Miscellaneous Potential psychological harms of psychedelics, and why I will never try them!

[Neuroprotection]

well there has to be endogenous psychedelic kicking in during emotional states, but the existence of receptors for natural and unnatural chemical psychedelics only proves that having evolved by random mutation, these receptors have not killed us as a species.
I am glad that they have randomly evolved. like extra fingers.

Well, if there is an endogenous psychedelic in our brain, it’s most likely DMT. however, as I’ve said previously, I feel like the best way of proving it is to administer very selective 5HT2A antagonists to human volunteers under different emotional circumstances and compare their reactions with people not being given the drug.
Regarding the evolution of the psychedelic receptor(5HT2A), that is actually a serotonin receptor which doesn’t produce any hallucinogenic effects when activated by serotonin. psychedelics activate that receptor in a very specific and bias signalling way, which trick is very specific downstream pathways and changes glutamate sensitivity or release across important parts of the brain. this tremendous enhancement of glutamate signalling temporarily screws up brain connectivity/communication, induces a state of hyper awareness and sensory overload and permits all sorts of emotions to be mixed up. this is the mechanism that classical serotonergic psychedelics share with the dissociative NMDA receptor antagonist class of hallucinogens. and likely other classes as well. natural serotonin, even in very high concentrations like those released by MDMA, does not cause hallucinations.
If there is an endogenous psychedelic active in our brain, I agree with you that it probably modulates certain emotional states though I have a feeling it may play a more significant roll in mental illnesses with psychotic features.

 

[emkee_reinvented]

Sorry for going off on a tangent, but I hope this information helps you better understand my perspective

No worry, its not only your answer but also my experience that you cover win win situation , inluding the kid's,. Something greatly underestimated by me in hindsight.

To bad not all life changing event's come announced. But they are very deep wanted, expected or not. Deeper emotionally as psychedelic's imo.

And go for your own intiution on this, "Given my emotional state, I feel like psychedelics would be an extremely risky and possibly foolish experience to pursue".
They won't run away

 

[Neuroprotection]

No worry, its not only your answer but also my experience that you cover win win situation , inluding the kid's,. Something greatly underestimated by me in hindsight.

To bad not all life changing event's come announced. But they are very deep wanted, expected or not. Deeper emotionally as psychedelic's imo.

And go for your own intiution on this, "Given my emotional state, I feel like psychedelics would be an extremely risky and possibly foolish experience to pursue".
They won't run away

Apologies, not sure what you meant by the last line of your post “They won’t run away“. if you mean my emotional state won’t change that much, that’s not my only concern.
However, given my anxiety and chronic stress which have continued long-term, Confusion brought about by reality loopholes introduced by psychedelics sound like an added stressor I don’t need.

 

[pupnik]

@Neuroprotection
endogenous DMT can only be proven by detecting Endogenous DMT in the brain not by looking at receptors which have affinity to several molecules.

I cannot think of a good way to assay it in-vivo., attempts to do so, so far, have sucked.

 

[Neuroprotection]

@Neuroprotection
endogenous DMT can only be proven by detecting Endogenous DMT in the brain not by looking at receptors which have affinity to several molecules.

I cannot think of a good way to assay it in-vivo., attempts to do so, so far, have sucked.

Oh sorry, I wasn’t referring just to endogenous DMT. my point was. that if an endogenous psychedelic is actually active in our brain under certain emotional circumstances, the best way to prove it is administering a drug which blocks the psychedelic receptor 5HT2A to human subjects and seeing how they respond. Such drugs, known as. selective 5HT2A receptor antagonists have been developed and proven safe in humans.

