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Interactions Between
LSD and Antidepressants
by Mike Brown
v 2.1 (Last Major Update Apr 6 2002, minor updates Oct 16 2003)
Citation:   Brown M. "Interactions Between LSD and Antidepressants". Oct 16 2003.


  1. Introduction
  2. Summary
  3. Who To Contact
  4. Anecdotes
  5. Research References
  6. Revision History

1. Introduction

In May of 1994, I posted to a Usenet newsgroup an inquiry about the interaction of LSD with antidepressants. At the time, I had a friend who was interested in trying LSD, but she was concerned about its potential interaction with Lithium, which she was taking to control a bipolar disorder. My friend ended up never trying LSD.

Because there was, at the time, no other information on this subject available online, I put the responses I received on a web site (which is what you are now looking at) for the benefit of others. This resource is expanded as new information and anecdotes continue to trickle in.

If you have another anecdote or something else to add, please write to me.

-- Mike Brown <>

2. Summary

If you don't feel like reading this whole thing, here are the essential points you need to know:

1. There is still very little legitimate, thorough medical research on this subject. LSD's outlaw status makes it very difficult to obtain permission & funding for research. Therefore, you should regard all of the anecdotes and conclusions here as being scientifically unproven, and you should note that any experimentation you choose to do carries a significant risk.

2. Lithium or tricyclics (like Amitriptyline, Anafranil, Asendin, Aventyl, Elavil, Endep, Norfranil, Norpramin, Pamelor, Sinequan, Surmontil, Tipramine, Tofranil, Vivactil) are fairly consistently reported as being very bad in combination with LSD. People attempting this combination are unable to communicate with others, they go into "fugue states" where they end up in other places and don't know how they got there, and they are generally in a terrible place psychologically. Life-threatening seizures and at least one DEATH have been reported to be triggered by the combination of LSD and lithium.

3. SSRIs (like Prozac, Paxil, Zoloft, Celexa, Desyrel) or MAOIs (like Nardil, Parnate, Marplan, Eldepryl, Aurorix, Manerix) are fairly consistently reported to noticeably reduce the effects of LSD. MAOIs seem to cause a greater reduction in the effects of LSD than SSRIs.

3. Who To Contact

If you have an anecdote to share: email Mike Brown <>
All email will be treated confidentially, and will be made anonymous if I decide to incorporate it into this resource.

If you have a question about the interaction between a specific antidepressant and popular psychedelics, or you'd like to contribute to legitimate medical research on this topic: email Kit Bonson, Ph.D. <>
Kit has been studying the interactions between antidepressants and psychedelics for a number of years at the National Institute of Mental Health. If you or someone you know has info to contribute, she can send you a questionnaire that they have been using to collect information. Your info might one day help save a life, and don't worry -- all contributions are kept confidential.

If you are taking any medications whatsoever, consult your personal physician before combining them with anything. Doctors have much information at their disposal regarding the medications they prescribe, and what combinations are relatively dangerous. Be honest with your doctor about what you put into your body. Of course they won't like to hear that you're experimenting, but they may be able to help reduce the risks you are taking by switching your prescription, for example.

4. Anecdotes

Each of these contributions came from people who claim to have some kind of experience with LSD and antidepressant interactions. While the subjective experiences described herein are not scientific, there does seem to be a reasonable conclusion that one can draw from them: that it's generally not a good idea to take LSD while under the influence of antidepressants. You will either have difficulty experiencing the usual effects of LSD, or you will enter a very bad psychological state.

General advice: LSD + lithium is risky

Not advisable. Potentially very dangerous.

If your friend is planning to do this, then she MUST research LSD intensively before taking it...and get a good understanding of exactly what risks she will be taking.

LSD has been known to 'trigger' latent mental illnesses - it doesn't cause them, but it can exacerbate the condition - even if the person doesn't yet know that they have any 'condition'. This is probably where the myth that "lsd can make you crazy" originally came from.

On the other hand, hallucinogens can cause a profound change in outlook...enough to lift a severe depression - I know that this can happen because it happened to me when I was around 22 - I'm 27 now. I attribute my current mental health, and even my continued existence, to a batch of mushrooms I took when I was suicidally depressed - turned my head around completely, and within a few weeks I was well on the road to recovery. It wasn't an instantaneous, magic cure but it provided the impetus that I needed to get started. I would probably have topped myself within a few months otherwise - suicide was constantly on my mind, and I was evaluating different methods trying to come to a way to be sure, but I expect that I would be dead by now if it weren't for that mushroom trip.

So, tell your friend to BE VERY VERY CAREFUL. LSD could teach her something, or it could send her into a downward spiral.

LSD + bipolar cycles, no medication: A report of an apparent manic episode

I'm not sure if there are any known harmful interactions between LSD and lithium. In fact, I don't think anyone is _sure_ why Lithium is effective in stopping bipolar cycles.

