This is a topic I’ve been thinking long and hard about. We often hear rumors about psychedelics worsening schizophrenia or even bringing the disorder on in susceptible individuals. It may be possible that, not only is this untrue, but we might wonder if psychedelics may be able to actually treat schizophrenia. This may seem radical and very counter-intuitive, but I believe if you follow this post to the end, you may find yourself agreeing with this claim. First, I must warn you that this is theoretical and while there may be decent evidence supporting this hypothesis, I am not comfortable advising anybody with schizophrenia to ingest psychedelic drugs until further research has been done, which might be difficult due to the dogmas around this topic.
On that note, this article will first explore the dogmas, questioning their validity. Next we will explore the research that supports this hypothesis. This includes research on mechanisms of psychosis, neurogenesis, plasticity, cannabis, psychotomimetics, among other things.
There is a long standing dogma that psychedelics can bring out schizophrenia in susceptible individuals. This appears to be assumed based on the dramatic subjective effects that psychedelics cause during intoxication.
People report hallucinations, delusions, paranoia, and more, although I am not sure about this because of how common it is for psychedelic users to also consume cannabis, very often together as well. When people experience psychotic reactions after consuming psychedelics, we must look and see if these individuals are or were using cannabis, actually have HPPD which is probably closer to migraine aura, or even experiencing manic symptoms, which does seem to occur. In my experience, I have yet to meet someone who actually had clear psychotic symptoms after psychedelic use without cannabis use. I’ve had people claim this and then upon further investigation, these people were either not experiencing psychotic symptoms or were using cannabis, usually daily.
Furthermore, there is no research suggesting a link between psychosis and psychedelics besides research that assumes the state is psychotomimetic. In one study they described psychedelic intoxication as similar to first episode psychosis in schizophrenia, but that it was worsened when typical antipsychotics were administered. There is also no link between psychedelics and mental health problems, in fact it’s quite the opposite, psychedelic use is associated with decreased psychological distress and suicidality. There are also cancelled studies from the 60s that involved giving many high doses of psychedelics to young children with schizophrenic symptoms, showing an improvement in their life quality, to the point that children who couldn’t attend school were able to after the treatments. The studies were cancelled due to the political tension surrounding psychedelics during this time. A 2020 study on 3 case reports of LSD overdoses revealed on individual who recovered from their bipolar disorder with psychotic features with 20 years of persistent benefits. None of these case reports involved bad outcomes, including one report of an LSD overdose in a pregnant women. All of this together shows that there is little, if any, evidence of psychedelics being associated to schizophrenia.
Cannabis vs Psychedelics
All of this is further complicated by the fact that cannabis does appear to bring out schizophrenic symptoms in susceptible individuals, and even in mentally health individuals. Cannabis psychosis in non-schizophrenics seems to last less than a week after the drug has worn off and psychotic symptoms are experienced in up to half of the population tested. Even in those not susceptible to schizophrenia, it can start a cycle of persisting psychotic symptoms. There is even a cannabinoid hypothesis of schizophrenia. Cannabis was also found to worsen depression over time with continued use, despite reports of increasing mood in the short term. On the contrary, a single large dose of psilocybin produced long-lasting (6 months+) strong decreases in depression in 80% of patients who were dying of terminal illness. Body dysmorphic disorder, which has associated to psychosis, was found to be reduced by psilocybin use but worsened by cannabis use.
People conflate cannabis with psychedelics, assuming that psychedelic drugs may be a more powerful yet similar drug to cannabis. While cannabis does in fact have an area of overlap in mechanisms with psychedelics, there is a lot more about the mechanisms of cannabis that could explain different outcomes and effects. For example, cannabis causes hypofunction of glutamate NMDA receptors (NMDAr) and decreases glutamate activity. The glutamate hypothesis of schizophrenia posits that many of the symptoms are due to hypofunction of NMDAr. Drugs that block the function of NMDAr are extremely psychotomimetic and include ketamine and PCP. CB1 receptors are the main target for THC in cannabis, and CB1 receptors colocalize and interact with D2 receptors. The dopamine hypothesis of schizophrenia explores hyperactive D2 receptors as a possible mechanism for psychotic symptoms which has lead to the use of D2 receptor blocking drugs in schizophrenia. Lastly, cannabis also causes dynorphin levels to increase.
