Meta Information
ID:cannabis
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/cns-depressants
Target name:
CNS Depressants (Alcohol, Opioids, Benzodiazepines)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Cannabis has CNS depressant effects that are additive with other depressants, leading to excessive drowsiness, dizziness, and severely impaired motor coordination and judgment.
Actionable advice:
Cannabis should not be combined with alcohol, opioids, benzodiazepines, or other sedating medications.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Pharmacokinetic interactions with anticonvulsant medications have also been reported, as have pharmacodynamic interactions between cannabinoids and medications with sympathomimetic effects (e.g., tachycardia, hypertension), central nervous system depressants (e.g., drowsiness, ataxia), and anticholinergics (e.g., tachycardia and somnolence).
Label source:
PubMed: Drug-Cannabinoid Interactions in Selected Therapeutics for Symptoms Associated with Epilepsy, Autism Spectrum Disorder, Cancer, Multiple Sclerosis, and Pain. (PMID 38794183)
Action type:
avoid
Target id:
/intervention/warfarin
Target name:
Warfarin
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Cannabis, particularly CBD, strongly inhibits the CYP2C9 enzyme responsible for metabolizing warfarin, which can lead to dangerously high warfarin levels and an increased risk of severe bleeding.
Actionable advice:
Cannabis should not be used with warfarin; if use is unavoidable, frequent and vigilant blood monitoring (INR) is essential.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The in vitro study indicated that THC inhibits the CYP2C9-mediated metabolism of warfarin.
Label source:
PubMed: Interaction between warfarin and cannabis. (PMID 30326170)
Action type:
avoid
Target id:
/class/immunosuppressants
Target name:
Calcineurin Inhibitors (Tacrolimus, Cyclosporine)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Cannabis, especially CBD, inhibits the CYP3A4 enzyme, which can dangerously increase blood levels of narrow-therapeutic-index drugs like tacrolimus, raising the risk of toxicity.
Actionable advice:
Concurrent use should be avoided unless under the direct supervision of a specialist with therapeutic drug monitoring.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Tacrolimus, a widely used drug in transplant patients, is metabolized by CYP3A4 and CYP3A5. Cannabidiol (CBD) use after transplant is common. Clinical cases suggest CBD may alter tacrolimus exposure, but the mechanism of this interaction is unknown. We hypothesize that cannabidiol will inhibit tacrolimus metabolism in vitro mainly through CYP3A5 inhibition.
Label source:
PubMed: Clinical and translational science (2025)
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:
Cannabis use during pregnancy is associated with significant risks to the fetus, including low birth weight and potential for long-term adverse neurodevelopmental outcomes.
Actionable advice:
Cannabis should be avoided completely during pregnancy.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
Smoking cannabis during pregnancy is linked to lower birth weight in the offspring.
Label source:
Anecdotal: NCBI
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:
Cannabinoids are excreted into breast milk and can be consumed by the infant, with unknown but potentially harmful effects on brain development.
Actionable advice:
Cannabis should be avoided completely while breastfeeding.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
In general, professional guidelines recommend that cannabis use should be avoided by nursing mothers, and nursing mothers should be informed of possible adverse effects on infant development from exposure to cannabis compounds in breastmilk.
Label source:
Anecdotal: LactMed (NCBI)
Action type:
avoid
Target id:
/condition/psychosis-history
Target name:
History of Psychosis or Schizophrenia
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
THC can induce psychosis in vulnerable individuals and worsen symptoms in those with a pre-existing psychotic disorder like schizophrenia.
Actionable advice:
All THC-containing cannabis products should be avoided with a personal or strong family history of psychosis.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
If you already have schizophrenia and use the drug, your symptoms may get worse.
Label source:
Anecdotal: WebMD
Action type:
avoid
Target id:
/class/antipsychotics
Target name:
Antipsychotic Medications
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The psychoactive properties of THC can directly counteract the therapeutic effects of antipsychotic medications and may exacerbate the underlying symptoms of psychosis.
Actionable advice:
THC-containing cannabis should not be used when taking antipsychotic medication.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
By binding to the same receptors, THC is psychoactive, while CBD has anxiolytic and antipsychotic properties.
Label source:
PubMed: THC and CBD: Villain versus Hero? Insights into Adolescent Exposure. (PMID 36982327)
Action type:
avoid
Target id:
/condition/cardiovascular-disease
Target name:
Unstable Cardiovascular Disease
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Cannabis can cause temporary increases in heart rate and fluctuations in blood pressure, which may pose a significant risk to individuals with unstable angina, severe arrhythmias, or a recent heart attack.