However, I am SURE that LSD is not something that should be introduced to anyone with manic-depressive disorder. My girlfriend is also bipolar, and LSD will cause a triggering effect in her that sends her straight into mania, almost immediately. All it took was one trip. She had gone without an episode for more than 5 years until she decided to dose one day. Can you imagine how unpleasant that must feel? Full blown mania PLUS an acid trip (which would probably become a bad trip.)

I hate to be one of those types that perpetuates these drug horror stories, but it's just not a good idea for anyone who has a clinical disorder to take mood altering drugs. Clara actually had to drop out of school that semester and seek treatment at a hospital she ended up staying at for six weeks. Mind you, she wasn't being treated for "Post LSD psychosis" ( a condition which is a complete myth in my opinion.) but for the mania which the LSD catalyzed.

I've also had positive experiences with LSD, so I have no bias against it. but please don't let your friend take it! If you do decide to do it, keep a close eye on her! (as if you wouldn't :) )

A postulation that LSD counteracts stabilizing effects of Lithium

I've never heard of this exact situation before, but it seems like it Might be dangerous to me.. Lithium, as I understand it is used to stabilize a person's personality, to lop off the manic and the depressive parts , and leave the person more level.. but LSD can really send a person reeling in either direction quite quickly.. I wouldn't recommend that anyone with mental problems severe enough to me medicated in the long term try LSD...

LSD + lithium: An observation of increased LSD tolerance

Generally I lurk here in alt.drugs for lack of pertinent info, but here I must comment... I was diagnosed manic-depressive in March, and was put on lithium soon after. Contrary to popular belief, being manic-depressive is not an "I'm so out of control everyday" sort of problem. It comes and it goes, many people go years without a significant episode of mania or depression.

I have combined my lithium with LSD and had no problems. The only effect I noticed at all with a slight increase in my tolerance of LSD (previously I had very little - when friends dropped 2 tabs, I dropped 1, etc.). The LSD didn't swing me into a mania or depression.

However, this is my experience. In the drug books I've read, the warning with mixing lithium with pot or LSD is "possible psychosis". although no one in any manic-depressive support group or online group I've talked to has experienced such.

Just a little slice o' my life

Observation of long-term negative effects of drug abuse, including LSD + lithium

I knew a guy last year, and I started hanging out with him. I soon relized that he was heavily into drugs. He took several prescriptions, including lithium, and I know he had dropped LSD many of times. Ever since Ive known him hes seemed kinda "not all there", and the longer i knew him the worse it got. About 2 months ago he was put in a "half-way" house. His mother did not think he could take care of himself. I personally think he is gone insane due to taking to many drugs. I just thought I would write and give you my opionion.

LSD + Depakote: a report of no adverse side-effects

I am bi-polar manic depressive. I have been so all my life, but have only recently been diagnosed. The doc recommended I take Depakote instead of Lithium. I have also taken 380 doses of LSD in 4 years, which is not counting the acid parties I attended before that. So far there have been no adverse side effects, only positive effects(i.e., higher I.Q., better grades and a new awareness of my conscious self). I cannot offer any info on Lithium and LSD interactions, but advocate the use and further study of LSD. Then again, I may be just an exceptional case.

LSD + lithium: a report of no adverse side-effects

I have been taking lithium for almost one year now. I started last October after I experienced my first (and only to date) manic episode of my life and was hospitalized. I had tripped four times before the episode, all within a year of the episode. I have also tripped twice since then, once in May and again in July. I did take smaller doses the past two times, half a hit and three quarters respectively, but I would say it was quite potent acid since I tripped for around 10 hours both times. Also, all six of my experiences with LSD have been positive, especially the last two.

I would like to finish with my opinion that both LSD and manic-depression are EXTREMELY profound and powerful experiences and I treat both with the respect that they deserve and I recommend that you and your girlfriend do the same.

LSD + lithium: no adverse side-effects reported, but this person has other problems...

Suggested Text: Human encounter with death by stanislav grof

lithium subsides within 24 hours.

lsd does exacerbate but only to show you what is wrong in order for you to choose a different approach. lsd showed me my ego behaivior. It revealed that was otherwise suppresed. I recognized the importance of caring. and accknowlgeing god and that my way is not real only imagined.

I never really figured out a way to change my energy consuming thinking which is the cause of my disoroder, mania) the time I had some bad acid. How it effected me and what happened when I went back on lithium and what I did to fix it. what my problems with acid are and how I solve them. how to never be bored with lsd. shrooms and their advatages and how they differ from lsd. Lithium what it does for me. lithium and brian's lsd expierence. lsd should be few and far between and why.

