An approach to treating schizophrenia with psychedelics (2022)

[Jabberwocky]

I've seen discussion here around this topic which I have scoffed at and called outright dubious or dangerous. The approach here seems much more rational and appropriate.

The main difference here is that they are referring to using psychedelics and/or non-psychedelic derivatives in micro or sub-psychedelic dosing, but also importantly blocking the 5-HT2a psychedelic effect. The main goal being treating the cerebral atrophy associated with negative schizophrenia symptoms. @Skorpio I'm trying to get past the paywall. I found it on scihub but when you click the pdf link it 404s ;( if you know any tricks

Could psychedelic drugs have a role in the treatment of schizophrenia? Rationale and strategy for safe implementation​

Could psychedelic drugs have a role in the treatment of schizophrenia? Rationale and strategy for safe implementation - Molecular Psychiatry

Schizophrenia is a widespread psychiatric disorder that affects 0.5–1.0% of the world’s population and induces significant, long-term disability that exacts high personal and societal cost. Negative symptoms, which respond poorly to available antipsychotic drugs, are the primary cause of this...

www.nature.com

"Schizophrenia is a widespread psychiatric disorder that affects 0.5–1.0% of the world’s population and induces significant, long-term disability that exacts high personal and societal cost. Negative symptoms, which respond poorly to available antipsychotic drugs, are the primary cause of this disability. Association of negative symptoms with cortical atrophy and cell loss is widely reported. Psychedelic drugs are undergoing a significant renaissance in psychiatric disorders with efficacy reported in several conditions including depression, in individuals facing terminal cancer, posttraumatic stress disorder, and addiction. There is considerable evidence from preclinical studies and some support from human studies that psychedelics enhance neuroplasticity. In this Perspective, we consider the possibility that psychedelic drugs could have a role in treating cortical atrophy and cell loss in schizophrenia, and ameliorating the negative symptoms associated with these pathological manifestations. The foremost concern in treating schizophrenia patients with psychedelic drugs is induction or exacerbation of psychosis. We consider several strategies that could be implemented to mitigate the danger of psychotogenic effects and allow treatment of schizophrenia patients with psychedelics to be implemented. These include use of non-hallucinogenic derivatives, which are currently the focus of intense study, implementation of sub-psychedelic or microdosing, harnessing of entourage effects in extracts of psychedelic mushrooms, and blocking 5-HT2A receptor-mediated hallucinogenic effects. Preclinical studies that employ appropriate animal models are a prerequisite and clinical studies will need to be carefully designed on the basis of preclinical and translational data. Careful research in this area could significantly impact the treatment of one of the most severe and socially debilitating psychiatric disorders and open an exciting new frontier in psychopharmacology."

 

[Skorpio]

I've seen discussion here around this topic which I have scoffed at and called outright dubious or dangerous. The approach here seems much more rational and appropriate.

The main difference here is that they are referring to using psychedelics in micro or sub-psychedelic dosing, but also importantly blocking the 5-HT2a psychedelic effect. The main goal being treating the cerebral atrophy associated with negative schizophrenia symptoms. @Skorpio I'm trying to get past the paywall. I found it on scihub but when you click the pdf link it 404s ;( if you know any tricks

Could psychedelic drugs have a role in the treatment of schizophrenia? Rationale and strategy for safe implementation​

Could psychedelic drugs have a role in the treatment of schizophrenia? Rationale and strategy for safe implementation - Molecular Psychiatry

Schizophrenia is a widespread psychiatric disorder that affects 0.5–1.0% of the world’s population and induces significant, long-term disability that exacts high personal and societal cost. Negative symptoms, which respond poorly to available antipsychotic drugs, are the primary cause of this...

www.nature.com

"Schizophrenia is a widespread psychiatric disorder that affects 0.5–1.0% of the world’s population and induces significant, long-term disability that exacts high personal and societal cost. Negative symptoms, which respond poorly to available antipsychotic drugs, are the primary cause of this disability. Association of negative symptoms with cortical atrophy and cell loss is widely reported. Psychedelic drugs are undergoing a significant renaissance in psychiatric disorders with efficacy reported in several conditions including depression, in individuals facing terminal cancer, posttraumatic stress disorder, and addiction. There is considerable evidence from preclinical studies and some support from human studies that psychedelics enhance neuroplasticity. In this Perspective, we consider the possibility that psychedelic drugs could have a role in treating cortical atrophy and cell loss in schizophrenia, and ameliorating the negative symptoms associated with these pathological manifestations. The foremost concern in treating schizophrenia patients with psychedelic drugs is induction or exacerbation of psychosis. We consider several strategies that could be implemented to mitigate the danger of psychotogenic effects and allow treatment of schizophrenia patients with psychedelics to be implemented. These include use of non-hallucinogenic derivatives, which are currently the focus of intense study, implementation of sub-psychedelic or microdosing, harnessing of entourage effects in extracts of psychedelic mushrooms, and blocking 5-HT2A receptor-mediated hallucinogenic effects. Preclinical studies that employ appropriate animal models are a prerequisite and clinical studies will need to be carefully designed on the basis of preclinical and translational data. Careful research in this area could significantly impact the treatment of one of the most severe and socially debilitating psychiatric disorders and open an exciting new frontier in psychopharmacology."

