Psychedelics, Serotonin, And Dopamine

[Dopamine]

I have a theory that psychedelics are serotonergic in high doses (overdose) but dopaminergic in low doses. I have found that my best trips on psychedelics have been on sub-visual doses and I have begun to associate visuals with overdose. I think when psychedelics are ingested to the point of visuals that this indicates overdose and increases in serotonin release...

Ray says that psychedelics like LSD are dopaminergic and I would agree with him in regards to sub visual doses. When doses are not physiologically overwhelming I find psychedelics to warm my hands and feet like a furnace, erase depressive symptoms and anhedonia, increase creativity and attention, increase appetite and sensual enjoyment, increase sexual arousal etc... These are all symptoms of high dopamine...

Once I cross a certain threshold- the physiological effects of psychedelics practically reverse themselves.

Highly visual trips always increase my depressive symptoms massively, increase fear, make me cold, eliminate my sex drive, decrease attention, make me less social... These are all symptoms of high serotonin.

People always put some metaphysical spin on these effects claiming that the visuals are there to teach you something or that the visuals allow you a glimpse into "the truth" of the universe. A peek behind the curtain of reality... Basically the visuals are worth it due to the perceived religious experience. I completely disagree and haven't found I've learned more from highly visual trips then from less visual trips. The "profound" thoughts that I have while in the grip of psychedelia are practically useless as I sober up and realize how disordered and logically inconsistent my thoughts were.

Perhaps the pooling up of subconscious images can have an orienting and creative effect on the psyche similar to dream interpretation however i'm on the fence as to whether we can actually learn and benefit from these experiences or not. I do think that pain, sadness, and other symptoms reminiscent of serotonin can be a catalyst for growth and creativity therefore I recognize the usefulness of serotonergic states.

I always experience a nice afterglow following a trip- even a bad trip. which suggests that the high serotonin is more or less an acute episode and doesn't last. It is compensating for something.

My theory is that psychedelics are extremely dopaminergic. Like caffeine x100 but with less physiologically stimulating effects. If dopamine is pushed too high then the resources of the body are overwhelmed and serotonin is released to compensate by bringing metabolism down and preventing hyperthermia and exhaustion. The more psychedelics you take... the more visuals you will get as the body releases higher amounts of serotonin to compensate the sharp increases in dopamine.

Overdosing on dopaminergic stimulants like caffeine and ritalin can lead to psychosis and the same sorts of symptoms experienced on psychedelics. Mania experienced in bipolar disorder can lead to psychosis. The mania symptoms of bipolar are reminiscent of excesses in dopamine and if mania is pushed too high then you would expect the compensatory action of serotonin release and psychosis.

I think psychosis is a spectrum and deeper levels of psychosis suggest increasingly higher levels of serotonin. Schizophrenia is a state of very highly/chronically elevated serotonin and thus chronic hallucinations, paranoia, delusional thinking etc... these are all symptoms that can be generated dose dependently with psychedelics. It is also interesting that over 60% of schizophrenics smoke cigarettes... this would be because nicotine has dopaminergic effects and probaly helps alleviate symptoms of high serotonin... Unless of course the high serotonin is compensating for high dopamine (mania induced psychosis) in which case the nicotine would make things worse.

I think MDMA probaly ratchets up dopamine levels while blocking serotonin release. or ratchets up dopamine levels through blocking serotonin release. This is the crucial difference between LSD and MDMA. MDMA blocks the compensatory release of serotonin while LSD doesn't. MDMA can cause dopaminergic neurotoxicity probaly through inducing a hypoxic state in the brain as glucose is burned throughout the brain and body at an enormous rate. MDMA can also cause serotonin syndrome which is probaly mostly caused by extremely high levels of dopamine with elevated but subpar levels of serotonin release. LSD doesn't have the same propensity for serotonin syndrome and neurotoxicity because it doesn't block serotonin release.

So psychosis is a spectrum and is symptomatic of very high serotonin. You can induce psychosis in 2 ways. The first way through increasing serotonin directly (schizophrenia)... the 2nd way through increasing dopamine to the point of massive compensatory serotonin release (mania induced psychosis and psychedelic psychosis)

Thoughts? Experiences?

 

[ecstatichamster]

Not sure. But one thing I notice, slightly on topic, is that MB gives me the same stomach feeling as LSD. Small amounts. LSD was much worse an effect but at the MB dosages, I feel the stomach thing the same as with LSD only less intense. I suppose it's the serotonin effect.

 

[Dopamine]

Not sure. But one thing I notice, slightly on topic, is that MB gives me the same stomach feeling as LSD. Small amounts. LSD was much worse an effect but at the MB dosages, I feel the stomach thing the same as with LSD only less intense. I suppose it's the serotonin effect.

