The formulary

cannabinoid_ratio

1:1 THC:CBD or THC-containing, titrated; CBD alone is not established here. Rationale: the RCT-validated cannabinoid comparator with a labeled dose unit is nabiximols 1:1 (2.7 mg THC + 2.5 mg CBD per spray, for MS spasticity — the closest labeled anchor); Allan 2018 lists neuropathic/spasticity-adjacent pain in the "some evidence" tier. Grade B (guideline consensus; no dispensary-product RCT).

titration_steps

Busse schedule — if response unsatisfactory on nabiximols-class 1:1 (max 12 sprays/day equivalent), add THC 1–2.5 mg/day, titrate +1–2.5 mg every 2–7 days, max 40 mg/day. For dispensary oral analog: THC:CBD 1:1 oil starting at 1–2.5 mg THC / 2.5–5 mg CBD once daily in the evening. Reassessments per 5×-half-life window (EP-01). Strict stop rule adapted from the Sativex SmPC precedent: if no clinically meaningful improvement after ~4 weeks at tolerated dose, discontinue and refer back (the labeled 20%-improvement-or-stop rule is specific to MS spasticity — its use here is DERIVED, flagged).

route + onset_profile

oromucosal/sublingual preferred where a measured-dose transmucosal product exists (intermediate onset); oral oil otherwise. Sublingual bioavailability figures circulating in the wider literature (~12–35%) are UNVERIFIED — absent from corpus.

contraindications

as EP-01.

interaction_flags

as EP-01.

evidence_grade

B

citations

1. 1. Busse JW et al. 2021, BMJ 374:n2040, PMID 34497062 — busse-bmj.txt / memo 03 §2.2.
2. 2. Sativex SmPC (EMA/HMA), ratio + stop rule — memo 03 §1.3 (verified text on disk via spec corpus).
3. 3. Allan GM et al. 2018, Can Fam Physician 64(2):e78–e94 (verified against the full text, 2026-09-15; the earlier 111–120 was wrong) — allan2018-cfp.txt / memo 03 §1.1.

cannabinoid_ratio

CBD-dominant oral baseline (same ladder as EP-01), plus optional topical for localized joints (patient-preference adjunct, not dose-equivalent — see EP-13). Grade B/C split: oral ladder B (consensus); topical C (mechanistic/limited — see below).

titration_steps

as EP-01 oral ladder. Topical: no evidence-graded systemic dosing exists — present to patients as a local option with no claimed systemic dose (memo 03 §3.4).

route + onset_profile

oral oil (titration backbone); topical for local complaints with the explicit caveat that Busse 2021, BMJ 374:n2040, PMID 34497062 states topicals "may lack pharmacokinetic data establishing their ability to cross the aqueous layer and remain localised" — local delivery is not PK-verified.

contraindications

IBD-adjacent caution does not apply here, but any patient with active inflammatory disease requiring immunosuppressants triggers the tacrolimus/everolimus flag.

interaction_flags

as EP-01.

evidence_grade

B (oral) / C (topical adjunct)

citations

1. 1. Busse JW et al. 2021, BMJ 374:n2040, PMID 34497062 (topical PK caveat) — memo 03 §3.4.
2. 2. cbd_permeation2004 skin-permeation study (MECH: penetration demonstrated; no systemic-dosing claim supportable) — memo 03 §3.4 Appendix A.
3. 3. MacCallum & Russo Delphi — maccallum-delphi.txt.

cannabinoid_ratio

same ladder as EP-01; evening-dominant THC scheduling (CAMH titration starts THC in the evening). Grade B for the pain claim; Grade C for sleep — CFPC 2021 Recommendation 4 states cannabis is "not an appropriate therapy" for insomnia pending further research; the sleep benefit observed in pain RCTs (Busse 2021, BMJ 374:n2040, PMID 34497062, small-to-very-small, moderate certainty) is a co-benefit, not a standalone indication. This entry explicitly does not sell sleep improvement.

titration_steps

EP-01 ladder, with THC portion dosed in the evening (CAMH). Sulak's optimal-dose framing (titrate down when effects fade) is [ANECD] — may be mentioned as a practice-style de-escalation habit, never as evidence-grade dosing.

route + onset_profile

oral oil evening dose; warn the daytime-impairment risk is back-loaded — oral peak 2–4 h with a long half-life tail (dronabinol t½ 25–36 h; 11-OH-THC 44–59 h).

contraindications

any patient whose primary complaint is insomnia without pain is out of scope — routed to the Grade-D exclusion list, not to a protocol.

interaction_flags

as EP-01; additive CNS-depressant sedation risk is amplified by evening dosing with alcohol/benzodiazepines (labels corrected 2026-09-12: Marinol = "potential for additive central nervous system depression"; Cesamet = "Additive drowsiness and CNS depression"; Cesamet: "This combination should be avoided").

evidence_grade

B (pain) / C (sleep co-benefit)

citations

1. 1. Busse JW et al. 2021, BMJ 374:n2040, PMID 34497062 (sleep co-benefit, moderate certainty) — memo 03 §1.1.
2. 2. CFPC 2021 (Moulin et al.), Guidance in Authorizing Cannabis Products Within Primary Care, Recommendation 4 — cfpc-guidance2021.txt / memo 03 §1.5.
3. 3. CAMH, Cannabis and the Cannabinoids medical guide, Appendix 5 — camh-appendix.txt / memo 03 §2.1–2.2.

cannabinoid_ratio

CBD-dominant, most conservative ladder (MacCallum & Russo conservative protocol). Grade B (expert consensus; CAMH explicitly flags this cohort as lowest-tolerance).

titration_steps

CAMH lower bounds govern: may tolerate only 2.5 mg CBD or 1 mg THC at initiation. CBD: 5 mg once daily; titrate +10 mg every 2–3 days to goal or 40 mg/day; then THC per EP-01 with 7-day (not 2-day) titration intervals, max 40 mg/day. Extended reassessment given half-life accumulation and polypharmacy: full steady-state review at ~14 days (DERIVED — flagged).

route + onset_profile

oral oil only at initiation; avoid inhaled (uncontrolled delivered dose: 0.5 g of 10%-THC flower ≈ 7.5–25 mg delivered — a wide band incompatible with this cohort's dose control).

contraindications

as EP-01; fall-risk and cognitive-impairment framing explicitly part of counseling (guideline-tier caution; euphoria is not required for symptom relief — CAMH).

interaction_flags

full consolidated screen mandatory before any dosing — this cohort is the reason the product exists. Clobazam, warfarin, tacrolimus/everolimus, buprenorphine, CNS depressants (benzodiazepines, barbiturates, opioids, alcohol, TCAs, antihistamines, lithium), strong CYP3A4/CYP2C19 inducers (rifampin class).

evidence_grade

B

citations

1. 1. CAMH Appendix 5 (low-tolerance cohort numbers) — memo 03 §2.2.
2. 2. MacCallum & Russo Delphi (conservative protocol) — maccallum-delphi.txt.
3. 3. Marinol/Cesamet labels (additive CNS depression) — marinol-label.txt, cesamet-label.txt / memo 03 §4.3.

cannabinoid_ratio

1:1 THC:CBD anchoring on the labeled nabiximols ratio (2.7 mg THC + 2.5 mg CBD per spray); dispensary analog = measured 1:1 ratio oil titrated. Grade B/C.

titration_steps

Busse schedule: 1–2.5 mg THC/day, titrate 1–2.5 mg every 2–7 days to max 40 mg/day, after an initial 1:1-class trial. Reassessments per 5×-half-life window (EP-01).

route + onset_profile

oromucosal preferred where a measured 1:1 transmucosal product is stocked; oral oil otherwise. Inhaled only for breakthrough (EP-08).

contraindications

patients on narrow-therapeutic-index chemotherapy or immunosuppressants trigger immediate review — the interaction surface is the dominant risk. CINV management belongs to prescription synthetics (Marinol 5 mg/m² per label) outside this protocol's scope.

interaction_flags

as EP-05 (full screen); tacrolimus/everolimus especially material here (+358%/+200%/+77% plasma increases with CBD — Anton 2022, two case reports + one 6-person trial).

evidence_grade

B

citations

1. 1. Busse JW et al. 2021, BMJ 374:n2040, PMID 34497062 (cancer pain scope + titration) — busse-bmj.txt.
2. 2. Anton J et al. 2022, J Clin Med (tacrolimus Level 2 numbers) — anton2022_clinrelevance.txt / memo 03 §4.2.
3. 3. Marinol label (dronabinol CINV dosing, adjacent context) — marinol-label.txt / memo 03 §1.2.

cannabinoid_ratio

CBD-dominant ladder as EP-01. Grade B for the titration mechanics (Sihota 2021 consensus exists specifically for titrating cannabinoids while tapering opioids); Grade C/very low certainty for any opioid-sparing effect.

titration_steps

EP-01 ladder; titration and tapering coordinated by the prescriber — the consultant guides the cannabinoid side only. Sihota 2021 is the named consensus source for THC titration — note its actual schedule (start 0.5–3 mg, increase 1–2 mg once or twice weekly, up to 30–40 mg/day) differs from the "+1–2.5 mg every 2–7 days" figure used elsewhere in this library; see the EP-01 correction note of 2026-09-15.

route + onset_profile

oral oil.

contraindications

forced opioid tapering is ineffective and may cause harm (Busse 2021, BMJ 374:n2040, PMID 34497062, quoting the guideline's own caution) — no taper is initiated or accelerated by this protocol.

interaction_flags

opioids appear in the CNS-depressant additive-sedation flag (pharmacodynamic overlap) — distinguish this from the therapeutic sparing strategy, which is a separate, weakly-evidenced claim.

evidence_grade

B (mechanics) / honest sub-grade C–D for the sparing effect itself (very low certainty evidence)

citations

1. 1. Busse 2021, BMJ 374:n2040, PMID 34497062 citing Noori et al., SR/MA: "The opioid sparing effects of medical cannabis for chronic pain remain uncertain due to very low certainty evidence" — memo 03 §1.9.
2. 2. Sihota A et al. 2021, Int J Clin Pract (titrating cannabinoids + tapering opioids protocol) — memo 03 §2.3.
3. 3. Anton J et al. 2022, J Clin Med (buprenorphine Level 2: dose-adjust and monitor) — memo 03 §4.2.

cannabinoid_ratio

patient-specific (inherits the stable regimen's ratio); inhaled is the rescue route, not a separate ratio decision. Grade C (PK/observational rationale; no inhaled dosing validation exists).