LSD for self-medication of schizoaffective disorder and severe depression: a report that it might hurt more than it helps

I lost a loved one to a suicide in October of 1998. It hurts in ways that words can not describe. Since his death, we have learned that before we got professional help for him, he tried to solve his own problems himself and using LSD was one of the chemicals that were used. I read a study that reported that if one has predisposed tendencies for schizophrenia and related mood disorders, LSD can help bring on the emergence of the symptoms. Our loved one had been diagnosed with schizoaffective disorder and had suicidal ideations present in October of 1997. When one of your readers asked about using lithium with LSD, I felt compelled to write. Talk to your parents or loved ones. We are part of your treatment team and want to help. Now it is over for us. We can not help him.

LSD + lithium: a report of positive side-effects

yeah dude. yur friend can trip and use lithium at the same time her trip will just b a lot better. ive done it b fore infact a few times

Editor's Note: Take this with a grain of salt, obviously. Dude.

LSD + various antidepressants: a report of no adverse side-effects

I'm a manac-depressant, ere, I have Bi-polar disorder. I've taken drugs on Depakote, Zoloft, lithium, Wellbutrin, Ritalin, Prozac, and Toferrinal. They all say not to mix with alcohol or other drugs. But what the hell, they mix each other up without a problem. I've been on at the most, 3 of these drugs and either drank plenty of alcohol, smoked plenty of reefer, tripped my fuckin' balls off, or a combonation of all three along with three of the other drugs. I'm still alive and taking my meds. regularly and attending school and getting above a 3.0. I say, let your friend trip her brains out. Just make sure you are tripping with her so that way she doesn't get some kind of crazy trip where she wigs bad. A peson with bi-polar and a bad trip don't mix too good. I just had one for the first time about a month ago. I never thought I'd have a bad trip until that night. The imagination and loss of reality can be twice as bad in a person suffering depression. It could bring out the worst in the mind. But as long as you are with your friend, she'll be fine.

LSD alone: a report of emergence of bipolar disorder symptoms
LSD + Aropax (Paxil) + Valium: a report of no negative side-effects
LSD + Amitriptyline: a report of no negative side-effects

A friend of mine was a normal kinda guy until one mushroom trip sent him out of control into a kind of bi-polar disorder, he is now on arapax and had had no contact with any form of drugs until he had a smoke with us not long ago. One session sent him into an episode in which he hid behind a heater from us as he thought we were going to kill him. He is no longer using any form of illegal drugs. Another friend suffered an episode of bi-polar disorder after an acid trip and is now also on valium and arapax and has no problems with pot or LSD. I am on amytriptylene and despite having taken acid and smoking pot regularly, have suffered no ill effects, if anything, i feel a lot better for having taken them. Drugs seem to have lifted me out of several suicidal episodes throughout my life.

However, given that i know of at least 4 people who have come to suffer from bi-polar disorder bought on by a single LSD trip i would definately not reccomend it for someone who is already suffering from this disorder, it seems that it would be likely to bring it on worse. In saying this, there is also the chance it could turn it completely around in the same way it brings these episodes on. It really depends whether it is worth the experiment, given that someones mental health is at risk.

LSD + bipolar disorder, no medications: a report of no negative side-effects
LSD + Paxil: a report of reduced LSD effects

i had bi-polar problems long before i started taking any medication. long before i started taking medication i took LSD, and i swore i finnally found out how to feel "normal". once i was on medication [PAXIL] i found that LSD did not work the same for me. weird, huh?

LSD + lithium: a report of seizures

I Am Bipoler Like You Friend.
I Also Take Lithieum
And LSD Has Ben Realy Bad While On It.
I Sugest That A Person On Lithum Stop Taking 2 Days Befor Thay "TRIP"
I Dident Once And I Almost Died! So So Bad I Was In The ER Intensif Care And
Haveing Convolstions So If You Whant To Trip And Are Takeing Lithieum Stop
Taking It For Atleast 2 Days!
If You Whant To Hear The Hole Storey E-mail Me Back!

Editor's Note: I don't make up this stuff.

LSD + lithium + Prozac: a report of hospitalization

ive got a friend who was prescribed to lithium and prozac. he dropped some acid and then took his pills while he was trippin, he wound up goin to the hospital. i dont know if it was the lithium or prozac, most likely the prozac.

LSD + various bipolar disorder medications: a report of no negative side-effects

hey ok um i have bi polar disorder im on a shit load of medications and i take lsd and ecstasy all the time and my life has been better my parents trust me more and my grades have gone way up i think im smarter so like your friend should take lsd just watch her you know

High doses of LSD + lithium + Wellbutrin: a report of no negative side-effects

I was diagnosed with bipolar disorder 3 years ago and have been taking lithium and antidepressants since. I am presently taking Wellbutrin along with lithium. I tried lsd several months ago, and have taken it twice since, 4 hits the second time and 5 the last. Pschologically, I didn't see a terrible danger, only slight paranoia that the trips would never end. Also, my last trip lasted about 20 hours. Personally, I wouldn't recommend lsd to anyone, since everyone's reactions are different, but to say I didn't enjoy it would be a lie.