This leads us to:
Dynorphin and Schizophrenia
Schizophrenia appears to be a condition of extreme stress with issues in stress recovery, leading to an accumulation of negative consequences. There is evidence that extreme levels of stress may be hallucinogenic via Kappa Opioid Receptor (KOR) agonizing and NMDAr blocking mechanisms. It may be that anyone can suffer psychosis with enough prolonged stress and suffering while those with schizophrenia are more susceptible to the effects of stress, less able to recover, and there may even be genes that predispose someone to seek out stressful and nonconformist situations naturally. In this section we will look at the hallucinogenic stress mechanisms.
Dynorphin seems to be capable of binding many theories of schizophrenia together. Dynorphin is an endogenous opioid that is involved in stress-induced dysphoria, anhedonia, anxiety, addiction, depressive and even psychotic effects. Dynorphin directly blocks NMDAr which would produce NMDAr hypoactivity, satisfying the glutamate hypothesis of schizophrenia. Chronically elevated dopamine is thought to play a role in schizophrenia and upregulates dynorphin, likely through interactions at D1 and NMDAr complexes. Dynorphin potentiates D2 receptors and reduces dopamine release, satisfying the dopamine hypothesis of schizophrenia. Dynorphin is implicated in trauma, explaining the association of schizophrenia with trauma. Dynorphin mediates the effects of social defeat stress and upregulates from early childhood social isolation, satisfying the social defeat theory of schizophrenia.
The link of social defeat and schizophrenia may represent how crucial social support is for dealing with symptoms of stress, potentially from any cause. If you are persecuted, it is likely an even worse stressor because not only can you not get social support, but you have social stress and offense. The severity of symptoms in schizophrenia correlated with a lack of friends. Frequent interactions with friends was found to be crucial to recovery in schizophrenia, more than the self-reported quality of friendships although this likely doesn’t mean that abusive friends are better than none. Reducing loneliness reduces paranoia while inducing loneliness increases paranoia. Those with schizophrenia often feel excluded due to stigma. Differences in status, social class and political views was found to generate paranoia. It may be that social exclusion, otherness, loneliness are all very stressful and hindering to stress recovery. The picture of social defeat may often begin with interest in the taboo and social deviance, which is found to occur before any psychotic symptoms in schizophrenics. Then as stigma and social exclusion sets in, symptoms get worse, perpetuating further exclusion. Socializing may be key to treating our stresses in life and for those who lack a social support system, they may be unable to recover and cope. Lacking a social support system may be one of the worst possible stressors when living in a society of humans.
Low IQ correlates with schizophrenia and dynorphin may be able to help explain this. Microinjections of dynorphin into the hippocampus produced spatial memory deficits. Individuals with schizophrenia also face spatial memory deficits. Dynorphin levels rise with aging and spatial memory declines with aging. Knocking out dynorphin prevents age-related cognitive decline. Alcohol-related memory and learning impairment is mediated by dynorphin upregulation. Stress-induced deficits in learning and memory are mediated by dynorphin. Occlusal disharmony, a painful condition, also involved memory and learning impairments mediated by dynorphin, which could be due to a role that dynorphin may play in pain aversion.
Speaking of pain, dynorphin plays a role in PTSD which is also linked to low IQ. The linked research on PTSD and IQ has noted that premorbid IQ being lower also made PTSD worse, but this may be due to early life stress or that prior trauma is limiting IQ and even promoting more severe stress reactions in adulthood. For example, it was found that exposure to domestic violence suppressed IQ. Prior trauma is a risk factor for experiencing further trauma. So it seems likely that prior trauma and stress may be at play here with premorbid IQ scores. This article explores research showing up to a 14 point IQ difference based on stress.
On top of all of that, social rejection was found to drastically decrease IQ (25%) and reasoning ability (30%) in the short term. This is important as social defeat stress is mediated by dynorphin. The low IQs found in schizophrenics might be explained by chronic rejection for being socially deviant.
