Amazing #GPCR Tethered agonist– and GAIN domain–independent signaling of an adhesion GPCR www.science.org/doi/10.1126/...

WOW, WOW, WOW!!! Technological and conceptually awesome. Turbocharging synaptic transmission: 12 SNAREpins are required for rapid release of reconstituted synaptic vesicles www.science.org/doi/10.1126/...

No evidence for direct physical interaction of 5-HT2A-mGluR2 receptors in vitro or in vivo https://www.biorxiv.org/content/10.64898/2026.06.28.734515v1

No evidence for direct physical interaction of 5-HT2A-mGluR2 receptors in vitro or in vivo www.biorxiv.org/content/10.6...

No evidence for direct physical interaction of 5-HT2A-mGluR2 receptors in vitro or in vivo www.biorxiv.org/content/10.6...

ONGOING HUMAN CLINICAL TRIALS WITH CHEMOGENETICS (DREADDs) for: Pain Parkinson's Disease ctv.veeva.com/study/a-stud... ctv.veeva.com/study/clinic... ctv.veeva.com/study/a-clin...

Pharmaceutical companies are not hiding breakthrough treatments Why "Greed is good" zendudest.substack.com/p/pharmaceut...

Cool paper: Sex differences in insular cortex function in persistent alcohol drinking despite aversion in mice. Mol Psychiatry (2026). doi.org/10.1038/s413... rdcu.be/fqF3z

Two researchers — one in Massachusetts and one in Shanghai — hoped for the same breakthrough: a gene therapy for deaf children. New Chinese investment in science propelled the one who got there first. n.pr/4weVi49

"I have enough money to do research," says Shu, laughing. Meanwhile HHS shut off the NIH grant that funded related work on gene therapy for deafness at Harvard Medical School, because “woke” or something like that Shu trained in the very same lab that HHS defunded

MS ID#: BIORXIV/2026/734515 MS TITLE: No evidence for direct physical interaction of 5-HT2A-mGluR2 receptors in vitro or in vivo Yuuge congrats to Blake from RothLabUNC

Very cool! www.nature.com/articles/s41...

'These findings indicate that 5-HT2BRs are required for psilocybin's behavioral effects in the FST, but are not required for its HTR....psilocybin's predictive validity in the FST can be dissociated from its 5-HT2A-mediated psychedelic effects.' pubmed.ncbi.nlm.nih.gov/42334341/

WOW!! Structural basis of opioid receptor activation by PCP and #ketamine @TaoChelab www.nature.com/articles/s41...

Consider diminishing your meat intake to save the planet!

Consider diminishing your meat intake to save the planet!

Cool paper! Nice to see use of PRESTO-Tango and TRUPATH in the same paper! www.science.org/doi/10.1126/...

My quote of the day Inside every cynical person, there is a disappointed idealist. George Carlin

May his memory be a blessing Robert Thurman

May his memory be a blessing Robert Thurman

DSP-2342, a novel 5-hydroxytryptamine 2A/7 receptor antagonist, has therapeutic potential for behavioral and psychological symptoms of dementia pubmed.ncbi.nlm.nih.gov/42302487/

My thoughts on 'curing brain diseases' open.substack.com/pub/zendudes...

My thoughts on 'curing brain diseases' open.substack.com/pub/zendudes...

THIS IS AN IMPORTANT PAPER FOR TRANSLATIONAL-CIRCUIT-BASED THERAPEUTICS Circuit-specific gene therapy reverses core symptoms in a primate Parkinson’s disease model: Cell www.cell.com/cell/fulltex...

THIS IS AN IMPORTANT PAPER FOR TRANSLATIONAL-CIRCUIT-BASED THERAPEUTICS Circuit-specific gene therapy reverses core symptoms in a primate Parkinson’s disease model: Cell www.cell.com/cell/fulltex...

From ai: “Overall sentiment in visible forums appears more supportive among early-career or grant-struggling researchers than among senior PIs with multiple awards, but it is far from unanimous and includes detailed pushback on details rather than outright rejection of the concept.”

From ai: “Overall sentiment in visible forums appears more supportive among early-career or grant-struggling researchers than among senior PIs with multiple awards, but it is far from unanimous and includes detailed pushback on details rather than outright rejection of the concept.”

Interesting title but there is NO EVIDENCE FOR TARGET ENGAGEMENT (e.g. D3/D2 receptor occupancy)! Title: 'Efficacy and target engagement of dopamine agonist pramipexole for anhedonic depression: a randomized placebo-controlled trial.' nature.com/articles/s41...

Receptor and cell-type-specific mechanisms in mesocortical dopamine circuits gate chronic pain and comorbid anxiodepression: Neuron www.cell.com/neuron/fullt...

An entire issue of @pubs.acs.org on #GPCR biased signaling pubs.acs.org/page/bichaw/...

My latest perspective on #GPCR biased signaling! GPCR Biased Signaling: Opportunities and Challengeshttps://pubs.acs.org/doi/10.1021/acs.biochem.6c00433

Zen thought of the day:

Memory reactivation underlies experience-dependent adaptive regulation of sleep | Science Another win for chemogenetics www.science.org/doi/10.1126/...

Memory reactivation underlies experience-dependent adaptive regulation of sleep | Science Another win for chemogenetics www.science.org/doi/10.1126/...

Proximity labelling of D1-like dopamine receptors reveals distinct cellular environments and uncovers trafficking proteins that regulate DA mediated behaviors in Drosophila https://www.biorxiv.org/content/10.64898/2026.05.28.728438v1

#gpcr Dimers! Here, we demonstrate stable κOR dimer formation in living cells ... revealing a parallel assembly distinct from previously characterized GPCR dimers that engage only single G protein. pubmed.ncbi.nlm.nih.gov/42215488/

I'm looking for the HD10.6 cell line--does anyone have it and can they share? Please RT

NEW CHEMOGENETIC PLATFORM Genetically engineered rapamycin responsive K2P channels www.biorxiv.org/content/10.6...

The slow-acting G-protein Gz defines the duration of circadian rest time https://www.biorxiv.org/content/10.64898/2026.05.23.727383v1

the "heck" reaction in the abstract image doesn't make any sense for that isomer of benzazepine. Fig 3.2.1. also has a nonsensical molecule. Both are obvious GenAI. Authors, reviewers and editors should have done a bit better effort to at least factcheck and clean up the mistakes in the GenAI output

Hippocampal astrocytes contribute to encoding context-specific aversive stimuli to regulate fear-related behavior https://www.biorxiv.org/content/10.64898/2026.05.22.727208v1

I'm now recognized as 'an expert in chemogenetics'!

"Our results show that psilocybin induces stereotypies and anxiolytic-like effects in planarians, likely through mechanisms involving 5-HT2AR, and suggest conservation of certain aspects of psilocybin pharmacology." #psychedelics pubmed.ncbi.nlm.nih.gov/42186402/

Benzazepines Derivatives: Synthetic Strategy, Structural-Activity Relationships, and Medical Potential as Dopamine and Serotonin Receptor Modulators | ACS Omega pubs.acs.org/doi/10.1021/...

"This exploratory study found that hallucinogen use was associated with modestly increased VHD odds after adjustment, requiring confirmation through longitudinal research." #psychedelics Avoid 2B pubmed.ncbi.nlm.nih.gov/42152600/

A gentle reminder

A balanced view of the NIMH, Tom Insel's legacy and the future! open.substack.com/pub/zendudes...

A balanced view of the NIMH, Tom Insel's legacy and the future! open.substack.com/pub/zendudes...

What's the deal with IBOGAINE? open.substack.com/pub/zendudes...