 

[pupnik]

except that not all are working on 5ht2a

abstracting from

Psychedelics and the Human Receptorome - PMC

We currently understand the mental effects of psychedelics to be caused by agonism or partial agonism of 5-HT2A (and possibly 5-HT2C) receptors, and we understand that psychedelic drugs, especially phenylalkylamines, are fairly selective for these ...

www.ncbi.nlm.nih.gov

I think in this chart the higher numbers are more activity at the named receptor, and ND (no data?(not tested?)) & 00 means no activity at that receptor

5-MeO-DMT: 4.00 5ht1a, 3.69 5ht7, 3.48 5ht1d, 2.73 5ht6, 2.41 5ht1b, 2.38 D1, 1.84 5ht5a, 1.72 5ht1e, 1.58 D3, 1.57 Alpha2C, 1.55 5ht2c, 1.00 Alpha2A, 0.98 5ht2a, 0.97 SERT, 0.88 Imidazoline1, 0.86 Alpha2B, 0.82 NET, 0.78 D4, 0.73 D2, 0.69 5ht2b; 0.00: Alpha1B, Beta2, Beta1, DAT, D5, Alpha1A, Sigma1, Sigma2, CB2, KOR, Ca+Channel, M1, M2, M3, M4, M5, H2, CB1; ND: H1, DOR, MOR, NMDA


DMT: 4.00 5ht7, 3.97 5ht1d, 3.91 5ht2b, 3.53 Alpha2B, 3.53 Alpha2C, 3.51 D1, 3.42 5ht2c, 3.28 5ht1e, 3.25 5ht6, 3.16 5ht5a, 3.13 Imidazoline1, 2.95 Alpha1B, 2.75 Alpha2A, 2.70 Alpha1A, 2.58 5ht2a, 2.37 SERT, 2.23 Sigma1; 0.00: 5ht1a, D4, D5, Beta1, D2, D3, DAT, NET, 5ht1b, Beta2, Sigma2, CB2, KOR, Ca+Channel, M1, M2, M3, M4, M5, H2, CB1; ND: H1, DOR, MOR, NMDA


LSD: 4.00 5ht1b, 3.77 5ht7, 3.75 5ht6, 3.73 5ht1a, 3.70 5ht1d, 3.64 5ht5a, 3.54 5ht2a, 3.16 D3, 3.11 5ht2b, 3.11 5ht2c, 2.93 Alpha2A, 2.62 5ht1e, 2.55 D2, 2.39 D4, 2.34 D1, 2.05 D5, 1.54 Alpha1A, 1.40 H1, 1.39 Beta1, 1.05 Beta2, 0.65 Alpha1B; 0.00: KOR, DOR, DAT, SERT, MOR, NET; ND: Sigma2, Alpha2B, Alpha2C, Imidazoline1, M1, M2, M3, M4, M5, Sigma1, H2, CB2, CB1, Ca+Channel, NMDA


Psilocin: 4.00 5ht2b, 3.40 5ht1d, 3.37 D1, 3.03 5ht1e, 2.88 5ht1a, 2.83 5ht5a, 2.82 5ht7, 2.82 5ht6, 2.67 D3, 2.52 5ht2c, 2.19 5ht1b, 2.14 5ht2a, 1.77 Imidazoline1, 1.74 SERT, 1.57 Alpha2B, 1.36 Alpha2A, 1.03 Alpha2C; 0.00: D2, Alpha1B, D5, D4, Beta2, Beta1, DAT, NET, Alpha1A, Sigma1, Sigma2, DOR, KOR, MOR, M1, M2, M3, M4, Ca+Channel, H1, H2, CB2, CB1; ND: M5, NMDA


THC: 4.00 CB1, 3.78 CB2; ND: 5ht2a, 5ht2c, 5ht1b, 5ht1d, 5ht1e, 5ht2b, 5ht1a, 5ht7, D1, D2, D3, D4, D5, Alpha1A, Alpha1B, 5ht5a, 5ht6, Alpha2C, Beta1, Beta2, SERT, DAT, NET, Imidazoline1, Sigma1, Sigma2, DOR, KOR, MOR, M1, M2, M3, M4, M5, H1, H2, Alpha2A, Alpha2B, Ca+Channel, NMDA


