Methylphenidate

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: Methylphenidate

Examples of brand names: Ritalin [DE]; Medikinet [DE]

ATC code: N06BA04

Main use (for orientation): ADHD

Documented research summary

CBD crossover pharmacokinetics, n=12: AUC geometric mean ratio 1.09 (90% CI 0.89–1.32), Cmax 1.08 (0.85–1.37); small mean change, but neither bioequivalence nor safety proven, and no established CBD steady state. Controlled THC/methylphenidate study, n=16, shows additive heart-rate/rate–pressure-product effects. CES1 models distinguished from human measurements.

Uncertainties and limitations

Full-text downloads of PMC4250392 and PMC11022897 failed; abstract-based plus available full text 36467779. Documented individual title/abstract assessment with selected relevant full texts; not an exhaustive worldwide systematic review or independent human specialist approval. Missing data do not establish safety. All 28 cannabinoids are within the search scope, not 28 clinically investigated pairs per drug.

Separately recorded findings

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

CBD – clinically studied

Finding ID: B0088

Type of result: Human pharmacokinetics with small mean changes but insufficient precision for equivalence

Observation: AUC ratio 1.09 (90% CI 0.89–1.32); Cmax 1.08 (0.85–1.37). Small mean changes.

Mechanism: CES1 inhibition as a hypothesis; clinical pharmacokinetics assessed

Study type: Randomised placebo-controlled crossover pharmacokinetic study

Context studied: 12 healthy people; CBD 750 mg twice daily, short pretreatment, methylphenidate 10 mg once.

Clinical interpretation: Individual medical / pharmaceutical assessment; do not use as dosage instructions

Limitations and uncertainties: The 90% confidence intervals cross the upper 1.25 limit: complete bioequivalence not demonstrated. CBD was not at an established steady state after 3.5 days. Twelve healthy people and one methylphenidate dose provide neither long-term nor general safety assurance.

Original sources for this finding: The Influence of Cannabidiol on the Pharmacokinetics of Methylphenidate in Healthy Subjects [EX01]

THC – clinically investigated

Finding ID: B0097

Type of result: Direct acute human pharmacodynamic evidence of additive cardiovascular effects

Observation: Heart rate and rate–pressure product increased additively with the combination.

Mechanism: Additive pharmacodynamic cardiovascular effects

Study type: Double-blind crossover study; online 2014

Context studied: 16 healthy adults without ADHD; single oral THC/methylphenidate doses.

Clinical interpretation: Individual medical / pharmaceutical assessment; do not use as dosage instructions

Limitations and uncertainties: Small experimental study, not evidence of the frequency of serious cardiac events.

Original sources for this finding: An exploratory study of the combined effects of orally administered methylphenidate and delta-9-tetrahydrocannabinol (THC) on cardiovascular function, subjective effects, and performance in healthy adults [EX09]

CBD – laboratory and animal studies

Finding ID: B0112

Type of result: In-vitro inhibition and modelled exposure; not observed human AUC

Observation: Unbound Ki 0.091 µM; repeated CBD in the PBPK model: AUC up to +55%.

Mechanism: Reversible CES1 inhibition

Study type: In vitro and PBPK model

Context studied: Model scenario: CBD 10 mg/kg twice daily.

Clinical interpretation: Assess clinical validation separately

Limitations and uncertainties: Not observed patient AUC; the later human study must be considered in the overall assessment.

Original sources for this finding: Prediction of Carboxylesterase 1-mediated In Vivo Drug Interaction between Methylphenidate and Cannabinoids using Static and Physiologically Based Pharmacokinetic Models [ME27]

THC – laboratory and animal studies

Finding ID: B0113

Type of result: In-vitro inhibition and modelled exposure; not observed human AUC

Observation: Unbound Ki 0.031 µM; static prediction AUC +34%.

Mechanism: Reversible CES1 inhibition

Study type: In vitro and static modelling

Context studied: Human liver S9; prediction using exposure after cannabis smoking.

Clinical interpretation: Clinical validation unresolved

Limitations and uncertainties: Do not equate modelled THC exposure with smoke-induced CYP induction.

