Non-hallucinogenic Psychedelics: Guardian Reports on New Findings

This week, the Guardian reported on a paper published in the paper Cell that found non-hallucinogenic psychedelics analog with antidepressant properties using a novel biosensor, called "psychLight".

The psychLight is a genetically encoded 5-HT sensor that predicts hallucinogenic potential via the measurements of 5-HT dynamics. The sensor glows in the presence of a hallucinogenic compound when it interacts with a serotonin receptor; this receptor is the target of both psychedelic drugs and classic antipsychotic medicines. Crucially though, these findings have only been reported in mice.

However, the reporting by the Guardian enthuses the potential of this treatment could be a "Goldilocks compound" as it could allow for therapeutic potential without needing the clinical supervision required when taking a classic psychedelic.

"The importance of the hallucinogenic effects in the therapeutic properties of psychedelics is highly debated; some scientists think they are essential to the compounds’ perceived therapeutic benefit. If that’s the case, then the sensor can be really useful for drug discovery efforts to identify new hallucinogenic and non-hallucinogenic psychedelic compounds."

See the article summary below, or for more updates on the latest psychedelic news and research, visit the psychedelic health professional network homepage.

SUMMARY

Ligands can induce G protein-coupled receptors (GPCRs) to adopt a myriad of conformations, many of which play critical roles in determining the activation of specific signaling cascades associated with distinct functional and behavioral consequences. For example, the 5-hydroxytryptamine 2A receptor (5-HT2AR) is the target of classic hallucinogens, atypical antipsychotics, and psychoplastogens. However, currently available methods are inadequate for directly assessing 5-HT2AR conformation both in vitro and in vivo. Here, we developed psychLight, a genetically encoded fluorescent sensor based on the 5-HT2AR structure. PsychLight detects behaviorally relevant serotonin release and correctly predicts the hallucinogenic behavioral effects of structurally similar 5-HT2AR ligands. We further used psychLight to identify a non-hallucinogenic psychedelic analog, which produced rapid-onset and long-lasting antidepressant-like effects after a single administration. The advent of psychLight will enable in vivodetection of serotonin dynamics, early identification of designer drugs of abuse, and the development of 5-HT2AR-dependent non-hallucinogenic therapeutics.