Fluoxetine
For an informed discussion with your doctor or pharmacist. This information collection is not a clinically validated interaction checker. Missing data do not establish safety. Do not change or stop prescribed medicines on the basis of this information. The findings apply to the specific conditions studied; laboratory and animal studies cannot be directly extrapolated to humans.
Active substance: Fluoxetine
Examples of brand names: Fluctin [DE]
ATC code: N06AB03
Main use (for orientation): Depression; obsessive–compulsive disorder
Documented research summary
CBD only slightly impairs fluoxetine metabolism in vitro. A suspected CBD–fluoxetine case is accessible through a secondary source, with the original not fully accessible; genotype causality unproven. Animal pharmacodynamic effects depend on timing/model and are partly negative. Reversible cerebral vasoconstriction syndrome with cannabis plus fluoxetine is a confounded single case.
Uncertainties and limitations
Oral single-ingredient fluoxetine hydrochloride capsules, not an olanzapine combination.
Shared enzymes must not be equated with clinical evidence of an interaction; CBD/THC findings cannot be extrapolated to other cannabinoids.
Original 35652796 inaccessible; symptoms through secondary source 39719830; no double counting of the case. Shifted reference numbers and the review's blanket CYP2D6 statement not adopted.
1647392 remains a research gap without an abstract.
Separately recorded findings
9 separately recorded findings. Each statement applies to its documented study context.
CBD – laboratory and animal studies
Finding ID: B0302
Type of result: Direct in-vitro pair assessment
Observation: Weak inhibition of CYP2D6-mediated fluoxetine metabolism (Ki >10 µM) in the recombinant enzyme experiment, versus CYP2C9 inhibition with Ki 2.6 µM. Not a human fluoxetine interaction experiment.
Mechanism: Direct in-vitro assessment of antidepressant metabolism
Study type: In-vitro metabolism experiment
Context studied: Human pharmacokinetics in the same paper concern citalopram/escitalopram, not fluoxetine.
Clinical interpretation: Negative/small laboratory finding
Limitations and uncertainties: Do not read as a human fluoxetine safety study; do not extrapolate the citalopram increase to fluoxetine.
Original sources for this finding: Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young People [CL10]
CBD – clinical signals
Finding ID: B0303
Type of result: Suspected clinical signal; original report content assessed only through a secondary source
Observation: Secondary case analysis describes insomnia, agitation, hyperactivity and worsening OCD.
Mechanism: Suspected drug–gene–drug interaction; mechanism unresolved
Study type: One 17-year-old patient; original 2022, analysis 2025
Context studied: CBD oil added to fluoxetine; DIPS score 5 in secondary assessment, improvement after discontinuation reported.
Clinical interpretation: Clinical signal; original access limited
Limitations and uncertainties: Original bibliographically verified only. No established concentration measurement or CYP2D6*4 causality claim; prior condition is an alternative explanation; case not counted twice.
Original sources for this finding: A Potential Drug-Gene-Drug Interaction Between Cannabidiol, CYP2D6*4, and Fluoxetine: A Case Report. [BMED35652796]; Part 1: Evaluation of Pediatric Cannabis-Drug Interaction Reports. [BMED39719830]
CBD – laboratory and animal studies
Finding ID: B0304
Type of result: Preclinical sequential exposure; not a simultaneous pair interaction
Observation: Subsequent fluoxetine effect in the forced-swim test reduced.
Mechanism: Long-term developmental modulation after perinatal exposure
Study type: Mice after perinatal exposure
Context studied: Maternal exposure to 3 mg/kg of each cannabinoid; offspring later tested with fluoxetine.
Clinical interpretation: Not a simultaneous drug interaction
Limitations and uncertainties: Not a human-pregnancy prediction or proof of treatment resistance; same paper in both rows.
Original sources for this finding: Perinatal CBD or THC Exposure Results in Lasting Resistance to Fluoxetine in the Forced Swim Test: Reversal by Fatty Acid Amide Hydrolase Inhibition. [BMED34182795]
THC – laboratory and animal studies
Finding ID: B0305
Type of result: Preclinical sequential exposure; not a simultaneous pair interaction
Observation: Subsequent fluoxetine effect in the forced-swim test reduced.
Mechanism: Long-term developmental modulation after perinatal exposure
Study type: Mice after perinatal exposure
Context studied: Maternal exposure to 3 mg/kg of each cannabinoid; offspring later tested with fluoxetine.