titration_steps

No validated inhaled dosing exists and this is stated plainly (CAMH: "limited evidence on dosage and interval; there are no validated dosing recommendations"). Reference math only, disclosed as approximate: 0.5 g of 10%-THC flower ≈ 7.5–25 mg THC delivered (CAMH). Counsel lowest-quantity trial, wait, reassess.

route + onset_profile

inhaled — onset within minutes, higher blood levels, shorter duration (Health Canada clinical review, hc-html.txt). Bioavailability CONTESTED: smoked THC 2–56% (Sexton & Ziskind 2013) vs inhaled 15–50% (CAMH) — both reported, not averaged (memo 03 §3.1).

contraindications

smoking-vulnerable respiratory patients steered to vaporized or held at oral-only; inhaled variability makes it a poor primary titration vehicle (memo 03 §3.1).

interaction_flags

as EP-01; additive sedation with the baseline regimen itself.

evidence_grade

C

citations

1. 1. Health Canada clinical review (hc-html.txt) — inhaled PK — memo 03 §3.1.
2. 2. CAMH Appendix 5 — delivered-dose math and absence of validated dosing — memo 03 §2.4, §3.1.
3. 3. Sexton M & Ziskind J 2013 (smoked THC 2–56%) — memo 03 §3.1.

cannabinoid_ratio

CBD-dominant; THC introduced only per EP-01 and at the lowest tolerated dose (THC is anxiolytic at low dose, anxiogenic at high dose — MECH, dose-dependent). The secondary literature's claim that CBD "may reduce anxiety associated with THC" applied in Washington-state packaging rules only above CBD:THC ratio 1:5 — [MECH/regulatory interpretation, not clinical proof]. Grade C.

titration_steps

EP-01 conservative ladder; the high-dose-THC ceiling (40 mg/day) is rarely the goal in this cohort. Reassessments per 5×-half-life window.

route + onset_profile

oral oil.

contraindications

patients whose primary complaint is an anxiety disorder are out of scope — CFPC 2021 Rec 4: cannabis "is not an appropriate therapy" for anxiety pending further research; no RCT of dispensary products for anxiety exists in the corpus. Such presentations are routed to the Grade-D exclusion list.

interaction_flags

as EP-01; SSRIs/most antidepressants: no corpus evidence of clinically significant PK interaction — counseled on additive sedation only via the CNS-depressant class; no specific SSRI-PK numbers may be cited.

evidence_grade

C (contested/mechanistic for the anxiety-related elements; B-grade pain ladder underneath)

citations

1. 1. Anton J et al. 2022, J Clin Med (absence of clinically significant PK evidence for most classes) — memo 03 §4.3–4.4.
2. 2. CFPC 2021, Recommendation 4 — cfpc-guidance2021.txt / memo 03 §1.6.
3. 3. Sexton M & Ziskind J 2013 (low-dose anxiolytic / high-dose anxiogenic; CBD-THC ratio claim) — memo 03 §1.6.

cannabinoid_ratio

CBD-dominant ladder as EP-01. Grade B (pain-family consensus; no surgery-specific cannabinoid RCTs in corpus).

titration_steps

EP-01 ladder; delay initiation until perioperative analgesic regimens are resolved — additive CNS depression with post-operative opioids is a pharmacodynamic, label-grade risk, not a theorized one.

route + onset_profile

oral oil.

contraindications

active post-operative opioid co-medication → hold cannabinoid initiation pending prescriber coordination (Marinol/Cesamet label additive-depression language).

interaction_flags

as EP-01; opioids (sedation) material here; warfarin flag if on perioperative anticoagulation (INR monitoring around any cannabis start/stop/dose change — Anton 2022 Level 1, probable, CYP2C9).

evidence_grade

B

citations

1. 1. Busse JW et al. 2021, BMJ 374:n2040, PMID 34497062 — memo 03 §1.1, §2.2.
2. 2. Marinol/Cesamet labels (additive CNS depression) — memo 03 §4.3.
3. 3. Anton J et al. 2022, J Clin Med (warfarin Level 1) — anton2022_clinrelevance.txt / memo 03 §4.2.

cannabinoid_ratio

CBD-dominant ladder as EP-01. Grade C — the corpus has no fibromyalgia-specific RCT; the entry rests on the general chronic-pain guideline tier plus observational non-response data (Allan 2018). This entry exists to give a disciplined posture, not to affirm efficacy.

titration_steps

EP-01 conservative ladder; stop rules at 4 weeks absent meaningful improvement (adapted; DERIVED — flagged). Disclose honestly that the pain benefit is small and uncertain, that larger/longer trials found no benefit, and that adverse effects are very common (dizziness NNH 5, sedation NNH 5) (Allan 2018, recovered full text [corrected 2026-09-15 against the recovered primary source]).

route + onset_profile

oral oil.

contraindications

as EP-01.

interaction_flags

as EP-01.

evidence_grade

C

citations

1. 1. Busse JW et al. 2021, BMJ 374:n2040, PMID 34497062 — busse-bmj.txt.
2. 2. Allan GM et al. 2018, Can Fam Physician 64(2):e78–e94 (small/uncertain pain benefit; common adverse effects) — allan2018-cfp.txt.
3. 3. MacCallum & Russo Delphi — maccallum-delphi.txt.

cannabinoid_ratio

CBD-dominant, at reduced doses with prescriber oversight — the only corpus-verified hepatic-impairment dose-adjustment precedent is the Epidiolex label (pharmaceutical CBD). The dispensary-dose analog is DERIVED, not on label — flagged for the reviewer. Grade C (label-derived, off-label context).

titration_steps

Baseline transaminases + bilirubin required (Epidiolex label §) before any CBD-dominant initiation; initiate at the conservative ladder's floor (5 mg CBD OD; 1–2.5 mg THC max as added) with weekly review. Any transaminase signal stops the trial pending review.

route + onset_profile

oral oil (route cannot avoid first-pass metabolism; the impairment axis is metabolic, not route-dependent).

contraindications

moderate–severe hepatic impairment without prescriber co-management is out of scope; the consultant defers, does not adjudicate.

interaction_flags

as EP-01, plus the hepatic-interaction cluster: valproate 30% ALT >3×ULN when co-administered with clobazam + high-dose CBD; 21% valproate alone; 4% clobazam alone; 3% neither (Epidiolex label, at 10–20 mg/kg/day — exposures far above dispensary dosing; stated for mechanism, not as a dispensary-dose risk number). Clobazam N-desmethylclobazam Cmax/AUC ≈ 3-fold; 7-OH-CBD Cmax +73% / AUC +47% (Epidiolex label, verified verbatim).

evidence_grade

C

citations

1. 1. Epidiolex FDA label (hepatic impairment, ALT >3×ULN incidence, clobazam interaction) — epidiolex-label.txt / memo 03 §4.2 (verified verbatim).
2. 2. Busse JW et al. 2021, BMJ 374:n2040, PMID 34497062 — memo 03 §1.1.
3. 3. Anton J et al. 2022, J Clin Med (the interaction-risk-concentration verdict) — memo 03 §4 preamble.

cannabinoid_ratio

no ratio claim — no evidence-graded systemic dosing for topicals exists in the corpus (memo 03 §3.4). Patient-preference adjunct or primary preference only. Grade C/D boundary; recorded as C with the honesty field carrying the negative.

titration_steps

none evidence-graded. Any topical is applied local-use-per-label with no implied systemic dose; escalation moves to the oral ladder (EP-01) if systemic treatment becomes the goal.

route + onset_profile

topical/transdermal — Busse 2021, BMJ 374:n2040, PMID 34497062: topicals "may lack pharmacokinetic data establishing their ability to cross the aqueous layer and remain localised"; cbd_permeation2004 demonstrates skin permeation in vitro (MECH) only.

contraindications

broken skin (standard caution; not corpus-sourced — flagged for reviewer); do not combine with occlusive dressings (practice caution — flagged).

interaction_flags

none evidence-based; systemic transdermal products (not plain topicals) could reach systemic levels and would fold into the full screen.

evidence_grade

C

citations

1. 1. Busse JW et al. 2021, BMJ 374:n2040, PMID 34497062 — topical PK caveat — memo 03 §3.4.
2. 2. Skin-permeation study cbd_permeation2004 (MECH) — memo 03 §3.4 Appendix A.

cannabinoid_ratio

no separate ratio decision — inherits the underlying condition's ladder (e.g. EP-01 CBD-dominant oral ladder), with any THC portion dosed in the evening per CAMH titration convention (camh-appendix.txt). Grade C (observational/guideline; the sleep improvement seen in pain RCTs is real but small — Busse 2021, BMJ 374:n2040, PMID 34497062 BMJ: "small-to-very-small improvement in sleep quality" [moderate certainty] — and is a co-benefit of the pain claim, never a sleep claim).

titration_steps

the underlying condition's ladder unchanged. Evening scheduling only. Reassessments per the 5×-half-life window (dronabinol t½ 25–36 h; 11-OH-THC 44–59 h; CBD 56–61 h — Marinol label / Busse 2021, BMJ 374:n2040, PMID 34497062): no increment judged inside 5 days. Adjunct observational anchor (corrected 2026-09-12 — two adjacent studies in the source were previously conflated): (a) Skrabek 2008 — 40 fibromyalgia patients on nabilone 1 mg BID for 4 weeks; pain, Fibromyalgia Impact Questionnaire and anxiety scores benefited vs placebo (p < 0.02); (b) Ware 2010 — 31 patients, nabilone 0.5–1 mg at bedtime, compared with amitriptyline 10–20 mg (NOT placebo); nabilone was superior on an Insomnia Severity Index, with no stated p-value in the quoted review and no benefit on pain, mood or quality of life. Both cited within russo-ced.txt. Observational context only — nabilone is a prescription synthetic, not a dispensary product, and both trial populations are fibromyalgia, not primary insomnia.

route + onset_profile

oral oil, evening dose. Onset 30–60 min, peak 2–4 h, bioavailability 6–20% (CAMH). Warn explicitly that daytime-impairment risk is back-loaded (peak 2–4 h plus long half-life tail — next-morning sedation is a pharmacokinetic expectation, not an idiosyncrasy).

contraindications

a patient whose primary complaint is insomnia is out of scope — routed to the Grade-D exclusion table, not to this protocol. Pregnancy/breastfeeding; uncontrolled psychiatric illness / psychosis history (guideline-tier standard; flagged for reviewer per chronic-pain library open question 5). Sulak's titrate-down-when-effects-fade framing is [ANECD] (projectcbd-sulak.txt) — permissible as a practice-style de-escalation habit, never as dosing evidence.

