12 replies to this topic

[tobicles]

Just thought I would let everyone know about an adverse effect I had with Huperzine A. I've been diagnosed with depression with schizophrenoid features (voices and all that) and one thing that has made the psychotic features noticably, drastically worse, is Huperzine A. According to my understanding, the NMDA pathways are implicated somewhat in schizophrenia as malfunctioning. Huperzine A is a  noncompetitive NMDA receptor antagonist, and this would be my guess as to the source of the problem. The change is drastic, since starting on a new medication and having stabilised that dosage the psychotic features completely vanished, but taking Huperzine A for a couple of days at the low dose of 100mcg brought them back in full force, a terrifying experience. I know that there are many people who have used huperzine A for a long time with no ill effects, but I just thought that it should be known that (in my case at least) it had a large negative effect upon me. On a related note, anyone in Australia want to buy my Huperzine A? :P

Edited by tobicles, 02 September 2011 - 08:17 AM.

[stablemind]

Thats crazy.. does anyone know the mechanisms behind this? I have BPII and this is bothering.

[tobicles]

Well similarly Ketamine can cause psychosis and it is the same type of inhibitor as Huperzine A - broad strokes to be sure, but there is definitely some grounds to that line of thinking. Kynenuric Acid is also a NMDA receptor agonist, a glycine antagonist though, and this has been found to be implicated in schizophrenias cognitive dysfunction somewhat, through acting on both a7 nicotinic receptors and NMDA receptors. It's a shame because otherwise this chemical has so many positive effects, increasing memory and NGF in the brain as well as preventing certain types of excitotoxicity. I may just be an anomaly, but I might not be. However Huperzine A also increased dopamine in certain areas of the brain - maybe this is the cause?

[AbolishtheState]

Does anyone know of any empirical or anecdotal evidence suggesting a causal relationship between use of huperzine A and the development of latent schizophrenic spectrum disorders in susceptible individuals? I have an unclear family history of undiagnosed schizophrenia, and have recently developed symptoms that may indicate prodomal schizophrenia (cognitive decline, depression, anxiety, social withdrawal, amotivation, poverty of speech); however my thinking is still quite rational, and the only instance of auditory hallucination I have experienced occured in my early teen years while I was rather sleep deprived. I began taking "Get Smart" by Smart Nutrition a few days ago, which contains huperzine A, hoping that it might provide nootropic, in addition to anti-depressant and anxiolytic benefits. If huperzine A has the potential to trigger latent schizophrenia, I would have to seriously reconsider using it until I am past the age of typical onset. I should mention that I frequently used dextromethorphan in recreational doses in the past without triggering any lasting psychotic episodes, delusions, or hallucinations; and since they work by similar mechanisms (DXMs active metabolite, dextrorphan, is a NMDA antagonist) perhaps I should not be worried.

Edited by AbolishtheState, 02 September 2011 - 05:13 PM.

[MrHappy]

Hmm interesting.. did anyone notice that the guys at Yale have synthesised huperzine a now? Estimated price will be 50 cents per mg.

[Spectre]

Excessive NMDA receptor antagonism is definitely linked with schizophrenic-like effects in people, I know from personal experience. I used to use DXM recreationally while I was a teenager and it triggered an intense psychosis in me that took years of therapy and nootropics to finally alleviate. (there's a huge thread I started a while back about it, and if it wasn't for the intelligent people on this forum and my in-depth research, I would still be suffering from the effects I'm sure). I would definitely advise against continued use of Huperzine A if it's causing such effects in you, prolonged use will just exacerbate the psychosis. I would start supplementing with the following:

- Piracetam (1g a day to start off)
- Fish Oil (3g a day minimum)
- SAMe (200mg)
- Glycine (3-5g)
- Acetyl-l-Carnitine (ALCAR, 1g)
- Niacin (in nicotinic acid form, 500mg)
- Vitamin C (1g, better if taken in magnesium acorbate form)
- Sulbutiamine (200mg)

This regimen should help alleviate the effects you're experiencing. It may definitely seem like overkill at first, but I believe it will help you. It took me years to tweak my regimen and finally come up with something to drive my psychosis away for good. As of the moment, I don't really even need nootropics, I am functioning fine without anything now, I just take a multi, fish oil, whey protein, and a couple other basic supplements. I still take nootropics when I need to study, ALCAR and Sulbutiamine are my personal favorites (and Deprenyl of course). If you don't want to start off with everything on this list, go ahead and try out the fish oil + piracetam..they work very well together and you should see some positive effects with it. Good luck and let me know how your progress goes.