Psychosis and dynorphin have been explored very lightly in the research so far. Kappa Opioid Receptor (KOR) agonists like dynorphin produce psychosis in healthy humans. It is thought that dynorphin releases during seizures to curb overactive glutamate activity, but also induces a psychosis post-seizure. Receptor complexes of dopamine D1 and D2 localize on dynorphin neurons in schizophrenia and meth users. Dynorphin levels were found to be increased in the cerebral spinal fluid of schizophrenics and correlated with their psychotic symptom severity. Stimulants like cocaine, amphetamine, and nicotine upregulate dynorphin activity which could explain related psychotic symptoms such as stimulant psychosis. There is something known as ‘coke bugs‘ which is formication, an effect that dynorphin injections were found to produce in 1 out of 4 people.
Exogenous KOR agonists have shown psychosis inducing effects. A quote from this study,
The inhalation of vaporized salvinorin-A led to very strong psychotropic effects of rapid onset and short duration. Perceptual modifications included the visual domain, and in contrast with 5HT2A agonists, auditory hallucinations were very common. Also in contrast with the classical serotonergic psychedelics, loss of contact with external reality was prominent with the participants being unreactive to external visual and verbal cues, especially after the medium and high doses. While at the low and medium doses there was an increase in bodily sensations, at 1.0mg there was an almost complete loss of body ownership and an increase in out-of-body experiences. These results suggest that the dynorphins – KOR system may play a previously underestimated role in the regulation of sensory perception, interoception, and the sense of body ownership in humans.
This study is great because it distinguishes the dynorphin-like psychotic effects such as hearing voices from serotonergic psychedelic states, which don’t often contain auditory voice hallucinations.
To recap, dynorphin is a KOR agonist similar to the drug Salvia Divinorum. It is essentially the body’s endogenous Salvia. This means social defeat and even stress, in general, should promote salvia-like hallucinogenic and psychotic effects. Those with genes related to schizophrenia likely have a natural sensitivity to stress, a decreased ability to recover from stress, a higher likelihood of living stressful lifestyles or engaging in potentially socially defeating behaviors.
Neurogenesis and Plasticity
Neurogenesis is the process of neuron birth. Neuroplasticity is the ability to reorganize synaptic connections, especially in response to learning. Neurogenesis in adults takes place primarily in the hippocampus and dentate gyrus. Individuals with schizophrenia have impaired neurogenesis and neuroplasticity. Impaired neurogenesis and stress were found to differentially lead to reduced hippocampal volume. Hippocampal volume was found to be reduced in schizophrenic and schizoaffective individuals but not bipolar 1 individuals. Neurogenesis is enhanced by Long Term Potentiation (LTP) which relies on NMDAr function. There is evidence that schizophrenics have impaired LTP, likely mediated by NMDAr hypofunction. It is thought that this hypofunction of NMDAr seen in schizophrenia may explain the reduced neurogenesis. The NMDA receptor also plays a critical role in plasticity, so hypofunction of these receptors could also explain the reduced plasticity seen in schizophrenia.
Stress was found to reduce neurogenesis which might involve dynorphin, since it is implicated in stress reactions. Blocking dynorphin may lead to stress resilience and functions as a rapid-acting and pronounced antipsychotic. Dynorphin reduces LTP and reduces excitatory signaling in the hippocampus and also the dentate gyrus, likely at least partly explaining the stress-linked reduction of hippocampal volume. Chronic opiate use both upregulates dynorphin activity and inhibits neurogenesis. It isn’t clear that dynorphin inhibits neurogenesis itself, but it seems likely due to the above research. Some studies mention a hypothesis that dynorphin increases neuroplasticity. Addiction may certainly involve dynorphin upregulation, neuroplasticity, learning and LTP, but it also involves so many different mechanisms and fluctuations due to repeated dosing and withdrawals.
It is thought that increasing neuroplasticity may have potential in treating schizophrenia. Theanine is an NMDAr partial agonist that was found to function as an antipsychotic and also enhances neurogenesis.
Psychedelics and Schizophrenia
It is possible that psychedelics may be able to treat schizophrenia. Psychedelic drugs induce neurogenesis in the hippocampus, a region that has reduced volume in individuals with schizophrenia. Serotonin also is able to induce neurogenesis. Psychedelics also promote structural and functional neuroplasticity, which, as previously mentioned, is impaired in schizophrenia.
