Trazodone

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: Trazodone

Examples of brand names: Trittico [CH]; Desyrel [USA]

ATC code: N06AX05

Main use (for orientation): Depression

Documented research summary

Suspected case involving THC cannabis and canine CBD co-administration, with no measured human pharmacokinetics. Nematode preprint is purely exploratory; CUD case series/as-needed medication provide context only.

Uncertainties and limitations

Oral immediate-release trazodone HCl single-ingredient tablet, not the prolonged-release formulation used in CUD case series.

Shared enzymes must not be equated with clinical evidence of an interaction; CBD/THC findings cannot be extrapolated to other cannabinoids.

Proposed CYP3A4 inhibition by trazodone was not accepted as established.

Separately recorded findings

6 separately recorded findings. Each statement applies to its documented study context.

THC-rich cannabis (19% THC, CBD <1%) – clinical signals

Finding ID: B0277

Type of result: Suspected clinical signal during multiple-drug treatment

Observation: Disorientation, memory impairment and sedation reported.

Mechanism: Suspected case, possible additive CNS effects; pharmacokinetic explanation hypothetical

Study type: Retrospective reporting series, one trazodone case

Context studied: 58-year-old man, trazodone 300 mg/day, tamsulosin/gabapentin/metamizole; cannabis for prostate symptoms.

Clinical interpretation: Warning signal during polytherapy

Limitations and uncertainties: No measured concentration change. Claimed CYP3A4 inhibition by trazodone was not accepted as verified; other CNS-active substances are confounders.

Original sources for this finding: Green rush and red warnings: Retrospective chart review of adverse events of interactions between cannabinoids and psychotropic drugs. [CA_P_39502532]

CBD – laboratory and animal studies

Finding ID: B0278

Type of result: Direct veterinary investigation of the pair

Observation: Trazodone reduced cortisol; no significant CBD combination effect on this endpoint.

Mechanism: Direct co-administration in a noise-fear model

Study type: 16 dogs, 4×4 Latin square, 2×2 factorial design

Context studied: CBD 25 mg, approximately 1.4 mg/kg/day, 7 days; trazodone 100/200 mg depending on weight; cortisol, behaviour and cardiac measures.

Clinical interpretation: Veterinary model, not evidence of a human drug–drug interaction

Limitations and uncertainties: No confirmation of CBD efficacy as an anxiolytic in this model; no human pharmacokinetics.

Original sources for this finding: The Impact of Feeding Cannabidiol (CBD) Containing Treats on Canine Response to a Noise-Induced Fear Response Test. [BMED33195551]

CBD – laboratory and animal studies

Finding ID: B0279

Type of result: Preclinical investigation of the pair; non-peer-reviewed preprint

Observation: Improved motility and lifespan reported in Aβ/Tau nematode models.

Mechanism: Combined modulation of proteotoxicity

Study type: C. elegans preprint

Context studied: CBD and trazodone combined at different treatment time points.

Clinical interpretation: Non-peer-reviewed exploratory laboratory work

Limitations and uncertainties: Not an Alzheimer's treatment in humans; no established clinical synergy or drug pharmacokinetics.

Original sources for this finding: Cannabidiol and Trazodone Ameliorate Neuronal Proteotoxicity in C. elegans [BMEDPPR583977]

Cannabis, non-standardised composition – clinical signals

Finding ID: B0280

Type of result: Treatment context; no direct evidence of a drug–drug interaction

Observation: A small open case series describes improvement and no reported substantial adverse effects.

Mechanism: CUD treatment context

Study type: Three people, prolonged-release trazodone 150/300 mg

Context studied: Cannabis use disorder during the COVID lockdown, trazodone monotherapy.

Clinical interpretation: No evidence of an isolated interaction

Limitations and uncertainties: No control group or standardised cannabinoid dose; no conclusion about the immediate-release formulation or the safety of continued co-administration.

Original sources for this finding: Trazodone Prolonged-Release Monotherapy in Cannabis Dependent Patients during Lockdown Due to COVID-19 Pandemic: A Case Series. [BMED35742646]

THC – clinically investigated

Finding ID: B0281

Type of result: Clinical as-needed medication endpoint; no isolated investigation of the pair

Observation: In the Alzheimer's agitation RCT, trazodone use did not differ significantly.

Mechanism: As-needed medication as a study endpoint, not a pair-specific drug–drug interaction

Study type: 75 people, 3 weeks of dronabinol versus placebo

Context studied: Dronabinol up to 10 mg/day, trazodone as needed; somnolence was more frequent with dronabinol.

Clinical interpretation: Treatment context only

Limitations and uncertainties: No isolated trazodone subgroup risk or pharmacokinetic result; no difference in as-needed use is not evidence of safety.