Actionable advice:
Cannabis should be avoided with unstable cardiovascular disease; it is important to consult a cardiologist if considering use.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Marijuana and delta9-tetrahydrocannabinol (THC) increase heart rate, slightly increase supine blood pressure, and on occasion produce marked orthostatic hypotension.
Label source:
PubMed: Journal of clinical pharmacology (2002)
Source url:
Exact phrase from label:
S-THC and V-THC increased heart rate (S-THC: ∆17±15 bpm, V-THC: ∆16±16 bpm;both P<0.0001) and mean arterial pressure (S-THC: ∆7±6 mm Hg, V-THC: ∆5±5 mm Hg;both P<0.0001) whereas V-CBD did not (∆1±4 bpm, ∆3±4 mm Hg;both P>0.05).
Label source:
PubMed: Journal of the American Heart Association (2024)
Source url:
Exact phrase from label:
Marijuana smoking by people with cardiovascular disease poses health risks because of the consequences of the resulting increased cardiac work, increased catecholamine levels, carboxyhemoglobin, and postural hypotension.
Label source:
PubMed: Journal of clinical pharmacology (2002)
Action type:
avoid
Target id:
/condition/hepatic-impairment
Target name:
Hepatic Impairment
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Since cannabis is extensively metabolized by the liver, severe liver disease impairs its clearance, leading to much higher blood concentrations and a prolonged duration of effects.
Actionable advice:
This should be used only with extreme caution under medical supervision, starting with very low doses.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Due to decreased liver function, the plasma exposure of CBD increased 2.57-5.15 times compared to healthy adults, and the half-life and clearance showed a 2.58-fold increase and a 5.15-fold decrease, respectively.
Label source:
PubMed: Quantitative summary on the human pharmacokinetic properties of cannabidiol to accelerate scientific clinical application of cannabis. (PMID 38850302)
Action type:
informational_none
Target id:
/class/cyp3a4-strong-inhibitors
Target name:
Strong CYP3A4 Inhibitors
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) block the primary metabolic pathway for THC and CBD, leading to significantly higher blood concentrations and increased risk of toxicity.
Actionable advice:
Concurrent use should be avoided, or cannabis should be used only under strict medical supervision with significant dose reduction.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Ketoconazole co-administration with THC/CBD spray had the opposite effect, increasing the Cmax of the respective analytes from 2.65 to 3.36 ng/mL (+27%), 0.66 to 1.25 ng/mL (+89%) and 3.59 to 10.92 ng/mL (+204%).
Label source:
PubMed: SpringerPlus (2013)
Source url:
Exact phrase from label:
Conversely, conventional drugs with strong inhibitory or inductive effects on CYP3A4 are expected to affect CBD disposition.
Label source:
PubMed: Journal of clinical psychopharmacology (2019)
Action type:
avoid
Target id:
/intervention/clobazam
Target name:
Clobazam
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
CBD inhibits the enzyme that metabolizes clobazam's active metabolite, leading to a significant increase in its levels and associated sedation, which requires careful dose management.
Actionable advice:
Dose reduction of clobazam is often required when co-administered with CBD under medical supervision.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Cannabidiol has well-described inhibitory action on cytochrome P450 (CYP450) drug-metabolizing enzymes and significant drug-drug interactions (DDIs) between CBD and various anticonvulsant medications (eg, clobazam) have been described in the treatment of epilepsy.
Label source:
PubMed: Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young People. (PMID 34121064)
Action type:
adjust_with_prescriber
Target id:
/class/cyp3a4-moderate-inhibitors
Target name:
Moderate CYP3A4 Inhibitors
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Moderate CYP3A4 inhibitors (e.g., fluconazole, diltiazem) slow the metabolism of THC and CBD, increasing their levels and potential for adverse effects like dizziness and cognitive impairment.
Actionable advice:
This is best used with caution, and a lower cannabis dose may be worth considering, with monitoring for increased side effects.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
For example, the combination of cannabis-derived compounds and the antifungal drug ketoconazole, a CYP3A4 inhibitor, increases the plasma concentration of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In contrast, rifampicin, a CYP3A4 inducer, stands out for reducing plasma THC levels by approximately 20-40% and 50% to 60% for CBD.
