Mystical Experience or Micro-dosing?

Psychedelics are the most effective antidepressant drugs. However, these compunds remain under FDA schedule I. There are two different therapeutic strategies: a full blown psychedelic experience (in a therapeutic setting and with therapeutic intent) or by microdosing using 5-10% of the psychedelic dose every 3 or 4days. The microdosing strategy (popular in Silicon Valley) has similarities with the use of ketamine in depression. Ketamine is used in sub-anesthetic and sub-dissociative doses and may soon find FDA approval for clinical use.

Several reports have decribed the extremely rapid and sustained antidepressant efficay of psilocybin in treatment resistant depression.

www.thelancet.com/psychiatry Published online May 17, 2016 https://dx.doi.org/10.1016/S2215-0366(16)30065-

Patients were severely depressed for up to 18 years and did not respond to up to 11 antidepressant trials.

Psychedelics are 5HT2A agonists. A recent study that their effect can be traced to increased neurite growth, spine density and and synaptogenesis.

Depression can be defined as a syndrome leading to dendritic spine degeneration:

Ketamine's antidepressant action is mediated by increased spine density

Likewise, psychedelics from three different chemical classes stimulate neurite growth and synaptic spine formation.

Classical psychedelics and ketamine might share a related therapeutic mechanism.

Although the molecular targets of ketamine and psychedelics are different (NMDA and 5-HT2A receptors, respectively), they appear to cause similar downstream effects on structural plasticity by activating mTOR.

The exact mechanisms by which these compounds stimulate mTOR is still not entirely understood, but the  data suggest that, at least for classical psychedelics, TrkB and 5-HT2A receptors are involved.

There is a long-standing debate in the field concerning whether the subjective effects of psychedelics are necessary for their therapeutic effects.

Microdosing is likely to recruit the the same biochemical pathway and is predicted to have antidepressant activity.

For a detailed presentation view our talk on microdosing of psychdelics on our youtube chanel Psychiatry 2.0.

Click on the image below.