What stomach thing? Like stomach cramps and pains? I've never had this but I do experience lots of muscle tightness which I attribute to stress and over stimulation. I feel a very pleasant energy in my stomach/pelvis and throat on small doses or on the comedown of larger doses which I attribute to very high libido/dopamine.

 

[ecstatichamster]

What stomach thing? Like stomach cramps and pains? I've never had this but I do experience lots of muscle tightness which I attribute to stress and over stimulation. I feel a very pleasant energy in my stomach/pelvis and throat on small doses or on the comedown of larger doses which I attribute to very high libido/dopamine.

no, just a tightness. In the stomach area. It's the one effect I never liked about LSD/mescaline and to some extent 'shrooms. It's dose dependent. I think it's pharmacological noise from the basic effects of all these substances, which work the same way in the body.

 

[michael94]

I also think a large part of the negative effects of high LSD doses are related to oxidative stress from outstripping your antioxidant capacity with increased metabolism. Especially true if you have a sub-optimal liver/heart/kidney function.

LSD and shrooms will increase your metabolism immensely no doubt about it but if you can't keep up with the metabolic waste then....bad things. I wonder if you would have the same sort of bad effects on trips if you coupled the LSD with high dose astaxanthin or glutathione + taurine.

My reasoning for this theory is that I had much better experiences with high dose LSD when I was healthier.

 

[Dopamine]

I also think a large part of the negative effects of high LSD doses are related to oxidative stress from outstripping your antioxidant capacity with increased metabolism. Especially true if you have a sub-optimal liver/heart/kidney function.

LSD and shrooms will increase your metabolism immensely no doubt about it but if you can't keep up with the metabolic waste then....bad things. I wonder if you would have the same sort of bad effects on trips if you coupled the LSD with high dose astaxanthin or glutathione + taurine.

My reasoning for this theory is that I had much better experiences with high dose LSD when I was healthier.

Thats a good point and I agree. Especially relevant for people who trip very often- like every week.

 

[Elron]

LSD antagonizes various 5HT subtype recetpors. It also works on dopamine neurons. I am guessing it activates the same cascade of negative reactions in the body as serotonin, since it functions as a serotonin mimic at the top level. I personally notice my body feels a lot lighter, much like when vegeta goes super saiyan.

 

[Parsifal]

Not sure. But one thing I notice, slightly on topic, is that MB gives me the same stomach feeling as LSD. Small amounts. LSD was much worse an effect but at the MB dosages, I feel the stomach thing the same as with LSD only less intense. I suppose it's the serotonin effect.

How much MB are you talking about?

 

[Parsifal]

Have you tried to eat more when you get the hallucinations? Thyroid and coffee without proper fuel can make cold.

 

[ecstatichamster]

How much MB are you talking about?

3mg or so

 

[Barry Obummer]

LSD antagonizes various 5HT subtype recetpors. It also works on dopamine neurons. I am guessing it activates the same cascade of negative reactions in the body as serotonin, since it functions as a serotonin mimic at the top level. I personally notice my body feels a lot lighter, much like when vegeta goes super saiyan.

I can relate to the lighter thing. I wished my hair went a sweet blonde too though lol

 

[Barry Obummer]

I have a theory that psychedelics are serotonergic in high doses (overdose) but dopaminergic in low doses. I have found that my best trips on psychedelics have been on sub-visual doses and I have begun to associate visuals with overdose. I think when psychedelics are ingested to the point of visuals that this indicates overdose and increases in serotonin release...

Ray says that psychedelics like LSD are dopaminergic and I would agree with him in regards to sub visual doses. When doses are not physiologically overwhelming I find psychedelics to warm my hands and feet like a furnace, erase depressive symptoms and anhedonia, increase creativity and attention, increase appetite and sensual enjoyment, increase sexual arousal etc... These are all symptoms of high dopamine...

Once I cross a certain threshold- the physiological effects of psychedelics practically reverse themselves.

Highly visual trips always increase my depressive symptoms massively, increase fear, make me cold, eliminate my sex drive, decrease attention, make me less social... These are all symptoms of high serotonin.

People always put some metaphysical spin on these effects claiming that the visuals are there to teach you something or that the visuals allow you a glimpse into "the truth" of the universe. A peek behind the curtain of reality... Basically the visuals are worth it due to the perceived religious experience. I completely disagree and haven't found I've learned more from highly visual trips then from less visual trips. The "profound" thoughts that I have while in the grip of psychedelia are practically useless as I sober up and realize how disordered and logically inconsistent my thoughts were.

Perhaps the pooling up of subconscious images can have an orienting and creative effect on the psyche similar to dream interpretation however i'm on the fence as to whether we can actually learn and benefit from these experiences or not. I do think that pain, sadness, and other symptoms reminiscent of serotonin can be a catalyst for growth and creativity therefore I recognize the usefulness of serotonergic states.

