Ayahuasca and the depressed brain: Part 1

Dean Wright, PhD

As ayahuasca, the South American plant medicine has become more popular in the west, we have heard ever more anecdotes of how this brew has transformed the lives of many. They state how there psychedelic journey on ayahuasca brings their life into focus, and helps them overcome problems such as anxiety, depression and addiction.

But what is this substance doing in the brain, and how is it it helping relieve issues like depression?

Research in the brain of depressed patients has shown that one common action of antidepressants is an increase in new brain cells – known as neurogenesis. Neurogenesis occurs in an area of the brain called the hippocampus. The hippocampus acts as the memory centre  – it is the place where memories are ‘stored’. In the simplest explanation, when there is an increase in neurogenesis in the hippocampus, there is an increase in the storage of new memories.

If depressed patients aren’t creating as many new memories, then what is their mind doing? There is a tendency for depressed patients to ruminate – remain stuck in negative patterns of thought which are difficult to get out of. They may continuously criticise their own behaviour around a overly simplistic, generalised theme, such as “I can’t succeed at anything I do”. They will then go in cycles of old memories, reinforcing this idea. By increasing new memories, depressed patients may be able to create new, more healthy ways of thinking about their life.

Many depressed patients who use ayahuasca report that they are able to break away from dysfunctional patterns of thinking, and come away looking at their life from a new perspective. Could increased neurogenesis help explain how ayahuasca helps alleviate depression?

What is Ayahuasca?

Ayahuasca  is made up of two plants – the caapi vine and the chacruna leaves. The chacruna leaves contain DMT and the caapi vine contain beta-carbolines, such as harmaline. If you ingest the DMT-containing leaves alone, you will not experience any psychedelic effects, as the DMT is broken down in the gut by the enzyme, monoamine oxidase (MAO). It just so happens that when harmaline enters the gut, it blocks, or inhibits MAO from doing its job and breaking down DMT. This enables DMT to enter the blood stream, and subsequently into the brain.

Inhibitors of MAO, or MAOIs are also a type of antidepressant. This led researchers to ponder whether the MAOIs of ayahuasca also have antidepressant effects. Twostudies have shown that harmine exerts anti-depressant effects in animals, however, no studies have yet been done showing the effects of harmine in humans.

Harmine and neurogenesis

A recent study has shown that harmine is able to increase the proliferation of ‘neural progenitors’ from stem cells. Neural progenitors are stem cells that are half-way to becoming fully matured neurons. At the most optimal dose, they found that harmine increased the number of proliferated cells by 71.5%. This can been seen by the number of green cells in Figure A.

However, they are yet to show, that all of these cells mature fully into neurons – i.e. neurogenesis. In Figure C, some cells show protein markers of a different type of brain cell, a glial cell, which means that not all cells are becoming neurons.

Thus, there is promise that harmine increases the life and production of new brain cells,  but we can not yet be sure this is neurogenesis.

Furthermore, these experiments are in cells in a dish. To confirm that harmine causes neurogenesis in humans, three further experiments are needed:

1. we need to confirm harmine causes neurogenesis in a mammalian animal model. To do this protein markers of neurogenesis would need to be measured in the brain of these animals after they were dosed with harmine.
2. We need to confirm that harmine crosses the blood brain barrier in humans. A previous study conducted has shown that harmine was present in the blood of humans who ingested ayahuasca. This indicates that harmine makes it into the blood, however, it is notoriously difficult to cross the blood-brain barrier, so further experiments are needed to show this.
3. We need to show that the hippocampus size increases after treatment with harmine. Since we can not chop open the brain of a human and measure the amount of neurogenesis, we are left with imaging techniques. We can measure the density of the hippocampus using fMRI and if the previous two experiments show positive results, we can imply with confidence that this is due to increased neurogenesis. This is the same method that was employed with classical antidepressants.

So, currently we can not conclude whether or not harmine is causing increased neurogenesis similar to other classical MAOI antidepressants.

So, then, what is the other part of ayahuasca, DMT, doing to the depressed brain?
Answers to come in part 2…