Clinical interpretation: Not a simultaneous drug interaction
Limitations and uncertainties: Not a human-pregnancy prediction or proof of treatment resistance; same paper in both rows.
Original sources for this finding: Perinatal CBD or THC Exposure Results in Lasting Resistance to Fluoxetine in the Forced Swim Test: Reversal by Fatty Acid Amide Hydrolase Inhibition. [BMED34182795]
CBD – laboratory and animal studies
Finding ID: B0306
Type of result: Direct preclinical investigation of the pair
Observation: Individually subeffective doses were effective in combination in forced-swim and marble-burying tests.
Mechanism: Additive/synergistic behavioural effect
Study type: Mouse behavioural models
Context studied: CBD plus fluoxetine, serotonergic mechanisms; no general locomotor change.
Clinical interpretation: No clinical antidepressant enhancement proven
Limitations and uncertainties: Behavioural surrogates, not human pharmacokinetics or safety assessment.
Original sources for this finding: Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels. [BMED29885468]; Cannabidiol reverses the mCPP-induced increase in marble-burying behavior. [BMED24118015]
THC – laboratory and animal studies
Finding ID: B0307
Type of result: Direct preclinical pair assessment with protocol-dependent effects
Observation: Fluoxetine before THC reduced selected effects, while later administration could enhance them; other anxiety tests negative.
Mechanism: Time-dependent serotonergic modulation
Study type: Rat microdialysis/temperature/behaviour
Context studied: Striatal dopamine release and hypothermia depended on timing/route; co-administration in a 2010 behavioural study did not change anxiety/panic parameters.
Clinical interpretation: No uniform clinical direction
Limitations and uncertainties: Local perfusion and systemic administration are not equivalent; abstract 9723953 contains one delta4 typo, while title and remaining protocol say Delta9. No quantification of human risk.
Original sources for this finding: Modulation by fluoxetine of striatal dopamine release following Delta9-tetrahydrocannabinol: a microdialysis study in conscious rats. [BMED10498830]; Modulation of delta9-tetrahydrocannabinol-induced hypothermia by fluoxetine in the rat. [BMED9723953]; Behavioural effects of co-administration of delta9-tetrahydrocannabinol with fluoxetine in rats. [BMED20689343]
THC – laboratory and animal studies
Finding ID: B0308
Type of result: Specialised preclinical models
Observation: Withdrawal-like movements or enhanced aggression in specialised models.
Mechanism: Serotonergic modulation during chronic exposure/sleep deprivation
Study type: Historical rat experiments
Context studied: Chronic THC, fluoxetine 15 mg/kg in a withdrawal model; separate REM sleep-deprivation model.
Clinical interpretation: Endpoint-specific laboratory signal
Limitations and uncertainties: Not a general prediction of aggression or serotonin syndrome in humans.
Original sources for this finding: Withdrawal-like behaviour induced by inhibitors of biogenic amine reuptake in rats treated chronically with delta 9-tetrahydrocannabinol. [BMED6248916]; Effect of serotonergic drugs on the aggressiveness induced by delta 9-tetrahydrocannabinol in rem-sleep-deprived rats. [BMED6303479]
Cannabis, non-standardised composition – clinical signals
Finding ID: B0309
Type of result: Suspected clinical signal; isolated causality unresolved
Observation: Reversible cerebral vasoconstriction reported with fluoxetine and heavy cannabis use.
Mechanism: Multiple possible triggers of reversible cerebral vasoconstriction syndrome
Study type: One patient report
Context studied: Both substances discontinued; clinical/angiographic resolution.
Clinical interpretation: Warning signal without isolated pair causality
Limitations and uncertainties: No pharmacokinetic measurement; individual substances can themselves trigger the condition; no cannabis–fluoxetine mechanism proven.
Original sources for this finding: External carotid artery branches involvement in reversible cerebral vasoconstriction syndrome. [BMED22000400]
Cannabis, composition not standardised – clinically investigated
Finding ID: B0310
Type of result: Treatment context; no direct evidence of a drug–drug interaction
Observation: Inconsistent use outcomes in different patient groups.
Mechanism: Cannabis use disorder treatment context
Study type: Adolescent major-depression/cannabis-use-disorder RCT and small alcohol/depression subgroup analysis
Context studied: No fluoxetine advantage over placebo plus cognitive behavioural/motivational enhancement therapy in the adolescent study; less cannabis use in an older 22-person subgroup.
