Neuropsychiatric effects of HIV meds?

[phenethylamine]

Atripla: is a psychedelic (apparent also a ssri, dri, vmat2 inhibitor, benzodiazepine and serotonin substitute, metabolised into cannabis)
Complera: might cause depression/anxiety. (noone knows why)
Stribild: interacts with other drugs (causes dreams)
Other Meds: cause dreams... (something is up with that) noone knows why

I'm a little overwhelmed...For some reason I thought the effects would be strictly physical (one pill gives diarrhea the other causes constipation).  Now I feel like I'm blindly choosing a psychiatric med, with no information on how it will effect/change my mood/personality for LIFE. Further complicating things, It's hard to tell if new emerging mood changes are a result of withdrawal from the "old med".. caused by the "new med" or a combination of both. Theres no taking days off to remember what "normal" feels like.

I'm a little disturbed that the brain binding profile of Atripla was published YEARS after its release. I know some of you are going to say... treating hiv comes first, mental health comes second...But "I don't think" it would actually be that hard to test new/old compounds for psychoactivity with todays technology.

For example...the antidepressant trazodone

Serotonin receptor (ki (nM)
5-HT1A > 118
5-HT1B > 10000 
5-HT1D > 106
5-HT1E > 10000
etc..

Also I'm a bit frustrated with reading everywhere, "causes less neuropsychiatric effects then atripla". I've never taken Atripla, I have no idea what they mean by "less". Less intense, different? "neuropsychiatric side effects" to me is incredibly vague.

Anyays sorry If I this came out as a rant. Just wanted to put the idea of further testing out to the world. curious if anyone else is stressed about unknown mood/personality changes. Especially if it's a slow change over time.

[Jeff G]

I don't think you find anyone on the forum that would tell you that mental health is second to HIV treatment, we have come way to far and have enough options available so that you can choose a med combo that is right for you . The reality is its not a either or thing, you can have a combo that agrees with you so its mostly med anxiety that has you concerned .

Are you on meds now and what are they if you are ? Any HIV doctor worth their salt can help guide you away from HIV drugs that may be prone to causing depression or cns issues .   

[zach]

"Atripla: is a psychedelic"

not quite 

source: experienced

[phenethylamine]

Isn't it though?
I've been reading that it acts as a 5HT2A partial agonist.
Not a "full agonist"... so effects might be weaker than classic psychedelic.
I thought that was why it was advised to take it at night?

They did experiments on mice... and they produced the trademark "head twitches" indicative of an "altered visual state".

[Joe K]

I have severe mental health issues and I have been taking HAART for 28 years and there are many combos that will work, without affecting your mental health.  I know, as I am on one now and have been for 14 years and my psych meds have also remained unchanged during that time.

I suggest you speak with an HIV specialist, a psychiatrist and pharmacist to devise a drug plan that will work for you. You make a lot of assumptions about what various drugs may do and you need some experts to guide you.

Joe

[phenethylamine]

My point is that without brain binding studies... there is no proof of anything.
You can't say I'm wrong, just like I can't prove I'm right. If we had hard facts... this wouldn't even be a discussion. Someone telling me my experience will match their experience is "blind faith", and I'm a very transparent person. Even if a drug has so little affinity for a receptor that you wouldn't even be able to notice it. I still want to "know" about it.... cause I'm curious... and find the mind fascinating.

So if its not time consuming, or expensive to do. Would it be beneficial to have it done so not to be "over-reliant" on peoples opinions, or experiences.
I was curious what others thought? As a discussion sort of thing...

Also I'm a little bit confused about this forum. Is this a place for discussing all things HIV (treatment critic/optimization) ideas, theories or is this more of a strictly question and answer medical support group?  Problem and answer sort of thing?

[Joe K]

My point is that without brain binding studies... there is no proof of anything.
You can't say I'm wrong, just like I can't prove I'm right. If we had hard facts... this wouldn't even be a discussion. Someone telling me my experience will match their experience is "blind faith", and I'm a very transparent person. Even if a drug has so little affinity for a receptor that you wouldn't even be able to notice it. I still want to "know" about it.... cause I'm curious... and find the mind fascinating.

