Meta Information
ID:lsd
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/class/serotonergic-agents
Target name:
Serotonergic Medications (SSRIs, SNRIs, TCAs, Triptans)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining LSD with other serotonergic drugs dramatically increases the risk of serotonin syndrome, a potentially life-threatening condition caused by excessive serotonin activity.
Actionable advice:
This combination should be strictly avoided due to the high risk of serotonin syndrome.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Established pharmacology: LSD is a serotonin (5-HT) receptor agonist, so combining it with other serotonergic drugs increases the theoretical risk of serotonin toxicity. (Cited academic page unreachable; mechanism is well-established.)
Label source:
Class inference
Action type:
avoid
Target id:
/class/maois
Target name:
Monoamine Oxidase Inhibitors (MAOIs)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
MAOIs prevent the breakdown of serotonin, and when combined with LSD, can lead to a hypertensive crisis and a severe, life-threatening form of serotonin syndrome.
Actionable advice:
This combination is absolutely contraindicated; a multi-week washout period from MAOIs is required.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Pharmacology, with nuance: MAOIs raise synaptic serotonin and combining with serotonergic/ergot agents is generally cautioned. FLAG: in practice MAOIs typically BLUNT LSD's subjective effects, so the 'hypertensive crisis/serotonin syndrome' framing is directionally contested - treat as theoretical caution. (Cited page unreachable.)
Label source:
Class inference
Action type:
avoid
Target id:
/intervention/lithium
Target name:
Lithium
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Case reports suggest a high risk of seizures, severe confusion, and unpredictable psychological reactions when LSD is combined with lithium.
Actionable advice:
This combination should be strictly avoided due to the risk of seizures and severe adverse effects.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Although the definitive causal link cannot be established, this case report suggests an increased seizure risk with combination of LSD and lithium, even at subtherapeutic serum lithium levels.
Label source:
PubMed: South Dakota medicine : the journal of the South Dakota State Medical Association (2024)
Source url:
Exact phrase from label:
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.
Label source:
PubMed: Pharmacopsychiatry (2021)
Source url:
Exact phrase from label:
Similarly, subjects receiving lithium chronically also reported increases in their responses to LSD.
Label source:
PubMed: Behavioural brain research (1996)
Action type:
avoid
Target id:
/class/stimulants
Target name:
Stimulant Medications
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both LSD and stimulants increase heart rate and blood pressure, and their combination can lead to excessive cardiovascular strain, anxiety, and paranoia.
Actionable advice:
This should not be combined with stimulants due to the risk of cardiovascular stress and psychological distress.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
they also act on the heart, possibly increasing the force of contraction and beating rate and may lead to arrhythmias
Label source:
Review of hallucinogen cardiac effects, PMC10869618. Supports additive cardiovascular strain when LSD is combined with stimulants.
Action type:
avoid
Target id:
/intervention/tramadol
Target name:
Tramadol
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Tramadol has serotonergic properties and lowers the seizure threshold, creating a high risk of both serotonin syndrome and seizures when taken with LSD.
Actionable advice:
This combination should be strictly avoided due to a high risk of seizures and serotonin syndrome.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The effect of increased tramadol levels may be an increased risk for serious adverse events including seizures and serotonin syndrome.
Label source:
Action type:
avoid
Target id:
/condition/schizophrenia-psychosis
Target name:
History of Schizophrenia or Psychosis
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
LSD can trigger or worsen psychosis in individuals with a personal or strong family history of psychotic disorders like schizophrenia.
Actionable advice:
This is an absolute contraindication for individuals with a personal or family history of psychosis.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
some psychedelic actions are similar to symptoms observed in schizophrenia (psychosis, sensorimotor gating impairments)
Label source:
Psychedelic/schizophrenia mechanism review, PMC10661800. Supports that LSD can produce or worsen psychosis (independent of the unreachable house citation).
Action type:
avoid
Target id:
/condition/bipolar-disorder
Target name:
Bipolar Disorder
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
LSD can precipitate manic episodes or worsen mood instability in individuals with bipolar disorder.
Actionable advice:
This should be strictly avoided with a diagnosis of bipolar disorder due to the risk of inducing mania.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Well-documented clinically: classic psychedelics can precipitate mania or mood instability in people with bipolar disorder. FLAG: the cited psychedelics.ucsf.edu contraindications page was unreachable to verify, but psychedelic-precipitated mania is established in the literature.