LSD was found to attenuate the depressive effects of dynorphin/KOR agonism. On the other hand, a 5HT2a inverse agonist (opposite of agonist) were found to potentiate KOR signaling. 5HT2a receptor agonism was found to inhibit aversion in the DPAG, a region of the brain in which KORs are located and PTSD is implicated in. CBD was found to have antipsychotic properties and is a 5HT2a agonist and thought to reduce aversion in the DPAG as well. Psychedelics have also recently been considered as treatment for PTSD. Dynorphin has been implicated in depression as well. As mentioned before: a single large dose of psilocybin produced long-lasting (6 months+) strong decreases in depression in 80% of patients who were dying of terminal illness. In another study on psilocybin for depression, all patients showed benefits at 1 week after the dose, and many of them showed benefits many weeks later. The fMRI scans revealed that reduced blood flow to the amygdala induced by psilocybin correlated with reduced depressive symptoms. Dynorphin is known to control the gain on an amygdalar anxiety circuit, which further implies an interruption of dynorphin. On top of that, dynorphin plays a major role in addiction and psilocybin was able to get 80% of long-term smokers off of nicotine using only a single dose. A 2018 study found that psilocybin even reduces the pain of social exclusion which has implications for the connection of dynorphin, social defeat, and schizophrenia. All of this together suggests that psychedelics may interact with dynorphin, reducing its’ mechanisms and effects.
Dynorphin and psychedelics relate to fear extinction. Fear extinction is impaired in schizophrenics. During fear extinction, KOR mRNA is found to be dramatically downregulated while fear conditioning shows a dramatic upregulation of KOR mRNA. Blocking dynorphin/KOR was found to block conditioned fear. DMT microdosing in mice was found to enhance fear extinction. Low doses of psilocybin were found to increase neurogenesis and enhance fear extinction. High doses appear to do the opposite. D-cycloserine was found to facilitate fear extinction and is studied for treatment of schizophrenia. There are studies on psychedelics (MDMA) exploring fear extinction in relevance to PTSD, which involves altered fear extinction like schizophrenia. During fear recognition tasks that measure amygdala response, schizophrenics show hyperactivation of the amygdala to both fearful and even neutral faces while with LSD users there is a reduced response of the amygdala.
This altered fear extinction brings us back to the idea that individuals with schizophrenia may be less capable of recovering from stressful events, leading to an accumulation of negative effects. It seems that serotonin and dynorphin function with opposing and interconnecting roles in resilience and stress. This interaction relationship between dynorphin and serotonin seems to occur at p38 MAPK, KOR signaling induces the serotonin transporter (SERT) to reuptake serotonin, producing a hypo-serotonergic state. This induction of SERT was necessary for dynorphin to produce some of its effects which may be due to the anti-dynorphin/KOR effects of 5HT2a receptors. Blocking SERT is known to produce stress resilience. The removal of p38 MAPK on serotonergic neurons also produces stress resilience, likely by disrupting dynorphin. Blocking dynorphin directly leads to stress resilience as well. Serotonin itself is known to downregulate SERT, so when dynorphin levels are high its’ induction of SERT will lower extracellular serotonin levels and prevent SERT from downregulating. This should be expected to perpetuate a stressed tone, until something else either decreases the stressful trigger or increase serotonin levels and disrupt the low serotonin tone. Repeated doses of the KOR agonist, Salvia, were also found to upregulate SERT. Schizophrenics also appear to have increased SERT levels. Ultimately, a pattern of low serotonin activity and high dynorphin activity seems to be consistent. It may be that disruption of KOR mediated effects invoked by psychedelics stops this loop in which SERT is induced, thus allowing serotonin to accumulate again and restore a resilient state of mind.
Individuals with schizophrenia were found to have less functional 5HT2a receptors. A gene related to less 5HT2a receptors was linked to schizophrenia. This receptor forms complexes with mGlur2, which is thought to be a key to the psychedelic effects. Another study showed reduced function of these psychedelic receptor complexes in post-mortem brains of schizophrenic patients. They also show reduced 5HT2 receptor binding in the prefrontal cortex. Since mGlur2 agonism enhances 5HT2a binding, the reduced binding of 5HT2a may be explained by the reduced number of mGlur2 that are seen in post mortem schizophrenics. With less mGlur2, 5HT2a receptors will be less enhanced. This could mean they have a lower ability to activate the 5HT2a/psychedelic mechanism, and thus a lower ability to attenuate dynorphin/KOR mediated effects.