So if its not time consuming, or expensive to do. Would it be beneficial to have it done so not to be "over-reliant" on peoples opinions, or experiences.
I was curious what others thought? As a discussion sort of thing...

Also I'm a little bit confused about this forum. Is this a place for discussing all things HIV (treatment critic/optimization) ideas, theories or is this more of a strictly question and answer medical support group?  Problem and answer sort of thing?

Phen

If there are no studies that support what you claim, it's only your opinion.  It's not my job to prove you wrong, it's your responsibility to provide links when you claim things, that have yet to be proven.  This forum is to discuss all aspects of HIV, however, we do not allow anyone to post items, especially that can affect members, without proving what they say.  I already told you in another thread that you need to substantiate what you claim, otherwise you need to make it clear that's it's only your opinion and has no basis in fact.

This point is not up for debate.  You need to be very clear when posting that what you are presenting is simply your opinion.  You need to stop posting as if what you say is proven science.

Joe

[phenethylamine]

I can give sources...

_______________________________________

Wikipedia: Neuropsychiatric effects

Recently, efavirenz has been found to act as a(n) 5-HT2A receptor partial agonist (Ki = 2.2 μM),[12] 5-HT2C receptor ligand, serotonin and dopamine reuptake inhibitor (50% and 75% inhibition at 10 μM, respectively), vesicular monoamine transporter 2 (VMAT2) inhibitor (60% inhibition at 10 μM), and positive allosteric modulator of the GABAA receptor.[13] It is thought that these properties, especially its actions at the 5-HT2 receptors, are involved in its neuropsychiatric adverse effects (e.g., depression, anxiety, hallucinations, aggression, suicidal ideation, and sleep disturbance),[13][12] as they are alleviated by cyproheptadine, a drug with 5-HT2 receptor antagonist actions.[14][15]

Despite its actions at the GABAA receptor and the SERT, DAT, and VMAT2, efavirenz fails to produce self-administration or conditioned place preference in animals, suggesting that it lacks positive reinforcing effects.[13] However, efavirenz does show LSD-like effects in animals, including producing the head-twitch response and positive drug discrimination responding for LSD in rodents, and there is evidence that efavirenz produces LSD-like hallucinogenic effects in humans at sufficiently high doses.[13]

_____________________________

Scientists explore mystery of a psychedelic HIV/AIDS drug

April 22, 2013|By Melissa Healy

For those taking antiretroviral medications for HIV/AIDS, there is one drug in the mix that can put a particular kick in the cocktail: the drug efavirenz, marketed under the commercial names Sustiva and Stocrin, appears to have an "LSD-like interaction" with the receptors in the brain that govern the activity of serotonin, says a study presented in Boston today.

That may explain why roughly half of patients taking efavirenz at the prescribed dose have reported neuropsychiatric side effects that include suicidal depression, night terrors, hallucinations, paranoia, psychosis and delusions. And it may also explain why efavirenz tablets are reportedly being ground up and smoked by drug abusers looking for a hallucinogenic high.

Working with mice, a team led by Dr. John A. Schetz, a pharmacologist from the University of North Texas Health Science Center in Fort Worth, found that efavirenz activates the serotonin 5-HT 2A receptor in the brain, the same molecular site on which lysergic acid diethylamide (LSD) works. Mice that were given efavirenz responded with the same distinctive head-twitching behavior seen when they are given LSD, and mice bred without the serotonin 5-HT 2A receptor do not. And just as they are when under the influence of LSD, mice given efavirenz also were far less bold than would be expected normally when they were allowed to explore an environment filled with unfamiliar sights, smells and objects."Scientists explore mystery of a psychedelic HIV/AIDS drug

LINK:
http://articles.latimes.com/2013/apr/22/news/la-heb-hivaids-drug-lsd-20130422

____________________________


The HIV antiretroviral drug efavirenz has LSD-like properties.

Gatch MB1, Kozlenkov A, Huang RQ, Yang W, Nguyen JD, González-Maeso J, Rice KC, France CP, Dillon GH, Forster MJ, Schetz JA.

