This analysis of online reports (n=96) found that the use of psychedelics in combination with lithium led to seizures (47%), bad trips (64%), and emergency medical treatment (39%). The authors express the caution people should take when self-medicating/combining psychedelics with antidepressants (with lithium being commonly used for bipolar disorder).
Abstract
“Introduction: Psychedelics show promise in treating unipolar depression, though patients with bipolar disorder have been excluded from recent psychedelic trials. There is limited information on the use of classic psychedelics (e.g.LSD or psilocybin) in individuals using mood stabilizers to treat bipolar disorder. This is important to know as individuals with bipolar depression may attempt to treat themselves with psychedelics while on a mood stabilizer, particularly given enthusiastic media reports of the efficacy of psilocybin for depression.
Methods: This study analyzed reports of classic psychedelics administered with mood stabilizers from three websites (Erowid.org, Shroomery.org, and Reddit.com).
Results: Strikingly, 47% of 62 lithium plus psychedelic reports involved seizures and an additional 18% resulted in bad trips while none of 34 lamotrigine reports did. Further, 39% of lithium reports involved medical attention. Most of the lamotrigine reports (65%) but few (8%) of the lithium reports were judged to have no effect on the psychedelic experience.
Discussion: Although further research is needed, we provisionally conclude that psychedelic use may pose a significant seizure risk for patients on lithium.“
Authors: Sandeep Nayak, Natalie Gukasyan, Frederick S. Barrett, Earth Erowid, Fire Erowid & Roland R. Griffiths
Summary
Abstract
Psychedelics show promise in treating unipolar depression, though there is limited information on the use of classic psychedelics in individuals using mood stabilizers to treat bipolar disorder.
Results: 47% of lithium plus psychedelic reports involved seizures and 18% resulted in bad trips, while none of 34 lamotrigine reports did.
After more than six decades of research into and popular use of psychedelics, recent promising trials have inspired additional interest in using psychedelics as treatments for psychiatric disorders. However, concerns about adverse events in patients with bipolar disorder must be taken into account. Bipolar disorder is a chronic condition characterized by episodes of mania or hypomania and recurrent depressive episodes. Treatment usually includes mood stabilizers such as lithium and certain anti-epileptic drugs, though treatment options specifically targeting depressive episodes are limited.
Every treatment for major depression, including antidepressants, low-dose atypical antipsychotics, bright light therapy, sleep deprivation, and electroconvulsive therapy, can cause mania. Modern psychedelic trials typically exclude people with bipolar disorder, but the increasing availability of psilocybin mushrooms and positive media coverage may lead individuals with bipolar disorder to take psychedelic drugs in addition to their existing medications. There is little information concerning the effects of concurrent use of psychedelics and mood stabilizers. However, self-reported 4 experiences were drawn from a systematic search of public online forums focused on psychedelic drugs.
Data were collected from three websites, Erowid.org, Shroomery.org, and Reddit.com, which are publicly-accessible sites and online communities that include user-created and user-driven content. Mood stabilizers and antidepressants were not separately queried, but presence of an antipsychotic or antidepressant (among other psychoactive drugs) was coded in all selected experience reports.
Erowid is a curated online resource for information related to psychoactive drugs, which contains sections for user-generated and submitted content. An API was accessed via a custom python script on August 7, 2020 to identify and collect experience reports.
The Shroomery is an online community focused on psilocybin mushroom use, but contains information posted by users for a wide range of psychedelic substances. Experience report entries were accessed using a custom programming script written in the python coding language and using the Python Reddit API Wrapper.
Experience reports were collected from reddit that contained a mood stabilizer search term and a psychedelic search term. The experience reports were then manually coded for presence of direct first-person or witnessed second-person reports of the experience encountered when a psychedelic was consumed by an individual who was also taking a mood stabilizer.
Experience reports involving lithium and lamotrigine taken with psychedelics were removed, and three Reddit posts with duplicate content were identified and removed. Microdoses of psychedelics and lithium were not included. Effects were coded based on the author’s description of the effect of the concomitant mood-stabilizing medication on the psychedelic drug effect. Seizures, decreased psychedelic effect, no psychedelic effect, intensified psychedelic effects, and bad trips were all coded as “bad trips”.