In older studies this is backed up. Schizophrenics appear to be less sensitive to LSD and also showed reduced effects from DMT, experiencing a lack of visual effects at doses that worked in non-schizophrenics. Glycine-type drugs that can treat schizophrenia through NMDAr enhancement increase serotonin in the prefrontal cortex where 5HT2a receptors are. Another study found that low thalamocortical plasticity is modulated by dysfunctional 5HT2a receptors in schizophrenia. A major predictor of schizophrenia is low cognitive function. Individuals with schizophrenia also show impaired associative learning. Psychedelics were found to be cognitive enhancing and increase associative learning ability. Upregulation of 5HT2a receptors via inverse agonism is thought to underlie part of the mechanism of certain antipsychotic drugs. 5HT2a receptor antagonists were able to reduce verbal memory and spatial memory in SSRI pretreated individuals. Taken together this could mean that the lower functioning of the 5HT2a receptors may allow un-attenuated dynorphin activity to disrupt cognitive function in schizophrenia, in similar ways that is seen with stress-related cognitive decline. Since psychedelics attenuate the effects of dynorphin/KOR, it might be that cognitive impairments related to dynorphin are also attenuated.
This would include aging, which I recently explored on a post about Alzheimer’s and Psychedelics. Curiously, the brains of schizophrenics were found to be 8 years older than their true age. Another study revealed mGlur2 loss to correlate with age, rather than schizophrenia diagnosis. 5HT2a receptors are also lost with age. Also, when dynorphin producing genes are removed from mice, age-related loss of mGlur1 was attenuated, along with age-related cognitive decline. Somehow dynorphin activity leads to the loss mGlur1 in aging, so perhaps dynorphin may be implicated in the loss of mGlur2 that is seen in aging as well. The loss of mGlur2 with aging would mean that 5HT2a binding decreases, allowing dynorphin’s effects to increase, in what seems to be a vicious cycle. This might provide a model for cognitive aging as a dynamic between serotonin, dynorphin, and glutamate. In the case of schizophrenia, it may explain some of the accelerated aging.
A lot of research has focused on the idea that psychedelics are an axiomatic model for schizophrenia. Recent studies on schizophrenia that utilized an mGlur2 agonist drug failed phase 3 trials. This drug worked as an agonist of mGlur2 which is one of the receptors involved in the 5HT2a effect. The relationship here is that 5HT2a binding decreases mGlur2 binding which allows for increased glutamate release that is normally inhibited by mGlur2. This experimental drug functioned on the mGlur2 receptor in the opposite direction as psychedelics, enhancing the receptor rather than decreasing activity. This drug was found to correct some NMDAr antagonist mediated deficits in gamma oscillations but not restore NMDAr antagonist mediated cognitive function deficits. It was found that mGlur2 agonists prevent the neurotoxicity induced by NMDAr antagonists, but there is evidence that psychedelics also prevent the neurotoxicity associated with the typical NMDAr antagonists that model psychosis. A study found that mGlur2 binding causes enhanced dynorphin signaling, which means the experimental drug may also enhance dynorphin signaling. The dynorphin enhancement via mGlur2 agonism may also help explain how psychedelics attenuate dynorphin/KOR signaling and why 5HT2a inverse agonists enhance dynorphin/KOR signaling. It could be that this drug failed partly due to enhanced dynorphin activity but helped with certain symptoms by enhancing 5HT2a signaling, but also preventing some of the mechanisms of 5HT2a signaling by functioning in the opposite way.
Tolerance and receptor downregulation might be an issue. Short lasting psychedelics like DMT might produce less tolerance hypothetically, thus be preferred to longer lasting psychedelics like LSD. It was noticed that the later phase of LSD intoxication became more paranoid and seemingly psychotic which led to research show that chronic LSD use may be a model for psychosis. In this study, they mentioned changes to gene expression as an explanation. An alternate explanation could be that 5HT2a binding is reduced. Chronic administration of LSD was found to reduce 5HT2a binding in the brain and produce tolerance to the effects, which is a pattern seen in schizophrenics, both reduced binding and less sensitivity to the psychedelic effects. It was found that both acute and chronic dosing of LSD produced increases of serotonin levels. This increased serotonin activity may be able to downregulate the serotonin transporter, thus reducing the ability of dynorphin to exert effects and allow a higher tendency towards increased serotonin tone in general. In a way, it may reverse the sensitivity to stress and enhance a tendency towards resilience. Chronic use of psychedelics might produce a withdrawal like state, leading to enhanced dynorphin signaling, which may worsen problems. Use of DMT infrequently might be able to avoid some of these problems due to its short duration.