I always experience a nice afterglow following a trip- even a bad trip. which suggests that the high serotonin is more or less an acute episode and doesn't last. It is compensating for something.

My theory is that psychedelics are extremely dopaminergic. Like caffeine x100 but with less physiologically stimulating effects. If dopamine is pushed too high then the resources of the body are overwhelmed and serotonin is released to compensate by bringing metabolism down and preventing hyperthermia and exhaustion. The more psychedelics you take... the more visuals you will get as the body releases higher amounts of serotonin to compensate the sharp increases in dopamine.

Overdosing on dopaminergic stimulants like caffeine and ritalin can lead to psychosis and the same sorts of symptoms experienced on psychedelics. Mania experienced in bipolar disorder can lead to psychosis. The mania symptoms of bipolar are reminiscent of excesses in dopamine and if mania is pushed too high then you would expect the compensatory action of serotonin release and psychosis.

I think psychosis is a spectrum and deeper levels of psychosis suggest increasingly higher levels of serotonin. Schizophrenia is a state of very highly/chronically elevated serotonin and thus chronic hallucinations, paranoia, delusional thinking etc... these are all symptoms that can be generated dose dependently with psychedelics. It is also interesting that over 60% of schizophrenics smoke cigarettes... this would be because nicotine has dopaminergic effects and probaly helps alleviate symptoms of high serotonin... Unless of course the high serotonin is compensating for high dopamine (mania induced psychosis) in which case the nicotine would make things worse.

I think MDMA probaly ratchets up dopamine levels while blocking serotonin release. or ratchets up dopamine levels through blocking serotonin release. This is the crucial difference between LSD and MDMA. MDMA blocks the compensatory release of serotonin while LSD doesn't. MDMA can cause dopaminergic neurotoxicity probaly through inducing a hypoxic state in the brain as glucose is burned throughout the brain and body at an enormous rate. MDMA can also cause serotonin syndrome which is probaly mostly caused by extremely high levels of dopamine with elevated but subpar levels of serotonin release. LSD doesn't have the same propensity for serotonin syndrome and neurotoxicity because it doesn't block serotonin release.

So psychosis is a spectrum and is symptomatic of very high serotonin. You can induce psychosis in 2 ways. The first way through increasing serotonin directly (schizophrenia)... the 2nd way through increasing dopamine to the point of massive compensatory serotonin release (mania induced psychosis and psychedelic psychosis)

Thoughts? Experiences?

I think maybe you have to go through the high serotonin fearful state in the peak for a couple of hours in order to maximize that high dopamine state for the subsequent several hours.

 

[Parsifal]

Maybe dopamine is increased so much that it turns into adrenalin which increases lipid peroxidation like serotonin or oestrogen does, which increases nitric oxide and give hallucinations/bad trips?

Near death experiences: a multidisciplinary hypothesis
thirdworld.nl/phosphene-phenomenon-a-new-concept (Interesting scientist btw, worth reading Brain Dreams Imagery Imagination is more important than knowledge). @haidut you might be interested.

I wonder if there is a way to prevent dopamine to be changed in adrenaline (GABA agonists?), maybe someone should try that while tripping for science?

I think that there is a lack of direction with "doses". It seems that products like serotonin and oestrogen should be kept as close to 0 as possible and thyroid and dopamin as high as possible but it seems that some people are having diffiulties with that?

 

[Dopamine]

I think maybe you have to go through the high serotonin fearful state in the peak for a couple of hours in order to maximize that high dopamine state for the subsequent several hours.

I think so. I think maybe both serotonin and dopamine rise in a trip and afterward there should be downregulation of serotonin receptors. If this downregulation doesn't happen then maybe the trip could cause PTSD as serotonin remains high.

Maybe dopamine is increased so much that it turns into adrenalin which increases lipid peroxidation like serotonin or oestrogen does, which increases nitric oxide and give hallucinations/bad trips?

Near death experiences: a multidisciplinary hypothesis
thirdworld.nl/phosphene-phenomenon-a-new-concept (Interesting scientist btw, worth reading Brain Dreams Imagery Imagination is more important than knowledge). @haidut you might be interested.

I wonder if there is a way to prevent dopamine to be changed in adrenaline (GABA agonists?), maybe someone should try that while tripping for science?

I think that there is a lack of direction with "doses". It seems that products like serotonin and oestrogen should be kept as close to 0 as possible and thyroid and dopamin as high as possible but it seems that some people are having diffiulties with that?

The oxidation of adrenaline creates adrenochrome which is probaly involved in psychosis.

"Several small-scale studies (involving 15 or fewer test subjects) conducted in the 1950s and 1960s reported that adrenochrome triggered psychotic reactions such as thought disorder, derealization, and euphoria.[2] Researchers Abram Hoffer and Humphry Osmond claimed that adrenochrome is a neurotoxic, psychotomimetic substance and may play a role in schizophrenia and other mental illnesses.[3] In what they called the "adrenochrome hypothesis"

Serotonin can accelerate the oxidation of adrenaline to adrenochrome.