LSD + lithium: a report of severe dissociation and seizures

I take the drug Lithium for bi-polar disorder and I had taken it the night before i dropped 2 hits of acid. It was my 3rd time doing LSD and i was already worried about the effects of the 2 drugs together because the 2 previous times i was not on lithium. The trip was a very bad trip. It was completely auditory, giving me a schizophrenic-like feeling which was very strange, but, it wasn't 3 hours after i dropped that i started to go into a seizure. (I do not have a history with epilepsy or seizures of any kind). I went unconscious and, thank God, I had a sober friend their to help. After I came to, I was completely in an altered state for another 2 or 3 hours, barely conscious, still hearing voices all around me but seeing no visuals and then going into another seizure, this time i almost stopped breathing and my jaw locked down hard enough that i subconciously bit the sides of my tongue off. When I woke up from that I threw up, which isn't odd for someone who has taken a large dose of the drug, and it was through. Not even aftereffects of the drug like i usually experienced before. I have not had any flashbacks since then, and I seem to be fine, but i do not recommend mixing the two drugs together, at all.

High dose of LSD + lithium: a report of a possible seizure, followed by death.

I can prove that lithium and LSD do not interact well. Two weeks ago, a friend died while on a small dose of Lithium and a fairly large dose of LSD. He was Bi-polar and only on the medication for about four weeks. It looked as if he went into a downward spiral, then possibly have had a seizure. There were no other toxins in his blood, according to the coroner. Please do not mix these two powerful drugs, it's not worth the trouble and it's a gamble either way. If you do decide to take that gamble, then make sure someone sober is with you.

Editor's Note: This is the first time we have heard of a death resulting from this combination. I'm seeking more info from the contributor of this anecdote.

High dose of LSD + lithium: a report of severe dissociation and hospitalization

I had an experience 5 years ago when I was taking the drug Lithium for manic depression. I took 4 more pills of Lithium than I was supposed to take that night because I was depressed. I was at a party and smoking a lot of weed, I was also drinking alcohol, about 8 beers already. One of my friends came over and had some acid so I bought 50 hits for a very good price. I took two and about an hour later I didn't feel anything so I dropped 5 more to get this drug moving. Not to long after that I was sitting on the couch talking to a group of friends when I just started puking all over myself (talk about embarrassment) and ran to the bathroom. I got help from my friends and took a shower while the party is still going on. When I got out I started talking to people that weren't there and the walls, I sat down for a few minutes or a lot don't really know. I got up and that is all I remember. I woke up a few hours later in the hospital. It was weird, hours were going by like minutes. I was hospitalized for a few days, but it sucked, I don't know if it was the mixture of everything or what, but the doctor told me that no drug should be taken with Lithium, but of course I didn't listen.

LSD + lithium: a report of a seizure and heart attack

I almost died this weekend, and it was a result of mixing LSD with Lithium. I am bipolar and take Lithium. I was at a rave this weekend and had two hits of acid (which I heard were rather strong hits). I ended up having a seizure, foaming at the mouth, thrashing around (I have bruises all over my arms and legs now), and I turned blue in the face before anyone called 911. I later experienced cardiac arrest, where my heart stopped beating and I basically "died" for a little while before they brought me back to life. SCARY SHIT!!! I would not recommend it. If I had only known how deadly mixing LSD with Lithium was beforehand. I really hope someone reads this and learns from my story.

Not only did I almost die, but all my "friends" in the drug culture have dropped me totally. They won't even talk to me anymore. These were people I really thought were my friends. There were people at the rave (at people's apartment) who didn't even want to call 911 for fear that they would get busted for drugs.

Just be careful what drugs you do and who you do them with. It's hard to know who to trust.

LSD + lithium + Zoloft: no details, but it was apparently very bad

I did LSD recently while currently taking 900 mgs of lithium and 50 mgs of Zoloft. I WILL NEVER TAKE LSD AGAIN!!!

LSD + lithium: a report of psychosis and hospitalization

LISTEN TO ME! DO NOT MIX LITHIUM AND LSD. I have tripped countless times in my life and always maintained complete control. I tried it once on Lithium. I woke up in a hospital two days later. The police found me wandering around in an "acute psychotic episode". I was running into trees headfirst and trying to walk through physical objects. The doctors told me that if the police had found me an hour later, I would have been dead or a vegetable for the rest of my life. I lucked out by having the cops find me. Yes, I was expelled from my college, but am still alive and somewhat sane. Please learn from my mistake!