All of this taken together suggests psychedelics may be able to treat schizophrenia by disrupting psychotomimetic KOR signaling. It isn’t clear if frequent dosing would be required or, if like depression, a single dose might show lasting effects. I suspect that it will be a matter of stress exposure as the psychedelic system of mechanisms may help in resilience and adaptation. The next thing we should do is look for those diagnosed as schizophrenic who have had experience with psychedelics and do not use cannabis or hopefully any other drugs. Through my networking experiences I have found individuals that provide anecdotal reports of this.
But before we get carried away, there is one thing:
Psychedelia is Mania
We often lump mania and psychosis together, as they are both extreme states of minds. It seems this conflating may be analogous to the conflating of cannabis and psychedelics previously discussed. Despite having some overlap, bipolar disorder and schizophrenia show some opposing correlations in the research. For example, while low IQ correlates to schizophrenia, high IQ was associated to bipolar risk. Another study found that children with high IQ were more likely to be diagnosed as bipolar later in life, and manic severity correlated to IQ. High arithmetic ability revealed 12-fold increase risk of being diagnosed with bipolar disorder. Excellent school performance at age 16 was linked to a 4-fold increased risk of bipolar disorder. There is a candidate causal variant underlying both intelligence and bipolar risk that is currently under study. I’ve explored an intelligence theory of bipolar disorder in the post Xenotypy.
While cannabis seems to impair cognitive function in schizophrenics, it actually seems to increase cognitive function in bipolar disorder. One study found that schizophrenic, but not bipolar 1 disorder individuals had reduced hippocampal volume. During mania it was even found that hippocampal connectivity is increased, while schizophrenics have reduced connectivity. Prefrontal cortex glutamate is increased in mania, decreased in schizophrenia, and increased with psychedelics. Calcium channel and NMDAr antagonists were found to be anti-manic, while they can also induce psychotic symptoms. Lastly, while NMDAr enhancing drugs such as Theanine or glycine agonists were found to reduce psychosis, there are cases of mania induced by glycine/NMDAr enhancing drugs (cycloserine).
The real risk that comes along with psychedelics may be mania.
It’s important to mention that psychedelics may not represent all or even a majority of sober mania cases, but instead representing some specific type of mania. Some of the effects of psychedelics don’t match up with mania, such as neurogenesis. Sober mania likely involves some amount of serotonin mechanisms but also other mechanisms as well, such as general monoamine activity and glutamate activity. Also the trend of mania may be more focused on dysfunction of inhibitory dynorphin signaling, rather than always psychedelic mechanisms. Psychedelics may induce a kind of stress-free hypomania, increased risk-taking, and openness.
SSRI drugs have been shown to induce mania. Bipolar is associated with enhanced signal transduction of 5HT2a receptors, enhancing calcium release. Mania often involves disinhibition and fearlessness. LSD was shown to reduce fear responses in the amygdala. As mentioned before, dynorphin/KOR agonism controls the gain on amygdalar fear circuitry. KOR agonists seem to be effective in treating mania. This study also notes the risk of psychotomimetic effects from KOR agonists, which none occurred in the manic patients and instead a successful reduction of mania was observed. Dynorphin mRNA was found to be reduced in the amygdala of bipolar disorder. There are sometimes perceptual alterations in hypomanic or manic states. Patients report things like clearer vision, stronger sense of touch and taste, seeing auras around people. This is in contrast to what is usually reported in psychotic states, hearing voices, seeing things that aren’t there. There may be some overlap between the two, but it seems that there are general differential trends for each state of mind.