interaction_flags

full consolidated screen by reference; CNS-depressant row is amplified by evening dosing — alcohol and benzodiazepines at night compound the additive-sedation label warning (labels corrected 2026-09-12: Marinol — "potential for additive central nervous system depression" [§7.1 Additive CNS Effects: dizziness, confusion, sedation, somnolence]; Cesamet — "Additive drowsiness and CNS depression"; and Cesamet: "This combination should be avoided"; marinol-label.txt, cesamet-label.txt).

evidence_grade

C

citations

1. 1. Busse JW et al. 2021, BMJ 374:n2040, PMID 34497062 (sleep as small co-benefit, moderate certainty) — busse-bmj.txt / memo 03 §1.1, §1.5.
2. 2. Moulin et al., CFPC 2021, Guidance in Authorizing Cannabis Products Within Primary Care, Recommendation 4 (insomnia: "not an appropriate therapy") — cfpc-guidance2021.txt / memo 03 §1.5.
3. 3. CAMH, Cannabis and the Cannabinoids, Appendix 5 (evening THC initiation convention) — camh-appendix.txt / memo 03 §2.2.
4. 4. Ware MA et al. 2010, Anesth Analg 110:604–610 (nabilone fibromyalgia sleep RCT, cited within russo-ced.txt — the underlying trial text is not staged; grade as secondary citation).

cannabinoid_ratio

no initiation posture (the evidence does not support starting cannabis for sleep). The entry's function is screening + risk-reduction + referral: transition the patient toward the lowest-THC, least-frequency pattern they will accept, with explicit counseling that THC's sleep effects do not self-correct upward — CAMH states dose escalation does not restore effect ("euphoria is not required for effective symptom management"; restart titration on product change) and the corpus flags THC as dose-dependent in effect direction (anxiolytic low / anxiogenic high — Sexton & Ziskind 2013). Grade C.

titration_steps

1. 01 document current product, route, timing, dose if quantifiable;
2. 02 convert any inhaled bedtime use to a measured oral evening dose so quantity is numerable (oral onset 30–60 min — time it 60–90 min before intended sleep);
3. 03 hold any increment to the ≥5-day stability window;
4. 04 Sulak's 6-day "sensitization protocol" (2 days abstinence + 4 days careful re-titration — cannmed-sulak.txt, projectcbd-sulak.txt) is [ANECD] and may be offered as a practice-style reset explicitly labeled anecdotal;
5. 05 refer to the certifying practitioner for any upward drift the patient cannot self-limit.

route + onset_profile

oral oil preferred for dose control; inhaled carries the corpus's wide delivered-dose band (0.5 g of 10%-THC flower ≈ 7.5–25 mg THC — CAMH) which is incompatible with accountable dosing.

contraindications

any pattern suggesting a primary sleep disorder (sleep apnea signs, shift-work disorder) or untreated psychiatric condition → referral, not protocol management.

interaction_flags

CNS depressants (alcohol/benzodiazepine bedtime co-use is the highest-frequency real-world hazard in this cohort); the rest of the consolidated screen by reference.

evidence_grade

C

citations

1. 1. CAMH Appendix 5 (evening dosing; inhaled delivered-dose band; titration restart on product change) — camh-appendix.txt / memo 03 §2.2, §2.4, §3.1.
2. 2. Sulak D, Healer / Project CBD interview material (optimal-dose framing; 6-day sensitization protocol) — cannmed-sulak.txt, projectcbd-sulak.txt — graded [ANECD], physician case-series with no controlled trial.
3. 3. CFPC 2021 (Moulin et al.) Recommendation 4 — the reason this entry is harm-reduction rather than initiation — cfpc-guidance2021.txt / memo 03 §1.5.

cannabinoid_ratio

CBD-dominant only, lowest dose, stop-rule-heavy — THC is not introduced in this entry at all (the dose-dependent anxiogenic risk removes it from matching logic for an anxiety-adjacent presentation: THC is anxiolytic at low doses, anxiogenic at high doses — Sexton & Ziskind 2013, sexton-ziskind-2013-psychoactive-agents.txt [MECH/CONTESTED]). Even the CBD layer is fragile: the only directionally positive corpus material is the secondary-literature claim that CBD "may reduce anxiety associated with THC," which Washington-state packaging guidance permitted only above CBD:THC ratios of 1:5 — a regulatory interpretation, not clinical proof (memo 03 §1.6). Grade C — the thinnest evidence of any entry in either library; stated plainly to patients.

titration_steps

CBD oral oil at the CAMH conservative floor — 2.5–5 mg once daily in the evening, titrate +2.5–5 mg every 3 days to minimal effective dose, ceiling 40 mg/day (CAMH Appendix 5, camh-appendix.txt; Level III expert-consensus conventions, not dose-finding RCTs). Hard stop rules (DERIVED — flagged for reviewer): any increase in anxiety, agitation, or panic → stop and refer; no benefit at 4 weeks on the tolerated ceiling → stop and refer back to the treating clinician (4-week window adapted from the labeled nabiximols review window; DERIVED).

route + onset_profile

oral oil only (oral onset 30–60 min, peak 2–4 h, bioavailability 6–20% — CAMH; camh-appendix.txt). Inhaled excluded — the 7.5–25 mg delivered-dose band for 0.5 g of 10%-THC flower (CAMH) makes anxiolytic-vs-anxiogenic dose control impossible.

contraindications

diagnosed anxiety disorder as the treated condition → Grade D, not this entry. Any prior paradoxical anxiety response to cannabis or THC → decline and refer. Patients seeking primarily euphoric/anxiolytic THC effects → out of scope.

interaction_flags

SSRIs/most antidepressants: no corpus evidence of clinically significant PK interaction (Anton 2022, anton2022_clinrelevance.txt) — counsel on additive sedation only, via the CNS-depressant row; do not cite SSRI-PK numbers. Benzodiazepines: CNS-depressant row material (many anxiety-adjacent patients carry one; additive-sedation label language applies). Full consolidated screen by reference.

evidence_grade

C (contested/mechanistic throughout)

citations

1. 1. CFPC 2021 (Moulin et al.), Recommendation 4 — cfpc-guidance2021.txt / memo 03 §1.6.
2. 2. Sexton M & Ziskind J 2013 (THC dose-dependent anxiolysis/anxiogenesis; CBD "may reduce anxiety associated with THC" — Washington-state packaging permitted this claim only above CBD:THC 1:5; regulatory interpretation, not clinical proof) — sexton-ziskind-2013-psychoactive-agents.txt / memo 03 §1.6.
3. 3. CAMH Appendix 5 (CBD conservative titration numbers) — camh-appendix.txt / memo 03 §2.2.
4. 4. Anton J et al. 2022, J Clin Med (absence of clinically significant PK evidence for most psychiatric medication classes) — anton2022_clinrelevance.txt / memo 03 §4.3–4.4.

cannabinoid_ratio

none recommended. Grade D for the indication (see exclusion table). The entry exists because "the pharmacist went silent" is not a professional outcome; the legitimate function is screening, interaction-checking any existing self-medication, and referral.

titration_steps

1. 01 none. Where the treating clinician is already managing a cannabinoid trial (some PA PTSD cardholders arrive this way), the consultant's legitimate role is narrowed to:
2. 02 full consolidated interaction screen;
3. 03 dose-measurability counseling (oral over inhaled for accountability);
4. 04 documenting and reporting back to the treating clinician. No initiation, no titration advice. (DERIVED posture — flagged for reviewer approval.)

route + onset_profile

n/a.

contraindications

initiating or titrating any cannabinoid for PTSD is out of scope — CFPC 2021 Rec 4: cannabis "is not an appropriate therapy" for PTSD pending further research (cfpc-guidance2021.txt); no PTSD RCT is in the corpus (memo 03 §1.7). Russo 2011 (russo-2011-taming-thc.txt) discusses endocannabinoid-system involvement in PTSD — mechanistic plausibility only, not an indication.

interaction_flags

full consolidated screen; CNS-depressant row (this cohort's co-medication rates with benzodiazepines/opioids/alcohol are the real, actionable risk); SSRIs: no corpus PK evidence — additive-sedation counseling only.

evidence_grade

D for the indication (screen/referral posture entry: administrative, recommended as the honest handling of an unsupported request)

citations

1. 1. CFPC 2021 (Moulin et al.), Recommendation 4 — cfpc-guidance2021.txt / memo 03 §1.7.
2. 2. Russo EB 2011, Br J Pharmacol 163(7):1344–1364 (endocannabinoid-system discussion; MECH plausibility) — russo-2011-taming-thc.txt / memo 03 §1.7.

cannabinoid_ratio

none recommended from the dispensary side. The RCT-backed, labeled CINV evidence belongs to prescription synthetics: dronabinol (Marinol) — labeled for CINV "in patients who have failed to respond adequately to conventional antiemetic treatments," dosed 5 mg/m² 1–3 hours before chemotherapy, then every 2–4 hours after, 4–6 doses/day (marinol-label.txt, verified verbatim); nabilone (Cesamet), daily range 0.2–6 mg/day (Busse 2021, BMJ 374:n2040, PMID 34497062). Allan 2018 lists nausea/vomiting among the areas "with the best evidence" — but that evidence is molecule-level for the synthetics, not product-level for dispensary flower. The gap is the claim: no modern herbal-cannabis CINV RCT is in the corpus (memo 03 §1.2). Grade B for the synthetic-label facts; Grade D for any dispensary-CINV product claim.

titration_steps

1. 01 none dispensary-side. The consultant's legitimate functions:
2. 02 point the patient to the oncology prescriber for the labeled synthetics;
3. 03 run the full consolidated interaction screen against chemo/adjunctive regimens if oncology initiates a synthetic cannabinoid;
4. 04 document.

route + onset_profile

labeled dronabinol is oral (first dose on an empty stomach ≥30 min before meals — Marinol label). Dispensary-route counseling for CINV is not offered.

contraindications

any marketing-level "dispensary product for chemo nausea" positioning — that claim is Grade D and barred by the exclusion table.

interaction_flags

full consolidated screen material here — oncology regimens commonly hit the flagged classes (CNS depressants incl. opioids; narrow-therapeutic-index agents); the screen is the actual deliverable of this entry.