Morphine: 4.00 MOR, 2.21 KOR, 0.72 DOR; ND: 5ht2c, 5ht2a, 5ht1d, 5ht1e, 5ht2b, 5ht1a, 5ht1b, D1, D2, D3, D4, D5, Alpha1A, Alpha1B, Alpha2A, Alpha2B, Alpha2C, Beta1, Beta2, SERT, DAT, NET, Imidazoline1, Sigma1, Sigma2, 5ht5a, 5ht6, 5ht7, M1, M2, M3, M4, M5, H1, H2, CB2, CB1, Ca+Channel, NMDA


Salvinorin A: 4.00 KOR; 0.00: 5ht2a, 5ht2b, 5ht2c, 5ht1b, 5ht1d, 5ht1e, 5ht5a, 5ht1a, 5ht7, D1, D2, D3, D4, D5, Alpha1A, Alpha1B, SERT, DOR, 5ht6, Beta1, Beta2, M2, DAT, M4, M5, H1, M1, M3, MOR; ND: Alpha2A, Alpha2C, Sigma2, Alpha2B, NET, Imidazoline1, Sigma1, H2, CB2, CB1, Ca+Channel, NMDA

 

[Neuroprotection]

except that not all are working on 5ht2a

abstracting from

Psychedelics and the Human Receptorome - PMC

We currently understand the mental effects of psychedelics to be caused by agonism or partial agonism of 5-HT2A (and possibly 5-HT2C) receptors, and we understand that psychedelic drugs, especially phenylalkylamines, are fairly selective for these ...

www.ncbi.nlm.nih.gov

I think in this chart the higher numbers are more activity at the named receptor, and ND (no data?(not tested?)) & 00 means no activity at that receptor

I’ve actually read that study. I’m going to be honest about the fact that I really don’t understand receptor binding kinetics/numbers like those you posted.
However, it seems to be that all tryptamine and phenylethylamine hallucinogens, both natural and synthetic activate 5HT2A and this seems to be the mechanism by which they produce their hallucinations. from what I know, scientists have proven this with pretty much all of them by administering these drugs to animals. When very selective. 5HT2A receptor blocking agents are also mixed with these drugs, the animals don’t demonstrate the hallucinogen specific response, A pretty good indicator that 5HT2A receptors are the main, if not the only generator of typical psychedelic effects.
Of course, we know that all psychedelics have many other receptor targets and it would be silly to assume they don’t contribute to the experience. However, my assumption is that they contribute in a less direct manner, for example by modifying emotions/mood memory/cognition or physical/peripheral responses which can directly contribute to sensory perception, especially when under a psychedelic state.

Yes, there are some hallucinogens like salvia or disassociatives which produced the hallucinations by completely different targets, But they are not officially referred to as classical psychedelics which was the topic of this thread.

 

[Neuroprotection]

on the topic of receptors, causing psychedelic effects, it might be interesting to start comparing serotonergic/classical psychedelics with hallucinogens which have no effect on serotonin receptors whatsoever.
It would be good if people could share and compare personal experiences between classical psychedelics and other hallucinogens.
From the reading I’ve done, I get the impression that the classical psychedelics tend to provide the most challenging, difficult and sometimes transformative experiences as compared to other hallucinogens like salvia, disassociatives, anticholinergics or muscimol. I would appreciate any thoughts on that.
Finally, I would be fascinated to know about anyone who has either tried non-serotonergic hallucinogens before trying classical serotonergic psychedelics, or if they have only ever used non-serotonergic hallucinogens.

 

[pupnik]

We know that there are different regions of the brain that handle incoming sensory signals, that handle the sense of timing, that create and update a sense of proprioception from the activity in sensory areas for vision, balance, skin and muscle pressure, and there are areas that specialize in phoneme abstraction from hearing, and others that abstract language from phonemes... so some regions work in a chain of sequences of moments. and some like the frontal and prefrontal cortex actively suppress ongoing activity when something unusual is detected (i.e. while working or concentrating) while the DMN seems to otherwise just chugs along with ongoing activity.