Manic disorders could be understood as an extreme recovery and stress resilience tendency. While this may initially sound good, as hypomania/mania usually does, it can lead to a disinhibition and worryless-ness that becomes dangerous. We develop stress, aversion, and trauma in order to make us too ‘anhedonic’ towards certain high risk-taking reward seeking behaviors. Those who lack this and ultimately have too much stress resilience might engage in behaviors that everyone around them acknowledges as extremely stressful and scary. Hypersexuality, unsafe sex, spending savings, drug use and other potentially catastrophic behaviors. In a strange sense, society is more traumatized than the manic individual, thus behaving fearfully and hesitant towards risk due to prior bad experiences. Since those with manic disorders may have elevated mood recover, they may continue to behave in ways that elicit further traumatic and catastrophic experiences, bringing them back to depressive or psychotic states again. In the bipolar, psychotic states may be far more transient than with those who lean towards schizophrenia. The psychosis may manifest from trauma and catastrophe, but then one may become depressed, then slowly reach a stable mood, and eventually climax back to the elevated fearlessness that is mania. On the contrary, those with schizophrenia will often have poor mood recovery and remain depressed, anhedonic, psychotic, and traumatized.
As mentioned, here are some. . .
One person reported experiencing delusions of alien contact that were suddenly ‘cured’ by a large dose DMT experience. Another individual I’ve known for a long time has family relations to schizophrenic individuals and has shown mild symptoms as well. This individual appeared to gain some clarity after a medium dose of psilocybin. There is a third individual who reports extreme and terrifying effects from cannabis, even at small doses, and experiences very positive effects from psilocybin.
A schizophrenic scientist on reddit detailed their experience with multiple psychedelics, reporting that they experienced reduced symptoms for days after DMT and required a higher dose to experience any effects.
This schizophrenic individual reports multiple instances of psychedelic use that took them from a near catatonic dysfunctional state of schizophrenia to functioning member of society. The initial experiences alleviated hallucinations and with continued psychedelic trips, the individual reported improved school work and recovery from their schizophrenic disorder.
Another individual claims that their 76 year old father was cured from their 50 year long schizophrenic symptoms. Hallucinations and voices disappeared and medication was discontinued.
When I’ve used psilocybin there a few patterns to note. The first few times were most profound and completely alleviated psychotic-like symptoms. There were times where I’ve had profound manic-like thinking, elaborate theoretical ideas for example. The later experiences produced less effects and also came along with a 2-3 day worsening of issues, followed by a state of mental health long-lasting after these few days passed. I suspect this is because of downregulation of 5HT2a and a short period of enhanced sensitivity to dynorphin afterwards. On the other hand, the initial more profound experiences immediately lead to lasting benefits. It’s also worth noting that while I’m on the small doses of psilocybin I tend to be highly mentally stable and clear compared to my baseline state.
In my own personal experience, I’ve faced delusions, anhedonia, paranoia, hallucinations after growing up in very stressful conditions. I’ve had delusions of persecution, thought I was being poisoned, elaborately stalked, and much more. To be clear, much of this probably sounds more crazy than it is. It didn’t result in many issues, a lot of these things occurred in very short time spans except for when I was young. It also doesn’t seem like I would really be diagnosed schizophrenia. Maybe schizotypal and mild bipolar disorder. A lot of these things aren’t things I struggle with anymore or even to begin with. They were interesting experiences if anything. I was also perscribed psycho-stimulants which can lead to psychotic states. Many people didn’t even believe me about facing cognitive or mental issues because I seemed so high-functioning.
My own experience with social defeat was a combination of nerdism and artificial social exclusion. In short, due to family chaos I had to cut off communication from the rest of my family based on my mother’s instruction and because all of my friends were associated with my cousin, I dove head first into social isolation. This occurred during middle school. Paranoia grew as I drifted away from social experience. My mom also began to drink and slowly descend into alcoholism during this period. Religious prophetic delusions developed. In my transition to high school, I went from social outcast and loser to socially popular but still eccentric. The internet allowed me to constantly learn and seemed to push my rationality further away from the more absurd delusional ideas, they were no longer compatible with the way I saw the world. Still, delusions of telekinesis still occurred with some sort of pseudoscientific quantum physics justification.
Eventually my mother passed away after doing heroin when I was around 20 years old.
After a lot of distress, slowly I’ve sort of ‘cured’ myself. There were phases of life where I slowly felt rejected and stigmatized by family, which occurred on multiple levels. My own paranoia and feelings of social defeat made me act different around my family, ashamed, weak, submissive, almost guilty. I was trapped in this dynamic where my guilt seemed to cause others to perceive me as guilty of things. I seemed like a bad person. I think for many, this can actually escalate into chronic subordination throughout their lives, occurring across all social contexts.