I will check if I can get it at work, it's no good at home.

 

[AlphaMethylPhenyl]

I think that this may have merit, though I have no scientific basis. I think though that, since the most effective/used antipsychotics are "atypical", which blocks the psychedelic receptor, that this poses an issue. There's a greater risk of relapse when being taken off one's antipsychotic. Hard to know if it's worth it to get off one's medication in order to get the full therapeutic effect of psychedelics. Seems risky to me also because these trips can cause a lot of psychic pain even in the absence of mental illness with a strong component of anxiety. Just my layman's thoughts.

 

[arrall]

I recall reading a lengthy report somewhere (maybe MAPS’s website??) by a young individual suffering from schizophrenia who was able to treat and manage his symptoms using low-moderate doses of psilocybin.

I’ll see if I can dig it up.

 

[plumbus-nine]

Finally they begin to relativize the stupid and often repeated nonsense that psychoactives, specially psychedelics would induce paranoid schizophrenia. Hope they will do the same with the stuff that dissociatives would induce schizophrenia (I had a huge disso habit and never got schizo symptoms).

Yeah, the full text would be interesting if somebody can get it. Sci-Hub doesn't work for this one.

 

[Fertile]

I think this was tried in the 1960s. R.D Laing was certainly using LSD. Anti-psychiatry was the field most interested in their use. Of course, LSD does not replicate schizophrenia - MK-801 and it's ilk do that,

I know PCP will evoke all of the positive and negative effects of schizophrenia in patients for whom neuroleptic medication controlled symptoms.

It's a dangerous field. I'm sure advances have been made, but it doesn't appear that any severe mental illness is 5HT2a mediated.

 

[AlphaMethylPhenyl]

I think this was tried in the 1960s. R.D Laing was certainly using LSD. Anti-psychiatry was the field most interested in their use. Of course, LSD does not replicate schizophrenia - MK-801 and it's ilk do that,

I know PCP will evoke all of the positive and negative effects of schizophrenia in patients for whom neuroleptic medication controlled symptoms.

It's a dangerous field. I'm sure advances have been made, but it doesn't appear that any severe mental illness is 5HT2a mediated.

Aren't atypical antipsychotics 5-HT2a antagonists, which increases dopaminergic activity in the frontal lobe, leading to less negative symptomology?

 

[Fertile]

Not 5HT2a selective. Also, neuroleptics tend to have awful side-effects. It's accepted because it's treating such a serious illness.

As I said - PCP will produce ALL of the positive and negative symptoms of schizophrenia. NOT ketamine, interestingly. I think it's because PCP also vastly increases DAT.

I have to tell you that from time to time designers try new receptors... but other than NMDA antagonists (only worked for 10% of patients - BUT the refractive 10%), nothing good has emerged. The NMDA antagonist was dropped - even though it VASTLY helped 10% of patients. I was angry about that. 30 years ago I read that in CS fluid 90% of schizophrenia patients has too much DOPAC (dopamine metabolite), 10% had too much NMDA....

It's all a bit vague - they don't REALLY know how most of these medicines work.

I hate the fact that people have their lives destroyed by bad medication.

 

[Jabberwocky]

My schizo diagnosis and symptoms seem to be very 5-ht2a related

Outwardly mild, almost invisible, but internally any serotonergic drug seems to fuck with me at a high level

 

[Fertile]

I would be very careful about self-diagnosis. You know the old saying - a physician who treats them self has a fool for a doctor.

How do you know it's 6HT2a (don't forget - for a decade 'experts' were CERTAIN it was a 5h2a imbalance. How do you know the 5HT2a effects aren't downstream of one of the other effects?

If it was as simple as that, there are selective 5HT2a antagonists. Usually these are lysergamides with higher affinity than LSD but act as antagonists.

