University of California, Davis, researchers have developed a new, neuroplasticity-promoting drug closely related to LSD that harnesses the psychedelic’s therapeutic power with reduced hallucinogenic potential.

Understanding exactly how psychedelics promote new connections in the brain is critical to developing targeted, non-hallucinogenic therapeutics that can treat neurodegenerative and neuropsychiatric diseases. To achieve this, researchers are mapping the biochemical pathways involved in both neuroplasticity and hallucinations.  

Ibogaine — a psychoactive natural product — has attracted attention for its anti-addictive and anti-depressant properties. But ibogaine is a finite resource, extracted from plant materials like the iboga shrub (Tabernanthe iboga) and the small-fruited voacanga tree (Voacanga africana). Further, its use can lead to irregular heartbeats, introducing safety risks and an overall need to better understand how its molecular structure leads to its biological effects.

New research suggests that it could be possible to separate treatment from hallucinations when developing new drugs based on psychedelics. The anti-anxiety andhallucination-inducing qualities of psychedelic drugs work through different neural circuits, according to research using a mouse model. The work is published Nov. 15 in Science.

Our bodies are pharmaceutical factories. From the hormones that regulate our blood sugar to the neurotransmitters that act as the body’s natural painkillers, these endogenous — produced within the body — chemicals ensure our functionality and survival.

But did you know that our bodies also naturally produce psychedelics?

In the 1950s, researchers found chemical signatures of N,N-dimethyltryptamine (DMT) in mammalian bodies, including in humans.

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Researchers at the University of California, Davis have developed a rapid, noninvasive tool to track the neurons and biomolecules activated in the brain by psychedelic drugs. The protein-based tool, which is called Ca2+-activated Split-TurboID, or CaST, is described in research published in Nature Methods.

Location, location, location is the key for psychedelic drugs that could treat mental illness by rapidly rebuilding connections between nerve cells. In a paper published Feb. 17 in Science, researchers at the University of California, Davis, show that engaging serotonin 2A receptors inside neurons promotes growth of new connections but engaging the same receptor on the surface of nerve cells does not.

The University of California, Davis, has launched the Institute for Psychedelics and Neurotherapeutics to advance basic knowledge about the mechanisms of psychedelics and translate it into safe and effective treatments for diseases such as depression, post-traumatic stress disorder, addiction, Alzheimer’s disease and Parkinson’s disease, among others.

Evidence from human and animal testing suggests the brain-altering effects of psychedelics could be repurposed for treating addiction.

Now, researchers at the University of California, Davis, and the University of Colorado Anschutz Medical Campus plan to screen hundreds of compounds to discover new, nonhallucinogenic treatments for substance use disorders. The research is funded by a $2.7 million grant from the National Institute on Drug Abuse, part of the National Institutes of Health.