Original sources for this finding: Prediction of Carboxylesterase 1-mediated In Vivo Drug Interaction between Methylphenidate and Cannabinoids using Static and Physiologically Based Pharmacokinetic Models [ME27]

CBD – laboratory and animal studies

Finding ID: B0485

Type of result: Context-specific finding

Observation: CBD reduced reinstatement of methylphenidate place preference in an animal model.

Mechanism: Modification of reinstatement of methylphenidate-associated conditioned place preference.

Study type: Rat conditioned-place-preference model

Context studied: Intracerebroventricular CBD 10/50 µg; original abstract.

Clinical interpretation: Applicability to humans is unresolved; preclinical endpoint, not clinical evidence of treatment efficacy or safety.

Limitations and uncertainties: Not an oral human interaction or treatment recommendation for ADHD/dependence. Administration route is not comparable to shop products.

Original sources for this finding: Cannabidiol attenuated the maintenance and reinstatement of extinguished methylphenidate-induced conditioned place preference in rats. [VF_P_33264654]

THC – laboratory and animal studies

Finding ID: B0486

Type of result: Context-specific finding

Observation: THC reduced methylphenidate-induced locomotion but not the gnawing endpoint investigated.

Mechanism: Endpoint-specific modification of stimulant-induced motor behaviour.

Study type: Rat behavioural experiment, pharmacodynamics

Context studied: THC 10 mg/kg by gavage; historical original paper read in abstract.

Clinical interpretation: Applicability to humans is unresolved; preclinical endpoint, not clinical evidence of treatment efficacy or safety.

Limitations and uncertainties: Animal finding, not clinical methylphenidate dosage or safety guidance.

Original sources for this finding: Comparative effects of tetrahydrocannabinol on psychostimulant-induced behaviors. [VF_P_6150497]

References and access status

[VF_L_D0426] COTEMPLA XR-ODT (METHYLPHENIDATE) TABLET, ORALLY DISINTEGRATING [NEOS THERAPEUTICS BRANDS, LLC]

Original source / bibliographic reference

Authors: Marketing authorisation holder; official product information via DailyMed

Year: 2026

Source type: Official medicine information; relevant identity, PK, PD and DDI sections read individually

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

[EX09] An exploratory study of the combined effects of orally administered methylphenidate and delta-9-tetrahydrocannabinol (THC) on cardiovascular function, subjective effects, and performance in healthy adults

Original source / bibliographic reference

Authors: Kollins SH; Schoenfelder EN; English JS; Holdaway A; Van Voorhees E; O'Brien BR; Dew R; Chrisman AK

Year: 2015

Source type: Double-blind crossover study; online 2014

DOI: 10.1016/j.jsat.2014.07.014

PMID: 25175495

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[VF_P_33264654] Cannabidiol attenuated the maintenance and reinstatement of extinguished methylphenidate-induced conditioned place preference in rats.

Original source / bibliographic reference

Authors: Kashefi A, Tomaz C, Jamali S, Rashidy-Pour A, Vafaei AA, Haghparast A.

Year: 2021

Source type: Scientific publication; precise study type and suitability described in the finding or individual review

DOI: 10.1016/j.brainresbull.2020.11.021

PMID: 33264654

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)

[ME27] Prediction of Carboxylesterase 1-mediated In Vivo Drug Interaction between Methylphenidate and Cannabinoids using Static and Physiologically Based Pharmacokinetic Models

Original source / bibliographic reference

Authors: Qian Y; Markowitz JS

Year: 2022

Source type: Original study: in-vitro CES1 and PBPK

DOI: 10.1124/dmd.121.000823

PMID: 35512806

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[EX01] The Influence of Cannabidiol on the Pharmacokinetics of Methylphenidate in Healthy Subjects

Original source / bibliographic reference

Authors: Markowitz JS; De Faria L; Zhang Q; Melchert PW; Frye RF; Klee BO; Qian Y

Year: 2022

Source type: Randomised placebo-controlled crossover pharmacokinetic study

DOI: 10.1159/000527189

PMID: 36467779

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.

[VF_P_6150497] Comparative effects of tetrahydrocannabinol on psychostimulant-induced behaviors.

Original source / bibliographic reference

Authors: Moss DE, Koob GF, McMaster SB, Janowsky DS.

Year: 1984

Source type: Scientific publication; precise study type and suitability described in the finding or individual review

DOI: 10.1016/s0091-3057(84)80050-7

PMID: 6150497

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)

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.

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