I don't really agree with my theory posted above anymore though some of the observations still hold water, I don't know if I agree with Rays claim that LSD is an approximate serotonin antagonist either. I think psychedelics agonise some dopamine/serotonin receptors and antagonise other dopamine/serotonin receptors in the short term (for several hours after administration). the net effect of a trip however seems to be a reduction in serotonin (probaly through agonising 5HT receptors really hard for several hours then causing subsequent downregulation).

Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain. - PubMed - NCBI

 

[Drareg]

I'm guessing the same thing with LSDs effects on adrenoreceptors.
Ray Peat speculated somewhere that lSD might have direct effect on electric current, I'm guessing they may find its a potent demethylation agent with further research.

Speculating wildly I would say lSD tunes you into magnetism,DMT also, just like other creatures can see the fields.

Albert Hoffman said the problem with overuse of LSD is that people might view life as just chemicals and this may cause a severe existential crisis.

 

[Dopamine]

I just found out that there are studies showing LSD inhibits the firing of serotonergic nerves- this is probaly why Ray would call it an approximate serotonin antagonist. It looks like most of the psychedelic tryptamines such as psilocin and DMT act similarly.

Neuropsychopharmacology - Serotonin and Hallucinogens

"LSD was found to have a potent inhibitory effect upon the tonically firing 5-HT neurons of the dorsal raphe nucleus (Aghajanian et al. 1968); the local application of LSD by microiontophoresis indicated that the inhibition was through a direct action on the somatodendritic region of 5-HT neurons (Aghajanian et al. 1972). A reduction in 5-HT cell firing rate was consistent with earlier biochemical findings of reduced 5-HT turnover in brain after LSD (Freedman 1961). Simple indoleamine hallucinogens such as DMT (N,N-dimethyltryptamine) and psilocin were also shown to inhibit 5-HT neurons in the raphe nuclei (Aghajanian and Haigler 1975). "

 

[Parsifal]

I just found out that there are studies showing LSD inhibits the firing of serotonergic nerves- this is probaly why Ray would call it an approximate serotonin antagonist. It looks like most of the psychedelic tryptamines such as psilocin and DMT act similarly.

Neuropsychopharmacology - Serotonin and Hallucinogens

"LSD was found to have a potent inhibitory effect upon the tonically firing 5-HT neurons of the dorsal raphe nucleus (Aghajanian et al. 1968); the local application of LSD by microiontophoresis indicated that the inhibition was through a direct action on the somatodendritic region of 5-HT neurons (Aghajanian et al. 1972). A reduction in 5-HT cell firing rate was consistent with earlier biochemical findings of reduced 5-HT turnover in brain after LSD (Freedman 1961). Simple indoleamine hallucinogens such as DMT (N,N-dimethyltryptamine) and psilocin were also shown to inhibit 5-HT neurons in the raphe nuclei (Aghajanian and Haigler 1975). "

So all the bad effets one might experience with psychedelics might come from raised adrenaline/adenochrome? I've read that some people take benzodiazepine to stop bad trips.

 

[tomisonbottom]

I have a theory that psychedelics are serotonergic in high doses (overdose) but dopaminergic in low doses. I have found that my best trips on psychedelics have been on sub-visual doses and I have begun to associate visuals with overdose. I think when psychedelics are ingested to the point of visuals that this indicates overdose and increases in serotonin release...
I think MDMA probaly ratchets up dopamine levels while blocking serotonin release. or ratchets up dopamine levels through blocking serotonin release. This is the crucial difference between LSD and MDMA. MDMA blocks the compensatory release of serotonin while LSD doesn't. MDMA can cause dopaminergic neurotoxicity probaly through inducing a hypoxic state in the brain as glucose is burned throughout the brain and body at an enormous rate. MDMA can also cause serotonin syndrome which is probaly mostly caused by extremely high levels of dopamine with elevated but subpar levels of serotonin release. LSD doesn't have the same propensity for serotonin syndrome and neurotoxicity because it doesn't block serotonin release.

This makes sense to me, but I thought MDMA raised serotonin. Where did you get the idea it blocks it?

 

[Constatine]

LSD is an agonist to some serotonin receptors and an antagonist to others. Agonist activity of LSD and lisuride at cloned 5HT2A and 5HT2C receptors. - PubMed - NCBI. Dopamine toxicity is unlikely to be the cause of the visual effects as drugs like cocaine that are known to cause dopamine toxicity don't have visual effects. It's thought ( in the above study) that the effects are caused by 5HT2C agonism.

 

[Wagner83]

Didn't metergoline specifically abolish the lsd/psyllocybin trips?