Working draft — Scientific review: pending | Regulatory review: pending | Not for external clinical or promotional use without independent verification

Contraindications and Cautions

This page is sourced from MHRA-approved Summaries of Product Characteristics for licensed cannabinoid products, peer-reviewed RCT exclusion criteria, and UK regulatory standards.

How to Use This Page

Contraindications are graded absolute (prescribing is not appropriate under any circumstance) vs relative caution (prescribing may proceed with additional safeguards, MDT review, or enhanced monitoring). For MDT-trigger thresholds relating to relative cautions, see the Governance page.

Absolute Contraindications

DomainContraindicationSource — Primary Citation
HypersensitivityKnown hypersensitivity to CBD, THC, sesame oil (Epidyolex carrier), or excipientsEpidyolex SmPC [28], Sativex SmPC [67]
PregnancyPregnancy or planning pregnancyEpidyolex SmPC [28] (animal reproductive toxicity), Sativex SmPC [67]
BreastfeedingBreastfeedingEpidyolex SmPC [28], Sativex SmPC [67] (cannabinoids detected in breast milk)
Active psychosisCurrent psychotic episode (THC-containing products)Whiting JAMA 2015 [18]; Volkow NEJM 2014 [128]; Sativex SmPC [67] exclusion
Severe hepatic impairmentChild–Pugh CEpidyolex SmPC [28]; Millar PK review [56]
Active untreated substance dependenceCurrent cannabis use disorder, active drug-seekingTrial exclusion criteria from Hurd 2019 [13], Freeman 2020 [14]

Relative Cautions

DomainCautionSource — Primary Citation
CardiovascularRecent MI, stroke, dysrhythmia, uncontrolled HTN — especially THC-containing productsWhiting [18]; Sativex SmPC [67]
Moderate hepatic impairmentChild–Pugh A/B — dose adjustment may be requiredEpidyolex SmPC [28]
Renal impairmentNo dose adjustment data availableEpidyolex SmPC [28]
Psychosis / bipolar historyPersonal or first-degree family history of psychosis or bipolar disorder (THC products)Volkow [128]; Di Forti [129]
Active suicidal ideationCurrent active suicidal ideationMcGuire 2018 [6] exclusion criteria
CYP inhibitors / inducersConcomitant CYP3A4 / CYP2C19 inhibitors or inducersGaston 2017 [58]; Epidyolex SmPC [28]; see Interactions
Concomitant valproateHepatic risk amplified with CBD + valproateGaston [58]; Epidyolex SmPC [28]
Concomitant clobazamSomnolence risk amplifiedGaston [58]; Epidyolex SmPC [28]
Driving / safety-critical occupationPatients must be advised of impairment risk, especially THCSativex SmPC [67] driving warning
Polypharmacy>5 chronic medications — increased DDI riskBest practice under GMC [61]

Indication-Stratified Cautions

For each major indication, the following cautions are derived from the corresponding RCT exclusion criteria. Cross-link to the corresponding Evidence Matrix row.

Schizophrenia (adjunct)

Trial exclusion criteria from McGuire 2018 [6]: comorbid substance dependence; prior cannabis-induced psychosis; active suicidal ideation; significant hepatic impairment. Trial dose was 1000 mg/day on top of stable antipsychotic. Specials prescribing should follow the same exclusion logic.

CHR-P / Early Intervention

Trial exclusion criteria from Bhattacharyya 2018/2024 [8], [59]: current substance dependence; active psychotic episode; significant medical comorbidity; pregnancy/breastfeeding. Trial dose was 600 mg/day for 21 continuous days.

Generalised Anxiety Disorder

Trial exclusion criteria from Masataka 2019 [47], de Faria 2020 [49], Berger 2022 [50]: active psychosis; current substance dependence; unstable medical condition; pregnancy. Doses ranged 300–600 mg/day.

PTSD

Trial exclusion criteria from Bolsoni-Silva 2022 [12], Elms 2019 [25], Shannon 2019 [48]: active psychosis; current substance dependence; unstable cardiovascular disease. Dose not established.

Insomnia Disorder

Trial exclusion criteria from Kesner 2022 [26]: untreated sleep apnoea; current substance dependence; shift-work sleep disorder; pregnancy. Doses 75–300 mg/day.

Tourette's Syndrome

Trial exclusion criteria from Müller-Vahl 2002 [19]: psychotic disorder; substance dependence; pregnancy. THC 2.5–10 mg/day — additional psychosis-risk caution applies.

Opioid / Cannabis Use Disorder

Trial exclusion criteria from Hurd 2019 [13], Freeman 2020 [14]: active psychosis; unstable medical condition; pregnancy; concomitant opioid agonist therapy (for opioid-use trials). Doses 400–800 mg/day.

MS Spasticity

Per Sativex SmPC [67] and Novotna 2011 [20], Wade 2004 [21]: history of psychosis; significant cardiovascular disease; pregnancy/breastfeeding. Nabiximols titrated per SmPC.

Parkinson's Disease

Trial exclusion criteria from Chagas 2014 [52], de Faria 2020 [53], Leehey 2020 [54], Zuardi 2009 [55]: dementia (MMSE <24); active psychosis requiring antipsychotic escalation; significant hepatic impairment. Doses 75–300 mg/day.

Cancer Pain

Per Sativex SmPC [67] and Portenoy 2012 [22], Johnson 2010 [23], Lichtman 2018 [24]: history of psychosis; significant cardiovascular disease; active substance dependence. Nabiximols titrated per SmPC.

Endometriosis Pelvic Pain

Trial exclusion criteria from NCT04527003 [43], [44], [45], [106]: pregnancy/planning pregnancy; significant hepatic impairment; concomitant hormonal therapy outside protocol. Up to 12.5 mg/kg/day (Phase 2).

Paediatric Epilepsy (Dravet, LGS, TSC)

Per Epidyolex SmPC [28] and Devinsky 2017 [1], Devinsky 2018 [2], Thiele 2018 [3], Thiele 2021 [4]: severe hepatic impairment (Child–Pugh C); concomitant valproate requires enhanced LFT monitoring; hypersensitivity to sesame oil carrier. Licensed doses 10–25 mg/kg/day.

Paediatric Prescribing

Paediatric CBD prescribing is licensed for Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex with Epidyolex per SmPC [28] and BPNA standards [64]. Paediatric prescribing requires CQC paediatric licence per [66]. Under-18 prescribing outside Epidyolex / Sativex licensed indications requires specialist MDT review (see Governance).

Drug-Interaction Red Lines

The following four highest-risk drug–cannabinoid pairs require mandatory enhanced monitoring or dose adjustment. See the full CBD Drug Interactions and THC Drug Interactions pages for complete tables.

Clobazam

CBD inhibits CYP2C19 → 2–5× increase in N-desmethylclobazam. Somnolence, sedation. [58], [28]

Valproate

Additive hepatotoxicity risk. LFT monitoring mandatory. [58], [28]

Fluoxetine / Fluvoxamine

Strong CYP2C19/3A4 inhibition → increased CBD exposure. [58], [28]

Warfarin

CBD inhibits CYP2C9 → increased INR. Frequent INR monitoring required. [58], [28]

Related Pages

Last reviewed: 2026-04-30 · Reviewer: Grace Blest-Hopley PhD · Next review: 2026-10-30