evidence_grade

B (synthetic-label facts) / D (dispensary-CINV recommendation — excluded)

citations

1. 1. Marinol (dronabinol) FDA label — indication, 5 mg/m² dosing, administration cautions — marinol-label.txt / memo 03 §1.2 (verified verbatim).
2. 2. Allan GM et al. 2018, Can Fam Physician 64(2):e78–e94 (verified against the full text, 2026-09-15; the earlier 111–120 was wrong) (nausea/vomiting in the "best evidence" tier) — allan2018-cfp.txt / memo 03 §1.2.
3. 3. Busse JW et al. 2021, BMJ 374:n2040, PMID 34497062 (nabilone 0.2–6 mg/day range) — busse-bmj.txt / memo 03 §1.2.

cannabinoid_ratio

1:1 THC:CBD (balanced), nabiximols-anchored. The labelled anchor is nabiximols oromucosal spray: "Each single 100 microlitre spray contains: 2.7 mg THC and 2.5 mg CBD" (Sativex SmPC §2, sativex_smpc.txt — verified verbatim). The labelled product IS the ratio. There is no evidence that any dispensary chemovar outperforms the defined 1:1 molecule ratio, and none is claimed. Where a state pathway allows it, the guideline-preferred first move is a referral for the pharmaceutical product, not a dispensary substitute: CFPC 2021 Recommendation 1 — "Spasticity (due to multiple sclerosis or spinal cord injury), after failure to respond to standard therapies and preferably a trial of nabiximols or other pharmaceutical cannabinoids (level i)" (cfpc-guidance2021.txt line 498). Grade B — the strongest grade earned by any entry in V1 or V2; see evidence_grade below for why it is not A.

titration_steps

1. 01 Preferred path — labelled product, labelled schedule. The Sativex SmPC prescribes a fixed 14-day titration table, verbatim from sativex_smpc.txt §4.2: day 1 → 1 spray (evening); day 2 → 1; day 3 → 2; day 4 → 2; day 5 → 3 (1 morning / 2 evening); day 6 → 4; day 7 → 5; day 8 → 6; day 9 → 7; day 10 → 8; day 11 → 9; day 12 → 10; day 13 → 11; day 14 → 12 (5 morning / 7 evening). Thereafter "The patient may continue to gradually increase the dose by 1 spray per day, up to a maximum of 12 sprays per day, until they achieve optimum symptom relief. There should be at least a 15-minute gap between sprays." Evening dose any time between 4 pm and bedtime; morning dose any time between waking and midday.
2. 02 Dispensary-side analog (DERIVED — flagged). Where no labelled product is accessible, the closest defensible analog is a balanced 1:1 THC:CBD oral or sublingual oil, started at 2.5–5 mg of each cannabinoid once or twice daily and titrated by 2.5–5 mg of each cannabinoid every 2–3 days, to a maximum 40 mg/day THC — this is MacCallum & Russo's Delphi **rapid protocol verbatim (maccallum-delphi.txt lines 26–28), which is the only balanced-ratio consensus schedule in the corpus. The mapping of a chronic-pain consensus schedule onto an MS-spasticity presentation is DERIVED and is flagged for reviewer sign-off.* It is not* equivalent to the labelled spray schedule, and the patient must be told so.
3. 03 Reassessment window (5×-half-life rule, DERIVED — carried from V1 unchanged): dronabinol elimination t½ 25–36 h; main metabolite 11-OH-THC 44–59 h; CBD 56–61 h (Busse 2021, busse-bmj.txt lines 704–706; dronabinol figure independently confirmed in the Marinol label §12.3, marinol-label.txt line 1757: "terminal (beta) half-life of 25 to 36 hours"). No increment is judged inside 5 days of stable dosing; full steady-state review at ~14 days. The 5-day operating rule is memo 03 §3.2's stated practical inference; the 14-day conservative bound is DERIVED.
4. 04 Restart titration on any product change — "Consider restarting titration when switching products or licensed producers because effects may vary even when THC and CBD content appear identical. Cannabis products are not interchangeable" (CAMH Appendix 5, camh-appendix.txt). This matters more here than anywhere else in the library, because the labelled comparator is a fixed-composition pharmaceutical and the dispensary substitute is not.

route + onset_profile

Oromucosal spray where a labelled measured-dose product exists — it is the route the evidence was generated on. Otherwise oral/sublingual oil: onset 30–60 min, peak 2–4 h, oral bioavailability 6–20% (CAMH Appendix 5, camh-appendix.txt; Busse 2021 gives a narrower 13–19% for oral cannabinoids — a minor numeric discrepancy between two cited sources, flagged). Oil formulations are preferred by the guidance corpus because they are "easier to titrate and have more constant absorption and bioavailability"; edibles are not preferred (lack of standardisation, large absorption variability) and vaping is not preferred (absorption variability, no long-term safety data, vaping-related harms) — CAMH Appendix 5, verbatim. Sublingual bioavailability figures circulating in the wider literature (~12–35%) are UNVERIFIED — absent from the corpus, deliberately not cited.

contraindications

Labelled contraindications, verbatim from Sativex SmPC §4.3: hypersensitivity to cannabinoids or excipients; "any known or suspected history or family history of schizophrenia, or other psychotic illness; history of severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition"; breastfeeding ("in view of the considerable levels of cannabinoids likely in maternal breast milk and the potential adverse developmental effects in infants"). SmPC §4.4 adds: not recommended in serious cardiovascular disease (alterations in pulse rate and blood pressure observed on dose introduction; fainting episodes observed); not recommended under 18 years of age. Pregnancy is a standard exclusion across the guideline corpus. Hepatic impairment: see V1 EP-12.

interaction_flags

Full consolidated V1 screen by reference. Material rows for this entry: CNS depressants — most MS patients on baclofen/tizanidine/benzodiazepines are already carrying an additive-sedation burden, and the Cesamet label's cannabinoid-class interaction table names "Barbiturates, benzodiazepines, ethanol, lithium, opioids, buspirone, antihistamines, muscle relaxants, other CNS depressants → Additive drowsiness and CNS depression" (cesamet-label.txt) — the muscle-relaxant row is the specific hazard of this population. Also material: the SmPC's own note that "starting or stopping some concomitant medicinal products may require a new dose titration." Highly protein-bound narrow-therapeutic-index drugs (warfarin, cyclosporine, amphotericin B) per Marinol §7.4.

evidence_grade

B. Why not A, given that a Cochrane review and an FDA-class label both exist: the grade attaches to what this consult can actually recommend, which is a dispensary product, not the labelled spray. The molecule-level evidence is genuinely strong — Filippini 2022 Cochrane (PMID 35510826): "Compared with placebo, nabiximols probably reduces the severity of spasticity in the short-term in people with MS"; Whiting 2015 JAMA (PMID 26103030): "There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity"; Allan 2018: meta-analysis of 4 RCTs, positive global impression of change in spasticity RR 1.45 (95% CI 1.08–1.95), NNT 7, and where positive a ≥30% improvement carried NNT 10; CFPC 2021: ≥30% improvement in 35% on cannabinoids vs 25% on placebo, NNT 10, meta-analysis of 3 RCTs / 652 patients, "Most of the results are from multiple sclerosis patients (with a few spinal cord injury patients) using nabiximols." But Filippini also records: "We are uncertain about the effect on chronic neurological pain and health-related quality of life. Cannabinoids may increase slightly treatment discontinuation due to AEs, nervous system and psychiatric disorders compared with placebo." Grade B, and the ceiling is honest: roughly one additional patient in ten reaches a clinically meaningful improvement.

citations

1. 1. Sativex (nabiximols) SmPC, EMC — §2 composition (2.7 mg THC / 2.5 mg CBD per spray), §4.2 titration table and 4-week/20% stop rule, §4.3 contraindications, §4.4 warnings — sativex_smpc.txt (45,021 bytes; all quotations verified verbatim 2026-09-15).
2. 2. Filippini G et al. 2022, Cochrane Database Syst Rev, PMID 35510826 — nabiximols "probably reduces the severity of spasticity in the short-term." Abstract retrieved by PubMed efetch 2026-09-15; verbatim quote held in /home/mike/cannabinoid-evidence-summary.md §2. Full text not staged on disk — graded as a PubMed-verifiable review citation, not a corpus citation.
3. 3. Allan GM et al. 2018, Can Fam Physician 64(2):e78–e94, PMID 29449262 — spasticity RR 1.45 / NNT 7; harms NNH set — allan2018-cfp.txt (6,738 bytes, verified verbatim).
4. 4. Moulin D et al., CFPC 2021, Guidance in Authorizing Cannabis Products Within Primary Care, Recommendation 1 and the spasticity evidence section — cfpc-guidance2021.txt (212,029 bytes, verified verbatim at lines 498 and 2977–2990).
5. 5. MacCallum CA & Russo EB et al., Delphi consensus (20 experts, 9 countries) — rapid protocol balanced-ratio schedule — maccallum-delphi.txt (61,974 bytes, verified verbatim).
6. 6. Busse JW et al. 2021, BMJ 374:n2040, PMID 34497062 — cannabinoid half-lives; dose ranges — busse-bmj.txt (69,919 bytes). *V1 previously cited this source as "Busse 2018, BMJ 363:k4069" — a wrong and invalid identifier; corrected throughout V1 and the supporting memos on 2026-09-15 (see §Defects D-3).*
7. 7. CAMH, Cannabis and the Cannabinoids, Appendix 5 — route/onset/bioavailability, product-switch titration restart, strain-evidence statement — camh-appendix.txt (4,613 bytes, verified verbatim).

cannabinoid_ratio

1:1 balanced, as T1-01 — the guideline groups the two populations: CFPC 2021 Recommendation 1 covers "Spasticity (due to multiple sclerosis or spinal cord injury)" in one clause, on the same level-i footing, with the same nabiximols-first preference (cfpc-guidance2021.txt line 498). Grade C, not B — deliberately one grade below T1-01, because the trial population is overwhelmingly MS: CFPC states the meta-analysed 652 patients are "Most … from multiple sclerosis patients (with a few spinal cord injury patients) using nabiximols." The spinal-cord-injury signal is a minority subgroup inside an MS evidence base, and is labelled as such to the patient.

titration_steps

Identical to T1-01 steps 1–4 (labelled spray schedule preferred; MacCallum & Russo rapid balanced protocol as the DERIVED dispensary analog; 5-day reassessment floor; restart titration on product change). No separate schedule is invented for this population — the corpus contains none, and inventing one would be exactly the failure this library exists to avoid.

route + onset_profile

As T1-01. Added counselling point for wheelchair-using and transfer-dependent patients (DERIVED): the oral route's back-loaded profile (onset 30–60 min, peak 2–4 h, long half-life tail) means sedation and dizziness — the two most common adverse events, NNH 5 each — peak after the patient has typically committed to a transfer or a trip. Dose timing should be planned around transfers, not around mealtimes. This is a reasoned inference from the cited PK and the cited NNH figures; it is not stated in any source.