A high dose of LSD + Celexure: a report of a seizure
A high dose of LSD + Zoloft: a report of no adverse side-effects

hi i am writin to you because recestly me and a couple of friend were goin to the city to see alazer show and right after we got of the train my friend colapsed and had a sisure she took 3 tabs it was a scary sight she on celexure an anideppesant and i take zoloft and took 5 tabs and i didnt have a sisure

LSD + Wellbutrin: a report of no adverse side-effects.
Possibly poisoned morning glory seeds + Wellbutrin: a report of delusional thoughts

I am taking wellbutrin for depression, I take 2 150 mg SR (slow release) pills a day. I have tripped once on mushrooms, loved it, was a positive experience. I tripped on LSD once, same thing, although the changes in my mind seemed more permanent than mushrooms. Although last night I tried LSA (similar to LSD) (morning glories (heavenly blue)) and I did not feel suicidal, but thought that my life was going to come to an end, like the perfect ending of a movie, I felt my thought processes changing and I could not tell if what was happening was good or bad, it was just really wierd. I experiened nausea and actually came to a point where I felt like I had become a girl, I'm male, I can't explain that, (no, I do not think men are superior) then I felt weak, this was a few minutesd after I had felt invincible. When I came home I decided to go online to see if I could tell what was happening, I surely could not understand it. Then I found an article telling me that commercial seeds are treated with POISON that caused nausea and vomiting to discourage abuse, it also told me that to much of this poison could psychotic reactions, and at times I did feel a little psycho.

LSD + lithium: a report of intense psychological effects and life-threatening seizures

I have had horrific experiences with lithium and lsd. I was placed on lithium three years ago for bipolar disorder. Prior to this i had taken at least 150 doses of lsd, with absolutely no bad experiences. After taking 900 mg of lithium a day for three months or more, I dosed two hits of weak blotter. The trip spiralled out of controll, much more intense and all-encompassing than should be possible with that dosage, and the seven people with me, who had taken just as much or more, were having mild trips with nothing more exciting than tracers. I began hallucinating the sounds of hundreds of chainsaws, all around me, and that's the last thing I remember. Later, I was told that I fell to the ground and began convulsing, and was taken by ambulance to the er where I woke up within half an hour or so, was given back my urine-soaked clothing, and driven home. I assumed that the seizures had been a result of a bad trip and the hospital personnel didn't give too much consideration to one more acid-head rolling through, so they didn't have much to say to me one way or another so, being incredibly stupid, I thought that I could still trip and be fine, that it was a fluke. A month later I took two more hits of blotter with old high school friends and went to the park. It was a wonderful, warm, fantastic experience until I began seizing. This time the paramedics got there just as I swallowed my tongue, and I had at least 28 seperate grand mal seizures before they finally administered the last-ditch possiblility, a paralytic so strong it stopped my diaphragm so when i woke up this time I was on life support and unable to move so much as my eyelids. Of course, I blacked out again.

I no longer take lithium, am no longer considered manic depressive, but I am so terrified of lsd that I won't even kiss my boyfriend when he's tripping. I know that there is an overwhelming possiblity that it was merely the interaction of the lithim and the acid that caused my brain to short out, but the hell if I'm going to take that chance. I think that anyone taking any sort of psychoactive chemical needs to do a lot of research before mixing it with any other.

5. Research References

None of these are available online, as far as I know. You have to go to a medical library to find the original publications.

Article Title: Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans.

Article Source: Neuropsychopharmacology 1996 Jun;14(6):425-36

Author(s): Bonson KR; Buckholtz JW; Murphy DL

Abstract: This study investigates the possible interactions of antidepressant agents and hallucinogens in humans through structured interviews using a standardized questionnaire. Volunteer subjects recruited through announcements placed on the Internet or other sources were asked to describe the somatic, hallucinatory, and psychological effects of self-administered LSD prior to and during chronic administration of an antidepressant. Twenty-eight out of 32 subjects (88%) who had taken an antidepressant with inhibitory effects on serotonin (5-HT) reuptake (fluoxetine, paroxetine, sertraline, trazodone) for over 3 weeks had a subjective decrease or virtual elimination of their responses to LSD. An additional subject who had taken fluoxetine for only 1 week had an increased response to LSD. These data are in contrast to our previous study that reported increased responses to LSD during chronic administration of tricyclic antidepressants or lithium. Possible mechanisms of action for the effects from serotonergic antidepressants involve 5-HT2 and 5-HT1A receptors, changes in extracellular brain serotonin concentrations, and changes in brain catecholamine systems.

Article Title: Alterations in responses to LSD in humans associated with chronic administration of tricyclic antidepressants, monoamine oxidase inhibitors or lithium.

