5meO for Alcohol Use Disorder

UC Davis research on 5-MeO-DMT(a potent psychedelic found in the Sonoran Desert toad) is primarily led by the Institute for Psychedelics and Neurotherapeutics. The work focuses on the compound’s ability to promote neuroplasticity—the brain’s ability to form new connections—and its potential for treating addiction and depression.

Key Research Findings

Neuroplasticity Mechanism: Researchers discovered that 5-MeO-DMT promotes the growth of dendritic spines (connections between neurons) in the prefrontal cortex by activating the serotonin 2A (5-HT2A) receptor. This structural change is believed to be essential for its long-term antidepressant effects.

Dissociated State of Arousal: A 2024 study in mice found that 5-MeO-DMT induces a “paradoxical” brain state: animals show active behavior (wakefulness) while their brain waves resemble deep sleep(NREM-like slow waves). This state may be a key window for high synaptic malleability.

Addiction Treatment: In collaborative trials with Johns Hopkins, researchers reported that 68% of participants with treatment-resistant substance use disorders remained abstinent 12 months after a single supervised 5-MeO-DMT session.

Intracellular Signaling: UC Davis scientists identified that 5-MeO-DMT works by reaching receptors inside neurons, rather than just on the surface. This “location bias” helps explain why it is more effective at promoting plasticity than standard serotonin.

Development of Non-Hallucinogenic Analogs

A major focus of the Olson Lab is creating “non-hallucinogenic” versions of 5-MeO-DMT, such as Tabernanthalog (TBG).

Targeting Plasticity without “the Trip”: Research shows that while 5-MeO-DMT is a “full agonist” (turning the receptor on all the way to cause hallucinations), partial agonists like TBG can still trigger the same neuroplasticity pathways without the hallucinogenic side effects.

Gene Expression: They found that the “glutamate burst” and certain gene activations previously thought to be necessary for healing are actually only related to the hallucinations, not the therapeutic growth of neurons. 

While scientists continue try to remove the hallucinogenic effects because it doesn’t affect neuroplasticity, we at Awake feel strongly that the it is those hallucinogenic effects that are instrumental to healing the psychospiritual factors of addiction and that the medicine is more holistic in its natural form.