Psychedelic-Like Drug Produces Antidepressant Effects Without Hallucinations

Benefitting from psychedelics without experiencing hallucinations could be possible.
Derya Ozdemir
Psychedelic psilocybin mushroomsYarygin/iStock

Some psychedelic drugs, such as psilocybin which is a compound found in so-called magic mushrooms, are increasingly being investigated for their medical benefits in controlled environments --  but here is a tiny catch -- they tend to trigger hallucinations.

These hallucinations can range from walls appearing as if they are "breathing" to seeing entire objects or people who are not really there, which is why some researchers are trying to identify drugs that could offer the benefits of psychedelics in clinical settings without the hallucinations. 

Now, scientists from the University of California, Davis (UC Davis) say they've discovered one such psychedelic-like drug that can produce long-lasting antidepressant effects in mice without hallucinations.


According to the study published in Cell, the researchers genetically encoded PsychLight, a green fluorescent sensor, into a specific form of serotonin receptor responsible for hallucinations. 

"This sensor allows us to image serotonin dynamics in real time when animals learn or are stressed and visualize the interaction between the compound of interest and the receptor in real time," explained senior author Lin Tian, an associate professor in the Department of Biochemistry and Molecular Medicine in the School of Medicine at UC Davis.

When the researchers applied this novel sensor to 34 compounds with similar structures and unknown hallucinogenic potentials, they discovered that one molecule in particular, AAZ-A-154, a previously unstudied molecule, demonstrated high selectivity for the receptor with little side effects.

Rapid, long-lasting, and ditches the hallucinations

The compound was then administered to mice, and researchers discovered that it produced an antidepressant-like effect within 30 minutes. Furthermore, there was no evidence of head twitching, which is an indication in mice that the compound would induce hallucinations in humans. Also at extremely high doses, the results were consistent, and the cognitive benefits continued for more than a week.

The tests have only been done in mice and scientists don't know enough about the underlying mechanisms, so it's too early to say anything about human trials. This is the second non-hallucinogenic drug the researchers have found that has shown clinical benefits similar to psyhedelics. The other synthetic molecule is called tabernanthalog (TBG), and it also had outstanding results.

Psychedelic therapies require guidance and supervision from a medical team due to the often distressing, sometimes very-welcome hallucinations; however, a non-hallucinogenic drug -- which works in a single or small number of doses --  that can be taken at home could get rid of this problem.  

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