Label source:
PubMed: Pharmaceuticals (Basel, Switzerland) (2024)
Source url:
Exact phrase from label:
The plasma concentrations of THC and its active metabolite 11-OH-THC can be increased by strong CYP3A4 inhibitors (verapamil, clarithromycin) and decreased by strong CYP3A4 inductors (rifampicin, carbamazepine).
Label source:
PubMed: Deutsches Arzteblatt international (2023)
Source url:
Exact phrase from label:
a pharmacokinetic interaction study using ketoconazole with oromucosal cannabis extract further supports CYP3A4 as a significant metabolic pathway for THC and CBD.
Label source:
PubMed: Drug metabolism reviews (2014)
Action type:
monitor
Target id:
/class/cyp2c9-inhibitors
Target name:
CYP2C9 Inhibitors
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
These drugs (e.g., amiodarone, fluconazole) inhibit the CYP2C9 enzyme, a key pathway for THC metabolism, which can lead to elevated THC levels and increased psychoactive effects.
Actionable advice:
This is best used with caution, especially with THC-dominant products, and dose reduction may be worth considering.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The effect of microsomal incubation pH on in vitro enzyme kinetic parameters for CYP2C9 (diclofenac, (S)-warfarin) and CYP3A4 (midazolam, dextromethorphan, testosterone) substrates, enzyme specific reversible inhibitors (amiodarone, desethylamiodarone, clozapine, nicardipine, fluconazole, fluvoxamine, itraconazole) and a mechanism-based inhibitor (amiodarone) was investigated.
Label source:
PubMed: The Impact of the Hepatocyte-to-Plasma pH Gradient on the Prediction of Hepatic Clearance and Drug-Drug Interactions for CYP2C9 and CYP3A4 Substrates. (PMID 28679672)
Action type:
adjust_with_prescriber
Target id:
/class/broad-spectrum-inducers
Target name:
Broad-Spectrum Metabolic Enzyme Inducers
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
These agents (e.g., rifampin, carbamazepine) speed up the metabolic breakdown of THC and CBD by inducing CYP enzymes, potentially reducing the therapeutic effects of cannabis.
Actionable advice:
It is worth being aware that the effects of cannabis may be significantly reduced; dose adjustments may be necessary.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
As both THC and CBD are hepatically metabolized, the potential exists for pharmacokinetic drug interactions via inhibition or induction of enzymes or transporters.
Label source:
PubMed PMID 30001569
Action type:
adjust_with_prescriber
Target id:
/intervention/saint-johns-wort
Target name:
Saint John's Wort
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
St. John's Wort induces CYP3A4, accelerating the metabolism of THC and CBD and potentially decreasing their effectiveness.
Actionable advice:
Using these together is best avoided if consistent cannabis effects are desired.
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:
Action type:
avoid
Target id:
/class/antihypertensives
Target name:
Antihypertensive Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Cannabis can cause a drop in blood pressure upon standing (orthostatic hypotension), which can be enhanced by antihypertensive medications, increasing the risk of dizziness and falls.
Actionable advice:
This is best used with caution, rising slowly from sitting or lying positions, with blood pressure monitoring.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Acute cannabis consumption has been shown to cause an increase in blood pressure, specifically systolic blood pressure (SBP), and orthostatic hypotension.
Label source:
PubMed: Role of cannabis in cardiovascular disorders. (PMID 28840009)
Action type:
monitor
Target id:
/class/antidiabetic-medications
Target name:
Diabetes Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Cannabis can alter blood glucose levels and appetite ('the munchies'), potentially complicating glycemic control for individuals on diabetes medications.
Actionable advice:
Blood glucose levels are best monitored closely when initiating or changing cannabis use.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Intervention: When such drugs are administered to a patient receiving metformin hydrochloride, observe the patient closely for loss of blood glucose control.
Label source:
Action type:
monitor
Target id:
/class/cyp3a4-substrates
Target name:
CYP3A4 Substrates
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Cannabis can inhibit CYP3A4, potentially increasing concentrations of many common medications like certain statins (atorvastatin, simvastatin), calcium channel blockers, and sildenafil.
Actionable advice:
It is worth watching out for increased side effects of drugs metabolized by CYP3A4 when using cannabis.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The extracts with a single major cannabinoid (CBD or CBG) inhibited CYP2C9- and CYP3A4-mediated metabolism stronger than the extracts containing both major cannabinoids (THC and CBD).