contraindications

As T1-01 (Sativex SmPC §4.3/§4.4 set, verbatim). Amplified: serious cardiovascular disease and orthostatic vulnerability, given documented pulse/BP alterations and fainting episodes on dose introduction.

interaction_flags

Full consolidated V1 screen by reference. Material rows: muscle relaxants (baclofen, tizanidine — the Cesamet class table's "Additive drowsiness and CNS depression" row); opioids (high co-prescription in this population); benzodiazepines; anticholinergics (very common for neurogenic bladder in SCI — the Cesamet table records "Atropine, scopolamine, antihistamines, other anticholinergic agents → Additive or super-additive tachycardia, drowsiness", verbatim, cesamet-label.txt).

evidence_grade

C

citations

1. 1. CFPC 2021 Recommendation 1 and spasticity evidence section (MS and spinal cord injury; the "few spinal cord injury patients" caveat) — cfpc-guidance2021.txt.
2. 2. Sativex SmPC — ratio, titration, stop rule, contraindications — sativex_smpc.txt.
3. 3. Cesamet (nabilone) FDA label, cannabinoid-class drug-interaction table — cesamet-label.txt (34,008 bytes, verified verbatim).
4. 4. Marín AG et al. 2017, Complement Ther Med, PMID 28917371 — "Cannabinoids for spasticity due to multiple sclerosis or paraplegia" — the one review in the evidence pass whose title names the non-MS population. Abstract identified via the 2026-09-15 PubMed pass (/home/mike/cannabinoid-evidence-summary.md §2); full text not staged, effect sizes not quoted here — UNVERIFIED at the numeric level and deliberately not used to support any number.
5. 5. PA Act 16 Serious Medical Conditions roster — research/08-qualifying-conditions-inventory.md §A.0 (VERIFIED against PA-DOH SMC Annual Summary PDF).

cannabinoid_ratio

1:1 THC:CBD or THC-containing, titrated. CBD alone is NOT established here. The RCT-validated cannabinoid comparator with a labelled dose unit remains nabiximols 1:1 (2.7 mg THC + 2.5 mg CBD per spray). Guideline support for the indication exists — the CFPC route is "refractory neuropathic pain … after reasonable trials of standard therapies have failed. If considering medical cannabinoids and criteria are met, the guideline recommends nabilone or nabiximols be tried first" (cfpc-guidance2021.txt line 1572, verbatim) — but the pooled evidence is worse than V1 assumed. Grade C.

titration_steps

1. 01 CBD-predominant first, THC added second — MacCallum & Russo Delphi routine protocol, verbatim: "initiates the patient on a CBD-predominant variety at a dose of 5 mg CBD twice daily and titrates the CBD-predominant dose by 10 mg every 2 to 3 days until the patient reaches their goals, or up to 40 mg/day" (maccallum-delphi.txt).
2. 02 Adding THC — the CONTESTED step. The corpus contains two consensus schedules that disagree, and the entry cites both rather than choosing: - Sihota 2021 (Int J Clin Pract 75(8):e13871, PMID 33249713), verbatim: "When adding THC, start with 0.5-3 mg, and increase by 1-2 mg once or twice weekly up to 30-40 mg/day." (clinther-dosing-pubmed.txt / sihota-consensus.txt) - MacCallum & Russo Delphi routine, verbatim: "clinicians may consider adding THC at 2.5 mg and titrate by 2.5 mg every 2 to 7 days until a maximum daily dose of 40 mg/day of THC." (maccallum-delphi.txt) CONTESTED — escalated to the reviewer as a clinical judgement, not resolved by substitution. Sihota's is materially slower. A conservative reviewer may prefer it; that is the reviewer's call to make, in writing. - Conservative variant for older adults / polypharmacy, MacCallum & Russo conservative protocol verbatim: CBD-predominant 5 mg once daily, titrate 10 mg every 2–3 days to 40 mg/day; then THC at 1 mg/day, titrate by 1 mg every 7 days to max 40 mg/day. CAMH adds the floor: "Inexperienced users, older adults or patients with comorbidity or polypharmacy may only tolerate 2.5 mg CBD or 1 mg THC" (camh-appendix.txt).
3. 03 Reassessment window: 5×-half-life rule as T1-01 — no increment judged inside 5 days.

route + onset_profile

Oromucosal/sublingual preferred where a measured-dose transmucosal product exists (intermediate onset); oral oil otherwise (onset 30–60 min, peak 2–4 h, bioavailability 6–20%, CAMH). Inhaled reserved for breakthrough only, per V1 EP-08 — and the reason is dose accountability: "For a patient using inhaled THC 10%, a 0.5 g joint may provide 7.5–25 mg THC" (CAMH, verbatim), a delivered-dose band too wide to titrate against. Route-first, potency-second.

contraindications

As T1-01's labelled set (psychosis history/family history; severe personality disorder or significant psychiatric disorder; breastfeeding; serious cardiovascular disease; under 18). Pregnancy. Hepatic impairment per V1 EP-12. Added, and specific to this entry: a patient for whom the benefit-harm balance has already tipped — Mücke 2018's conclusion is not a footnote, it is a gate.

interaction_flags

Full consolidated V1 screen by reference. Material rows: CNS depressants (this cohort's opioid and gabapentinoid co-prescription rate is the real hazard); TCAs (amitriptyline is first-line for neuropathic pain and the Cesamet class table records "Amitriptyline, amoxapine, desipramine, other tricyclic antidepressants → Additive tachycardia, hypertension, drowsiness", verbatim); warfarin; highly protein-bound NTI drugs per Marinol §7.4.

evidence_grade

C (downgraded from V1's B)

citations

1. 1. *Mücke M et al. 2018, Cochrane Database Syst Rev, PMID 29513392 — "Cannabis-based medicines for chronic neuropathic pain in adults"; 16 studies, 1,750 participants. Authors' conclusions, verbatim: "The potential benefits of cannabis-based medicine (herbal cannabis, plant-derived or synthetic THC, THC/CBD oromucosal spray) in chronic neuropathic pain might be outweighed by their potential harms."* Abstract retrieved by PubMed efetch 2026-09-15; verbatim quote held in /home/mike/cannabinoid-evidence-summary.md §1 and research/08-qualifying-conditions-inventory.md Part B. Full text not staged on disk — PubMed-verifiable review citation.
2. 2. Allan GM et al. 2018, Can Fam Physician 64(2):e78–e94 — harms NNH set; and the conclusion, verbatim: "There is some uncertainty about whether cannabinoids improve pain, but if they do, it is neuropathic pain and the benefit is likely small." — allan2018-cfp.txt.
3. 3. Busse JW et al. 2021, BMJ 374:n2040, PMID 34497062 — weak recommendation to offer a trial of non-inhaled medical cannabis in addition to standard care; "The recommendation is weak because of the close balance between benefits and harms" — busse-bmj.txt, verified verbatim.
4. 4. Sihota A, Smith BK, Ahmed SA et al. 2021, Int J Clin Pract 75(8):e13871, PMID 33249713 — THC titration — clinther-dosing-pubmed.txt / sihota-consensus.txt.
5. 5. MacCallum CA & Russo EB et al., Delphi consensus — routine and conservative protocols — maccallum-delphi.txt.
6. 6. CFPC 2021 — refractory-neuropathic-pain routing; pharmaceutical-cannabinoid-first — cfpc-guidance2021.txt.
7. 7. CAMH Appendix 5 — conservative floors, route/onset, inhaled delivered-dose band — camh-appendix.txt.

cannabinoid_ratio

NONE RECOMMENDED FROM THE DISPENSARY SIDE. This is the single most important posture statement in the document. Every RCT-backed, labelled CINV claim in the corpus belongs to a prescription synthetic cannabinoid — dronabinol (Marinol) or nabilone (Cesamet) — administered under an oncology prescriber. There is no modern herbal-cannabis CINV RCT anywhere in the corpus, and the guideline route is explicitly through the pharmaceutical: CFPC 2021 Recommendation 1, verbatim — "Nausea/vomiting due to chemotherapy, after failure to respond to standard therapies and a trial of the pharmaceutical cannabinoid nabilone (level i)" (cfpc-guidance2021.txt line 502). A dispensary product recommended for CINV is a Grade D claim and is barred by the refusal list. The distinction is not a technicality: the labelled products are single molecules at a stated milligram dose, taken on a fixed schedule relative to the chemotherapy infusion. A dispensary flower or edible is none of those things. Grade B for the labelled-synthetic facts below; Grade D for any dispensary-CINV product claim.

titration_steps

1. 01 These are the labelled prescribing schedules of drugs this service does not dispense, reproduced so the consultant can counsel accurately and screen interactions against them. They are not a dispensary protocol and must never be presented as one. - Dronabinol (Marinol), CINV indication — labelled for "Nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments" (§1). Starting dosage verbatim (§2.2): "5 mg/m2, orally administered 1 to 3 hours prior to the administration of chemotherapy and then every 2 to 4 hours after chemotherapy, for a total of 4 to 6 doses per day." Elderly: "consider initiating MARINOL at 2.5 mg/m2 once daily 1 to 3 hours prior to chemotherapy." Administration: "Administer the first dose on an empty stomach at least 30 minutes before eating. Subsequent doses can be taken without regard to meals." Titration: "in increments of 2.5 mg/m2." "The maximum dosage is 15 mg/m2 per dose for 4 to 6 doses per day." The label adds, verbatim: "Adverse reactions are dose-related and psychiatric symptoms increase significantly at the maximum dosage." Capsules: 2.5 mg, 5 mg, 10 mg. (marinol-label.txt, all verified verbatim.) - Nabilone (Cesamet), CINV indication — labelled for the same refractory population, with the label's own unusually blunt rationale, verbatim: "This restriction is required because a substantial proportion of any group of patients treated with Cesamet can be expected to experience disturbing psychotomimetic reactions not observed with other antiemetic agents." Dosage verbatim: "The usual adult dosage is 1 or 2 mg b.i.d. On the day of chemotherapy, the initial dose should be given 1 to 3 hours before the chemotherapeutic agent is administered. To minimize side effects, it is recommended that the lower starting dose be used and that the dose be increased as necessary. A dose of 1 or 2 mg the night before may be useful. The maximum recommended daily dose is 6 mg given in divided doses t.i.d." May be given 2–3× daily through each chemotherapy cycle "and, if needed, for 48 hours after the last dose of each cycle." (cesamet-label.txt, verified verbatim.) Busse 2021 gives the same daily range independently: "from 0.2 mg to 6 mg/day for nabilone" (busse-bmj.txt line 676). - Dispensary-side titration: none is offered. Not a conservative one, not a low-dose one, not an "at least let's make it safer" one. The consult's dispensary-side actions are
2. 02 refer to the oncology prescriber,
3. 03 run the interaction screen,
4. 04 document.

