LSD and Lithium: Why This Combination Causes Seizures

Combining LSD with lithium can cause seizures, and it is one of the few psychedelic drug interactions with enough documented harm to treat as a hard stop. Lithium is a mood stabilizer prescribed for bipolar disorder, and when people take a classic psychedelic like LSD or psilocybin while on it, the reports include not just bad trips but tonic-clonic seizures, loss of consciousness, and hospitalization. The largest analysis of these reports, published in Pharmacopsychiatry in 2021, found that roughly 47% of lithium-plus-psychedelic experiences involved a seizure (PMID 34348413). That is not a subtle interaction. If you take lithium, do not take LSD.

Quick answers

Is it dangerous to take LSD on lithium? Yes. This is one of the highest-risk psychedelic interactions documented. The combination is associated with seizures, prolonged unconsciousness, and emergency hospitalization.

Why does LSD and lithium cause seizures? Both lower the seizure threshold through overlapping effects on neuronal excitability and serotonergic signaling. Lithium alone can be pro-convulsant at higher levels, and adding a serotonergic psychedelic appears to push some people over the edge.

Does this apply to psilocybin and other psychedelics too? Yes. The same reports show seizures with lithium plus psilocybin, 2C-I, and 2C-C, not just LSD. The risk is a class effect of classic serotonergic psychedelics on lithium.

Is lamotrigine safer than lithium with psychedelics? In the same dataset, none of the 34 lamotrigine-plus-psychedelic reports involved seizures. That is not a green light, but lamotrigine did not show the same signal.

What if I want to use psychedelics and I’m on lithium for bipolar? Talk to a prescriber. Stopping lithium abruptly carries its own serious risks, including relapse and rebound mania. This is not a do-it-yourself taper.

What the evidence actually shows

The strongest data comes from a Johns Hopkins analysis of online experience reports from Erowid, Shroomery, and Reddit (PMID 34348413). Researchers found 62 reports of lithium combined with a classic psychedelic. Of those, 47% described a seizure and another 18% described a bad trip or other medical emergency. By contrast, 0 of 34 reports involving lamotrigine, a different mood stabilizer, described a seizure.

This is case-report-tier evidence (the bottom of the evidence hierarchy), and it has real limitations: self-reported online accounts, no toxicology confirmation, no way to verify doses or what else was taken. But the signal is unusually strong and consistent, and it is biologically plausible. When the relative risk in a dataset jumps from zero to nearly half depending on which mood stabilizer is involved, that pattern is hard to dismiss.

A separate population-based survey of 613 lifetime psychedelic users adds context (PMID 35981469). Among people who reported a psychedelic-related seizure, nearly half were taking antidepressants, mood stabilizers, or opioid replacement medication at the time. Seizures were also more common in people with a personal or family history of epilepsy. A 2024 case report documented new-onset seizures in an adolescent who took LSD while on a low dose of lithium (PMID 38986146), which shows the interaction does not require a high lithium level to be dangerous.

Why the combination lowers the seizure threshold

A seizure happens when neurons fire in a synchronized, uncontrolled burst. Anything that increases neuronal excitability, or reduces the brain’s ability to dampen runaway firing, lowers the threshold at which this happens. LSD and lithium each nudge the brain in that direction, and together they appear to stack.

Lithium has a narrow therapeutic window, and at the upper end it is known to be pro-convulsant. It alters intracellular signaling (including inositol and GSK-3 pathways) and increases neuronal excitability in ways that can predispose to seizures even within the normal dosing range in susceptible people.

LSD is a serotonin 5-HT2A receptor agonist. Strong 5-HT2A activation increases cortical glutamate release and boosts excitatory signaling across the cortex. On its own, LSD rarely causes seizures in healthy people. But layered onto lithium’s pro-convulsant baseline, the added excitatory drive appears to be enough to trigger generalized seizures in a meaningful fraction of users. The mechanism is not fully mapped, and the exact interaction is still labeled provisional in the literature, but the convergence of two pro-excitatory effects on the same circuitry is the leading explanation.

This is why the risk is not limited to LSD. Psilocybin, mescaline, and the 2C-x compounds are also 5-HT2A agonists, and the reports show seizures across that whole class when combined with lithium.

What to do if you take lithium

The safe answer is simple: do not combine lithium with LSD or any classic psychedelic. The interaction is not dose-dependent in a way you can manage, and a seizure in an unmonitored setting (a festival, a friend’s apartment) carries risks of injury, aspiration, and status epilepticus.

If you are on lithium and want to explore psychedelics:

• Do not stop lithium on your own to make room for a trip. Abrupt lithium discontinuation is linked to rapid relapse and rebound mania in bipolar disorder. Any change has to be managed by a prescriber over time.
• Be honest with a clinician. They cannot help you reduce risk if they do not know what you are considering.
• Know that bipolar disorder itself is an exclusion criterion in most psychedelic clinical trials, partly because of mania risk and partly because of this seizure signal. The research community treats this population as high-risk for good reason.

If you witness a seizure after someone has combined these:

• Clear the area of hard or sharp objects and cushion their head.
• Do not put anything in their mouth and do not restrain them.
• Time the seizure. Call emergency services if it lasts longer than 5 minutes, if a second seizure follows, or if the person does not regain consciousness.
• Roll them onto their side (recovery position) once the convulsing stops, to protect the airway.
• Tell paramedics exactly what was taken, including the lithium. This changes how they treat it.

The bottom line

LSD and lithium is a documented, mechanistically plausible, high-risk interaction. Roughly half of reported combinations involved a seizure, and the effect extends to psilocybin and other serotonergic psychedelics. This is not a “be careful” interaction; it is an “avoid entirely” one. If you take lithium, the psychedelic is the thing to skip, and any change to your lithium has to go through a prescriber.

For more on how psychedelics interact with other substances, use our interaction checker. For a full breakdown of LSD’s effects, dosing, and risks, see our LSD harm reduction guide, and if you do use psychedelics, our guide to psilocybin safety and our walkthrough on how to stop a bad trip cover what to do when an experience goes sideways.

If you want to confirm that what you have is actually LSD and not a substituted research chemical, DanceSafe sells LSD reagent test kits.

Sources: PMID 34348413 | PMID 35981469 | PMID 38986146