Abstract

Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one) by HIV patients and non-infected teens who crush the pills and smoke the powder for its psychoactive effects. Molecular profiling of the receptor pharmacology of efavirenz pinpointed interactions with multiple established sites of action for other known drugs of abuse including catecholamine and indolamine transporters, and GABAA and 5-HT(2A) receptors. In rodents, interaction with the 5-HT(2A) receptor, a primary site of action of lysergic acid diethylamine (LSD), appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz reduce ambulation in a novel open-field environment. Efavirenz occasions drug-lever responding in rats discriminating LSD from saline, and this effect is abolished by selective blockade of the 5-HT(2A) receptor. Similar to LSD, efavirenz induces head-twitch responses in wild-type, but not in 5-HT(2A)-knockout, mice. Despite having GABAA-potentiating effects (like benzodiazepines and barbiturates), and interactions with dopamine transporter, serotonin transporter, and vesicular monoamine transporter 2 (like cocaine and methamphetamine), efavirenz fails to maintain responding in rats that self-administer cocaine, and it fails to produce a conditioned place preference. Although its molecular pharmacology is multifarious, efavirenz's prevailing behavioral effect in rodents is consistent with LSD-like activity mediated via the 5-HT(2A) receptor. This finding correlates, in part, with the subjective experiences in humans who abuse efavirenz and with specific dose-dependent adverse neuropsychiatric events, such as hallucinations and night terrors, reported by HIV patients taking it as a medication.

LINK: http://www.ncbi.nlm.nih.gov/pubmed/23702798
__________________________

YouTube Video: "getting high on HIV medication full documentary
LINK: https://www.youtube.com/watch?v=wyuFBmlQS_s
__________________________

[Joe K]

I van give sources...

_______________________________________

Wikipedia: (not reliable, I know)

Neuropsychiatric effects[edit]

Recently, efavirenz has been found to act as a(n) 5-HT2A receptor partial agonist (Ki = 2.2 μM),[12] 5-HT2C receptor ligand, serotonin and dopamine reuptake inhibitor (50% and 75% inhibition at 10 μM, respectively), vesicular monoamine transporter 2 (VMAT2) inhibitor (60% inhibition at 10 μM), and positive allosteric modulator of the GABAA receptor.[13] It is thought that these properties, especially its actions at the 5-HT2 receptors, are involved in its neuropsychiatric adverse effects (e.g., depression, anxiety, hallucinations, aggression, suicidal ideation, and sleep disturbance),[13][12] as they are alleviated by cyproheptadine, a drug with 5-HT2 receptor antagonist actions.[14][15]

Despite its actions at the GABAA receptor and the SERT, DAT, and VMAT2, efavirenz fails to produce self-administration or conditioned place preference in animals, suggesting that it lacks positive reinforcing effects.[13] However, efavirenz does show LSD-like effects in animals, including producing the head-twitch response and positive drug discrimination responding for LSD in rodents, and there is evidence that efavirenz produces LSD-like hallucinogenic effects in humans at sufficiently high doses.[13]

_____________________________

Scientists explore mystery of a psychedelic HIV/AIDS drug

April 22, 2013|By Melissa Healy

For those taking antiretroviral medications for HIV/AIDS, there is one drug in the mix that can put a particular kick in the cocktail: the drug efavirenz, marketed under the commercial names Sustiva and Stocrin, appears to have an "LSD-like interaction" with the receptors in the brain that govern the activity of serotonin, says a study presented in Boston today.

That may explain why roughly half of patients taking efavirenz at the prescribed dose have reported neuropsychiatric side effects that include suicidal depression, night terrors, hallucinations, paranoia, psychosis and delusions. And it may also explain why efavirenz tablets are reportedly being ground up and smoked by drug abusers looking for a hallucinogenic high.