route + onset_profile

Labelled dronabinol and nabilone are oral capsules. Dronabinol's first dose is timed to the infusion (1–3 h prior) and taken on an empty stomach ≥30 min before eating; the label adds that "The timing of dosing in relation to meal times should be kept consistent for each chemotherapy cycle." No dispensary-route counselling for CINV is offered — not oral, not inhaled, not sublingual. A patient actively vomiting cannot reliably retain an oral dispensary product either, which is precisely why the labelled schedule is anchored to the pre-infusion window rather than to symptom onset (DERIVED — the clinical logic is ours, the schedule is the label's).

contraindications

Marinol §4, verbatim: "History of a hypersensitivity reaction to dronabinol or sesame oil." Marinol §5.1: "Avoid use in patients with a psychiatric history." Marinol §5.2 hemodynamic instability in cardiac disorders. Marinol §5.3 seizure history — "Weigh this potential risk against the benefits before prescribing MARINOL to patients with a history of seizures, including those receiving anti-epileptic medication" (see T1-09/T1-10). Pregnancy: CFPC 2021, verbatim — "guidelines strongly recommend against their use in pregnancy." And the categorical one: any marketing-level "dispensary product for chemo nausea" positioning is contraindicated as a matter of policy, not pharmacology.

interaction_flags

This entry's real deliverable. Full consolidated V1 screen by reference, plus: highly protein-bound narrow-therapeutic-index drugs — Marinol §7.4 verbatim: "Dronabinol is highly bound to plasma proteins, and therefore, might displace and increase the free fraction of other concomitantly administered protein-bound drugs… monitor patients for increased adverse reactions to narrow therapeutic index drugs that are highly protein-bound (e.g., warfarin, cyclosporine, amphotericin B)." CYP inhibitors/inducers — Marinol §7.3 verbatim: dronabinol "is primarily metabolized by CYP2C9 and CYP3A4"; monitor with CYP2C9 inhibitors ("amiodarone, fluconazole") and CYP3A4 inhibitors ("ketoconazole, itraconazole, clarithromycin, ritonavir, erythromycin, grapefruit juice") — fluconazole and the azoles are routine supportive care in oncology, which makes this row live rather than theoretical. CNS depressants — opioid analgesia is near-universal in this population; Marinol §7.1 verbatim: "Additive CNS effects (e.g., dizziness, confusion, sedation, somnolence) may occur when MARINOL is taken concomitantly with drugs that have similar effects on the central nervous system"; Cesamet: "Additive drowsiness and CNS depression." Additive cardiac effects — Marinol §7.2 (hypotension, hypertension, syncope, tachycardia), relevant with anthracycline-exposed patients (the anthracycline linkage is DERIVED — the label names the class effect, not the chemotherapy agent). Interaction with the antiemetic regimen itself: no corpus evidence of a clinically significant PK interaction between cannabinoids and the 5-HT3 antagonist (ondansetron-class) or NK1 antagonist regimens — UNVERIFIED, absent from the corpus, and therefore counselled as additive-sedation risk only, with no specific PK numbers cited.

evidence_grade

B (labelled-synthetic facts) / D (dispensary-CINV recommendation — excluded to the refusal list)

citations

1. 1. Marinol (dronabinol) FDA label — §1 indication, §2.2 dosing/titration/maximum, §4 contraindication, §5.1–5.5 warnings, §7.1–7.4 interactions — marinol-label.txt (59,379 bytes, all quotations verified verbatim 2026-09-15).
2. 2. Cesamet (nabilone) FDA label — indication + psychotomimetic-reaction rationale, dosage, class interaction table — cesamet-label.txt (34,008 bytes, verified verbatim).
3. 3. CFPC 2021, Recommendation 1 and the CINV evidence section — cfpc-guidance2021.txt: control of nausea/vomiting in 47% of cannabinoid users vs 13% placebo (NNT 3, meta-analysis of 7 RCTs, 500 patients); vs neuroleptics 31% vs 16% (NNT 7, 14 RCTs, 1,022 patients); "Most studies lasted one day (after chemotherapy) and involved nabilone or dronabinol"; and the caveat that matters — "The RCTs were often quite old (e.g., four of seven in the placebo meta-analysis were more than 35 years old) and treatment regimens have changed considerably." All verified verbatim at lines 2954–2976.
4. 4. Allan GM et al. 2018, Can Fam Physician — CINV meta-analysis of 7 RCTs, RR 3.60 (95% CI 2.55–5.09), NNT 3; conclusion verbatim: "There is reasonable evidence that cannabinoids improve nausea and vomiting after chemotherapy" — allan2018-cfp.txt.
5. 5. *Grimison P et al. 2020, Support Care Cancer, PMID 31916006 — the modern-comparator caveat, verbatim: "Although there exists some evidence suggesting that oral cannabinoids may have a role in controlling for emesis from a neurophysiological perspective, these conclusions are currently not mirrored in the published RCTs to date."* PubMed efetch 2026-09-15; quote held in /home/mike/cannabinoid-evidence-summary.md §3. Full text not staged — PubMed-verifiable review citation.
6. 6. Whiting PF et al. 2015, JAMA, PMID 26103030 — "There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy" — same source file.
7. 7. Busse JW et al. 2021, BMJ 374:n2040 — labelled daily dose ranges (dronabinol 2.5–40 mg; nabilone 0.2–6 mg) — busse-bmj.txt.

cannabinoid_ratio

None recommended. See T1-04. The entry's function is (1) the honest decline, delivered without abandoning the patient, (2) the referral to oncology for the labelled synthetics, (3) the full interaction screen against the chemotherapy and supportive-care regimen, (4) documentation back to the treating team.

titration_steps

None. Where oncology has already initiated dronabinol or nabilone, the consultant's legitimate role narrows to: (a) reconciling the labelled schedule against what the patient is actually doing — the dronabinol empty-stomach and infusion-timing instructions are the two most commonly missed; (b) the full interaction screen; (c) reporting discrepancies to the oncology prescriber. No initiation, no titration advice, no dose suggestion. (DERIVED posture — flagged for reviewer approval.)

route + onset_profile

n/a — no dispensary route is recommended. Counselling point where a patient is already inhaling: the CAMH delivered-dose band for inhaled product ("a 0.5 g joint may provide 7.5–25 mg THC") is incompatible with any accountable dosing conversation during active chemotherapy.

contraindications

Active chemotherapy with an uncontrolled emetic burden is an oncology problem, not a dispensary problem. Neutropenia and smoked/vaporised product: UNVERIFIED — no corpus source addresses inhalational risk in neutropenic patients. It is flagged here rather than asserted, because it is an obvious reviewer question and the honest answer is that the corpus does not answer it.

interaction_flags

As T1-04 — this is the entry's entire clinical value. Screen the full V1 consolidated list plus: azole antifungals and macrolides (CYP3A4 inhibitors, routine oncology supportive care); warfarin and cyclosporine (Marinol §7.4 protein-binding displacement); opioid analgesia (additive CNS depression); the antiemetic regimen (additive sedation only — no PK numbers, none exist in the corpus).

evidence_grade

D for the indication (refusal-and-referral posture entry; the interaction-screening function is graded B, resting on labelled §7 text)

citations

1. 1. Marinol FDA label §5.5 (paradoxical nausea/vomiting/abdominal pain), §7.1–7.4 — marinol-label.txt.
2. 2. Cesamet FDA label — psychotomimetic reactions; class interaction table — cesamet-label.txt.
3. 3. CFPC 2021 Recommendation 1 (nabilone-first routing) and CINV evidence section (age of the trial base) — cfpc-guidance2021.txt.
4. 4. CAMH Appendix 5 — inhaled delivered-dose band — camh-appendix.txt.
5. 5. V1 NAU-CINV-01 and SLP-HR-01 — the refusal and harm-reduction patterns this entry extends — build/PROTOCOL-LIBRARY-V1-sleep-anxiety-ptsd-nausea.md.

cannabinoid_ratio

THC-containing; the labelled anchor is dronabinol, a single molecule. Dronabinol is labelled for "Anorexia associated with weight loss in patients with AIDS" (Marinol §1, verbatim) — this is one of only two FDA-labelled cannabinoid indications in the corpus and it is specific to this population. Where a state pathway permits, the guideline-consistent first move is the prescription synthetic via the treating HIV clinician, not a dispensary substitute. Grade C — and the grade is low on purpose, because the underlying trial evidence is weak and partly negative (see evidence_grade).

titration_steps

1. 01 "The recommended adult starting dosage of MARINOL is 2.5 mg orally twice daily, one hour before lunch and dinner."
2. 02 "In elderly patients or patients unable to tolerate 2.5 mg twice daily, consider initiating MARINOL at 2.5 mg once daily one hour before dinner or at bedtime to reduce the risk of central nervous system (CNS) symptoms." The label notes "Dosing later in the day may reduce the frequency of CNS adverse reactions" and that CNS reactions "usually resolve in 1 to 3 days and usually do not require dosage reduction."
3. 03 "If tolerated and further therapeutic effect is desired, the dosage may be increased gradually to 2.5 mg one hour before lunch and 5 mg one hour before dinner… Most patients respond to 2.5 mg twice daily, but the dose may be further increased to 5 mg one hour before lunch and 5 mg one hour before dinner, as tolerated."
4. 04 "Maximum Dosage: 10 mg twice daily." Dispensary-side (DERIVED — flagged): where a patient holds a card and a labelled product is not accessible, the only defensible analog is a measured oral THC-containing oil at the corpus's conservative floor — CAMH: "Starting doses for THC may be 1–2.5 mg THC, once daily in the evening," titrated "by 1–2.5 mg THC every 5 days to minimal effective dose, with maximum dose of 40 mg per day", with the explicit floor that "Inexperienced users, older adults or patients with comorbidity or polypharmacy may only tolerate 2.5 mg CBD or 1 mg THC" (camh-appendix.txt, verbatim). Dose timing is the one place the labelled schedule genuinely informs the dispensary analog: dronabinol's labelled timing is one hour before a meal, because the therapeutic target is the meal. Carrying that timing across is DERIVED but well-grounded. The polypharmacy floor is the operative one in this population, which is by definition on lifelong combination antiretroviral therapy.