Article Source: Behav Brain Res 1996;73(1-2):229-33

Author(s): Bonson KR; Murphy DL

Abstract: This study sought to investigate possible interactions between antidepressant agents and lysergic acid diethylamide (LSD) in humans through the use of retrospective questionnaires. Ten subjects were identified who used LSD during chronic (3 weeks or longer) periods of antidepressant administration. These subjects were asked to describe the phenomenological effects of self-administered hallucinogens prior to and during antidepressant treatment; a structured, standardized questionnaire was used to evaluate LSD experiences. Chronic tricyclic antidepressant administration was associated with subjective increases in physical, hallucinatory and psychological responses to LSD. Similarly, subjects receiving lithium chronically also reported increases in their responses to LSD. In contrast, subjects who had been chronically taking an monoamine oxidase (MAO) inhibitor reported subjective decreases in the effects of LSD. This is similar to a previous report by our group of a decreased response to LSD in individuals who were chronically taking serotonin-selective antidepressants. These altered responses to LSD most likely involve differential changes in central serotonin and dopamine receptor systems and are consistent with other recent data suggesting that the clinical efficacy of different classes of antidepressants may not necessarily rely on a common mechanism of action in the brain.

Article Title: LSD flashback syndrome exacerbated by selective serotonin reuptake inhibitor antidepressants in adolescents.

Article Source: J Pediatr 1994 Nov;125(5 Pt 1):817-9

Author(s): Markel H; Lee A; Holmes RD; Domino EF

Abstract: Two adolescents with a long history of abuse of lysergic acid diethylamide (LSD) and symptoms consistent with major depressive disorder, on initiation of antidepressant therapy with selective serotonin reuptake inhibitor agents, had the new onset or worsening of LSD flashback syndrome. The similarity in neuroreceptor physiology for both LSD and serotonin suggests that the LSD flashback syndrome may be induced by these drugs in patients with a history of LSD abuse.

Article Title: On the central antiserotonin action of trazodone.

Article Source: Pol J Pharmacol Pharm 1979 Jan-Feb;31(1):25-33

Author(s): Baran L; Maj J; Rogoz Z; Skuza G

Abstract: Trazodone, an antidepressant drug with an unknown mechanism of action, has been examined in order to demonstrate its central antiserotonin action. Trazodone antagonizes the head twitch response induced by 5-hydroxytryptophan in rats and mice, or by-5-methoxytryptamine in rats (the ED50 values are 9.3, 5.2, and 10.8 mg/kg respectively). It counteracts convulsions induced by tryptamine in rats (ED50=3.75 mg/kg). Trazodone abolishes hyperthermia induced by serotoninomimetics (LSD, quipazine, fenfluramine) in rabbits. It does not affect ptosis induced by reserpine, and diminishes stimulation of the locomotor activity induced by amphetamine. Our findings demonstrate that trazodone has a central antiserotonin action, similarly as three other antidepressant drugs: mianserin, danitracen and doxepin, whose central antiserotonin action has been found previously.

Article Title: Doxepin as a blocker of central serotonin receptors.

Article Source: Pharmakopsychiatr Neuropsychopharmakol 1977 Dec;10(6):318-24

Author(s): Maj J; Gancarczyk L; Gorszczyk L; Rawlow A

Abstract: The antidepressant drug-Doxepin (DX) was examined in order to investigate its central antiserotonin activity. The drug antagonized the behavioral syndrome elecited by L-5-hydroxytryptophan in rats and mice, but did not affect the pinna reflex. In the flexor reflex preparation, DX acted like other sero-tonin receptor blockers: By itself, it had no influence on the flexor reflex but it prevented the potentiation induced by serotonergic agents (fenfluramine, LDS, mescaline). The hyperthermia provoked by serotonergic agent (fenfluramine, LSD)in rabbits was antagonized by DX. DX abolished the syndrome induced by oxotremorine. The results obtained indicate that DX blocks central 5-HT receptors, like the two other antidepressants, mianserin and danitracen.

Article Title: Effect of chronic tricylic antidepressant treatment on the serotoninergic autoreceptor: a microiontophoretic study in the rat.

Article Source: Naunyn Schmiedebergs Arch Pharmacol 1980 Nov;314(2):123-8

Author(s): Blier P; de Montigny C

Abstract: Chronic treatment with tricyclic antidepressant (TCA) drugs has been shown to enhance the responsiveness of rat forebrain neurons to serotonin (5-HT). In the present study, imipramine (5 mg and 10 mg/kg), iprindole (2.5 mg/kg), desipramine and femoxetine (5 mg/kg) were administered daily for 14 days. The response of dorsal raphe neurons to intravenous injection of LSD (4 microgram/kg) and to microiontophoretic applications of 5-HT and LSD was assessed 24 h after the last dose. The responsiveness to intravenous LSD and the effectiveness of microiontophoretic applications of 5-HT and LSD were not altered by TCA drug pretreatments. Furthermore, the treatments did not change the mean firing rate of these 5-HT neurons. Those results suggest that chronic treatment with TCA drugs does not alter the sensitivity of the 5-HT autoreceptor. Thus, the effect of the previously reported increase of postsynaptic neuron responsiveness to 5-HT would not be dampened by a decreased activity of the presynaptic neurons.

