GDNF and BDNF: What the Growth Factor Claim Rests On

These two acronyms appear on six pages of this site and in almost every popular account of ibogaine. This page is what they mean, and what the experiment behind them actually found.

What they are

GDNF, glial cell line-derived neurotrophic factor, was described in 1993 as a protein that supports the survival of the midbrain dopamine neurons that die in Parkinson’s disease. Its discoverers proposed Parkinson’s as the indication in the paper that named it.

BDNF, brain-derived neurotrophic factor, is the molecule most often reached for when anyone says “neuroplasticity”. It supports neuronal survival and strengthens synaptic connections.

Neither is specific to ibogaine, to psychedelics, or to anything else. Exercise raises BDNF. So does an antidepressant. So does learning a task. A drug that raises a growth factor is in very ordinary company, which is worth holding on to when the fact is presented as remarkable.

What ibogaine actually did to them

One study is doing nearly all the work in this argument, and it is worth reading at the level of its own results table.

Rats received a single injection at one of two doses, or vehicle, and expression was measured at three and twenty-four hours in four regions: the ventral tegmental area, the substantia nigra, the nucleus accumbens and the prefrontal cortex.

The precursor is not the product

The one thing that did rise as protein alongside all that messenger RNA was proBDNF, in the nucleus accumbens, at both doses.

proBDNF is the precursor from which mature BDNF is cleaved, and the two are not interchangeable. The literature describes them as carrying opposed signals, with proBDNF associated with synapse elimination where mature BDNF is associated with strengthening.

So the growth-factor result in the reward region most associated with addiction is an increase in the form that is not the one the neuroplasticity story means. That is not a debunking of the paper, which reports it plainly. It is a warning about the summary.

GDNF is the one that has been tested in people

This is where the argument can be checked rather than argued about.

GDNF has not only been measured, it has been given. It was infused directly into the brains of people with Parkinson’s disease in two randomised controlled trials, and both missed their primary clinical endpoint while the brain imaging showed the protein had arrived.

Ibogaine for Parkinson’s sets that out in full, including the detail that matters most here: target engagement was demonstrated and benefit was not.

If delivering the growth factor itself, at the dose and site of your choosing, does not produce a clinical effect, then raising it modestly and indirectly in a rat is a long way from a treatment.

GDNF also supports repair in peripheral nerve, which is a substantial literature in its own right and the basis of a separate claim. Ibogaine for peripheral neuropathy and CIDP examines it, and the gap there is that ibogaine’s GDNF effect has only ever been measured in the midbrain.

Where the alcohol result fits

The strongest positive finding is real and narrower than it is usually reported.

In rats, ibogaine reduced alcohol self-administration, and microinjection into the ventral tegmental area worked while microinjection into the substantia nigra did not. Injecting GDNF itself into the same region reproduced the effect.

That is a coherent chain within one species and one behaviour. Where the alkaloids act puts it in its anatomy, and ibogaine for alcoholism covers what did and did not follow in humans.

What to do with the phrase

“It increases neuroplasticity” is doing a lot of work in this field, and it is usually standing in for a chain that has not been completed: a transcript rose in a rat, therefore a protein rose, therefore synapses changed, therefore a person stopped using drugs.

Each of those steps is a separate empirical claim. In the study most often cited, the first step held and the second did not.

How ibogaine works sets the growth-factor proposal beside the four others, and what we do not know keeps the list of things nobody has measured.