Label source:
PubMed: Phytochemical Comparison of Medicinal Cannabis Extracts and Study of Their CYP-Mediated Interactions with Coumarinic Oral Anticoagulants. (PMID 36814687)
Action type:
monitor
Target id:
/class/cyp2c9-substrates
Target name:
Drugs Metabolized by CYP2C9
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Cannabis (especially CBD) inhibits the CYP2C9 enzyme, which can increase the levels of other drugs metabolized by this pathway, such as some NSAIDs (celecoxib) and antidiabetic agents (glipizide).
Actionable advice:
This is best used with caution, and it is a good idea to monitor for increased side effects of the co-administered drug.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Delta-9-tetrahydrocannabinol (THC), the main psychoactive cannabinoid in cannabis, may inhibit the cytochrome P450 enzyme CYP2C9.
Label source:
PubMed: Interaction between warfarin and cannabis. (PMID 30326170)
Action type:
monitor
Target id:
/condition/geriatric
Target name:
Geriatric (Older Adults)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Older adults are more sensitive to the psychoactive effects of cannabis and are at a higher risk for adverse events like confusion, dizziness, falls, and orthostatic hypotension.
Actionable advice:
If using, start with a very low dose and increase slowly ('start low, go slow') under medical guidance.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Adverse effects were reported by 308 participants (61.2%) and included dry mouth (36.2%), feeling high (25.9%), and adverse effects impacting balance (22.1%) and mental alertness (20.3%).
Label source:
PubMed: Drugs & aging (2025)
Source url:
Exact phrase from label:
The results indicate a higher fall risk, worse one leg standing balance performance, and slower gait speed in Users vs. Non-Users. No significant differences in cognitive function were found.
Label source:
PubMed: Brain sciences (2021)
Source url:
Exact phrase from label:
Postural hypotension, tachycardia, palpitations, and alterations in mental status occurred with such frequency as to mitigate against the routine used in the general glaucoma population.
Label source:
PubMed: Ophthalmology (1980)
Action type:
adjust_with_prescriber
Target id:
/circadian/sleep
Target name:
Going to Sleep
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
While THC may decrease the time it takes to fall asleep, chronic use suppresses REM sleep, which is crucial for memory consolidation and emotional regulation, thereby reducing overall sleep quality.
Actionable advice:
Chronic, nightly use of THC-containing cannabis for sleep is best avoided to preserve healthy sleep architecture.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Delta-9 tetrahydrocannabinol (THC) may decrease sleep latency but could impair sleep quality long-term.
Label source:
PubMed: Current psychiatry reports (2017)
Source url:
Exact phrase from label:
The CB1-R agonist disrupted these mechanisms, restructuring IS-REMS episodes; IS lengthened sixfold and intruded REMS, where ongoing theta was drastically reduced.
Label source:
PubMed: Proceedings of the National Academy of Sciences of the United States of America (2025)
Source url:
Exact phrase from label:
While early studies suggested reductions in rapid eye movement sleep, these were primarily based on small-scale trials with high tetrahydrocannabinol doses and significant methodological limitations. More recent studies using larger samples and lower therapeutic doses of tetrahydrocannabinol have reported mixed (and often no) evidence of rapid eye movement (REM) suppression, and the evidence base remains very limited.
Label source:
PubMed: Sleep medicine reviews (2025)
Action type:
avoid
Target id:
/intervention/theophylline
Target name:
Theophylline
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The combustion products in smoked cannabis induce the CYP1A2 enzyme, which accelerates the metabolism of theophylline, reducing its effectiveness. This does not apply to oral or vaporized cannabis.
Actionable advice:
If smoking cannabis, monitor for reduced theophylline efficacy; consider alternative consumption methods.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Theophylline was cleared from the blood more rapidly in both marihuana and tobacco smokers with a mean increase in total clearance from 52 ml/kg/hr in nonsmokers to 74 ml/kg/hr in subjects who smoked either material alone.
Label source:
PubMed: Clinical pharmacology and therapeutics (1978)
Source url:
Exact phrase from label:
Smoked cannabis herb (marijuana) likely induces CYP1A2 mediated theophylline metabolism, although the role of cannabinoids specifically in eliciting this effect is questionable.
Label source:
PubMed: Drug metabolism reviews (2014)
Source url:
Exact phrase from label:
Studies with theophylline have demonstrated that both tobacco and marijuana markedly alter its clearance in man.