Article Title: Effects of atypical antidepressants on LSD potentiated apomorphine hypermotility in rats.

Article Source: Acta Biol Med Ger 1980;39(8-9):917-21

Author(s): Gold R; Morgenstern R; Fink H

Abstract: The model of LSD potentiated apomorphine hypermotility [5] was used to classify different atypical antidepressants (danitracen, mianserin, cyproheptadine) and pizotifen. All drugs have been shown to inhibit specifically the locomotor activity potentiating effect of LSD in a low dosage range (0.1-0.5 mg/kg i. p.) without influencing the apomorphine effect. Since there is some evidence that the effect of LSD is due to the inhibition of the activity of serotonergic raphe neurons, the marked antagonizing effects of danitracen, mainserin, cyproheptadine and pizotifen are regarded to be an expression of pronounced antiserotonin activity.

Article Title: Effect of fluvoxamine on platelet 5-HT2A receptors as studied by [3H]lysergic acid diethylamide ([3H]LSD) binding in healthy volunteers.

Article Source: Psychopharmacology (Berl) 1997 Sep;133(1):39-42

Author(s): Spigset O; Mjorndal T

Abstract: Alterations in platelet 5-HT2A receptor characteristics have been reported in major depression as well as in other psychiatric diseases, and some effort has been made to utilize platelet 5-HT2A receptor status as a biological correlate to antidepressant drug response. In order to investigate whether treatment with a selective serotonin reuptake inhibitor affects platelet 5-HT2A receptors, we have studied platelet [3H]lysergic acid diethylamide ([3H]LSD) binding in healthy subjects treated with fluvoxamine in increasing dosage once weekly for 4 weeks. After 1 week of fluvoxamine treatment (25 mg/day), both Bmax and Kd were significantly lower than before the start of the treatment (19.9 versus 25.5 fmol/mg protein, P = 0.005 for Bmax; 0.45 versus 0.93 nM, P = 0.006 for Kd). Bmax returned to baseline during week 2, whereas Kd was lower than the baseline value throughout the treatment period. After discontinuation of fluvoxamine treatment, there was a significant increase in Kd (0.50 nM before discontinuation vs. 1.14 nM after discontinuation; P = 0.001), but not in Bmax. The study demonstrates that fluvoxamine affects platelet 5-HT2A receptor status irrespective of underlying psychiatric disease, and that this effect is evident already after 1 week at a subtherapeutic fluvoxamine dose.

Article Title: Alterations of blood platelet MAO-B activity and LSD-binding in humans after sleep deprivation and recovery sleep.

Article Source: J Psychiatr Res 1997 May-Jun;31(3):323-31

Author(s): Schreiber W; Opper C; Dickhaus B; Heiser P; Wesemann W; Krieg JC

Abstract: Sleep deprivation (SD) is an effective, however short-lived, method of treatment of depression. Preliminary findings suggest that the antidepressive effect of sleep deprivation is mediated by serotoninergic (5-HT) mechanisms. We therefore assessed serotoninergic activity before and after total SD (TSD) as well as after the following night sleep by investigating platelet LSD-binding, MAO B-activity, and 5-HT-content as well as plasma norepinephnne (NE) in 10 healthy men (age: 27.4 +/- 2.8 years). Blood samples were drawn on three consecutive days at 0700, 1300 and 1900 h, respectively. After TSD, a significant increase of LSD-binding KD and Bmax as well as of MAO-B KM and plasma NE could be observed, which, however, vanished after consecutive night sleep. Our findings favour an increased serotoninergic transmission after TSD and thus support the hypothesis, that sleep deprivation exerts its antidepressant effects by pro-serotoninergic mechanisms.

Article Title: Human platelet 5-hydroxytryptamine receptors: binding of [3H]-lysergic acid diethylamide (LSD). Effects of chronic neuroleptic and antidepressant drug administration.