route + onset_profile

Oral, timed to meals — onset 30–60 min, peak 2–4 h (CAMH), which is why the labelled instruction is one hour pre-meal. Oral oil preferred over edibles ("Edibles are not preferred due to lack of standardization and large variability in absorption and bioavailability" — CAMH, verbatim). Inhaled is not recommended for an appetite indication: the 7.5–25 mg delivered-dose band makes the dose unaccountable, and — separately and importantly — *the one corpus-documented antiretroviral PK interaction is specific to smoked cannabis* (see interaction_flags), which makes the route choice a drug-interaction decision, not just a titration one.

contraindications

Marinol §4 (hypersensitivity to dronabinol or sesame oil); §5.1 psychiatric history; §5.2 cardiac disorders / hemodynamic instability; §5.3 seizure history; §5.4 — verbatim: "Patients with a history of substance abuse or dependence, including marijuana or alcohol, may be more likely to abuse MARINOL as well" — a row that must be handled without stigma but not skipped. Pregnancy/breastfeeding. Uncontrolled or newly diagnosed HIV, or any suspicion of treatment failure or opportunistic infection → referral, not protocol management.

interaction_flags

The antiretroviral screen is this entry's deliverable, and it is a real, documented interaction — not a theoretical one. Full V1 consolidated screen by reference, plus: - HIV protease inhibitors as CYP3A4 inhibitors (direction: they raise THC). Health Canada's monograph names the class explicitly, verbatim: "HIV protease inhibitors (e.g. ritonavir, indinavir, nelfinavir, saquinavir, telaprevir, atazanavir, boceprevir, lopinavir), … can potentially increase the bioavailability of Δ9-THC (and metabolites such as 11-hydroxy-THC) as well as the risk of experiencing THC- and 11-hydroxy-THC-related side effects" (hc-html.txt). Ritonavir is independently named as a CYP3A4 inhibitor in the Marinol label §7.3 (marinol-label.txt, verbatim) — two independent on-disk sources agree. Action: treat a ritonavir- or cobicistat-boosted regimen as a reason to start at the bottom of the dose range and titrate more slowly than the schedule above. (Cobicistat is a pharmacologic booster of the same mechanism; it is UNVERIFIED — named in neither source — and is flagged as an obvious reviewer question rather than asserted.) - Cannabis effects on protease-inhibitor levels (direction: smoked cannabis lowers them). Antón 2022's interaction table, verbatim: Indinavir — "Minor / Defined / Possible CYP3A4 inhibition. In a clinical trial, the maximum concentration of indinavir decreased by 14.1% using THC cigarettes in patients who use indinavir. There were no statistically significant changes with dronabinol usage." Nelfinavir — "Lack / Defined. Co-administration with THC cigarettes does not lead to significant changes in nelfinavir levels and AUC." (anton2022_clinrelevance.txt, verified verbatim.) Health Canada records the same underlying study and the crucial clinical qualifier, verbatim: "smoking cannabis was associated with lower plasma concentrations of the protease inhibitors indinavir and nelfinavir; whereas dronabinol or placebo had no effect… However, the decreased plasma levels of protease inhibitors were not associated with an elevated viral load, or changes in CD4+ or CD8+ cell counts." (hc-html.txt.) Action: do not tell a patient cannabis will cause treatment failure — the corpus does not support that. Do tell them the smoked route has a measured PK effect that the oral route did not, and route the conversation to oral. Any viral-load question goes to the HIV clinician, not to this consult. - Efavirenz (CYP2B6). The Epidiolex label §7.2 names "CYP2B6 substrates (e.g., bupropion, efavirenz)" among in-vitro-predicted CBD interactions, with the instruction to "consider adjusting dosage of substrates of CYP1A2 and CYP2B6, as clinically appropriate" (epidiolex_label2018.txt, verbatim). This is in-vitro prediction at pharmaceutical CBD exposure, not a measured dispensary-dose interaction — flagged as such, and it is a flag-and-refer, not a dose instruction. - CNS depressants; highly protein-bound NTI drugs (Marinol §7.4) — by reference.

evidence_grade

C — and the entry states the weakness to the patient rather than burying it. Mücke 2018 (J Cachexia Sarcopenia Muscle, PMID 29400010), verbatim: "In human immunodeficiency virus (HIV) patients, cannabinoids were superior to placebo for weight gain (SMD: 0.57 [0.22; 0.92]; P = 0.001) and appetite (SMD: 0.57 [0.11; 1.03]; P = 0.02)." Whiting 2015 grades the same signal: "There was low-quality evidence suggesting that cannabinoids were associated with improvements in … weight gain in HIV infection." And the corpus's most sobering number, CFPC 2021 verbatim: "Four RCTs have examined the use of cannabinoids for appetite stimulation in HIV, with two finding no difference between cannabinoids and placebo, one finding a 2 kg greater improvement with cannabinoids over placebo, and one finding megestrol resulted in an 8.5 kg greater weight gain compared with cannabinoids." (cfpc-guidance2021.txt lines 2641–2645.) An existing, non-cannabinoid drug outperformed cannabinoids by 8.5 kg in one of the four trials. The patient is told that.

citations

1. 1. Marinol (dronabinol) FDA label — §1 AIDS-anorexia indication, §2.1 full titration and 10 mg BID maximum, §4–§5.5 warnings, §7.3 ritonavir — marinol-label.txt (59,379 bytes, verified verbatim).
2. 2. CFPC 2021 — the four-RCT HIV appetite summary including the megestrol comparison — cfpc-guidance2021.txt (212,029 bytes, verified verbatim at lines 2641–2645).
3. 3. *Mücke M et al. 2018, J Cachexia Sarcopenia Muscle, PMID 29400010* — HIV weight/appetite SMDs. PubMed efetch 2026-09-15; verbatim quote in /home/mike/cannabinoid-evidence-summary.md §5. Full text not staged — PubMed-verifiable review citation.
4. 4. Whiting PF et al. 2015, JAMA, PMID 26103030 — low-quality-evidence grading for HIV weight gain — same source.
5. 5. Antón J et al. 2022, J Clin Med — indinavir/nelfinavir interaction rows — anton2022_clinrelevance.txt (45,022 bytes, verified verbatim).
6. 6. Health Canada, Information for Health Care Professionals: Cannabis and the cannabinoids — protease-inhibitor CYP3A4 class list; the indinavir/nelfinavir study and its viral-load qualifier — hc-html.txt (1,408,670 bytes, verified verbatim).
7. 7. Epidiolex FDA label §7.2 — CYP2B6/efavirenz in-vitro prediction — epidiolex_label2018.txt (91,275 bytes, verified verbatim).
8. 8. CAMH Appendix 5 — conservative THC floor, polypharmacy floor, route preferences — camh-appendix.txt.

cannabinoid_ratio

As T1-03 (NEU-PN-03) — 1:1 balanced or THC-containing, titrated; CBD alone not established. No separate ratio logic is invented for this population. Grade C, inherited from T1-03 and not upgraded: the corpus contains bibliographic evidence that HIV-neuropathy RCTs exist — CFPC 2021's reference list includes "HIV-associated sensory neuropathy: a randomized placebo-controlled trial" and "Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover…" (cfpc-guidance2021.txt lines 3228, 3234) — but those trials' methods and numbers are NOT staged on disk and are therefore UNVERIFIED. No figure from them is used anywhere in this entry. Their existence is disclosed; their results are not borrowed.

titration_steps

T1-03 steps 1–3 unchanged, with the polypharmacy floor applied by default (CAMH: "patients with comorbidity or polypharmacy may only tolerate 2.5 mg CBD or 1 mg THC") — every patient in this entry is on combination antiretroviral therapy, so the conservative protocol is the starting assumption rather than the exception. Both CONTESTED consensus THC schedules (Sihota 2021 vs MacCallum & Russo Delphi) are carried across and both are disclosed to the reviewer.

route + onset_profile

Oral oil, and the route choice is an interaction decision here. The one measured antiretroviral PK interaction in the corpus (indinavir Cmax −14.1%) was observed with THC cigarettes, and explicitly not with dronabinol (Antón 2022, verbatim). Oral is therefore preferred on interaction grounds as well as dose-accountability grounds — which is an unusually well-supported route recommendation by this library's standards, and is stated to the patient as such. Onset 30–60 min, peak 2–4 h, bioavailability 6–20% (CAMH).

contraindications

As T1-03 / T1-06. Plus: a patient with uncontrolled HIV, suspected treatment failure, or a new opportunistic process → referral, not protocol management.

interaction_flags

The full T1-06 antiretroviral panel applies unchanged — protease inhibitors as CYP3A4 inhibitors raising THC (Health Canada class list; ritonavir also named in Marinol §7.3); smoked cannabis lowering indinavir Cmax by 14.1% with no dronabinol effect and no viral-load change (Antón 2022; Health Canada); efavirenz/CYP2B6 in-vitro prediction (Epidiolex §7.2). Plus the T1-03 neuropathic rows: TCAs (amitriptyline — additive tachycardia/hypertension/drowsiness per the Cesamet class table), gabapentinoids and opioids via the CNS-depressant row, warfarin, protein-bound NTI drugs.

evidence_grade

C

citations

1. 1. Mücke M et al. 2018, Cochrane, PMID 29513392 — the neuropathic benefit-harm conclusion that sets this entry's ceiling — PubMed-verifiable; quote held in /home/mike/cannabinoid-evidence-summary.md §1.
2. 2. Allan GM et al. 2018, Can Fam Physician — "if they do, it is neuropathic pain and the benefit is likely small"; harms NNH set — allan2018-cfp.txt.
3. 3. Antón J et al. 2022, J Clin Med — indinavir/nelfinavir rows — anton2022_clinrelevance.txt.
4. 4. Health Canada monograph — protease-inhibitor class; the viral-load qualifier — hc-html.txt.
5. 5. CFPC 2021 — refractory-neuropathic-pain routing; and its reference list as the disclosure that HIV-neuropathy RCTs exist but are not staged here — cfpc-guidance2021.txt lines 1572, 3228, 3234.
6. 6. CAMH Appendix 5 — polypharmacy floor; route/onset — camh-appendix.txt.
7. 7. Sihota 2021 (clinther-dosing-pubmed.txt) and MacCallum & Russo Delphi (maccallum-delphi.txt) — the two CONTESTED THC schedules.

