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.”

http://psychedelicfronti...-help-mice-unlearn-fear/

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.

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.
http://psychedelic-infor...chedelic-Neuroplasticity

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

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

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...?

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

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