For example, I found people at the store looking at me with somewhat dirty looks. I would sometimes feel guilty if I was in somebody’s way. Sometimes I wasn’t actually in someone’s way, but I would get really apologetic regardless. This actually provoked people into feeling justifiably offended that I was in their way, regardless of whether it was true or not. This example could be extended across my life situations, where I noticed myself causing my own social demise, in ways that weren’t actually justified. My own delusional mindset was creating a social narrative in which other people followed along and believed.
I noticed this especially when I used cannabis starting at 24(?) years old. The effects of cannabis clearly changed my mindset to a defeated one many times. When this happened it almost always lead to the strange effect of people seeming to turn against me. Only after experiencing this repeatedly did I catch on to what was occurring. Then I began to purposely engineer my social experience and project mindsets that were not ridden with defeat. It entirely worked. I even experimented with changing the tone from one sentence to the next, with the other person dramatically altering their behavior.
Eventually, due to cannabis use, I developed a long-lasting persecutory and defeated mindset that was impacting my family situation in very subtle ways. There was no attacks on me, but only this vocal tone of disappointment and facial expressions that likely reflected my state. This state was definitely unjustified because my life was improving yet it was as if I was becoming more defeated. I also felt paranoid that I was rejected for using cannabis, even though I was reassured that this wasn’t the case. At this time I also developed frequent formication, the sensation that insects were crawling on my skin.
Then I dosed psilocybin (only 0.6 grams). It erased these narratives of shame that I had built up. It was as if it set my mind back before I accumulated all of these stressors, assumptions, and delusional mindsets. When I returned home that night, I walked in confidently and the feedback from my family was immediate. They were smiling. This continued and it changed my relationship ongoing.
I’ve found myself using very low doses after major stressful events to sort of erase their negative impact on me. As an example (didn’t happen to me), one may lose their job and become intensely defeated and ready to spiral out into a mental breakdown. I find that psilocybin removes the negative and hyper-focused mindset and narrative, pulling you back out to see the bigger picture, bringing back the resilience. This resilience hacking using psychedelics is what I believe draws the entrepeneurial types. They can take risks, fail, get stuck in a rut fueled by self-doubt, take psychedelics and start fresh and manic again.
Since I’ve used psychedelics I’ve generally experienced far less psychotic-like symptoms. The worst symptoms I face now is occasional anhedonia. On the other hand, I do get insomnia, functional hypomania, and some acute catastrophic thinking at times. My current mentally healthy status doesn’t seem to be only due to psychedelic use, I’ve also maximized my nutrition, focused heavily on education and learning, started regularly sleeping, and live in a more positive environment. It’s worth noting, I do not take any psychiatric medication anymore and it has been years since. Lastly, while I’ve experienced lots of psychotic symptoms, it doesn’t seem that I am schizophrenic. I seem to have more hypomanic or manic tendencies in general, including strong manic reactions to SSRI drugs at even low doses.
Currently, my self-awareness of my mental state is extremely fine-detail. I’ve mapped and learned what choices in my daily life lead to different states of mind. Sleep seems to be the most important factor above all else. Staying up until just 1-2am leads to ongoing hypomanic effects, floods of ideas, epiphanies, but eventually leads to crashes or continual insomnia, problems maintaining my diet and so on. Psychotic symptoms do not really occur. It has been years and I am attending university with good grades. My life has reached a space of calmness, control, and ongoing growth. That’s not to say I don’t face any conflicts. They just don’t become catastrophic issues anymore.
Given the vast success of psychedelics in the treatment of traumas, stress, depression, addiction, and even producing a reduction of suicidality, it almost seems absurd to think that psychedelics would increase schizophrenia, a disorder characterized by depressive symptoms, often involves addictions, is stress-linked, trauma-linked, and suicide-linked. Lastly, we must be cautious approaching this topic because we simply don’t fully know what is happening yet. This theory seems to make sense to me, but it could very well be wrong. Fixing schizophrenia or psychosis does not inherently mean becoming mentally healthy, as mentioned there is the possible mania induction that may come with psychedelics.
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