Working with mice, a team led by Dr. John A. Schetz, a pharmacologist from the University of North Texas Health Science Center in Fort Worth, found that efavirenz activates the serotonin 5-HT 2A receptor in the brain, the same molecular site on which lysergic acid diethylamide (LSD) works. Mice that were given efavirenz responded with the same distinctive head-twitching behavior seen when they are given LSD, and mice bred without the serotonin 5-HT 2A receptor do not. And just as they are when under the influence of LSD, mice given efavirenz also were far less bold than would be expected normally when they were allowed to explore an environment filled with unfamiliar sights, smells and objects."Scientists explore mystery of a psychedelic HIV/AIDS drug

LINK:
http://articles.latimes.com/2013/apr/22/news/la-heb-hivaids-drug-lsd-20130422

____________________________


The HIV antiretroviral drug efavirenz has LSD-like properties.

Gatch MB1, Kozlenkov A, Huang RQ, Yang W, Nguyen JD, González-Maeso J, Rice KC, France CP, Dillon GH, Forster MJ, Schetz JA.

Abstract

Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one) by HIV patients and non-infected teens who crush the pills and smoke the powder for its psychoactive effects. Molecular profiling of the receptor pharmacology of efavirenz pinpointed interactions with multiple established sites of action for other known drugs of abuse including catecholamine and indolamine transporters, and GABAA and 5-HT(2A) receptors. In rodents, interaction with the 5-HT(2A) receptor, a primary site of action of lysergic acid diethylamine (LSD), appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz reduce ambulation in a novel open-field environment. Efavirenz occasions drug-lever responding in rats discriminating LSD from saline, and this effect is abolished by selective blockade of the 5-HT(2A) receptor. Similar to LSD, efavirenz induces head-twitch responses in wild-type, but not in 5-HT(2A)-knockout, mice. Despite having GABAA-potentiating effects (like benzodiazepines and barbiturates), and interactions with dopamine transporter, serotonin transporter, and vesicular monoamine transporter 2 (like cocaine and methamphetamine), efavirenz fails to maintain responding in rats that self-administer cocaine, and it fails to produce a conditioned place preference. Although its molecular pharmacology is multifarious, efavirenz's prevailing behavioral effect in rodents is consistent with LSD-like activity mediated via the 5-HT(2A) receptor. This finding correlates, in part, with the subjective experiences in humans who abuse efavirenz and with specific dose-dependent adverse neuropsychiatric events, such as hallucinations and night terrors, reported by HIV patients taking it as a medication.

LINK: http://www.ncbi.nlm.nih.gov/pubmed/23702798
__________________________

YouTube Video: "getting high on HIV medication full documentary
LINK: https://www.youtube.com/watch?v=wyuFBmlQS_s

Phen,

The sources you present are simply articles that make claims, based on anecdotal reports, which can be highly unreliable.  You have not presented any sources that reference first-tier peer-reviewed studies that substantiate anything the articles claim.  Stop posting such references as anything other than one persons opinion.

Joe

[phenethylamine]

How are experiments involving genetically engineered mice anecdotal?
Doesn't this topic at least merit discussion? Do you feel that it adds unnecessary stigma towards treatment? I'm not trying to be sensational in saying HIV meds make you crazy... don't take them... I'm not trying to demonize the companies that create these meds, its a learning experience...but can we at least acknowledge these studies and post if we believe them or not?

Also I thought pubmed was reliable?

[zach]

all this talk of lsd has me nostalgic

[phenethylamine]

I'm really stressed right now
These pills are having strange effects on me...

Complera : felt a lot like an antidepressant...I was really tired, poor concentration the first few weeks... but then I started feeling strangely happier after 2 weeks. (exactly like an ssri again).

Stribild: feeling really depressed, angry, physically I feel better, more productive but constantly want to fight someone. I snap at people for everything.

I can't figure out if its the cobicistat boosting or inhibiting my other drugs, effects of the Elvitegravir in my brain, or the lack of Rilpivirine in my brain. If the Rilpivirine did function like an ssri that could explain why abruptly stopping it has made me so depressed. Complera had depression listed as a side effect. Why is the opposite happening with me? I'm thinking of switching back to Complera cause I was nicer on it... but I'm afraid that me nicer/happier... is a result of me being slowed down, sedated. I'm just really scared of things that slow me down/ impair concentration.

