Baclofen

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: Baclofen

Examples of brand names: Lioresal [DE]

ATC code: M03BX01

Main use (for orientation): Spasticity

Documented research summary

Direct human experiment, n=8: baclofen 25/50 mg enhanced discriminative THC effects with oral THC 5/15/30 mg (Lile 2012); no pharmacokinetic measurement. THC–baclofen in a patient with high cervical tetraplegia and respiratory failure is a severe single case with strong predisposition. Nabiximols plus baclofen/methylprednisolone with behavioural changes/suicidal thoughts after four weeks has unclear causality. An intrathecal baclofen–nabiximols case showed improvement with possible dose reduction, not proven universal synergy. The 2024 RELEASE-MSS1 RCT, n=68, on baclofen/tizanidine/dantrolene background therapy missed its primary muscle-tone endpoint (p=0.7152); not an isolated pair pharmacokinetic or superiority study.

Uncertainties and limitations

Very small human experiments, different doses/populations; severe single cases confounded by illness/additional medicines. Clinical add-on efficacy is not a pharmacokinetic interaction. No safety conclusion for intrathecal treatment or renal impairment.

Separately recorded findings

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

CBD + Δ9-THC (nabiximols) – theoretical plausibility

Finding ID: B0048

Type of result: Untested clinical possibility

Observation: Theoretically increased fall risk; no corresponding additional signal in studies.

Mechanism: Possible additive muscle relaxation

Study type: Regulatory class/pair warning

Context studied: No targeted baclofen pair study specified.

Clinical interpretation: Possible

Limitations and uncertainties: Theory and absence of a study signal retained.

Original sources for this finding: Sativex Oromucosal Spray – Summary of Product Characteristics [CL19]

Oral THC – clinically investigated

Finding ID: B0162

Type of result: Positive finding / indication

Observation: Baclofen shifted discriminative THC effects left/upwards; baclofen 50 mg alone substituted for the THC cue. Related THC-sensitive endpoints also changed.

Mechanism: Pharmacodynamic interaction of GABA-B/THC effects

Study type: Controlled combination testing

Context studied: n=8 cannabis users; baclofen 25/50 mg, THC 5/15/30 mg individually/combined.

Clinical interpretation: Clinically possible enhancement of psychomotor/subjective effects

Limitations and uncertainties: Small selected population, acute administration, no pharmacokinetics; no quantitative clinical dose rule.

Original sources for this finding: Separate and combined effects of the GABA(B) agonist baclofen and Δ9-THC in humans discriminating Δ9-THC. [CA_P_22699093]

Oral THC – clinical signals

Finding ID: B0163

Type of result: Suspected clinical signal

Observation: Respiratory failure after THC initiation, requiring one week of ventilatory support in a patient with high cervical tetraplegia.

Mechanism: Possible additive sedation/muscle weakness; cause not established

Study type: Case report

Context studied: Incomplete tetraplegia below C2, daytime breathing using accessory respiratory muscles; THC 2.5 mg twice daily, dyspnoea on day 3, discontinued on day 5; concomitant baclofen discussed as a possible cause.

Clinical interpretation: Particularly predisposed population

Limitations and uncertainties: No isolated causality or pharmacokinetics; do not present as a general event rate.

Original sources for this finding: [Respiratory failure due to delta-9-tetrahydrocannabinol in a tetraplegic patient]. [CA_P_16541267]

Nabiximols (THC/CBD) – clinical signals

Finding ID: B0164

Type of result: Suspected clinical signal

Observation: Behavioural changes including suicidal thoughts after four weeks of nabiximols.

Mechanism: Possible additive neuropsychiatric effect

Study type: Case report

Context studied: Woman with MS receiving baclofen and methylprednisolone.

Clinical interpretation: Possible neuropsychiatric signal

Limitations and uncertainties: Authors could not distinguish nabiximols alone from combined causes; no pharmacokinetics.

Original sources for this finding: Sativex-induced neurobehavioral effects: causal or concausal? A practical advice! [CA_P_25881038]

Nabiximols (THC/CBD) – clinical signals

Finding ID: B0165

Type of result: Co-medication context without an isolated interaction

Observation: Spasticity/function improved; intrathecal baclofen could be reduced, decreasing adverse effects.

Mechanism: Possible complementary antispastic effect

Study type: Case report

Context studied: Secondary progressive MS with tetraparesis, EDSS 8.5, intrathecal baclofen plus low-dose nabiximols.

Clinical interpretation: Hypothesis-generating benefit context

Limitations and uncertainties: Supra-additivity explained only hypothetically; no factorial comparison/pharmacokinetics or general dose recommendation.