Each area has a slightly different recepterome, or combination of psychedelic receptors on its cortical neurons, and the thalamus also has 5HT receptors

Hallucinogens make the neurons more reactive - specifically they fire more easily by lowering the required action potential of them.
In the brain this means that a neural feedback sequence (eg cortico-thalamic feedback) that usually peters out after 3 cycles will go on longer, in a dose dependent way. That means that mental content from the affected sensation processing area will fade more slowly - overlapping subsequent events, and sustaining images, ideas, sounds and feelings.

It's not just one receptor that makes hallucination, but a wide family of receptors can make neurons more reactive to mental stimulation.

From an evolutionary point of view, emotions, subtending from fight or flight, or from curious and investigative play, or from sexual arousal etc. do the same thing, they force a change in the current resonant state of mind to enable wider perceptions from resonantly expanded consciousness.

Anyway, it is fun to explore and hack our resonant consciousness in times that do not require too much sanity and conformity, and I am pretty sure it works because of our emotional infrastructure in the brain, and the "psychedelic" receptors are part of that.

 

[Neuroprotection]

We know that there are different regions of the brain that handle incoming sensory signals, that handle the sense of timing, that create and update a sense of proprioception from the activity in sensory areas for vision, balance, skin and muscle pressure, and there are areas that specialize in phoneme abstraction from hearing, and others that abstract language from phonemes... so some regions work in a chain of sequences of moments. and some like the frontal and prefrontal cortex actively suppress ongoing activity when something unusual is detected (i.e. while working or concentrating) while the DMN seems to otherwise just chugs along with ongoing activity.

Each area has a slightly different recepterome, or combination of psychedelic receptors on its cortical neurons, and the thalamus also has 5HT receptors

Hallucinogens make the neurons more reactive - specifically they fire more easily by lowering the required action potential of them.
In the brain this means that a neural feedback sequence (eg cortico-thalamic feedback) that usually peters out after 3 cycles will go on longer, in a dose dependent way. That means that mental content from the affected sensation processing area will fade more slowly - overlapping subsequent events, and sustaining images, ideas, sounds and feelings.

It's not just one receptor that makes hallucination, but a wide family of receptors can make neurons more reactive to mental stimulation.

From an evolutionary point of view, emotions, subtending from fight or flight, or from curious and investigative play, or from sexual arousal etc. do the same thing, they force a change in the current resonant state of mind to enable wider perceptions from resonantly expanded consciousness.

Anyway, it is fun to explore and hack our resonant consciousness in times that do not require too much sanity and conformity, and I am pretty sure it works because of our emotional infrastructure in the brain, and the "psychedelic" receptors are part of that.

Very interesting perspective. I assume you’re talking about hallucinogens in general, as in all classes of hallucinogens.
However, in terms of the classical psychedelics like LSD, psilocybin, DMT etc, 5HT2A is known to be an absolute requirement for the hallucinogenic/psychedelic effects.
Other serotonin receptors that these classical serotonin psychedelic compounds activate do contribute to the experience, but do so by modifying it rather than being a direct cause of the hallucination. I believe this has already been tested and proven in animals and possibly humans, but I will need to doublecheck.
But yes, as you rightly said, hallucinogens from all classes activate different brain regions and dramatically alter information processing in the brain

 

[emkee_reinvented]

“They won’t run away“.

That ment Drugs.

They will be around, so I ment taking them when you allready feel emotional, anxious and like you wrote feel risky taking them. Which I found an very smart and honoust/ important thing to mention. Was imo a answer to your own question, yes it could be a disaster. If its really true? But MAPS psychedelic therapy's are alway's prepared and with guides. Other's take 1000 mcg recreational and feel fine, I hope veteran user's not first timer's. An bizar high dose, if you ask me.

