Note added by Rhodium (Oct 2003) upon request from Dr. Bonson:
You can contact Dr. Katherine Bonson, the pharmacologist who has published two scientific papers on the interactions of antidepressants and hallucinogens, if you have information to contribute on this important subject. She can be reached at <kbonson@earthlink.net>.
I posted this article to Usenet in May 1994. Over the years I have received the anecdotal responses that follow.
If you have something to add, please write to me.
-- Mike Brown <mike@hyperreal.org>
> I have a friend who is bipolar and is taking Lithium to control
> her chemical imbalance. I've been telling her about my positive
> experiences with LSD and she is interested in trying it.
> I checked the FTP sites and I don't recall seeing this being discussed
> here before, but I could be wrong.
> Can someone post or email me with any information they have concerning
> the interaction of LSD with Lithium? Surely there are some bipolar
> folks on the net who have tripped before. Is it too risky? What are
> the dangers? What advice can you offer?
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 decision...no 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.
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 :) )
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...
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
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.
I am bi-polar manic depressive. I have been so all my life, but have only recently been diagnosed. The doc recommended I take Depekote 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.
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 am very interested to hear any information you have or any experiences your girlfriend has had. I found the homepage because I am planning to trip again in a month or two with my yoga teacher in a retreat-like setting which I have never done before. I would write more, but I have to go. 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.
I would like to add this to the text on LSD and lithium interactions.
Suggested Text:
human encounter with death by stanislav grof
course in miracles
lithium subsides within 24 hours.
lsd does exacerbate but only to show you what is wrong in order for you to chose a different approach. lsd showed me my ego behaivior. It revealed what 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.
Further 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: 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: 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. |