I do appreciate that patients know exactly what is happening - often their are no words to convey these terms... but I also know that the doctors who go into this field require far more qualifications than almost every other field.

So peak up if the meds don't work, but it seems ALL meds have a price.

 

[paracelsius]

Very bad idea imho. Either psychedelic 5HT2A agonists won't do anything to schizophrenics or would fck them up really really bad. Very unsafe. Here is why I am saying this. These guys in Finland

https://pubmed.ncbi.nlm.nih.gov/11763413/

they found very high levels of a cocktail of psychoactive tryptamines (DMT, 5MeO-DMT, bufonenin and N-methyltryptamine) in the urine of schizophrenic patients, (non drug users!!), just schizos. 7x higher (all 4 tryptamines) than in non-psychiatric patients!!

These Japanese found same thing too: https://pubmed.ncbi.nlm.nih.gov/8747157/

Somehow, schizophrenics metabolize tryptamine and serotonin abnormally to a bunch of psychoactive tryptamines instead of to inactive indole acetic acid metabolites in non-schizophrenics.
So that means schizophrenics are either (already) desensitized to the effects of 5HT2A psychedelics (tolerance). In that case, 5HT2A agonist (in normal dose) would have no effects on them. Or they don't develop tolerance (highly unlikely) and you risk ODing them on normal doses since they already have high levels of 5HT2A agonists in their system. Either way, I think it is a bad idea!

 

[Pissed_and_messed]

I would be very careful about self-diagnosis. You know the old saying - a physician who treats them self has a fool for a doctor.

How do you know it's 6HT2a (don't forget - for a decade 'experts' were CERTAIN it was a 5h2a imbalance. How do you know the 5HT2a effects aren't downstream of one of the other effects?

If it was as simple as that, there are selective 5HT2a antagonists. Usually these are lysergamides with higher affinity than LSD but act as antagonists.

I do appreciate that patients know exactly what is happening - often their are no words to convey these terms... but I also know that the doctors who go into this field require far more qualifications than almost every other field.

So peak up if the meds don't work, but it seems ALL meds have a price.

I think doctor diagnosed him.

 

[Pjotr777]

There is an article on MAPS’ website about treating childhood schizophrenia with psychedelics. I have a book “LSD psychotherapy” from Stanislav Grof where they treat psychotic patients with weekly high doses of LSD and after many sessions the LSD had a paradoxical effect making the patient grounded and clear headed. It also briefly mentions treating bipolar patients but mention it should be done inpatient because of the risk of triggering a manic episode. I’m bipolar myself and hope one day there will be more research in curing (as opposed to treating) bipolar and other psychotic disorders.

I also read a study about LSD “overdoses” and a bipolar woman with psychotic symptoms was symptom free for over 20 years after ingesting an accidental high dose.

LSD Overdoses: Three Case Reports

Objective: In academic settings around the world, there is a resurgence of interest in using psychedelic substances for the treatment of addictions, posttraumatic stress disorder, depression, anxiety, and other diagnoses. This case series describes the medical consequences of accidental...

www.jsad.com

MAPS - Volume 7 Number 3 Summer 1997 - Treatment of Childhood Schizophrenia Utilizing LSD and Psilocybin

 

[kiely]

There is an article on MAPS’ website about treating childhood schizophrenia with psychedelics. I have a book “LSD psychotherapy” from Stanislav Grof where they treat psychotic patients with weekly high doses of LSD and after many sessions the LSD had a paradoxical effect making the patient grounded and clear headed. It also briefly mentions treating bipolar patients but mention it should be done inpatient because of the risk of triggering a manic episode. I’m bipolar myself and hope one day there will be more research in curing (as opposed to treating) bipolar and other psychotic disorders.

I also read a study about LSD “overdoses” and a bipolar woman with psychotic symptoms was symptom free for over 20 years after ingesting an accidental high dose.

LSD Overdoses: Three Case Reports

Objective: In academic settings around the world, there is a resurgence of interest in using psychedelic substances for the treatment of addictions, posttraumatic stress disorder, depression, anxiety, and other diagnoses. This case series describes the medical consequences of accidental...

www.jsad.com

MAPS - Volume 7 Number 3 Summer 1997 - Treatment of Childhood Schizophrenia Utilizing LSD and Psilocybin

Thank you for your support. And very much appreciated. Thank you so much for posting.

 

[Pjotr777]

Thank you for your support. And very much appreciated. Thank you so much for posting.

You’re mostly welcome.