[Dirk_Diggler]

I thought that Huperzine A had MAOI effects, albeit somewhat mild. If you have schizophrenia, an MAOI would allow even more dopamine to be floating around (and using the dopamine hypothesis of schizophrenia) and that is not good at all for a schizophrenic. Although I believe many different systems are affected in schizophrenia, dopamine seems to be one of the major players since all antipsychotics are dopamine receptor antagonists. That would be my theory as to why the symptoms are excacerbated. But then again, I could have it all wrong.

But if Huperzine A does in fact inhibit MAO, then it makes sense that it caused that reaction.

[QuantumTubule]

Hmmm Huperzine is a werid beast, while it does antagonise some NMDA receptor systems, it also significantly potentiates others. Really all cholinergnics may do the same to differing extents, ALCAR and some of the choline nutritional supplements maybe ok, Ache inhibtitors not so much, alpha gpc again,

You probably dont have the neuroplasticity left to benefit from many nootropics, usually these work by making major shifts. Healthy people may find that they can improve some metrics by this without suffering determint.
Spectars ideas are quite good

Edited by QuantumTubule, 06 September 2011 - 04:46 AM.

[lourdaud]

Whoa, maybe you're a bit too quick to come to conclusions there? Whether you're right or not, I don't see any reason to state such things.. at least not to put it like that.
However, may I ask what you think of amphetamine + memantine as a therapeutical conjunction in regards to neuroplasticity, learning and higher cognitive functions - working memory in particular? I suffer from Tourettes along with my ADHD so amph really is a pain in the ass although I absolutely need it... Hope the Memantine will help with OCD etc, but I really really fear the risks for cognitive and adaptive decline, my brain is impaired as it is already!! :(

[tobicles]

AbolishTheState: I've used DXM in the past as well with no negative results, as well as lots of psychedelics and never had anything resembling psychosis. I can't say for sure that Huperzine A caused my illness, but I WAS taking it most days during and leading up to my episode, and have found that after recovery the symptoms return if I begin taking it again. Tread carefully, I have no history of schizophrenia in my family (one case of bipolar though) and this has happened to me, despite massive doses of psychedelics and other drugs such as DXM that have NOT led to me developing symptoms. It had been over 6 months since my last psychedelic experience when I started taking huperzine A and began developing symptoms, if that lends any credibility. I have basically all the same symptoms as you have listed for yourself, with no disordered thinking, the only clear cut 'schizophrenic' symptom I had is the presence of voices remarking on my every action, normally quite negatively. These voices were so normal sounding I at first thought I was hearing my neighbours, then, people spying on me, and then the only conclusion I could come to was that I was either psychic or psychotic. Now, I'm a scientist and so I'm putting my money on the latter :P (I believe I have concomitant ADHD-PI as well, should be getting tested soon now that my psychotic symptoms are on the mend)
Dirk Diggler: I'm not sure if it has MAOI properties, so I can't really say. I've heard that it increases dopamine through its effects on acetylcholine, but the specifics are beyond me for now.
Klantskalle: I'm not sure if you are talking to me with the jumping to conclusions? I'm not saying that it for sure CAUSED my problems, but it DEFINITELY does make them worse, and make them recur. Whether this is purely in those liable to develop it or not, I personally cannot see any clearer evidence then my own experience. If I take it, the voices come back, if I don't, they stay away (I am on anti-psychotics as well).

Neuroplasticity can be triggered through many mechanisms, enriched environment, exercise, healthy relationships and constant mental challenges all help. If there is NGF being expressed, there is plasticity in some form underway. While the plasticity of the child and adolescent brain is much greater than that of an adult, the adult still has plasticity. If not, then how does the hippocampus of london taxi drivers grow larger after undertaking their intense memory exercises? These people aren't children or adolescents, most are older adults.

Edited by tobicles, 10 September 2011 - 06:33 AM.