I'm stressed cause I wasn't expecting these pills to affect my mood... and I can't explain it to people cause my diagnosis is private. My psychologist doesn't give a crap, talks more about himself then me. I wind up having to do my own homework on what he gives me cause he never knows.... In this case I can't do that... cause these meds are new, prescribed to small percentage of population... and only have one small paragraph written on Wikipedia lol

[phenethylamine]

And yeah Zack, I've done LSD to haha
I've pretty much done all the drugs... Serotonin, Dopamine, Norepinephrine Reuptake inhibitors/Releasing agents/antagonists, Cannabinoid agonists, Nicotine agonist/antagonist, Norepinephrine agonists..I dunno shrooms, salvia, Ketamine, GHB, benzodiazepines ... so sometimes I make connections... like this drug feels a lot like this one, or those effects sound very familiar. It's funny cause in a weird way I feel like this gives me more "experience" with mind altering drugs than even a psychologist who "prescribes" but never "takes". Man most of the time they never even heard of the drugs I've taken, and I'm like... how are you supposed to help me then? I keep thinking they will be interested in my comparisons... but always look at me like....ooook there crazy lil hippy... whatever you say...I believe, you believe... as they write "psycho" on the pad.

...but I am often right about this stuff

PS: I'm clean now haha

But yeah, this is why if I knew what receptors these HIV meds hit as a side target (if any) , I could instantly predict the effects, know what to expect, and prepare for them instead of the other way around... having them hit me, try to figure out what they are, THEN fix them... and if there are none..I would like to know... so I don't waste time "suspecting" its the HIV meds, when I'm really just low in vitamin b12 or something stupid like that.

[phenethylamine]

Man something is up with this Stribild though,
It's 1:00pm and I can't shut the F up. I feel like I'm "over sharing" and will probably regret this tomorrow. Normally I'm sleepy around 9:pm
I did have a massive cola at KFC earlier.. Is the caffeine being boosted?
I had to quit my inhaler due to interactions... so low oxygen?
I'm strangely liking this though... even though I feel a bit crazy... but I don't like not having control over it. I'm feeling bipolar... that's probably the one condition I haven't had yet. Two hours ago I was sad, before that angry... now I'm inexplicably happy. Damn it.

[zach]

pick a thread phen, difficult enough to follow you without jumping around

feeling kinda worried about you

whats up with the way you do a chemical breakdown of everything?


http://forums.poz.com/index.php?topic=58424.msg675782#msg675782

[mecch]

phenethylamine -  how do you have time to do all this research and all this attention to the minute shifts in your moods and body chemistry?

Do you work?

Study?

If yes, concentrate on that for awhile. Do well.

If not, then you need something outside your mind, body and self, to occupy yourself. A project or hobby to be passionate about.

[phenethylamine]

I think I've isolated my problem to a negative interaction between Stribild and my Symbicort (budenoside/formoterol) inhaler. The Cobicistat in Stribild inhibits CYP3A4...and that's the same liver enzyme that Oxidizes the Budenoside (Glucorticoid) portion out of the body. So my mood changes could very well have been steroid induced haha Not quite "roid rage" but one of the symptoms of overdose IS psychosis and abdominal cramps. I'm testing day #4 without it. Yesterday I could barely breath, but today is much better (will start a new topic about this). I also might have isolated the source of my breathing problems to the damn perfume in my laundry detergent, such a simple overlooked thing following me around everywhere.

Sadly I figured this out to late, and the prescription was already changed back to Complera during a bout of anxiety and I guess I'm stuck with the food again for a while   (I know I can't keep changing) I hope the dizziness doesn't start back at the beginning... but at least I know what to expect this time around.

Mecch, I have way to much free time.
I'm actually aware it's a problem, and am trying to change that, but it's an incredibly slow process... but gaining traction I think.

Zach,
I do a chemical breakdown of everything cause... I'm a sexy nerd? Mad genius?  (Yay science!)

