Microdosing psychedelics involves taking about 1/20 to 1/10 of a standard active dose of LSD or psilocybin, well below the threshold needed to produce full hallucinogenic effects. Clinical interest centers on using these sub-perceptual doses to treat depression: because the dose is too low to cause overt psychoactive effects, it is hypothesized to still produce subtle cognitive-stimulating (LSD) or mood-elevating (psilocybin) benefits with fewer of the risks associated with a full dose. Such micro-dosing treatments are generally reported as well-tolerated in clinical and general populations.

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Psychedelics, in particular LSD and psilocybin, have been investigated as potential treatments for depressive symptoms. There is evidence for short-, medium-, and long-term usefulness in both micro-dosing and regular studies. In addition to the potential cognitive stimulation (LSD) or emotional well-being effects (psilocybin), these treatments are generally well-tolerated in clinical and general populations. In addition, MDMA has received breakthrough treatment status with the FDA for the treatment of PTSD.

Potential clinical uses for psychedelics

Psilocybin is a 5HT-2A (serotonin 2A) receptor agonist, which seems to play a role in both the hallucinogenic and therapeutic impacts. Studies in treatment-resistant depression patients show increased functional connectivity during emotional processing tasks, particularly in the amygdala and the prefrontal cortex. This is similar to the neural plasticity induced by psychedelics in general. 

All of these processes/regions have been implicated in the antidepressant action of typical antidepressants like SSRIs, which may explain why psilocybin has observed antidepressant properties.

Therapeutic mechanisms of psilocybin

In 2021 the FDA approved the use of 3,4-methylenedioxymethamphetamine (MDMA) for the treatment of PTSD. The compound was studied as a treatment as studies suggest it acts by binding to the presynaptic serotonin transporters inducing a release of serotonin. The trials conducted administered three doses of MDMA paired with manualized therapy during an eighteen-week treatment plan. The results of the study showed significantly reduced symptoms of depression as well as regulated amygdalar serotonergic function in comparison to the control (placebo) group. Each study conducted showed similar results which led to the approval for the regulated use of MDMA to treat PTSD symptoms.

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