Article Source: Experientia 1988 Feb 15;44(2):142-5

Author(s): Grahame-Smith DG; Geaney DP; Schachter M; Elliott JM

Abstract: Chronic treatment with phenothiazines and thioxanthenes has been found to enhance 5-HT-induced aggregation of human platelets. A method has been developed to study 5-HT2 receptor binding sites on platelets utilising [3H]-LSD and more recently 125I/LSD. Results are presented which suggest that the LSD binding site is indeed the 5-HT2 binding site and that the LSD binding characterises the specific receptor responsible for 5-HT-induced shape change and aggregation. In a group of patients receiving phenothiazines or thioxanthenes, the Bmax of LSD binding was increased. The mean binding affinity was decreased possibly due to a persistence of neuroleptic in the platelet membrane preparation. Analysis showed that this was not the reason why the mean binding capacity was increased. The results show that chronic phenothiazine and thioxanthene delta treatment 'up-regulates' platelet 5-HT2 binding sites and that this may be accompanied by increased sensitivity to platelet aggregation by 5-HT. In normal subjects desipramine treatment increased the Bmax of platelet LSD binding and this was accompanied by an increased prolactin response to tryptophan which is thought to be mediated by central 5-HT function.

Article Title: Effects of antidepressant drugs on different receptors in the brain.

Article Source: Eur J Pharmacol 1981 Mar 26;70(3):393-407

Author(s): Hall H; Ogren SO

Abstract: Radioligand receptor binding techniques were used to characterize the effects of different structural types of antidepressant drugs on neurotransmitter receptors. The tricyclic antidepressants more or less potently inhibited the binding to rat brain preparations of several different radiolabelled ligands [3H]WB4101, [3H]QNB, [3H]-d-LSD, [3H]mepyramine). The potency of the nontricyclic antidepressants varied greatly. Mianserin, potently displaced [3H]mepyramine, [3H]d-LSD and [3H]WB4101 while it was very weak on [3H]QNB-binding. Nomifensine and the specific 5-HT uptake inhibitors zimelidine and alaproclate had very low affinity for these receptors. All the antidepressants tested were practically devoid of activity on [3H]DHA binding, [3H]spiroperidol binding, [3H]flunitrazepam binding, [3H]muscimol binding and [3H]naloxone binding. The implications of these findings for biogenic amine theories of affective disorders are discussed.

Article Title: Reevaluation of the indoleamine hypothesis of depression. Evidence for a reduction of functional activity of central 5-HT systems by antidepressant drugs.

Article Source: J Neural Transm 1979;46(2):85-103

Author(s): Ogren SO; Fuxe K; Agnati LF; Gustafsson JA; Jonsson G; Holm AC

Abstract: The effects of antidepressant drugs on central 5-HT receptor activity were studied in rats and mice. Antidepressant drugs were evaluated for their ability to displace 3H-5-HT and 3H-d-LSD from membrane binding sites in the dorsal neocortex of rats in vitro and for their ability to block 5-HTP and d-LSD induced behavioral effects in mice. The degree of blockade of head-twitches in mice produced by the antidepressants was highly correlated with their affinity for 3H-d-LSD binding sites. A number of antidepressant drugs such as amitriptyline, nortriptyline, mianserine, doxepine, nomifensine and dibenzepine appear to possess marked 5-HT receptor blocking activity at some type of 5-HT receptors in brain. New antidepressant drugs such as zimelidine, which specifically inhibit 5-HT reuptake and do not block 5-HT receptor sites, may after chronic treatment also reduce the functional activity of 5-HT systems by producing adaptive changes in postsynaptic 5-HT mechanisms. Thus, a new indoleamine hypothesis of depression is presented: the therapeutic action of antidepressant drugs may in part be due to a reduced functional acitivity of some central 5-HT systems.

Article Title: Tricyclic antidepressant drugs: attenuation of excitatory effects of d-lysergic acid diethylamide (LSD) on acoustic startle response.

Article Source: Life Sci 1977 Apr 1;20(7):1249-57

Author(s): Davis M; Gallager DW; Aghamanian GK

Article Title: Tricyclic antidepressant drugs: antagonism of effect of D-lysergic acid diethylamide (LSD) on shock elicited aggression.

Article Source: Commun Psychopharmacol 1977;1(2):167-73

Author(s): Sheard M; Astrachan D; Davis M

Article Title: Interactions of [3H]LSD with serotonin receptors in human brain.

Article Source: Eur J Pharmacol 1982 Aug 13;82(1-2):77-80

Author(s): Cross AJ

Abstract: The binding of [3H]LSD to serotonergic sites in human brain was studied. The pharmacological profile of [3H]LSD binding in frontal cortex differed to that in hippocampus. Analysis of the inhibition of [3H]LSD binding by serotonin and spiperone was consistent with the presence of two binding sites, which differed in pharmacological specificity. The results are discussed in relation to previously published findings in experimental animals.

Revision History

Oct 16 2003: Minor Edits
  • changed kit bonson's email address
  • Added links to erowid references database for Dr Bonson's papers

April 06, 2002: Major Update
  • summary of reported interactions, for the impatient
  • many new anecdotes
  • summary of each anecdote
  • direction to contact kit bonson for certain q's
  • table of contents

1994 : First Version