Thanks for taking the time to write the long kind messages, I really appreciate it

[mecch]

1) My doctors never changed combos so quickly.
2) Shouldn't doctors and pharmacists be pronouncing on counter-indications?  Why is this up to you?  Do you really understand this chemistry? Is it possible you think you do, but you may not, in fact?
3) Why so much free time? May I ask - are you disabled?
4) Are you self-medicating? Just checking again. I forget which thread I asked this question. 

[phenethylamine]

Mecch:

1) I dunno lol

2.a) My interactions were checked by a student. My meds are delivered so I never actually go in to pick them up. Sometimes they call, sometimes not.   

b) it shouldn't be up to me, but it's easy to fall through the cracks of digital systems. Pharmacies just receive prescriptions, the context isn't always clear.

c) yes

d) Anything is possible but I doubt it. I've been researching this stuff for years. I didn't just pick it up in a few days. I'm suprised your so surprised someone would want to learn about what they put in their bodies. Is this unusual? If you explain to me the part you think I'm wrong about/don't understand maybe we could discuss that further?

3. A lil personal there... why do you ask?

4. Self medicating? What do you mean? Nothing illegal if that's what your implying?

[mecch]

I am wondering if you are spending too much time monitoring yourself and also possibly treating yourself.  That is what doctors are for.  You didn't answer the question about self-medicating. 

I asked if you are disabled because if you are unemployed and on disability, maybe that is the main challenge. Not your HIV and not your HIV treatment. Maybe you need something more constructive and life-affirming to do with your time. 

Maybe you need to get out of your head about yourself.  Either with projects.  Or by being involved with other people. Or both.

When I had little manageable acid trips on my efavirenz, i was at work or commuting to work.  I just enjoyed it and let it pass. I had a job to do. Places to go. People to deal with.

I suppose some people have this character and others don't.  I think it runs in my family.  People just deal with their infirmities and keep on trucking.  I know many people who worked right on through cancer and chemo, for example.  I believe this helps manage the infirmities and also the mindset.  But just an opinion.

[oksikoko]

Phen,  I don't see anything wrong with wanting to know what goes into your body,  especially with such powerful chemicals as we're discussing here. I find it funny that people would question your curiosity; on the contrary,  I would question anyone's lack of it.

As for Stribild,  everything you said: yes. I experience something very similar and I'm about two years into it.

Don't let people convince you to 'just get a hobby,  dear' or urge you into ignorance. Curiosity may have killed the cat,  but it brought us humans such things as penicillin,  democracy and air conditioning. Always question.

[phenethylamine]

Oksikoko: Really appreciate your post  
It's refreshing to see someone on here who shares my views on curiosity.

Mecch: I understand what you are saying... your coping strategy is to ignore and push through... mine is to dissect and question shall we agree to disagree? I'm not really stressed anymore...but I'm still crazy curious.

So my question still stands.
Positron Emission Tomography (PET) scan paired with radiolabeling/isotopic labeling). Essentially the molecule is marked with a glowstick and scientist follow it through the brain and observe if it binds to any receptors and publish results. This can be observed in real time, and would take a day, maybe a week to publish results. That extra week of research could provide psychiatrists "insight" on how to help patients and avoid interactions. Yet it's never been done... and I'm wondering why?

[zach]

Yet it's never been done... and I'm wondering why?

yes it has

[phenethylamine]

Can you be more specific Zach... haha
Also can you teach me how to do quotes?
I gotta get in on this quoting action.

[phenethylamine]

I think they must use similar technology to predict if a medicine is a ligand (capable of binding to) one of the HIV enzymes. Is the tech to different maybe? Maybe each drug researcher has it's own dedicated software and aren't willing to cooperate with each other or freelance for a competing company? I feel like I'm missing something...I would think the HIV imaging is more complex and  expensive cause it's always changing...but brain receptors (Serotonin, Dopamine, Norepinephrine) for the most part don't change.

Haven't seen any binding studies for Dolutegravir either... and that's kind of surprising cause I think Viiv is combination of two major pharmaceutical companies GSK and Pfizer and that's what they do. They certainly have the resources to do it.  I will double check though.