Original sources for this finding: Treatment failure of intrathecal baclofen and supra-additive effect of nabiximols in multiple sclerosis-related spasticity: a case report. [CA_P_23634192]

Smoked cannabis (3.3% THC) – clinically investigated

Finding ID: B0166

Type of result: Mixed/context-dependent finding

Observation: Baclofen dose-dependently reduced craving during active cannabis smoking and impaired cognitive performance regardless of cannabis condition; no relapse advantage.

Mechanism: Human pharmacodynamics during maintenance administration

Study type: Laboratory study of intoxication/withdrawal/relapse

Context studied: n=10 daily users; baclofen 60/90 mg/day for 16 days per condition versus placebo, active cannabis/abstinence phases.

Clinical interpretation: Cognitive risk; pure THC–baclofen synergy not proven

Limitations and uncertainties: Dependent high-use sample; dose/condition-specific, no pharmacokinetics.

Original sources for this finding: Effects of baclofen and mirtazapine on a laboratory model of marijuana withdrawal and relapse. [CA_P_20521030]

References and access status

[CA_L_D0176] Baclofen – Human-SPL (D0176_Human_label.json)

Original source / bibliographic reference

Authors: Par Health USA, LLC

Year: 2026

Source type: Official human-use SPL / DailyMed

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

Bibliographic attribution or source identity cross-checked.

[CA_P_22699093] Separate and combined effects of the GABA(B) agonist baclofen and Δ9-THC in humans discriminating Δ9-THC.

Original source / bibliographic reference

Authors: Lile JA, Kelly TH, Hays LR.

Year: 2012

Source type: Primary / secondary publication; design and use described in the individual review

DOI: 10.1016/j.drugalcdep.2012.05.023

PMID: 22699093

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)

[CA_P_25881038] Sativex-induced neurobehavioral effects: causal or concausal? A practical advice!

Original source / bibliographic reference

Authors: Russo M, Rifici C, Sessa E, D'Aleo G, Bramanti P, Calabrò RS.

Year: 2015

Source type: Primary / secondary publication; design and use described in the individual review

DOI: 10.1186/s40199-015-0109-6

PMID: 25881038

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)

[CA_P_23634192] Treatment failure of intrathecal baclofen and supra-additive effect of nabiximols in multiple sclerosis-related spasticity: a case report.

Original source / bibliographic reference

Authors: Stroet A, Trampe N, Chan A.

Year: 2013

Source type: Primary / secondary publication; design and use described in the individual review

DOI: 10.1177/1756285613475835

PMID: 23634192

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)

[CA_P_16541267] [Respiratory failure due to delta-9-tetrahydrocannabinol in a tetraplegic patient].

Original source / bibliographic reference

Authors: Neuburger M, Schley M, Schmelz M, Schuepfer G, Konrad C.

Year: 2006

Source type: Primary / secondary publication; design and use described in the individual review

DOI: 10.1007/s00482-006-0474-7

PMID: 16541267

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)

[CA_P_20521030] Effects of baclofen and mirtazapine on a laboratory model of marijuana withdrawal and relapse.

Original source / bibliographic reference

Authors: Haney M, Hart CL, Vosburg SK, Comer SD, Reed SC, Cooper ZD, Foltin RW.

Year: 2010

Source type: Primary / secondary publication; design and use described in the individual review

DOI: 10.1007/s00213-010-1888-6

PMID: 20521030

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.

[CA_P_39106541] A randomized, double-blind, placebo-controlled trial to evaluate the effect of nabiximols oromucosal spray on clinical measures of spasticity in patients with multiple sclerosis.

Original source / bibliographic reference

Authors: Bethoux FA, Farrell R, Checketts D, Sahr N, Berwaerts J, Alexander JK, Skobieranda F.

Year: 2024

Source type: Primary / secondary publication; design and use described in the individual review

DOI: 10.1016/j.msard.2024.105740

PMID: 39106541

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)

[CA_P_2854226] Drugs which stimulate or facilitate central GABAergic transmission interact synergistically with delta-9-tetrahydrocannabinol to produce marked catalepsy in mice.

Original source / bibliographic reference

Authors: Pertwee RG, Greentree SG, Swift PA.

Year: 1988

Source type: Primary / secondary publication; design and use described in the individual review

DOI: 10.1016/0028-3908(88)90029-9

PMID: 2854226

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)

[CL19] Sativex Oromucosal Spray – Summary of Product Characteristics

Original source / bibliographic reference

Authors: SVX Therapeutics Limited

Year: 2026

Source type: Regulatory product information

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

Bibliographic attribution or source identity cross-checked.

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