Clinical interpretation: No isolated pair interaction
Limitations and uncertainties: Different populations/endpoints, no standardised cannabinoid dose or pharmacokinetics.
Original sources for this finding: Double-blind fluoxetine trial in comorbid MDD-CUD youth and young adults. [BMED20576364]; Fluoxetine versus placebo for the marijuana use of depressed alcoholics. [BMED10189977]
References and access status
[V2_LABEL_D0093] FLUOXETINE (FLUOXETINE HYDROCHLORIDE) CAPSULE [CARDINAL HEALTH 107, LLC]
Original source / bibliographic reference
Authors: Cardinal Health 107, LLC
Year: 2026
Source type: Official US SPL / DailyMed
Source access – 23 October 2026: Source destination was accessible when checked.
Bibliographic attribution or source identity cross-checked.
[BMED34182795] Perinatal CBD or THC Exposure Results in Lasting Resistance to Fluoxetine in the Forced Swim Test: Reversal by Fatty Acid Amide Hydrolase Inhibition.
Original source / bibliographic reference
Authors: Maciel IS, Abreu GHD, Johnson CT, Bonday R, Bradshaw HB, Mackie K, Lu HC.
Year: 2022
Source type: Publication; title and abstract reviewed
DOI: 10.1089/can.2021.0015
PMID: 34182795
Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.
Bibliographic attribution or source identity cross-checked.
PubMed – bibliographic reference / abstract
PubMed Central – archived text
DOI – publisher access (access restrictions may apply)
[CL10] Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young People
Original source / bibliographic reference
Authors: Anderson LL; Doohan PT; Oldfield L; Kevin RC; Arnold JC; Berger M; Amminger GP; McGregor IS
Year: 2021
Source type: In-vitro study plus a small accompanying clinical investigation
DOI: 10.1097/JCP.0000000000001427
PMID: 34121064
Source access – 23 October 2026: Direct retrieval could not be fully verified; availability remains unresolved.
Bibliographic attribution or source identity cross-checked.
DOI – publisher access (access restrictions may apply)
[BMED39719830] Part 1: Evaluation of Pediatric Cannabis-Drug Interaction Reports.
Original source / bibliographic reference
Authors: Chapin MR, Kane-Gill SL, Li X, Abanyie K, Taneja SB, Egbert S, Paine MF, Boyce RD.
Year: 2025
Source type: Secondary case review and FAERS analysis
DOI: 10.1002/prp2.70046
PMID: 39719830
Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.
Bibliographic attribution or source identity cross-checked.
PubMed – bibliographic reference / abstract
PubMed Central – archived text
DOI – publisher access (access restrictions may apply)
[BMED29885468] Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels.
Original source / bibliographic reference
Authors: Sales AJ, Crestani CC, Guimarães FS, Joca SRL.
Year: 2018
Source type: Publication; title and abstract reviewed
DOI: 10.1016/j.pnpbp.2018.06.002
PMID: 29885468
Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.
Bibliographic attribution or source identity cross-checked.
PubMed – bibliographic reference / abstract
DOI – publisher access (access restrictions may apply)
[BMED24118015] Cannabidiol reverses the mCPP-induced increase in marble-burying behavior.
Original source / bibliographic reference
Authors: Nardo M, Casarotto PC, Gomes FV, Guimarães FS.
Year: 2014
Source type: Publication; title and abstract reviewed
DOI: 10.1111/fcp.12051
PMID: 24118015
Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.
Bibliographic attribution or source identity cross-checked.
PubMed – bibliographic reference / abstract
DOI – publisher access (access restrictions may apply)
[BMED20576364] Double-blind fluoxetine trial in comorbid MDD-CUD youth and young adults.
Original source / bibliographic reference
Authors: Cornelius JR, Bukstein OG, Douaihy AB, Clark DB, Chung TA, Daley DC, Wood DS, Brown SJ.
Year: 2010
Source type: Publication; title and abstract reviewed
DOI: 10.1016/j.drugalcdep.2010.05.010
PMID: 20576364
Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.
Bibliographic attribution or source identity cross-checked.
PubMed – bibliographic reference / abstract
PubMed Central – archived text
DOI – publisher access (access restrictions may apply)
[BMED22000400] External carotid artery branches involvement in reversible cerebral vasoconstriction syndrome.
Original source / bibliographic reference
Authors: Melki E, Denier C, Théaudin-Saliou M, Sachet M, Ducreux D, Saliou G.
