Clonidine

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: Clonidine

Examples of brand names: Catapresan [DE]

ATC code: C02AC01

Main use (for orientation): Hypertension; withdrawal

Documented research summary

Marijuana–clonidine pilot, 1988, n=3: reduced heart-rate increase, not subjective effects. CBD plus clonidine in the 2024 rat fear model was ineffective without D-cycloserine. Preclinical THC withdrawal models show clonidine effects, not a routine clinical interaction. THCV 100 nM did not antagonise clonidine in isolated vas deferens.

Uncertainties and limitations

Very small human pilot, no pharmacokinetics; animal/tissue models do not support clinical dose recommendations. 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

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

Smoked cannabis – clinical signals

Finding ID: B0491

Type of result: Context-specific finding

Observation: Clonidine reduced but did not eliminate the heart-rate increase; subjective effects largely persisted.

Mechanism: α2 agonism attenuates part of the cannabis-associated cardiovascular response.

Study type: Human pilot, pharmacodynamics

Context studied: Three men; original pilot-study abstract.

Clinical interpretation: Limited clinical signal; sample size, multiple exposures or an uncontrolled design restrict causal and quantitative assessment.

Limitations and uncertainties: Extremely small sample; no preventive-use recommendation or general safety evidence.

Original sources for this finding: Clonidine partially blocks the physiologic effects but not the subjective effects produced by smoking marijuana in male human subjects. [VF_P_2834758]

CBD – laboratory and animal studies

Finding ID: B0492

Type of result: Context-specific finding

Observation: CBD plus clonidine alone did not show the investigated effect; additional D-cycloserine context must be considered separately.

Mechanism: Combination assessment in memory reconsolidation.

Study type: Rat fear-memory model

Context studied: Behaviour/memory model; original abstract.

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

Limitations and uncertainties: A null finding does not clinically exclude an interaction; do not store triple treatment as a two-substance effect.

Original sources for this finding: Dual-step pharmacological intervention for traumatic-like memories: implications from D-cycloserine and cannabidiol or clonidine in male and female rats. [VF_P_38691149]

THCV – laboratory and animal studies

Finding ID: B0493

Type of result: Context-specific finding

Observation: THCV did not antagonise clonidine-mediated inhibition of contraction in the model tested.

Mechanism: Assessment of adrenergic versus cannabinoid signalling responses.

Study type: Ex-vivo vas-deferens model

Context studied: THCV 100 nM; original abstract.

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

Limitations and uncertainties: Receptor-specificity/null finding; not human pharmacokinetics or general combination safety.

Original sources for this finding: Evidence that the plant cannabinoid Delta9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist. [VF_P_16205722]

THC – laboratory and animal studies

Finding ID: B0494

Type of result: Context-specific finding

Observation: Clonidine attenuated individual withdrawal signals, including paw tremor in a mouse model; monkey-model effects were partial and endpoint-dependent.

Mechanism: Modification of antagonist-precipitated THC withdrawal by α2 agonism.

Study type: Animal withdrawal models

Context studied: Mice and rhesus monkeys; experimentally induced withdrawal, original abstracts.

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

Limitations and uncertainties: No clinical withdrawal-treatment recommendation or blanket conclusion about acute co-administration.

Original sources for this finding: Precipitated cannabinoid withdrawal is reversed by Delta(9)-tetrahydrocannabinol or clonidine. [VF_P_11420084]; Rimonabant-induced Delta9-tetrahydrocannabinol withdrawal in rhesus monkeys: discriminative stimulus effects and other withdrawal signs. [VF_P_20375197]

THC – laboratory and animal studies

Finding ID: B0495

Type of result: Context-specific finding

Observation: Clonidine blocked THC-associated activation of mesoprefrontal dopamine function in the experiment.

Mechanism: Adrenergic modulation of mesoprefrontal dopamine activity.

Study type: Rat neurochemistry experiment

Context studied: Original abstract; animal neurotransmitter endpoint.

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

Limitations and uncertainties: No clinical behavioural or treatment effect established.

Original sources for this finding: Alpha-noradrenergic receptor modulation of the phencyclidine- and delta9-tetrahydrocannabinol-induced increases in dopamine utilization in rat prefrontal cortex. [VF_P_9414014]

THC – laboratory and animal studies

Finding ID: B0496

Type of result: Context-specific finding

Observation: THC enhanced clonidine-stimulated LHRH release in the tissue model investigated.