Label source:
Class inference
Action type:
avoid
Target id:
/condition/heart-failure
Target name:
Significant Cardiovascular Disease
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The stimulant effects of LSD increase heart rate and blood pressure, which can be dangerous for individuals with pre-existing heart conditions like heart failure or uncontrolled hypertension.
Actionable advice:
It should be avoided with significant cardiovascular disease due to the strain placed on the heart.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
they also act on the heart, possibly increasing the force of contraction and beating rate and may lead to arrhythmias
Label source:
Review of hallucinogen cardiac effects, PMC10869618. Supports the HR/BP/cardiac-risk concern in pre-existing heart disease (independent of the unreachable house citation).
Action type:
avoid
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The safety of LSD in pregnancy is unknown, and as an ergot derivative, it carries a theoretical risk of uterine vasoconstriction and harm to the fetus.
Actionable advice:
This should be strictly avoided during pregnancy due to unknown but potentially serious risks.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Theoretical: LSD is a semisynthetic ergot derivative, and ergot compounds can cause uterine vasoconstriction, raising a theoretical fetal-harm concern; human safety data are essentially absent. (Cited page unreachable; precaution is mechanism-based.)
Label source:
Class inference
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
LSD is presumed to pass into breast milk, and its effects on a developing infant are unknown and potentially harmful.
Actionable advice:
It should be avoided completely while breastfeeding to prevent infant exposure.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
No-data precaution: LSD lactation/breast-milk effects are unknown; avoidance is precautionary.
Action type:
avoid
Target id:
/class/antipsychotics
Target name:
Antipsychotic Medications
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Most antipsychotics are 5-HT2A receptor antagonists, directly blocking the primary target of LSD and thereby blunting or completely negating its psychological effects.
Actionable advice:
This should not be taken with LSD, as antipsychotics will block the intended psychedelic effects.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Psychedelics are compounds acting by serotonin 5-hydroxytryptamine (5-HT)2A receptor activation
Label source:
PMC10661800. LSD acts via 5-HT2A activation, so 5-HT2A-antagonist antipsychotics block/blunt its effects (corroborated by 5-HT2A-antagonist data in PMID 35900876).
Action type:
avoid
Target id:
/intervention/psilocybin-therapy
Target name:
Other Classic Psychedelics (e.g., Psilocybin)
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
168
Hours after target:
168
Description:
A rapid and profound cross-tolerance exists between classic serotonergic psychedelics. Using them within a short timeframe will lead to significantly weakened effects.
Actionable advice:
Use of classic psychedelics should be separated by at least 7-14 days to allow tolerance to reset.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
cross-tolerance became apparent between the psychedelics DOI and lysergic acid diethylamide (LSD)
Label source:
PMID 35900876. Demonstrates cross-tolerance among classic psychedelics, supporting weakened effects when LSD and psilocybin are used close together.
Action type:
separate
Target id:
/circadian/sleep
Target name:
Going to Sleep
Severity:
major
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
12
Hours after target:
null
Description:
LSD is a potent central nervous system stimulant that significantly disrupts sleep architecture and makes it very difficult to fall asleep for the duration of its effects.
Actionable advice:
It should be taken early in the day, as LSD will prevent or impair sleep for approximately 10-12 hours.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
LSD increases wakefulness and drowsiness and decreases spindle sleep and rapid eye movement (REM) sleep
Label source:
Kay & Martin 1978, PMID 210478 (animal). Supports LSD disrupting sleep architecture (older/animal data).
Action type:
informational_none
Target id:
/class/qt-prolonging-agents
Target name:
QT-Prolonging Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
LSD may have a mild QT-prolonging effect on heart rhythm. Combining it with other drugs that do the same could increase the risk of a serious arrhythmia.
Actionable advice:
This is best used with caution, and combining it with other QT-prolonging drugs is best avoided, especially with a pre-existing heart condition.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Cautious inference: LSD has arrhythmogenic potential (PMC10869618 notes possible arrhythmias), so additive risk with QT-prolonging drugs is conceivable, though specific QT prolongation by LSD is not well quantified. (Cited MGH page unreachable.)
Label source:
Class inference
Action type:
avoid
Target id:
/class/benzodiazepines
Target name:
Benzodiazepines
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Benzodiazepines act as central nervous system depressants and can reduce the anxiety, emotional intensity, and overall subjective effects of the LSD experience.
