Isotopic DMT as a Probe of Spin-Dependent Psychedelic Pharmacology
Zenodo (CERN European Organization for Nuclear Research) April 18, 2026 Peer reviewed DOI: 10.5281/zenodo.18965900 via OpenAlex
Summary
The study tests whether the radical pair mechanism (RPM) is involved in DMT-induced psychedelic states at the 5-HT2A receptor using isotopic substitution. By modifying nuclear spin content with 13C and 15N without affecting molecular geometry or receptor affinity, it aims to demonstrate that any observed changes indicate RPM involvement. The kinetic isotope effect for 13C is negligible, suggesting that any phenomenological changes provide evidence for the magnetic isotope effect at the receptor.
Study at a glance
| Population | mice in a pilot study |
|---|---|
| Key finding | Observed phenomenological changes would provide direct evidence for the magnetic isotope effect and RPM involvement at the receptor. |
Abstract
We propose a three-phase experimental protocol testing whether the radical pair mechanism (RPM) operates during N,N-dimethyltryptamine (DMT)-induced psychedelicstates at the 5-HT2A receptor. Position-specific isotopic substitution of the ligand (13C at C3a, 15N on indole nitrogen) modifies nuclear spin content without altering molecular geometry, receptor affinity, or metabolic half-life.Because the kinetic isotope effect is negligible for 13C (Δm = +8%, KIE < 1.04), any observed phenomenological change constitutes direct evidence for the magnetic isotope effect—and hence for RPM involvement—at the receptor. Structure-guided labelling (PDB: 9AS1), falsification criteria, and a ~$10,000 mouse HTR pilot are described. Version 2: removed speculative theoretical framework, muscled bibliography (46 refs), added quantitative feasibility bounds, integrated as part of a three-document research programme.