Low dose psychedelics increase neurogenesis, help mice unlearn fear

[entheogenic-gnosis]

new study of mice published in Experimental Brain Research shows that low doses (but not high doses) of psychedelics increase the rate of neuron creation in the hippocampus, and help the mice to rapidly unlearn conditioned fear responses.

From the abstract (paragraph breaks added for readability):

Drugs that modulate serotonin (5-HT) synaptic concentrations impact neurogenesis and hippocampal (HPC)-dependent learning. The primary objective is to determine the extent to which psilocybin (PSOP) modulates neurogenesis and thereby affects acquisition and extinction of HPC-dependent trace fear conditioning.

PSOP, the 5-HT2A agonist 25I-NBMeO and the 5-HT2A/Cantagonist ketanserin were administered via an acute intraperitoneal injection to mice. Trace fear conditioning was measured as the amount of time spent immobile in the presence of the conditioned stimulus (CS, auditory tone), trace (silent interval) and post-trace interval over 10 trials. Extinction was determined by the number of trials required to resume mobility during CS, trace and post-trace when the shock was not delivered. Neurogenesis was determined by unbiased counts of cells in the dentate gyrus of the HPC birth-dated with BrdU co-expressing a neuronal marker.

Mice treated with a range of doses of PSOP acquired a robust conditioned fear response. Mice injected with low doses of PSOP [psilocybin] extinguished cued fear conditioning significantly more rapidly than high-dose PSOP or saline-treated mice. Injection of PSOP, 25I-NBMeO or ketanserin resulted in significant dose-dependent decreases in number of newborn neurons in hippocampus. At the low doses of PSOP that enhanced extinction, neurogenesis was not decreased, but rather tended toward an increase. Extinction of “fear conditioning” may be mediated by actions of the drugs at sites other than hippocampus such as the amygdala, which is known to mediate the perception of fear. Another caveat is that PSOP is not purely selective for 5-HT2A receptors. PSOP facilitates extinction of the classically conditioned fear response, and this, and similar agents, should be explored as potential treatments for post-traumatic stress disorder and related conditions.

experimental-brain-researchThis will not surprise anybody who has been able to process deep-seated fears and insecurities with the help of a psychedelic. Nor will it surprise anyone familiar with other psychedelic research, such as Charles Grob’s 2010 study that found psilocybin remarkably effective in reducing “end-of-life anxiety” in twelve terminal cancer patients (actual study text here).

Research continues to confirm psychedelics’ ability to reduce the conditioned fear response, enabling patients to confront fearful stimuli without the usual baggage of anxiety and defense mechanisms. Their greatest power may be helping us confront our demons, mediating a partnership between everyday consciousness and the shadows that dwell beneath the surface.

As head researcher Dr. Briony Catlow explained to Real Clear Science: “Memory, learning, and the ability to relearn that a once threatening stimuli is no longer a danger absolutely depends on the ability of the brain to alter its connections…We believe that neuroplasticity plays a critical role in psilocybin accelerating fear extinction.”

Low dose psychedelics increase neurogenesis, help mice unlearn fear - Psychedelic Frontier

A new study of mice published in Experimental Brain Research shows that low doses (but not high doses) of psychedelics increase the rate of neuron creation in the hippocampus, and help the mice to rapidly unlearn conditioned fear responses. From the abstract (paragraph breaks added for...

psychedelicfrontier.com

-eg

 

[entheogenic-gnosis]

Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning

Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning - Experimental Brain Research

Drugs that modulate serotonin (5-HT) synaptic concentrations impact neurogenesis and hippocampal (HPC)-dependent learning. The primary objective is to determine the extent to which psilocybin (PSOP) modulates neurogenesis and thereby affects acquisition and extinction of HPC-dependent trace fear...

link.springer.com

(This was the actual research that the article from my initial post was referring to. )

-eg

 

[Praxis.]

new study of mice published in Experimental Brain Research shows that low doses (but not high doses) of psychedelics increase the rate of neuron creation in the hippocampus, and help the mice to rapidly unlearn conditioned fear responses.

...

Mice treated with a range of doses of PSOP acquired a robust conditioned fear response. Mice injected with low doses of PSOP [psilocybin] extinguished cued fear conditioning significantly more rapidly than high-dose PSOP or saline-treated mice.

Like the article said, the findings aren't much of a surprise, although it's great to see solid research supporting so many of our anecdotal experiences w/ psychedelics.

I am surprised, though, to see that high doses of psilocybin didn't have the same (or stronger) effect. Why do you think this could be?

