matching what I reported experiencing: + “felt like my consciousness was dialed up to 10/10.” + “I felt hyper aware and hyper alive.” + “I experienced sense of touch with awe.” + “my mind was insatiably curious and wanted to deploy its sensors into the world and discover all things.” + “My brain wanted to stare, study and marvel.” + “The flavor exploded in my mouth.” + “...restored my perception to youthful levels, returning them to factory settings and dissolving my aged numbness.” Why this could matter for longevity: + In people aged 65-85, higher happiness was linked to a 22% reduced risk of all-cause mortality over 15 years. + A meta-analysis showed that optimism correlated with a 35% decrease in heart attacks and a 16% decrease in all-cause mortality. + Having a strong purpose in life is associated with a 17% reduction in both heart attacks and all-cause mortality. + In psychedelic medicine, treating depression with ketamine has been shown to reverse biological age by up to 3 years. Together, these findings suggest a plausible mechanism by which psychedelics, including psilocybin, can prolong both health and lifespan by improving mental well-being and rewiring the brain to a more positive, creative, and curious state. My team and I hypothesized that neuroplasticity, the loosening of rigid inhibitory patterns that makes the brain more flexible, creative, and relaxed, and even the subjective psychedelic state itself may be as meaningful for longevity as methylation shifts, senescence reversal, or telomere biology. What’s happening mechanistically Earlier work shows that psilocin (the active metabolite of psilocybin) acts primarily as an agonist at 5-HT₂A serotonin receptors in the cortex. These receptors are especially dense in high-level association and sensory regions, as mapped in a high-resolution PET/MRI atlas of the human serotonin system. When these receptors are activated, brain imaging studies show an induced state of desynchronization, entropy, and neuroplasticity.  This process erodes the rigid brain hierarchy and default mode networks in favor of a brain-wide spontaneous, creative, curious, and child-like state. Kernel Flow data shows the same pattern: The recorded timepoints included: + baseline: directly before session start (not shown) + timepoint 1: 4 hrs after dose (acute phase effects). + timepoint 2: end of the day, before bedtime. + timepoint 3: the following morning. I continue to measure my brain daily. Image notes + The three maps show changes vs. baseline (not absolute activity) + Red = increased connectivity, blue = decreased connectivity vs. my baseline. + The left reference map shows the 5-HT₂A receptor distribution from PET, the main psilocybin target. Time Point 1 - 3 hrs post dose + Reduced connectivity in the prefrontal and premotor cortex, correlating with acute brain desynchronization. + Increased connectivity and hyperintegration between the primary motor and sensory cortex regions. + Enhanced connectivity in the auditory and speech areas of the cortex. + Inhibited connectivity in the medial prefrontal and posterior zones, areas associated with the Default Mode Network (DMN). Subjective experience: + Enhanced sensory vividness and bodily presence: The brain's top-down hierarchy, originating in the pre-frontal cortex, was attenuated. This reduced predictive filtering, leading to a flood of bottom-up sensory information and heightened bodily perception (e.g., a fascination with water and light dynamics in a jar, a restored, primal joy of touch and sensation). + Peak neuroplasticity and cortical entropy: A peak in cortical entropy and neuroplasticity contributed to a feeling of hyperawareness (e.g., heightened sensory perception, feeling "at one with existence," hyper-aware and hyper-alive). + Deeper appreciation of music and uninhibited movement and expression: Sharpened auditory senses and reduced top-down inhibition allowed music to be enjoyed on a profound level. Concomitant functional connectivity in speech-motor and auditory-motor integration areas facilitated uninhibited expression through both speech and movement (a restored, uninhibited, child-like joy of music). + Note: Full ego dissolution was not experienced, which may necessitate a higher dose to achieve more advanced desynchronization of the prefrontal and parietal cortices. Time point 2 - 5 hrs post dose, end of trip + Intensified sensory and motor hyperconnectivity. + Continued increased connectivity in auditory and speech centers, with a relative restoration of connectivity to the speech understanding area. + Partial re-emergence of the prefrontal parietal coupling, while prefrontal context remains partially inhibited. + Partial re-emergence of connectivity in areas related to the default mode network. Subjective Experience + High-order brain networks begin to restabilize, alongside persisting sensory, motor, auditory, and speech hyperconnectivity, suggesting neuroplasticity in action. + The narrative shifts from pure sensation and experience to meaning generation, accompanied by deep philosophical reflection (e.g., reconsidering the meaning of life and one's relationship with mortality in the time of AI, and pondering the future of human evolution). Time point 3 - next morning (afterglow) + Persistence: Patterns from the acute phase continue, including general prefrontal cortex inhibition, ongoing neuronal plasticity, and heightened senses. + Intensified connectivity: Increased connectivity is noted in the speech generation area and the somatic sensory association area. + DMN inhibition: The default mode network remains inhibited. Subjective Experience: + "Afterglow" effect: Characterized by continued sharpened senses, calm clarity, emotional openness, and low inhibitions. For instance, I felt more comfortable expressing uninhibited, self-deprecating humor (i.e. my post making fun of myself about the insane lengths I go for my Don’t Die experiment) + Integration of experience learnings: The heightened activity in the somatic sensory association area aligns with the process of integrating and "making sense" of the raw sensory experience of both the self and the external world. + Enhanced creativity: The intensified connectivity in the speech generation area contributed to the uninhibited bout of creative writing I undertook to report my experience.