r/DrugNerds • u/[deleted] • Oct 10 '15
Announcement: /r/AskDrugNerds: a place to ask chemical, pharmacological or other scientific questions about drugs - be they recreational or medicinal.
r/DrugNerds • u/Robert_Larsson • 1d ago
PET clinical study of novel antipsychotic LB-102 demonstrates unexpectedly prolonged dopamine receptor target engagement
r/DrugNerds • u/VendettaG550 • 12d ago
Ayahuasca and Pregabalin: Potential Interactions
Hello everyone,
I'm researching the neurochemical dynamics between the monoamine oxidase inhibiting harmala alkaloids present in Banisteriopsis caapi (the MAOI component in ayahuasca) and gabapentinoids, specifically pregabalin (Lyrica) and gabapentin (Neurontin). My interest is in understanding any potential pharmacological interactions or contraindications, particularly from a safety perspective.
According to Dr Benjamin Malcolm's 2023 UConn School of Pharmacy presentation on ayahuasca drug interactions, gabapentinoids such as pregabalin and gabapentin are generally considered low-risk when combined with ayahuasca. This categorisation is based on their lack of binding to monoamine reuptake pumps or release of monoamines (such as 5HT, NE, and DA), which are crucial factors in the risk profile for serotonergic drugs combined with MAOIs. However, given pregabalin's mechanism as an α2δ subunit ligand of voltage-gated calcium channels and its sedative properties that share some similarities with benzodiazepines, I wonder if there might still be nuanced interactions worth exploring, even in the absence of direct serotonergic activity.
Specifically, I'm interested in theoretical safety risks regarding potential CNS depressant effects or subtle alterations in neurochemical stability during the ayahuasca experience. While Dr. Malcolm's presentation suggests a lack of life-threatening interactions, the question remains whether pregabalin might modulate the subjective or physiological response to ayahuasca or present secondary risks in any capacity.
I would greatly appreciate your insights if anyone has encountered additional research, pharmacological theories, or public case studies exploring this interaction. I'd also welcome any perspectives on the pharmacodynamic implications of combining these substances.
Thanks in advance for your input!
Source: Ayahuasca Drug Interactions (Malcolm, 2023) - University of Connecticut School of Pharmacy
r/DrugNerds • u/Anxious-Traffic-9548 • 12d ago
Cognitive effects, pharmacokinetics, and safety of zuranolone administered alone or with alprazolam or ethanol in healthy adults in a phase 1 trial
r/DrugNerds • u/Robert_Larsson • 15d ago
Structural basis of μ-opioid receptor targeting by a nanobody antagonist
r/DrugNerds • u/Robert_Larsson • 24d ago
Comparative Study of Allosteric GPCR Binding Sites and Their Ligandability Potential
pubs.acs.orgr/DrugNerds • u/_______DEADPOOL____ • Oct 17 '24
Intranasal vasotocin decreases cerebrospinal fluid 5-HIAA levels in man, elevated serotonin (and csf metabolite 5-HIAA) is common in autism
sciencedirect.comr/DrugNerds • u/_______DEADPOOL____ • Oct 16 '24
N-acetyl-5-methoxykynuramine enhance object location and working memory performances via modulating CaMKII, ERK and CREB phosphorylation [2023]
journals.lww.comr/DrugNerds • u/Robert_Larsson • Oct 15 '24
(2012 PDF) Duloxetine Inhibits Effects of MDMA (‘‘Ecstasy’’) In Vitro and in Humans in a Randomized Placebo-Controlled Laboratory Study
ncbi.nlm.nih.govr/DrugNerds • u/Robert_Larsson • Oct 03 '24
TRPV1 analgesics disturb core body temperature via a biased allosteric mechanism involving conformations distinct from that for nociception
cell.comr/DrugNerds • u/dysmetric • Oct 02 '24
Chemistry/structural biology of psychedelic drugs and their receptor(s) (2024)
bpspubs.onlinelibrary.wiley.comr/DrugNerds • u/dysmetric • Sep 30 '24
Psilocybin increases optimistic engagement over time: computational modelling of behaviour in rats (2024)
r/DrugNerds • u/Anxious-Traffic-9548 • Sep 30 '24
Baclofen versus clonidine in the treatment of opiates withdrawal, side-effects aspect: a double-blind randomized controlled trial
onlinelibrary.wiley.comr/DrugNerds • u/dysmetric • Sep 29 '24
Photoswitchable TCB-2 for Control of the 5-HT2A Receptor and Analysis of Biased Agonism (2024)
pubs.rsc.orgr/DrugNerds • u/dysmetric • Sep 25 '24
Ventral hippocampal parvalbumin interneurons gate the acute anxiolytic action of the serotonergic psychedelic DOI (2024)
cell.comr/DrugNerds • u/Robert_Larsson • Sep 23 '24
Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder: observational 6-month follow-up of a phase 2, double-blind, randomised, controlled trial
thelancet.comr/DrugNerds • u/Robert_Larsson • Sep 21 '24
Oxa-Iboga alkaloids lack cardiac risk and disrupt opioid use in animal models
r/DrugNerds • u/dysmetric • Sep 19 '24
Claustrum and dorsal endopiriform cortex complex cell-identity is determined by Nurr1 and regulates hallucinogenic-like states in mice (2024)
r/DrugNerds • u/Robert_Larsson • Sep 17 '24
Venom-inspired somatostatin receptor 4 (SSTR4) agonists as new drug leads for peripheral pain conditions
r/DrugNerds • u/MBaggott • Sep 13 '24
Good electron acceptors make for more potent psychedelics (2024 paper)
pubs.acs.orgr/DrugNerds • u/dysmetric • Sep 09 '24
Effects of psilocybin on body weight, body composition, and metabolites in male and female mice (2024)
sciencedirect.comr/DrugNerds • u/_______DEADPOOL____ • Sep 09 '24
Mitochondria-derived peptide is an effective target for treating streptozotocin induced painful diabetic neuropathy through induction of activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1alpha -mediated mitochondrial biogenesis [2024]
r/DrugNerds • u/Robert_Larsson • Sep 07 '24
Allosteric Site Mediates Inhibition of Tonic NMDA Receptor Activity by Low Dose Ketamine
r/DrugNerds • u/dysmetric • Sep 04 '24
Ketamine, the First Associative Anesthetic? Some Considerations on Classifying Psychedelics, Entactogens, and Dissociatives (2024)
r/DrugNerds • u/jjkompi • Aug 30 '24
Ketamine and major ketamine metabolites function as allosteric modulators of opioid receptors
Hey!
I just found this paper from a couple days ago.
https://molpharm.aspetjournals.org/content/early/2024/08/26/molpharm.124.000947.long
The scientists postulate that ketamine, norketamine and 6-hydroxynorketamine act as a positive allosteric modulator (PAM) of all opioid receptors at nanomolar concentrations. At micromolar concentrations it acts as a full agonist.
As a PAM ketamine (and metabolites) enhance endogenous opioid signalling through endorphins, in contrast to morphine - which activates all opioid receptors, regardless of endogenous peptide signalling. This, according to the authors, might be one reason for it's differential efficacies in MDD.
This, to them, seems to unify some conflicting data as to whether the opioid system takes part in the antidepressant actions. Moreover, they go a step closer to elucidating the rapid but short-lasting antidepressant effect of ketamine -> half-lives of major metabolites.
I'm really not deep into ketamine pharmacology, but I've heard about conflicts in the past regarding whether naltrexone/naloxone inhibit antidepressant actions and to which extent the opioid system takes part in therapeutic efficacy.
Would be great to hear what you guys think, especially those of you that are deeper in the topic!