Label source:
PubMed: Drug metabolism reviews (1979)
Action type:
monitor
Target id:
/dietary/high-fat-meal
Target name:
High-Fat Meal
Severity:
major
Interaction type:
adverse
Nature:
conditional
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Consuming oral cannabis with a high-fat meal can increase the absorption and bioavailability of THC (and CBD) by up to four- to five-fold compared with an empty stomach. Because cannabis is a psychoactive, controlled substance with abuse potential, this large and unpredictable rise in exposure can precipitate unexpectedly strong effects or over-intoxication rather than a desirable boost.
Actionable advice:
A high-fat meal should not be treated as a way to 'improve' cannabis absorption - it can multiply THC exposure four- to five-fold and cause over-intoxication. Food intake is best kept consistent relative to dosing, starting low, with particular caution when pairing oral cannabis with a high-fat meal while titrating.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
the available data suggest that the absolute bioavailability of CBD after oral dosing under fasting conditions is approximately 6%, and increases fourfold when the medication is co-administered with a high-fat meal.
Label source:
PubMed: CNS drugs (2020)
Source url:
Exact phrase from label:
CBD has complex and variable pharmacokinetics, with a prominent first-pass effect and a low oral bioavailability that increases fourfold when CBD is taken with a high-fat/high-calorie meal.
Label source:
PubMed: Drugs (2019)
Source url:
Exact phrase from label:
oral co-administration of lipids enhanced the systemic exposure of rats to THC and CBD by 2.5-fold and 3-fold, respectively, compared to lipid-free formulations.
Label source:
PubMed: American journal of translational research (2016)
Action type:
monitor
Target id:
/class/serotonergic-agents
Target name:
Serotonergic Medications (SSRIs, SNRIs, TCAs, Triptans)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
There is a theoretical risk of additive serotonergic effects when combining cannabis with SSRIs or other serotonergic drugs, though the clinical significance is generally low.
Actionable advice:
There is a theoretical risk, and watching for symptoms like agitation or confusion may help.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Cannabis and CBD inhibit cytochrome activity, alter serotonergic transmission, and modulate SSRI response.
Label source:
PubMed: Journal of personalized medicine (2021)
Source url:
Exact phrase from label:
Most of the studies demonstrated a good interaction between CBD and the 5-HT1A neuro-receptor.
Label source:
PubMed: CNS & neurological disorders drug targets (2014)
Source url:
Exact phrase from label:
THC significantly increased plasma/jejunum serotonin and indole-3-propionate, enhancing gut-brain communication through up-regulation of serotonin receptors (HTR4/HTR7) and aryl hydrocarbon receptor (Ahr) signaling via a cannabinoid receptor (CBR)-2-mediated mechanism.
Label source:
PubMed: Science advances (2025)
Action type:
monitor
Target id:
/class/cyp1a2-substrates
Target name:
CYP1A2 Substrates
Severity:
minor
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Polycyclic aromatic hydrocarbons from smoking cannabis (not vaping or edibles) can induce CYP1A2, potentially decreasing levels of drugs like caffeine and clozapine.
Actionable advice:
The effects of CYP1A2 substrate drugs may be reduced when smoking cannabis.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Current regulatory guidelines focus primarily on CYP1A2 for drug interaction studies, neglecting CYP1A1, which is highly inducible and particularly relevant in populations exposed to pollutants like polycyclic aromatic hydrocarbons, commonly found in tobacco smoke.
Label source:
PubMed: Assessing granisetron as a specific CYP1A1 substrate in primary human hepatocytes: A comprehensive evaluation for drug development studies. (PMID 40286384)
Action type:
informational_none
Target id:
/intervention/cbd
Target name:
CBD
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
CBD can modulate or reduce some of the unwanted psychoactive effects of THC, such as anxiety and paranoia, a phenomenon known as the 'entourage effect'.
Actionable advice:
Consider using products with a balanced THC:CBD ratio to mitigate potential THC-induced anxiety.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Not all the observed effects can be ascribed to THC, and the other constituents may also modulate its action; for example CBD reduces anxiety induced by THC.
Label source:
PubMed: Drugs (2000)
Source url:
Exact phrase from label:
CBD, in contrast to THC, is less potent, and may require much higher doses for its adjunctive benefits on pain, inflammation, and attenuation of THC-associated anxiety and tachycardia.
Label source:
PubMed: European journal of internal medicine (2018)
Source url:
Exact phrase from label:
CBD does not produce the typical effects associated with THC and has anxiolytic and antipsychotic effects.
Label source:
PubMed: Advances in experimental medicine and biology (2021)
Action type:
informational_none