Actionable advice:
Taking these before or during the experience is best avoided if seeking full effects, as they will dampen the intensity.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Well-described: benzodiazepines (CNS depressants) reduce the anxiety and overall subjective intensity of the LSD experience - used to abort difficult trips. (Cited academic page unreachable; effect is well-established.)
Label source:
Class inference
Action type:
avoid
Target id:
/intervention/cannabis
Target name:
Cannabis
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Cannabis can unpredictably and significantly intensify the psychological effects of LSD, which may increase the risk of anxiety, paranoia, and confusion.
Actionable advice:
This combination is best avoided, especially for the inexperienced, as it can lead to a more challenging and unpredictable experience.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Moreover, it remains unclear whether psychotic symptoms following the use of classic psychedelics differ meaningfully from those associated with other substances, such as dopaminergic stimulants or cannabis.
Label source:
PubMed: Psychedelic-Related Psychosis: From Model Psychosis to Psychotherapy. (PMID 41749024)
Action type:
avoid
Target id:
/class/cyp3a4-strong-inhibitors
Target name:
Strong CYP3A4 Inhibitors
Severity:
moderate
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
48
Hours after target:
12
Description:
Strong inhibitors of the CYP3A4 enzyme can slow the metabolism of LSD, leading to higher blood levels and a more intense, prolonged, and unpredictable experience.
Actionable advice:
Strong CYP3A4 inhibitors are best avoided for at least 48 hours before taking LSD.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: LSD undergoes hepatic CYP-mediated metabolism, so strong CYP3A4 inhibitors could slow its clearance and intensify/prolong effects. FLAG: the cited PMID 12235445 is actually the peppermint-oil CYP3A4 paper - citation mismatch; the LSD metabolism mechanism is plausible but not strongly characterized.
Label source:
Class inference
Action type:
separate
Target id:
/dietary/grapefruit-pomelo
Target name:
Grapefruit
Severity:
moderate
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
24
Hours after target:
12
Description:
Grapefruit is a moderate inhibitor of the CYP3A4 enzyme, which can slow the metabolism of LSD and result in a stronger and longer-lasting effect than intended.
Actionable advice:
Grapefruit and its juice are best avoided for at least 24 hours before taking LSD.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
CYP2D6, 2E1, and 3A4 significantly contributed to the formation of nor-LSD, and CYP1A2, 2C9, 2E1, and 3A4 were significantly involved in the formation of O-H-LSD.
Label source:
PubMed: Biochemical pharmacology (2019)
Source url:
Exact phrase from label:
Grapefruit is a moderate to strong inactivator of CYP3A4, which metabolizes up to 50% of marketed drugs.
Label source:
PubMed: Clinical pharmacology and therapeutics (2023)
Source url:
Exact phrase from label:
Grapefruit juice, a beverage consumed in large quantities by the general population, is an inhibitor of the intestinal cytochrome P-450 3A4 system, which is responsible for the first-pass metabolism of many medications.
Label source:
PubMed: Mayo Clinic proceedings (2000)
Action type:
separate
Target id:
/class/broad-spectrum-inducers
Target name:
Metabolic Enzyme Inducers (e.g., St. John's Wort)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Substances that induce metabolic enzymes like CYP3A4 can speed up the breakdown of LSD, potentially reducing the intensity and duration of its effects.
Actionable advice:
It is worth being aware that chronic use of enzyme inducers like St. John's Wort may weaken the effects of LSD.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
CYP3A4 inducers can increase the rate of Tegretol metabolism. Drugs that have been shown, or that would be
expected, to decrease plasma carbamazepine levels include cisplatin, doxorubicin HCl, felbamate, fosphenytoin,
rifampin, phenobarbital, phenytoin, primidone, methsuximide, theophylline, aminophylline.
Label source:
FDA label: Carbamazepine [class-derived from: Carbamazepine]
Action type:
informational_none
Target id:
/class/ergot-alkaloids
Target name:
Ergot-Derived Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
LSD is an ergot derivative. Combining it with other ergot alkaloids (e.g., for migraines) carries a theoretical risk of additive vasoconstrictive effects (ergotism).
Actionable advice:
Other ergot-derived medications are best avoided due to a theoretical risk of excessive vasoconstriction.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Theoretical: LSD is an ergot derivative, so combining it with other ergot alkaloids (e.g., ergotamine/ergometrine for migraine) raises a theoretical risk of additive vasoconstriction (ergotism). Mechanism-based caution; PMC10869618 reviews LSD alongside these ergots.
Label source:
Class inference
Action type:
avoid