Especially the story of Jeannie I found very touching:

Jeannie

Jeannie was a girl who, when initially seen, lived in a totally encapsulated world. Her behavior consisted of hyperactive twirling, yelling a meaningless "word-salad," screaming, and violent attacks towards anyone who came within her personal space. She would work herself up into such manic frenzy that she would collapse in physical exhaustion. During her treatment course with psychedelic therapy Jeannie experienced a number of transcendental phenomena which established the core recovery from her psychosis.

In spite of being blind, burdened with congenital dislocation of hips and knees and raised by a completely psychotic mother, this girl overcame horrendous madness in a devastatingly sterile and chaotic environment of a state hospital ward, to become one of the most tender, loving, compassionate and courageous persons the author has ever known. If Jeannie had had the opportunity to continue her sessions in a benign, safe and nurturing environment, she would have become a functionally superior human being. Our experience with this one girl was all the proof that was needed to attest to the dramatic usefulness of psychedelic drugs in treating the most seemingly intractable psychotic states.

It is most noteworthy to report that at least four of the children had identifiable transcendental experiences and were capable of communicating such experiences to us. It may be that some of the other children had similar experiences but were unable to communicate to us. However, given the age and degree of psychopathology of these children we were amazed that these spiritual experiences occurred.

“Our experience with this one girl was all the proof that was needed to attest to the dramatic usefulness of psychedelic drugs in treating the most seemingly intractable psychotic states.”

 

[Pissed_and_messed]

There is an article on MAPS’ website about treating childhood schizophrenia with psychedelics. I have a book “LSD psychotherapy” from Stanislav Grof where they treat psychotic patients with weekly high doses of LSD and after many sessions the LSD had a paradoxical effect making the patient grounded and clear headed. It also briefly mentions treating bipolar patients but mention it should be done inpatient because of the risk of triggering a manic episode. I’m bipolar myself and hope one day there will be more research in curing (as opposed to treating) bipolar and other psychotic disorders.

I also read a study about LSD “overdoses” and a bipolar woman with psychotic symptoms was symptom free for over 20 years after ingesting an accidental high dose.

LSD Overdoses: Three Case Reports

Objective: In academic settings around the world, there is a resurgence of interest in using psychedelic substances for the treatment of addictions, posttraumatic stress disorder, depression, anxiety, and other diagnoses. This case series describes the medical consequences of accidental...

www.jsad.com

MAPS - Volume 7 Number 3 Summer 1997 - Treatment of Childhood Schizophrenia Utilizing LSD and Psilocybin

I have always believed by gut instinct that entheogens like weed and LSD and shrooms have set of contradictory effects when it comes to psychotic disorders. I am excited to see studies supporting the idea.

 

[Pjotr777]

Here’s one on self-administration of LSD and DMT treating psychosis.

Self-treatment of psychosis and complex post-traumatic stress disorder with LSD and DMT—A retrospective case study

This article describes a case of a teenager with early complex trauma due to chronic domestic violence. Cannabis use triggered auditory hallucinations…

www.sciencedirect.com

LSD used to be the most studied psychopharmaceutical drug in the previous century until it got scheduled. I wonder where has all that research gone?

 

[Jabberwocky]

Here’s one on self-administration of LSD and DMT treating psychosis.

Self-treatment of psychosis and complex post-traumatic stress disorder with LSD and DMT—A retrospective case study

This article describes a case of a teenager with early complex trauma due to chronic domestic violence. Cannabis use triggered auditory hallucinations…

www.sciencedirect.com

These types of things sound so bizzare to me, because self administered LSD and daily DMT is what caused my psychosis/schizophrenia. I did eventually recover, though.

 

[paranoid android]

i have had psychosis before and it was nothing like shrooms or acid. If anything it's the opposite of tripping as when your tripping your hyper aware. But when your psychotic tyou lack all insight into it. Psychosis reminded me alot of dramamine actually. I had negative symptoms as well for awile and can't say they where anything like pcp either. Granted i only had pcp once

 

[Pjotr777]

New Paradigms of Old Psychedelics in Schizophrenia

Psychedelics such as lysergic acid diethylamide (LSD), psilocybin (magic mushrooms), and mescaline exhibit intense effects on the human brain and behaviour. In recent years, there has been a surge in studies investigating these drugs because clinical ...

www.ncbi.nlm.nih.gov

“Emerging hypotheses suggest that psychedelic drugs work through a brain resetting mechanisms and could cure the underlying pathology of neuronal circuitry, which could benefit psychiatric disorders including schizophrenia.”