We searched for reports involving lithium and lamotrigine on Erowid and the Shroomery, and on Reddit. 96 reports involving lithium and lamotrigine were analyzed, and 4 reports involved lithium and lamotrigine and a concurrent psychedelic. Lithium reports were found on Erowid, The Shroomery, and Reddit. Of these, 16 were with LSD, 1 with psilocybin mushrooms, and 1 with DMT. Of 62 reports involving lithium plus a psychedelic, 29 were seizures, 11 were bad trips, 12 were intensified, and 8 were described as neutral. Of the 55 reports involving lithium plus LSD, 27 were seizures, 2 were psilocybin seizures, and 1 was DMT seizures.
There were 34 reports of lamotrigine combined with a psychedelic across the three sites. In 22 of 34 reports, the drug was not reported to have impacted the psychedelic experience one way or another, and in 6 of 34 reports the psychedelic effect was decreased.
Lithium Plus Lamictal Reports
There is little data about the concurrent use of psychedelic substances with commonly prescribed psychiatric medications, but it is likely that patients will try them.
In this study, 47% of reports of use of a classic psychedelic by individuals using lithium involved seizures. In addition, more lithium reports were categorized as bad trips than lamotrigine reports, and more lithium reports were categorized as bad trips than lamotrigine reports if seizures were excluded. Lithium can cause unpredictable reactions to dosing, such as wandering around Ridgewood, Queens all night with no shoes on in full ego death. I took lsd while on lithium and experienced the worst, most horrific trip of my life. I was unable to speak for several hours after I stopped hallucinating. I had always taken LSD on weekends for about 2 years and never had any problems, but after a while I started to get depressed so my Psychiatrist put me onto lithium. One night I took only one acid and went into another world where I couldn’t see anything around me.
The online reports used here are low quality evidence due to lack of standardization, selection bias, and lack of clinical verification. The risk of potentially lethal reactions suggests that a causal relationship exists.
We advise individuals taking lithium to avoid taking classic psychedelic drugs. It is unknown whether psychedelic microdoses might pose a lower risk of adverse events, but the benignity of experience reports with lamotrigine might aid future decision-making for clinical trials. There are several possible explanations for seizures in individuals who take psychedelics while using lithium, including a unique propensity for seizures, increased systemic concentrations of one or both drugs, or a metabolic interaction affecting systemic concentrations of either drug.
The metabolic pathways of LSD and psilocybin overlap, and lithium is principally renally excreted without undergoing any hepatic alteration. It is also possible that concomitant use of lithium and psychedelics results in a synergistic effect on neurotransmission or second messenger effects that increases likelihood of seizures. Psychedelics increase cortical excitability by 5-HT2A agonism, and reduce tonic activity of the locus coeruleus, which may be a potential mechanism by which psychedelics reduce seizure threshold.
Lithium has complex effects in the brain, including effects on serotonin neurotransmission. One study found that lithium pre-treated rats showed increased levels of neuronal c-Fos, a marker of cell firing, when given a classic psychedelic.
Conclusion
Almost half of online psychedelic experience reports involving lithium and a classic psychedelic involved seizures and 18% involved otherwise negative experiences. Lamotrigine was not judged to have impacted the experience of the psychedelic drug in the majority of lamotrigine plus psychedelic experiences.
Psilocybin-assisted therapy for major depressive disorder: a randomized clinical trial; psilocybin with psychological support for treatment-resistant depression; psilocybin for anxiety and depression in patients with life-threatening cancer; psilocybin for tobacco addiction; and psilocybin for alcohol dependence.
Bipolar disorder is a mental illness that can be treated with medication. There are several medications that can be used to treat bipolar disorder, including lithium, but there are also many other medications that can be used to treat bipolar disorder.
Antidepressants may increase the risk of mania and bipolar disorder in people with depression, according to a retrospective electronic case register cohort study. Additional studies have also suggested that ECT may induce mania in patients with bipolar disorder.
A review of the literature describing the quality of evidence for hallucinogens and their use in research. The review also covers the use of R, rvest, RSelenium and PRAW for harvesting data from reddit.
The GRADE working group found that major depression and suicide attempt were risk factors for incident unprovoked seizures in older adults, and that lithium and modified electroconvulsive therapy may interact.
Aghajanian GK, Marek GJ, Rasmussen K, Glennon RA, Aghajanian GK. Locus coeruleus neurons are activated by peripheral stimuli and phenethylamine hallucinogens enhance activity of noradrenergic locus coeruleus neurons.
In the locus coeruleus of the rat, serotonin receptors are downregulated by long-term lithium treatment, and the immediate-early gene c-fos is expressed in the brain during limbic seizures.
Study details
Participants
96