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

Discontinuation & Tolerance

Stop-treatment criteria, tapering schedules, withdrawal monitoring, and tolerance-management framework — anchored to SmPCs and peer-reviewed primaries only.

Why a Documented Stop-Plan Matters

A documented stop-plan is a GMC [61] and MHRA Specials [60] expectation for all unlicensed prescribing. It protects the patient from indefinite treatment without benefit, provides a framework for shared decision-making, and ensures that discontinuation is managed safely with appropriate monitoring.

Stop-Treatment Criteria

TriggerSource
No clinically meaningful benefit at adequate dose for the published trial duration (see Dosing)RCT efficacy thresholds: McGuire [6], Boggs [7], Bhattacharyya [8], [59]
Intolerable adverse effectsEpidyolex SmPC [28]; trial AE thresholds in [6], [7]
Suspected misuse / diversion / non-adherenceGMC [61]; Volkow [128]
Patient request / withdrawal of consentGMC consent [62]

Tapering Schedules

CBD-Only Products

  • Reduce by 25–50% every 2 weeks
  • No documented physical-withdrawal syndrome at therapeutic doses (Epidyolex SmPC [28]; Larsen review [51])
  • Watch for return of underlying symptom (especially seizure rebound — Epidyolex SmPC [28])

THC-Containing Products

  • Reduce by 25% every week
  • Monitor for cannabis withdrawal syndrome: irritability, anxiety, sleep disturbance, appetite change, mood change — peaks at days 2–6, resolves over 1–2 weeks ([120]; Freeman [14])
  • Consider symptomatic support during taper

Withdrawal Monitoring Schedule

Anchored to validated outcome instruments (detailed tools planned for Phase 2). Underlying primaries referenced.

1GAD-7 baseline assessment
2PHQ-9 baseline assessment
3Sleep score baseline
4Weekly check-in for first 4 weeks post-discontinuation
5Final review 2 weeks after last dose

Tolerance Management (THC-Containing Only)

  • THC tolerance is well-recognised in heavy users via CB1 receptor downregulation (Hindocha [120]; Colizzi [121]); CBD tolerance is not consistently observed at therapeutic doses (Larsen [51]).
  • For THC-containing products, planned 48–72-hour treatment breaks every 2–4 weeks may help maintain therapeutic response. Recommended practice for unlicensed prescribing under GMC [61] expectations — local services should adopt schedules appropriate to indication and patient response.
  • Document the tolerance-management plan in the clinic letter.

Documentation When Stopping

  • Reason for stop (per GMC [61])
  • Final dose
  • Taper plan
  • Symptoms during taper
  • Outcome (resolved / partial / lost to follow-up)
  • Yellow Card if AE-driven (per MHRA [60])

Indication-Specific Stop Criteria

Schizophrenia (adjunct)

Stop if no PANSS positive subscale change after 6 weeks at 1000 mg/day per McGuire [6].

CHR-P / Early Intervention

Stop if no CAARMS reduction after 21 days at 600 mg/day per Bhattacharyya [59].

Anxiety (acute / single-dose)

Single-dose use does not require a taper ([9], [10], [11]).

Cancer Pain (nabiximols)

Per Sativex SmPC [67] titration / discontinuation rules.

Refractory Epilepsy (Epidyolex)

Taper per SmPC [28] to avoid seizure rebound. Do not abruptly discontinue.

Generalised Anxiety Disorder

Stop if no clinically meaningful GAD-7 reduction after 8 weeks at 300–600 mg/day per [47], [49], [50].

Opioid / Cannabis Use Disorder

Stop if no reduction in craving/use measures after adequate trial duration per Hurd [13], Freeman [14].

Related Pages

DosingGovernanceDrug InteractionsConditions A–ZContraindicationsReferences

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