Mechanism: Modification of clonidine-stimulated LHRH release.

Study type: Ex-vivo neuroendocrine model

Context studied: THC 250 ng/ml; original abstract.

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

Limitations and uncertainties: Historical tissue endpoint, not a clinical hormonal or clonidine interaction.

Original sources for this finding: Acute delta 9-tetrahydrocannabinol exposure: effects on hypothalamic-pituitary-testicular activity in mice. [VF_P_3033703]

THC – laboratory and animal studies

Finding ID: B0497

Type of result: Context-specific finding

Observation: No cross-tolerance to clonidine in the vas-deferens model after THC pretreatment.

Mechanism: Assessment of cross-tolerance in adrenergic signalling responses.

Study type: Animal pretreatment with ex-vivo testing

Context studied: THC 20 mg/kg on two days; original abstract.

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

Limitations and uncertainties: Null finding specific to this model, not a general assurance of safety.

Original sources for this finding: A preliminary investigation of the mechanisms underlying cannabinoid tolerance in the mouse vas deferens. [VF_P_7713151]

References and access status

[VF_L_D0431] QLONILIK (CLONIDINE HYDROCHLORIDE) SOLUTION [CMP PHARMA, INC.]

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.

[VF_P_11420084] Precipitated cannabinoid withdrawal is reversed by Delta(9)-tetrahydrocannabinol or clonidine.

Original source / bibliographic reference

Authors: Lichtman AH, Fisher J, Martin BR.

Year: 2001

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

DOI: 10.1016/s0091-3057(01)00514-7

PMID: 11420084

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)

[VF_P_16205722] Evidence that the plant cannabinoid Delta9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist.

Original source / bibliographic reference

Authors: Thomas A, Stevenson LA, Wease KN, Price MR, Baillie G, Ross RA, Pertwee RG.

Year: 2005

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

DOI: 10.1038/sj.bjp.0706414

PMID: 16205722

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_20375197] Rimonabant-induced Delta9-tetrahydrocannabinol withdrawal in rhesus monkeys: discriminative stimulus effects and other withdrawal signs.

Original source / bibliographic reference

Authors: Stewart JL, McMahon LR.

Year: 2010

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

DOI: 10.1124/jpet.110.168435

PMID: 20375197

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_2834758] Clonidine partially blocks the physiologic effects but not the subjective effects produced by smoking marijuana in male human subjects.

Original source / bibliographic reference

Authors: Cone EJ, Welch P, Lange WR.

Year: 1988

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

DOI: 10.1016/0091-3057(88)90035-4

PMID: 2834758

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)

[VF_P_3033703] Acute delta 9-tetrahydrocannabinol exposure: effects on hypothalamic-pituitary-testicular activity in mice.

Original source / bibliographic reference

Authors: Dalterio S, Steger R, Peluso J, de Paolo L.

Year: 1987

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

DOI: 10.1016/0091-3057(87)90161-4

PMID: 3033703

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)

[VF_P_38691149] Dual-step pharmacological intervention for traumatic-like memories: implications from D-cycloserine and cannabidiol or clonidine in male and female rats.

Original source / bibliographic reference

Authors: Soares LA, Nascimento LMM, Guimarães FS, Gazarini L, Bertoglio LJ.

Year: 2024

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

DOI: 10.1007/s00213-024-06596-8

PMID: 38691149

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)

[VF_P_7713151] A preliminary investigation of the mechanisms underlying cannabinoid tolerance in the mouse vas deferens.

Original source / bibliographic reference

Authors: Pertwee RG, Griffin G.

Year: 1995

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

DOI: 10.1016/0014-2999(94)00617-g

PMID: 7713151

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_9414014] Alpha-noradrenergic receptor modulation of the phencyclidine- and delta9-tetrahydrocannabinol-induced increases in dopamine utilization in rat prefrontal cortex.

Original source / bibliographic reference

Authors: Jentsch JD, Wise A, Katz Z, Roth RH.

Year: 1998

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

DOI: 10.1002/(sici)1098-2396(199801)28:1<21::aid-syn3>3.0.co;2-e

PMID: 9414014

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.

Drug search and explanation of the evidence · Guide: cannabinoids and medicines · Author and responsibility