In my own experience, it's been my high-dose sessions that have really pushed me to overcome my fears and insecurities--I would argue far more so than my low-dose experiences (which are also certainly valuable). Insofar as neurogenesis is concerned, higher doses leave me feeling like my brain-capacity has literally doubled in size from all of the novel information I've processed, so it's surprising to me that they found the opposite to be true.

 

[entheogenic-gnosis]

new study of mice published in Experimental Brain Research shows that low doses (but not high doses) of psychedelics increase the rate of neuron creation in the hippocampus, and help the mice to rapidly unlearn conditioned fear responses.

...

Mice treated with a range of doses of PSOP acquired a robust conditioned fear response. Mice injected with low doses of PSOP [psilocybin] extinguished cued fear conditioning significantly more rapidly than high-dose PSOP or saline-treated mice.

Like the article said, the findings aren't much of a surprise, although it's great to see solid research supporting so many of our anecdotal experiences w/ psychedelics.

I am surprised, though, to see that high doses of psilocybin didn't have the same (or stronger) effect. Why do you think this could be?

In my own experience, it's been my high-dose sessions that have really pushed me to overcome my fears and insecurities--I would argue far more so than my low-dose experiences (which are also certainly valuable). Insofar as neurogenesis is concerned, higher doses leave me feeling like my brain-capacity has literally doubled in size from all of the novel information I've processed, so it's surprising to me that they found the opposite to be true.

I was puzzled by this as well...

And I can relate, it's my high dose ventures that have been the most signifigant and transformitive...

It seems that this beneficial Neuroplasticity would only be formed when the brain must build novel pathways to function under the implemented conditions created by the psychedelic compound, these novel pathways would be formed while the brain in functioning in novel states, these states are produced at high dose...

Your body is bombarded by something like 12 billion signals per second, all of which (except for smell) enter via the thalamus, which then filters these signals down to the essentials, and sends them to the cortex regions for higher processing...on a psychedelic your thalamus stops filtering these signals and your cortex is bombarded with all available signals entering the body, thalamic gating, is just like huxleys consciousness valve, the thalamus and the cortex are joined largely by 5HT2a/c receptors, which are primary targets for psychedelics...also...when you are awake your dorsal raphe nuclei are constantly firing serotonin, as you tire they slow, and when you sleep they stop, now, when you take a psychedelic these dorsal raphe nuclei cease firing, even though your fully awake...
...your brain must find novel neurological pathways to cope with this altered functioning, however, your brain is able to recall these same pathways later, when one is not on the psychedelic, giving psychedelic users a larger number of neuronal pathways to work with...

You figure high dose would have been essential in forming these novel pathways...

Neural axons in the human brain are always branching and creating new synaptic connections to facilitate learning and development. Like the toning and bulking of muscle mass, neural connectivity, developmental growth, and plasticity are based partly on genetics and partly on the “use it or lose it” principle; the more you use a neural pathway the more robust and responsive it will become, the less you use a pathway the weaker it will become. Training and repetition build faster and more responsive connections. The more a neuron or assembly of neurons is used in a specific exercise, the faster and more responsive those neurons will become when performing that exercise. This is how the brain learns new things and integrates new skills. Training, repetition, and reinforcement leads to long term changes in synaptic connectivity. These are the basics of neuroplasticity.
Psychedelic Neuroplasticity

...any way, yes, I was puzzled by benefits only occurring in low dose, though this may yield some credit to the micro-dose promoters out there.

-eg

 

[Nathanial.Dread]

EDIT - Removed

Blessings
~ND

 

[Mindlusion]

new study of mice published in Experimental Brain Research shows that low doses (but not high doses) of psychedelics increase the rate of neuron creation in the hippocampus, and help the mice to rapidly unlearn conditioned fear responses.

...

Mice treated with a range of doses of PSOP acquired a robust conditioned fear response. Mice injected with low doses of PSOP [psilocybin] extinguished cued fear conditioning significantly more rapidly than high-dose PSOP or saline-treated mice.

Like the article said, the findings aren't much of a surprise, although it's great to see solid research supporting so many of our anecdotal experiences w/ psychedelics.

I am surprised, though, to see that high doses of psilocybin didn't have the same (or stronger) effect. Why do you think this could be?

In my own experience, it's been my high-dose sessions that have really pushed me to overcome my fears and insecurities--I would argue far more so than my low-dose experiences (which are also certainly valuable). Insofar as neurogenesis is concerned, higher doses leave me feeling like my brain-capacity has literally doubled in size from all of the novel information I've processed, so it's surprising to me that they found the opposite to be true.

I think there's two different processes occurring here, that are related but distinct.