[sam7777]

How can huperzine-A be so great for memory enhancement if it antagonizes some receptors??

[angela86]

AbolishTheState: I've used DXM in the past as well with no negative results, as well as lots of psychedelics and never had anything resembling psychosis. I can't say for sure that Huperzine A caused my illness, but I WAS taking it most days during and leading up to my episode, and have found that after recovery the symptoms return if I begin taking it again. Tread carefully, I have no history of schizophrenia in my family (one case of bipolar though) and this has happened to me, despite massive doses of psychedelics and other drugs such as DXM that have NOT led to me developing symptoms. It had been over 6 months since my last psychedelic experience when I started taking huperzine A and began developing symptoms, if that lends any credibility. I have basically all the same symptoms as you have listed for yourself, with no disordered thinking, the only clear cut 'schizophrenic' symptom I had is the presence of voices remarking on my every action, normally quite negatively. These voices were so normal sounding I at first thought I was hearing my neighbours, then, people spying on me, and then the only conclusion I could come to was that I was either psychic or psychotic. Now, I'm a scientist and so I'm putting my money on the latter :P (I believe I have concomitant ADHD-PI as well, should be getting tested soon now that my psychotic symptoms are on the mend)
Dirk Diggler: I'm not sure if it has MAOI properties, so I can't really say. I've heard that it increases dopamine through its effects on acetylcholine, but the specifics are beyond me for now.
Klantskalle: I'm not sure if you are talking to me with the jumping to conclusions? I'm not saying that it for sure CAUSED my problems, but it DEFINITELY does make them worse, and make them recur. Whether this is purely in those liable to develop it or not, I personally cannot see any clearer evidence then my own experience. If I take it, the voices come back, if I don't, they stay away (I am on anti-psychotics as well).

Neuroplasticity can be triggered through many mechanisms, enriched environment, exercise, healthy relationships and constant mental challenges all help. If there is NGF being expressed, there is plasticity in some form underway. While the plasticity of the child and adolescent brain is much greater than that of an adult, the adult still has plasticity. If not, then how does the hippocampus of london taxi drivers grow larger after undertaking their intense memory exercises? These people aren't children or adolescents, most are older adults.

I just wanted to say that I am so happy you posted what you did. I am ADHD-PI as well, and I have been taking Huperzine A to combat the symptoms. It worked incredibly awesome for a little less than a year; I combined the Huperzine A with hydergine, and it completely enhanced my focus. Honestly, the synergy worked better for me than the Concerta I was taking prior. Anyways, I after about nine months, I started to experience some of what you discussed. More of the negative symptoms of Schizophrenia though; I literally felt unable to move, my affect was completely blunted, and I had a bunch of other catatonic symptoms. No hallucinations or delusions - although I was very paranoid. I also feel like it induced some type of depression. Depression was something I've never really struggled with on a daily basis - but i'm still struggling with anhedonia and just overall feelings of depletion. No more Huperzine A.

Edited by angela86, 24 March 2013 - 03:03 AM.

[gamesguru]

I just wanted to say in fact the NMDA antagonism is quite weak, and would actually HELP schizophrenia, according to modern hyperglutamatergic theories.  Stinky mentioned in another thread that acetylcholine plays a role in the pathogensis of schizophrenia:

The muscarinic hypothesis of schizophrenia
The muscarinic hypothesis of schizophrenia postulates that the muscarinic ACh system plays a crucial role in the pathology and treatment of schizophrenia. Data from clinical, postmortem, neuroimaging, and preclinical and clinical pharmacology studies support this hypothesis.

Postmortem and neuroimaging studies Postmortem studies have shown a decreased number of M₁ and M₄ muscarinic ACh receptors in persons with schizophrenia in several key areas, including caudate and putamen, hippocampus, anterior and posterior cingulate cortex, and prefrontal cortex. (For more information, see the work by Raedler and colleagues.¹) Similar changes were not found in persons with bipolar disorder or major depression.⁴ The levels of M₂ and M₄ muscarinic ACh receptors were unchanged in schizophrenia. These findings are supported by a single-photon emission CT (SPECT) study that found a significant decrease in vivo in the availability of muscarinic receptors in the cortex and basal ganglia in patients with schizophrenia compared with healthy controls.⁵