Year: 2012
Source type: Publication; title and abstract reviewed
DOI: 10.1016/j.jns.2011.09.033
PMID: 22000400
Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.
Bibliographic attribution or source identity cross-checked.
PubMed – bibliographic reference / abstract
DOI – publisher access (access restrictions may apply)
[BMED10498830] Modulation by fluoxetine of striatal dopamine release following Delta9-tetrahydrocannabinol: a microdialysis study in conscious rats.
Original source / bibliographic reference
Authors: Malone DT, Taylor DA.
Year: 1999
Source type: Publication; title and abstract reviewed
DOI: 10.1038/sj.bjp.0702753
PMID: 10498830
Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.
Bibliographic attribution or source identity cross-checked.
PubMed – bibliographic reference / abstract
PubMed Central – archived text
DOI – publisher access (access restrictions may apply)
[BMED9723953] Modulation of delta9-tetrahydrocannabinol-induced hypothermia by fluoxetine in the rat.
Original source / bibliographic reference
Authors: Malone DT, Taylor DA.
Year: 1998
Source type: Publication; title and abstract reviewed
DOI: 10.1038/sj.bjp.0701980
PMID: 9723953
Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.
Bibliographic attribution or source identity cross-checked.
PubMed – bibliographic reference / abstract
PubMed Central – archived text
DOI – publisher access (access restrictions may apply)
[BMED20689343] Behavioural effects of co-administration of delta9-tetrahydrocannabinol with fluoxetine in rats.
Original source / bibliographic reference
Authors: Goddard M, Smith PF, Ashton JC.
Year: 2010
Source type: Publication; title and abstract reviewed
DOI: 10.1159/000317059
PMID: 20689343
Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.
Bibliographic attribution or source identity cross-checked.
PubMed – bibliographic reference / abstract
DOI – publisher access (access restrictions may apply)
[BMED6248916] Withdrawal-like behaviour induced by inhibitors of biogenic amine reuptake in rats treated chronically with delta 9-tetrahydrocannabinol.
Original source / bibliographic reference
Authors: Verberne AJ, Taylor DA, Fennessy MR.
Year: 1980
Source type: Publication; title and abstract reviewed
DOI: 10.1007/bf00428113
PMID: 6248916
Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.
Bibliographic attribution or source identity cross-checked.
PubMed – bibliographic reference / abstract
DOI – publisher access (access restrictions may apply)
[BMED6303479] Effect of serotonergic drugs on the aggressiveness induced by delta 9-tetrahydrocannabinol in rem-sleep-deprived rats.
Original source / bibliographic reference
Authors: Carlini EA, Lindsey CJ.
Year: 1982
Source type: Publication; title and abstract reviewed
PMID: 6303479
Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.
Bibliographic attribution or source identity cross-checked.
PubMed – bibliographic reference / abstract
[BMED10189977] Fluoxetine versus placebo for the marijuana use of depressed alcoholics.
Original source / bibliographic reference
Authors: Cornelius JR, Salloum IM, Haskett RF, Ehler JG, Jarrett PJ, Thase ME, Perel JM.
Year: 1999
Source type: Publication; title and abstract reviewed
DOI: 10.1016/s0306-4603(98)00050-1
PMID: 10189977
Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.
Bibliographic attribution or source identity cross-checked.
PubMed – bibliographic reference / abstract
DOI – publisher access (access restrictions may apply)
[BMED35652796] A Potential Drug-Gene-Drug Interaction Between Cannabidiol, CYP2D6*4, and Fluoxetine: A Case Report.
Original source / bibliographic reference
Authors: Anderson LL, Arnold JC, McGregor IS, Nation TR.
Year: 2022
Source type: Primary case report, bibliographically verified only
DOI: 10.1097/jcp.0000000000001568
PMID: 35652796
Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.
Bibliographic attribution or source identity cross-checked.
PubMed – bibliographic reference / abstract
DOI – publisher access (access restrictions may apply)
Research as of 23 October 2026. Not all original full texts could be reviewed in full. Source accessibility and the strength of scientific evidence must be assessed separately. An accessible link does not establish medical approval; a bibliographic record with an abstract does not replace the original full text.
Drug search and explanation of the evidence · Guide: cannabinoids and medicines · Author and responsibility
Fluoxetine and cannabinoids: documented findings, evidence, sources and data gaps. Research information for discussion with your doctor or pharmacist.