Original sources for this finding: A Randomized Controlled Trial of the Safety and Efficacy of Dronabinol for Agitation in Alzheimer's Disease. [BMED41350162]

CBD/CBDA-rich hemp extract – laboratory and animal studies

Finding ID: B0282

Type of result: Veterinary as-needed medication endpoint; no isolated investigation of the pair

Observation: Less additional trazodone use with CBD/CBDA extract after 2 weeks.

Mechanism: As-needed medication in a postoperative canine model

Study type: 44 dogs randomised, 41 analysed after TPLO

Context studied: Four placebo dogs and no extract-treated dogs received trazodone to restrict activity; no significant pain benefit.

Clinical interpretation: Veterinary context, not a pair-specific interaction

Limitations and uncertainties: Multi-ingredient extract, not isolated CBD/CBDA; trazodone use is not a finding about metabolism. The same study appears in both cannabinoid rows. Additional context from merged row B0283: Four placebo dogs and no extract-treated dogs received trazodone to restrict activity; no significant pain benefit. Multi-ingredient extract, not isolated CBD/CBDA; trazodone use is not a finding about metabolism. The same study appears in both cannabinoid rows.

Original sources for this finding: Evaluation of the efficacy of a cannabidiol and cannabidiolic acid rich hemp extract for pain in dogs following a tibial plateau leveling osteotomy. [BMED36686184]

References and access status

[V2_LABEL_D0111] TRAZODONE HYDROCHLORIDE (TRAZODONE HYDROCHLORIDE) TABLET [REMEDYREPACK INC.]

Original source / bibliographic reference

Authors: REMEDYREPACK INC.

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.

[CA_P_39502532] Green rush and red warnings: Retrospective chart review of adverse events of interactions between cannabinoids and psychotropic drugs.

Original source / bibliographic reference

Authors: Chrobak AA, Woroń J, Siwek M.

Year: 2024

Source type: research-article; Journal Article

DOI: 10.3389/fphar.2024.1500312

PMID: 39502532

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)

PubMed Central – full-text access according to the literature database – Archive attribution confirmed by Europe PMC metadata. Direct retrieval was not fully verified here; access may require a browser check.

Europe PMC – full-text access according to the literature database – Listed as freely available HTML full text in the official Europe PMC metadata. Direct retrieval was not fully verified here.

[BMED33195551] The Impact of Feeding Cannabidiol (CBD) Containing Treats on Canine Response to a Noise-Induced Fear Response Test.

Original source / bibliographic reference

Authors: Morris EM, Kitts-Morgan SE, Spangler DM, McLeod KR, Costa JHC, Harmon DL.

Year: 2020

Source type: Publication; title and abstract reviewed

DOI: 10.3389/fvets.2020.569565

PMID: 33195551

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)

[BMEDPPR583977] Cannabidiol and Trazodone Ameliorate Neuronal Proteotoxicity in C. elegans

Original source / bibliographic reference

Authors: Gilberto VS, McGrath S, Alsulami AM, Vidrio-Aguirre A, Moreno J.

Year: 2022

Source type: Non-peer-reviewed preprint, preclinical

DOI: 10.21203/rs.3.rs-2351138/v1

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.

DOI – publisher access (access restrictions may apply)

[BMED35742646] Trazodone Prolonged-Release Monotherapy in Cannabis Dependent Patients during Lockdown Due to COVID-19 Pandemic: A Case Series.

Original source / bibliographic reference

Authors: Mazza M, Caroppo E, Marano G, Kotzalidis GD, Avallone C, Camardese G, Janiri D, Moccia L, Simonetti A, Janiri L, Sani G.

Year: 2022

Source type: Publication; title and abstract reviewed

DOI: 10.3390/ijerph19127397

PMID: 35742646

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)

[BMED41350162] A Randomized Controlled Trial of the Safety and Efficacy of Dronabinol for Agitation in Alzheimer's Disease.

Original source / bibliographic reference

Authors: Rosenberg PB, Amjad H, Burhanullah H, Nowrangi M, Vandrey R, Pierre MJ, Outen JD, Schultz M, Marano C, Agronin M, Wilkins JM, Harper D, Laffaye T, Reardon E, Turner K, Ozonsi R, Drury M, Nguyen A, Hasoğlu T, Cromwell J, Leoutsakos JM, Forester BP.

Year: 2026

Source type: Publication; title and abstract reviewed

DOI: 10.1016/j.jagp.2025.10.011

PMID: 41350162

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)

[BMED36686184] Evaluation of the efficacy of a cannabidiol and cannabidiolic acid rich hemp extract for pain in dogs following a tibial plateau leveling osteotomy.

Original source / bibliographic reference

Authors: Klatzkow S, Davis G, Shmalberg J, Gallastegui A, Miscioscia E, Tarricone J, Elam L, Johnson MD, Leonard KM, Wakshlag JJ.

Year: 2022

Source type: Publication; title and abstract reviewed

DOI: 10.3389/fvets.2022.1036056

PMID: 36686184

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)

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