But there is no way for me to imagine another person's state of mind, even my own is quite a mystery to me. So does that clear' it up a bit? Not my intention to be vague, but that's probably just my way of expressing. So your feedback I´ĺl try to incorparate later on, being a bit more to the point and not to vague for other's.

 

[Neuroprotection]

That ment Drugs.

They will be around, so I ment taking them when you allready feel emotional, anxious and like you wrote feel risky taking them. Which I found an very smart and honoust/ important thing to mention. Was imo a answer to your own question, yes it could be a disaster. If its really true? But MAPS psychedelic therapy's are alway's prepared and with guides. Other's take 1000 mcg recreational and feel fine, I hope veteran user's not first timer's. An bizar high dose, if you ask me.

But there is no way for me to imagine another person's state of mind, even my own is quite a mystery to me. So does that clear' it up a bit? Not my intention to be vague, but that's probably just my way of expressing. So your feedback I´ĺl try to incorparate later on, being a bit more to the point and not to vague for other's.

Thank you so much. Yes, that makes sense to me now.

 

[Bitchniggaz]

hello everyone. I know this is a very sensitive and emotive subject for some people, But its something I’ve been thinking about for a very long time and I feel it’s very important that we can discuss it in a respectful manner and develop our knowledge through exchanging opinions and possibly even personal experiences. i’ve always been fascinated by psychoactive substances especially by how their pharmacology influences their psychoactive effects and what this means for those under their influence. interestingly, there is one class of drugs that I grew to dislike the more I read about them. These are the hallucinogens, in particular the classical psychedelics(5HT2A agonists) even at the age of 15 when I was most fascinated by psychedelics and was in love with the idea of a non-addictive yet very powerful psychoactive experience, I always got a feeling of nervousness and unease as well as depression, whenever reading about them. when I would hear people talking about their experience of psychedelics, I would feel some sense of creepy/eerie Energy, it’s really difficult to describe. these feelings have been reinforced over the years. The more I read about psychedelics, and their ability to alter consciousness and shatter perceptions, as well as dissolve the ego, The more I feel they can be very dangerous to the stability of one’s psyche. i’ve read several stories about psychedelic experiences ruining previously healthy peoples lives and leaving them questioning their reality to the point of considering suicide. others say they became deluded and stopped interacting with friends/family because they felt like they had acquired some special wisdom and was superior to them. below, I will list some of the opinions I have developed through my reading over the years in the hope that we can share our thoughts and have an informative discussion on an area of psychedelics I feel is somewhat taboo.

1) The emotional/Consciousness altering effects of psychedelics are far more profound and Play the biggest role in determining whether a trip is wonderful, horrifying or both. The sensory disturbances/hallucinations are less relevant.

2) psychedelics can cause long-term changes in perception and outlook, making things people once enjoyed, seem pointless or counter-productive.

3) psychedelics may cause some people to start speaking in terms other people can’t understand or find strange. i’m not talking about people under the influence of the drug, or those suffering from psychosis, rather I’m talking about ordinary people who after experiencing a Serotonergic psychedelic trip begin to understand the world very differently and this comes through in the way they speak about life, our purpose, etc. whilst this could be amazingly positive in some cases, for others, this could be disastrous and lead to severe psychological stress as I mentioned earlier.

There’s much more, I would love to mention, but I already have a habit of writing very long posts and this post will turn from an essay into a book.

Dont be scared homie!

 

[pupnik]

sometimes the ability to be concise is all that is needed for a good time to ensue

 

[Jabberwocky]

"I suppose if you could set up a society, in an ideal way, that had a kind of right-of-passage.... which is what a lot of primitive societies do, and they put them through some pretty grueling things sometimes, to wipe out the abuse they've had as children.... I think a lot of people could probably benefit from a psychedelic experience at some time in their lives.

Ultimately, the goal of all people is to understand who we are, and psychedelics get us closer to that than anything I know of."

- Dr. David Nichols