Paper: Neurogenesis & Psychoactives: A Review of the Literature

[Bancopuma]

Hi y'all,

With the kind permission of Mr Traveler, I'm sharing this draft of a paper here, I'm wondering if any of the scientifically minded people here would possibly be good enough to give this a glance and provide any feedback, good or bad, they may have. This isn't an area I've done any research in personally and is an extra-curricular interest of mine. Mr Infundibulum has already been very helpful with comments and generous with his time - thank you good sir! The paper is written in the form of a review paper, looking at past and recent research on psychoactives and hippocampal neurogenesis, and I would really like to aim for a submission to the Journal of Psychoactive Drugs, if I can. They go for review papers of this nature, and that way it will be on pubmed and accessible to researchers and anybody interested, and I think a paper of this nature is relevant currently as research into drugs and neurogenesis is still in its relative infancy but is an area of increasing scientific interest.

Any input for anybody more familiar with the terrain than I, in their own time, would be much appreciated! Many thanks. :thumb_up:

 

[joedirt]

Great review paper :thumb_up:

Some feedback.

Neurons produced in the SGV have been found to migrate to the striatum in humans

I don't think you defined SGV before using it.... unless I missed it.


Also question for you. IN any of your research did you turn up anything with regards to LSD and neurogenesis?

 

[Bancopuma]

Hey Mr joedirt, thanks a bunch for taking a look at it, and good shout! Will amend the SGV definition, and interestingly when I was doing research before, I recall Franz Vollenweider hypothesising about LSD increasing neurogenesis, but as far as I could tell there wasn't any direct experimental evidence to back this up. Well turns out David Nichols has conducted research on this very topic I had somehow missed before...acute doses of LSD in rats substantially increases BDNF expression and synaptogenesis in their prefrontal cortex. Have emailed the man himself about this, so thanks a lot, always good to have another pair of eyes have a look at things! :thumb_up:

 

[joedirt]

Hey Mr joedirt, thanks a bunch for taking a look at it, and good shout! Will amend the SGV definition, and interestingly when I was doing research before, I recall Franz Vollenweider hypothesising about LSD increasing neurogenesis, but as far as I could tell there wasn't any direct experimental evidence to back this up. Well turns out David Nichols has conducted research on this very topic I had somehow missed before...acute doses of LSD in rats substantially increases BDNF expression and synaptogenesis. Have emailed the man himself about this, so thanks a lot, always good to have another pair of eyes have a look at things! :thumb_up:

Awesome. I pretty well figured it did.. I mean the after effects of LSD in the day's and weeks are just as profound as those from shrooms or aya! If David mentions a publication would you mind linking it here? I'd love to read it..

BTW your review article was very timely for me.. as I was really starting to open up more to the idea of depression and neurogenesis having a strong link.

 

[Bancopuma]

So David got back to me pretty sharpish! Turns out it was his son who did the study not him. David and his team have not done research on LSD and neurogenesis, and he being the world expert on the compound I think he's know of any such research. In the attached study it was found an acute dose of LSD in rats had a significant affect on gene expression, in genes regulating synaptic plasticity and glutamatergic signalling (the latter system has been implicated in neurogenesis), among others. An increase in BDNF expression was not found but it may not have been specifically looked for. But it definitely seems that LSD is definitely linked to changes in neuroplasticity of the brain, which perhaps shouldn't come as much surprise, but I don't think the data on neurogenesis is in yet. Interestingly very recent brain imaging studies have shown LSD affecting the hippocampus which is the main hub of neurogenesis in the brain. So perhaps a frontier ripe for further research.

Also worth a read.

"Several studies have presented evidence that there is an increase of glutamate-dependent activity in prefrontal areas, induced by agonism of 5-HT2A receptors by classical hallucinogens [Aghajanian and Marek, 1997, 1999; Beique et al. 2007]. Based on this finding, Vollenweider and Kometer have suggested that the indirect activation of glutamate networks by classical hallucinogens enhances neuroplasticity, specifically so via the AMPA (α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid) receptor, with subsequent downstream increases in the cellular protein brain-derived neurotrophic factor (BDNF) [Vollenweider and Kometer, 2010]. This is supported by the finding that agonist action on the 5-HT2A receptor may lead to increased expression of BDNF in prefrontal areas [Kometer and Vollenweider, 2010]."

From:

Classical hallucinogens as antidepressants? A review of pharmacodynamics and putative clinical roles

Hallucinogens have been part of spiritual practice for millennia, but controversy surrounding their mind-manifesting effects led to their proscription by the mid-20th century, largely without evidence of harm or toxicity and despite nascent data suggesting ...

www.ncbi.nlm.nih.gov

Study:

Baumeister, D., Barnes, G., Giaroli, G. & Tracy, D. (2014) Classical hallucinogens as antidepressants? A review of pharmacodynamics and putative clinical roles. Therapeutic Advances in Psychopharmacology, 4, (4), 156-169.


I'm glad you dug the review. And yeah from my research it seems that drugs and neurogenesis...at least the implications of altering or enhancing neurogenesis...is in its early stages. But from the data in so so far it seems that this process could play a key role in depression, anxiety disorders and PTSD among other things, and I think the next generation of antidepressants will likely be screened for their neurogenic potential as oppose to their effect on influencing serotonin levels.

 

[joedirt]

The neuroplasticity could either be a good thing or not. For instance receptor up/down regulation can change receptor plasticity.

Also some papers on chronic alcohol exposure showing obviously negative plasticity changes...

Chronic alcohol exposure alters behavioral and synaptic plasticity of the rodent prefrontal cortex - PubMed

In the present study, we used a mouse model of chronic intermittent ethanol (CIE) exposure to examine how CIE alters the plasticity of the medial prefrontal cortex (mPFC). In acute slices obtained either immediately or 1-week after the last episode of alcohol exposure, voltage-clamp recording of...

www.ncbi.nlm.nih.gov

This is fascinating research that is happening. I wish someone had a grant to collect all of this data for the compounds in Thikal and Phikal...

Personally I feel large doses of LSD are quite beneficial, but would like to see quantification!

And yes I agree all next gen anti depressant will likely be focusd on BDNF... As this is most likley why SSRI's work 2 weeks after starting the regime.