Low doses: Low doses act as a functional analog of 5-HT, and via activity at the 5-HT2Ar, enhance expression of genes associated with neurogenesis (BDNF and egr-1 being the two most-studied ones). Over time, this helps the brain learn NEW patterns of cognition and behavior, in much the same way that SSRIs or exercise (which both enhance BDNF) are supposed to.

High doses: High doses disrupt information processing across the entire brain (including large chunks of the neocortex), moving the brain up to a high entropic state, where existing patterns (which encode cognition and behavior) get 'scrambled.' When the experience ends, the brain falls back down to a lower entropy state (sobriety). When the brain returns, it may not reform old patterns, but rather, into a new 'default.' In this case, it's not about enhanced learning of new patterns, but rather, erasure of OLD established patterns.

I don't want to say too too much just in case someone connects me with my academic life.

Blessings
~ND

Hey ND,
I love your research, I really enjoyed reading your replies in my psilocybin thread, it has helped me out a great deal.

What I find brilliant about the concept of the entropic brain, regarding the number of possible states or ways to process information, really opens a whole new can of worms considering that all of these possible states or paths may be interacting with themselves as well. Talk about the information.... This opens up many questions of the nature of consciousness...

In the original reality bending quantum mechanics experiment, firing individual photons through a double slit one by one, yet receiving a wave interference pattern. The particles are well defined at both ends, when fired from the beam and where they land on the screen. But, the interference pattern tells us that this same particle is wave-like in-between. The particle must be going through both slits like a wave and interacting with itself. This wave-space must hold all the information of all the possible positions of the particle, it must map out all possible paths of the particle.

So in the brain, this is very similar. Instead of firing particles through slits, you have individual neurons firing impulses through a network, instead of an interference pattern you have brainwaves. The number of pathways or possible states and it`s effect on consciousness is described with entropy. The number of possible states or pathways the brain can take to process information. This has been described as a 'phase space' .

Keep in mind I am not alluding to the 'conscious observer collapse' as this all does too exist within the Copenhagen interpretation as well as many worlds interpretation.

What I am suggesting is that this neural 'phase space' is very similar or the same as the wave-like phase space of all the undefined probable positions of particles in quantum mechanics.


So this poses some questions. Is our waking consciousness a defined or collapsed wave function of our neural networks? Intuitively one would say yes, since we experience it as an integrated, uniform, seamless experience.

What does it mean for consciousness if all the information of the system is present but only defined when collapsed as such as in the human brain?

What what could this mean for consciousness in a highly entropic state, with many more probable pathways in the wave space? What is that infinite singularity we all witness in that entropic state on high doses of psychedelics, which can only be described as love?

Is the universe conscious?

I guess I seem to be parallel with integrated information theory, I should slow down my ramblings now or ill go way too far out left field.

 

[Praxis.]

new study of mice published in Experimental Brain Research shows that low doses (but not high doses) of psychedelics increase the rate of neuron creation in the hippocampus, and help the mice to rapidly unlearn conditioned fear responses.

...

Mice treated with a range of doses of PSOP acquired a robust conditioned fear response. Mice injected with low doses of PSOP [psilocybin] extinguished cued fear conditioning significantly more rapidly than high-dose PSOP or saline-treated mice.

Like the article said, the findings aren't much of a surprise, although it's great to see solid research supporting so many of our anecdotal experiences w/ psychedelics.

I am surprised, though, to see that high doses of psilocybin didn't have the same (or stronger) effect. Why do you think this could be?

In my own experience, it's been my high-dose sessions that have really pushed me to overcome my fears and insecurities--I would argue far more so than my low-dose experiences (which are also certainly valuable). Insofar as neurogenesis is concerned, higher doses leave me feeling like my brain-capacity has literally doubled in size from all of the novel information I've processed, so it's surprising to me that they found the opposite to be true.

I think there's two different processes occurring here, that are related but distinct.

Low doses: Low doses act as a functional analog of 5-HT, and via activity at the 5-HT2Ar, enhance expression of genes associated with neurogenesis (BDNF and egr-1 being the two most-studied ones). Over time, this helps the brain learn NEW patterns of cognition and behavior, in much the same way that SSRIs or exercise (which both enhance BDNF) are supposed to.

High doses: High doses disrupt information processing across the entire brain (including large chunks of the neocortex), moving the brain up to a high entropic state, where existing patterns (which encode cognition and behavior) get 'scrambled.' When the experience ends, the brain falls back down to a lower entropy state (sobriety). When the brain returns, it may not reform old patterns, but rather, into a new 'default.' In this case, it's not about enhanced learning of new patterns, but rather, erasure of OLD established patterns.

I don't want to say too too much just in case someone connects me with my academic life.

