Bryan Roth

Dose-response left-shifted...one now needs to be a very potent grant writer!

Xylazine's k-opioid agonist activity is not shared with other FDA-approved alpha2-adrenergic agonists https://www.biorxiv.org/content/10.64898/2026.03.04.709652v1

Methylone is negative at 2b!!

New paper inspired by @nanopharmnc.bsky.social
Xylazine's k-opioid agonist activity is not shared with other FDA-approved alpha2-adrenergic agonists

www.biorxiv.org/content/10.6...

New paper inspired by @nanopharmnc.bsky.social
Xylazine's k-opioid agonist activity is not shared with other FDA-approved alpha2-adrenergic agonists

www.biorxiv.org/content/10.6...

Is methylone the next big thing? And is is really different from MDMA??

What's up with methylone and PTSD?
open.substack.com/pub/zendudes...

Is methylone the next big thing? And is is really different from MDMA??

What's up with methylone and PTSD?
open.substack.com/pub/zendudes...

Inhibition of cortico-amygdala projections underlies affective bias modification by psilocybin https://www.biorxiv.org/content/10.64898/2026.03.02.709133v1

Do psychedelics require Gi for their actions? No, but perhaps Gz or GoA

Do psychedelics require Gi for their actions?
open.substack.com/pub/zendudes...

Do psychedelics require Gi for their actions? No, but perhaps Gz or GoA

Do psychedelics require Gi for their actions?
open.substack.com/pub/zendudes...

Restoring circadian rhythms in the hypothalamic paraventricular nucleus reverses aging biomarkers and extends lifespan in male mice Enhancing circadian amplitude in mouse hypothalamic paraventricular nucleus neurons by 3′-deoxyadenosine treatment alleviates age-related pathologies and extends lifespan.

Restoring circadian rhythms in the hypothalamic paraventricular nucleus reverses aging biomarkers and extends lifespan in male mice: Cell www.cell.com/cell/fulltex...

"To date we have distributed 65,001 samples on your behalf.
Requests in the Past 31 Day(s)
Total Requests: 486"
@addgene.bsky.social

Direct interaction of ribosomes with postsynaptic proteins gives rise to a privileged local synaptic translatome https://www.biorxiv.org/content/10.64898/2026.02.27.708433v1

For those who study #psychedelics --our 2A mice are now available at JAX
038934 Htr2a EGFP-CreERT2 www.jax.org/strain/038934

038935 Htr2a Cre 5 www.jax.org/strain/038935

038936 Htr2a A242S-EGFP-Cre www.jax.org/strain/038936

Please RT

For those who study #psychedelics --our 2A mice are now available at JAX
038934 Htr2a EGFP-CreERT2 www.jax.org/strain/038934

038935 Htr2a Cre 5 www.jax.org/strain/038935

038936 Htr2a A242S-EGFP-Cre www.jax.org/strain/038936

Please RT

Distinct interneuronal dynamics selectively gate target-specific cortical projections in drug seeking Jeong et al. show that interneuron- and projection-defined vmPFC sub-circuits differentially engage mesolimbic pathways to drive persistent cocaine seeking after abstinence. Distinct interneuron subty...

Distinct interneuronal dynamics selectively gate target-specific cortical projections in drug seeking: Neuron www.cell.com/neuron/fullt...

Isn't everything on @addgene.bsky.social ?

a cat is driving a car with the words see ya soon written on the bottom ALT: a cat is driving a car with the words see ya soon written on the bottom

Giving a talk today @biophysicalsoc.bsky.social —entire talk never seen before data.

a man in a suit and tie is giving a thank you sign . ALT: a man in a suit and tie is giving a thank you sign .

Last year @Addgene shipped 2,977 orders of @rothlab
#chemogenetic viruses.

a man in a suit and tie is giving a thank you sign . ALT: a man in a suit and tie is giving a thank you sign .

Last year @Addgene shipped 2,977 orders of @rothlab
#chemogenetic viruses.

The selectivity implications of docking libraries with greater and lesser similarities to bio-like molecules - PubMed As virtual libraries have expanded into the tens of billions via make-on-demand chemistry, their similarity to metabolites, natural products, and drugs ("bio-like" molecules) has rapidly diminished. Despite this divergence, molecular docking of these ultra-large libraries has yielded molecules at hi …

Must read for computational folks:
" these results may suggest that selectivity against off-targets, like affinity and hit-rates for on-targets, is divorced from library similarity to bio-like molecules."
pubmed.ncbi.nlm.nih.gov/41676518/

Structure-based design of an opioid receptor modulator for enhanced morphine analgesia - PubMed The alarming rates of deaths due to opioid overdose present an urgent need for safer opioid analgesics. Positive allosteric modulators (PAMs) of opioid receptors (ORs) offer a promising approach to enhance opioid efficacy while reducing risks of overdose. In this study, we unveil the selective mecha …

New paper of interest!
pubmed.ncbi.nlm.nih.gov/41671375/
"Structure-based design of an opioid receptor modulator for enhanced morphine analgesia"
PAMs for the win (PAM=positive allosteric modulator)

Here's the way to test the 2A -specific hypothesis:
1. Pretreat humans with pimavanserin and see if it blocks the therapeutic effects of psilocybin (clinical trial link: clinicaltrials.gov/study/NCT065... )
2. Create 2A-agonists for depression and test in humans (My lab is very close to this)

Defined media reveal the essential role of lipid scavenging in supporting cancer cell proliferation - PubMed Fetal bovine serum (FBS) is an undefined additive that is ubiquitous to mammalian cell culture media and whose functional contributions to promoting cell proliferation remain poorly understood. Efforts to replace serum supplementation in culture media have been hindered by an incomplete understandin …

Re: media. I've not tried this and the paper focuses on lines with driver mutants that therefore shouldn't need growth factors, but would love someone to show if hek293, cho, etc. perform well with this composition.

pubmed.ncbi.nlm.nih.gov/40930249/

If only we knew which aspects of the polypharmacology to keep and what to discard

Mirtazepine, trazodone and nefazodone are FDA approved 5-HT2A antagonist antidepressants; mianserin is/was approved in Europe and is another one

New lab logo from former postdoc Dewran

New lab logo from former postdoc Dewran

Why do I do science? For the über-Nerds only...

Why do you do science @superkash.bsky.social @mbeisen.bsky.social @odedrechavi.bsky.social ?
Here are my unvarnished thoughts:
open.substack.com/pub/zendudes...

Sympathetic-epithelial crosstalk governs tissue-resident memory T cell immunosurveillance in the skin Sympathetic nerves regulate skin immunity by engaging keratinocytes to modulate the density of tissue-resident memory T cells. This neuro-epithelial axis can enable the nervous system to dynamically t...

Nice review!
Sympathetic-epithelial crosstalk governs tissue-resident memory T cell immunosurveillance in the skin: Cell www.cell.com/cell/fulltex...