Blessings
~ND

This makes much more sense to me, thank you. My only further observation would be in regards to the findings that low doses help to unlearn conditioned fear responses, while high doses do not. Insofar as learning new patterns, everything you've said lines up--but if it's the case that high doses eliminate old patterns and create a new "default", I still don't understand how this study could have found the opposite to be true in the case of fear.

This is probably a naive guess, but I wonder if giving mice high doses of psychedelics simply induced overwhelming and terrifying experiences for them, whereas the lower doses were more manageable? An overpowering "bad" trip can leave humans far more anxious and fearful than they were to begin with, I can't imagine what a big dose might do to an unsuspecting mouse. This could be a silly assumption on my part, as I'm relatively uninformed on this kind of research...but I can't quite understand why else these findings would contradict everything that collective experience tells us about high dose trips.

So this poses some questions. Is our waking consciousness a defined or collapsed wave function of our neural networks? Intuitively one would say yes, since we experience it as an integrated, uniform, seamless experience.

What does it mean for consciousness if all the information of the system is present but only defined when collapsed as such as in the human brain?

What what could this mean for consciousness in a highly entropic state, with many more probable pathways in the wave space? What is that infinite singularity we all witness in that entropic state on high doses of psychedelics...?

Interesting thoughts. I don't really have anything to add, but I like your thinking.

 

[Nathanial.Dread]

EDIT - Removed

Blessings
~ND

 

[entheogenic-gnosis]

http://www.realclearscience.com/blog/2013/06/low-doses-of-psilocybin-help-extinguish-conditioned-fear.html

We believe that neuroplasticity plays a critical role in psilocybin accelerating fear extinction -from the link above

They are discussing neurogenesis and neuroplasticity, right?

I assumed neuroplasticity would require high dose, as the brain forms novel pathways to cope with altered brain function induced by the psychedelic compounds...

As for neurogenesis, I don't see any reason why neurogenesis would require high dose...

I'm still a little confused here...

-eg

 

[Nathanial.Dread]

http://www.realclearscience.com/blog/2013/06/low-doses-of-psilocybin-help-extinguish-conditioned-fear.html

We believe that neuroplasticity plays a critical role in psilocybin accelerating fear extinction -from the link above

They are discussing neurogenesis and neuroplasticity, right?

I assumed neuroplasticity would require high dose, as the brain forms novel pathways to cope with altered brain function induced by the psychedelic compounds...

As for neurogenesis, I don't see any reason why neurogenesis would require high dose...

I'm still a little confused here...

-eg

They're talking about the same Catlow paper in that link. Folks have been mining it for years now.

Neuroplasticity and neurogenesis are related, but distinct concepts. In general, neurogenesis is one route by which neuroplasticity MAY occur. Whether one requires higher or lower doses of a given drug depends on a number of factors.

Blessings
~ND

 

[Praxis.]

This makes much more sense to me, thank you. My only further observation would be in regards to the findings that low doses help to unlearn conditioned fear responses, while high doses do not. Insofar as learning new patterns, everything you've said lines up--but if it's the case that high doses eliminate old patterns and create a new "default", I still don't understand how this study could have found the opposite to be true in the case of fear.

I'm going to make a guess and say that how effective the pattern erasure is depends on how deeply they are ingrained. Plenty of people try psychedelics and find that, while there may be some immediate relief, preexisting patterns reassert themselves without sustained efforts or intentions (such as what you find in a therapeutic setting). This is consistent with my personal experiences.

In the case of the rats, it could be that, given the fact that their environment and all the accompanying cues did not change, the learned patterns were not as successful erased.

If you have two heroin users, and they both take ibogaine, and one goes back to his old house, sees all his old mates, and does the same stuff, he's much more likely to relapse than a user who moves to a new place, cuts of contact with fellow users, etc. Even w/out the psychedelic, that's a trueism in addiction therapy, and as we know, addiction is just a very, very well-ingrained cognitive/behavioral pattern.

I wonder if the high-dose results would change if the mice were put into a new environment after their experience.

Blessings
~ND

Ah gotcha, this makes a lot of sense. :thumb_up:

 

[soul-explorer]

I wonder if some low-to-medium dosage LSD, say 100-200mcg is very helpful in assisting things like Cognitive behavioral therapy?


I've been out once on ~150mcg LSD and facing some fears of mine (related to social anxiety). The LSD made me much more open and people were reacting very positively.

Now I'm not sure how much help this would be in achieving lasting change?

I've been doing this mostly sober lately, and my fear has been reduced greatly, so it's hard for me to tell if that one-time experience while tripping made a huge impact.
My Pharma trips alone at home were also very beneficial, without facing any situations directly.