cannabinoid_ratio

None recommended, and the reason is specific rather than generic. The entire labelled and RCT-backed cannabinoid antiemetic evidence base is chemotherapy-induced nausea and vomiting. CFPC 2021 states the boundary verbatim: "There is a lack of evidence to support the use of cannabinoids in other types of nausea and vomiting." (cfpc-guidance2021.txt line 2968.) Antiretroviral-associated nausea is "other types." Grade D for the indication. The dronabinol label reaches this population only through the appetite indication (T1-06), not through an antiemetic one — a distinction that is easy to blur and must not be.

titration_steps

1. 01 None. The consultant's legitimate functions:
2. 02 route the nausea question to the HIV clinician — antiretroviral-associated nausea is often a regimen problem with a regimen solution, and a cannabinoid layered on top can mask a tolerability signal that should prompt a switch (DERIVED — the clinical logic is ours);
3. 03 note that where the same patient has a separate, supportable indication under T1-06, any incidental nausea change is a co-benefit, never a nausea claim (the V1 SLP-CO-01 co-benefit pattern applied here);
4. 04 run the antiretroviral interaction screen;
5. 05 document.

route + onset_profile

n/a — no route recommended for this indication. Where the patient is on a T1-06 appetite protocol, that entry's oral, meal-timed route governs.

contraindications

As T1-06. Plus the categorical one: presenting any product as an antiemetic for non-chemotherapy nausea is barred by the refusal list.

interaction_flags

The full T1-06 antiretroviral panel by reference — protease inhibitors as CYP3A4 inhibitors (Health Canada class list; ritonavir in Marinol §7.3); smoked cannabis vs indinavir Cmax −14.1%, no dronabinol effect, no viral-load change (Antón 2022; Health Canada); efavirenz/CYP2B6 (Epidiolex §7.2, in-vitro). Plus the consolidated V1 screen.

evidence_grade

D for the indication (refusal-and-referral posture; the interaction-screening function is graded B on labelled §7 text)

citations

1. 1. CFPC 2021 — "There is a lack of evidence to support the use of cannabinoids in other types of nausea and vomiting"; and "use in pregnancy is strongly recommended against" — cfpc-guidance2021.txt, verified verbatim.
2. 2. Marinol FDA label — §1 (the indication is anorexia in AIDS, not nausea); §5.5 paradoxical nausea — marinol-label.txt.
3. 3. Antón J et al. 2022 — antiretroviral rows — anton2022_clinrelevance.txt.
4. 4. Health Canada monograph — protease-inhibitor class; viral-load qualifier — hc-html.txt.

cannabinoid_ratio

NONE. NO PRODUCT RECOMMENDATION IS MADE OR PERMITTED FROM THIS ENTRY. The paradox that defines it: epilepsy carries the strongest cannabinoid evidence in the entire review — and none of it transfers to a dispensary. The evidence is for purified pharmaceutical cannabidiol (Epidiolex-class), at weight-based milligram-per-kilogram doses, in two named rare syndromes, under a neurologist, with mandatory baseline and serial liver monitoring. Specifics, all verified verbatim: - Indication is narrow and named — Epidiolex label §1: "EPIDIOLEX is indicated for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) in patients 2 years of age and older." (epidiolex_label2018.txt.) Not "epilepsy." Two syndromes. - Dose is weight-based and pharmaceutical-scale — §2.2: "The starting dosage is 2.5 mg/kg twice daily (5 mg/kg/day). After one week, the dosage can be increased to a maintenance dosage of 5 mg/kg twice daily (10 mg/kg/day)… up to a maximum recommended maintenance dosage of 10 mg/kg twice daily (20 mg/kg/day), in weekly increments of 2.5 mg/kg twice daily." For a 70 kg adult that is 700 mg to 1,400 mg of CBD per day. A dispensary CBD product is not this, and no titration ladder in this library reaches it — the library's own CBD ceiling is 40 mg/day (CAMH/MacCallum), roughly 1/20th of the low end of the labelled maintenance dose (arithmetic is DERIVED; both inputs are verbatim). - Monitoring is mandatory before the first dose — §2.1: "Because of the risk of hepatocellular injury, obtain serum transaminases (ALT and AST) and total bilirubin levels in all patients prior to starting treatment." Then at 1, 3 and 6 months and periodically thereafter. A dispensary cannot order or act on these labs. That is the whole argument. - Who prescribes — CFPC 2021, verbatim: "This niche of therapy is more applicable to neurologists and pediatric neurologists and is far less applicable to comprehensive primary care clinicians," and "Family physicians would not initiate this treatment for this subpopulation." If a family physician would not initiate it, a dispensary consultant certainly does not. Grade: A for the molecule in its labelled syndromes; D — refused — for any dispensary product recommendation in epilepsy. (This is the only place in either library where Grade A appears, and it is attached to something the service does not and will not supply.)

titration_steps

1. 01 None. No dispensary titration exists for this entry and none may be created. The consultant's legitimate functions, in order: **
2. 02 confirm the patient stays on the prescribed regimen — the label's §5.5 is the reason (see stop_rule);
3. 03 run the antiepileptic interaction panel below and report it to the neurologist;
4. 04 screen for THC-containing products the patient may be using for an unrelated reason (see T1-10);
5. 05 document and refer. Where the patient is on prescribed Epidiolex, the reconciliation points worth checking are the labelled ones: whether baseline transaminases and bilirubin were drawn, whether the 1/3/6-month labs are current, and whether clobazam or valproate is co-prescribed. None of this is dosing advice; all of it is pharmacist medication-safety work.**

route + onset_profile

n/a. No route is recommended. The labelled product is an oral solution taken twice daily; that is a fact about someone else's prescription, not a route recommendation from this consult.

contraindications

The indication itself is out of scope for product matching. Additionally, and importantly for the rest of the library: a history of seizure disorder is a flagged caution for THC-containing products anywhere in this document — Marinol §5.3, verbatim: "Seizure and seizure-like activity have been reported in patients receiving dronabinol. Weigh this potential risk against the benefits before prescribing MARINOL to patients with a history of seizures, including those receiving anti-epileptic medication or with other factors that can lower the seizure threshold. Monitor patients with a history of seizure disorders for worsened seizure control during MARINOL therapy." See T1-10.

interaction_flags

This panel IS the entry. It is also the best-evidenced interaction content in either library. | Interacting drug | Source & strength | Documented magnitude (verbatim) | Action | |---|---|---|---| | Clobazam | Epidiolex label §7.2 + §12.3; Geffrey 2015 (PMID 26114620) clinical study; strongest interaction evidence in the corpus | Label: "Coadministration of EPIDIOLEX produces a 3-fold increase in plasma concentrations of N-desmethylclobazam"; §12.3: coadministration "increased the cannabidiol active metabolite 7-OH CBD mean Cmax by 73% and AUC by 47%; and increased the clobazam active metabolite, N-desmethylclobazam, Cmax and AUC by approximately 3-fold." Geffrey 2015 (13 children on CLB+CBD): "The mean increase in CLB levels was 60 ± 80%… the mean increase in nCLB levels was 500 ± 300% (95% CI [+90-610%] at 4 weeks)"; CLB doses were reduced in 10 of 13 (77%) subjects; side effects in 10 of 13 (77%), "alleviated with CLB dose reduction." | Report to the neurologist. Label action: "Consider a reduction in dosage of clobazam if adverse reactions known to occur with clobazam are experienced." Clobazam level monitoring is the named clinical requirement (Geffrey: "Monitoring of CLB and nCLB levels is necessary for clinical care"). | | Valproate (with CBD) — hepatic | Epidiolex label §5.1 + §7.3 | ALT >3× ULN incidence in Epidiolex-treated patients: 30% on concomitant valproate and clobazam; 21% on valproate without clobazam; 4% on clobazam without valproate; 3% on neither. Also dose-related: 17% at 20 mg/kg/day vs 1% at 10 mg/kg/day. Baseline ALT above ULN raises it further: 30% vs 12% at 20 mg/kg/day. Label: "The majority of ALT elevations occurred in patients taking concomitant valproate." | Baseline transaminases + bilirubin; §7.3: "Discontinuation or reduction of EPIDIOLEX and/or concomitant valproate should be considered." Note the exposures are pharmaceutical-dose; this is NOT asserted as a dispensary-dose risk — it is the reason a dispensary dose is not a small version of this drug. | | Warfarin (with CBD) | Grayson L et al., Epilepsy Behav Case Rep 2017;9:10–11, PMID 29387536 — case report in an epilepsy patient | Patient on warfarin 7.5 mg/day, INR goal 2–3, "stable for at least 6 months with levels ranging from 2.0 to 2.6." On CBD 5 mg/kg/day → INR 2.96; at CBD 10 mg/kg/day → INR 6.86. Warfarin dose ultimately "reduced by approximately 30%"; followed "without bleeding complications." Concurrent lamotrigine 400 mg BID and levetiracetam 1500 mg BID. | INR monitoring around any cannabinoid start, stop or dose change. Case-report evidence, consistent with the V1 warfarin row and with Marinol §7.4 protein-binding displacement. | | Sensitive CYP2C19 substrates (e.g. diazepam) | Epidiolex label §7.2 — in vivo | "In vivo data show that coadministration of EPIDIOLEX increases plasma concentrations of drugs that are metabolized by … CYP2C19 (e.g., diazepam)" | "Consider a reduction in dosage of sensitive CYP2C19 substrates." Report to prescriber. | | UGT2B7 substrates — lamotrigine, morphine, lorazepam | Epidiolex label §7.2 — in vitro prediction | Named class; no magnitude given in the label | Flag to the neurologist. In-vitro prediction, not a measured magnitude — do not quote a number. | | CYP2C8 / CYP2C9 substrates — phenytoin | Epidiolex label §7.2 — predicted "clinically significant" | "Coadministration of EPIDIOLEX is also predicted to cause clinically significant interactions with CYP2C8 and CYP2C9 (e.g., phenytoin) substrates" | Flag; consider substrate dose reduction per label. | | CYP1A2 / CYP2B6 substrates — theophylline, caffeine, bupropion, efavirenz | Epidiolex label §7.2 — in vitro | Named classes | "consider adjusting dosage of substrates of CYP1A2 and CYP2B6, as clinically appropriate." | | Moderate/strong CYP3A4 or CYP2C19 inhibitors and inducers | Epidiolex label §7.1 | Inhibitors raise CBD; strong inducers lower it | Dose adjustment is the prescriber's call; the consult flags and reports. | | Topiramate, zonisamide, rufinamide | Antón 2022 (anton2022_clinrelevance.txt) | "Co-administration with CBD (Epidiolex) does not lead to significant changes" in topiramate, zonisamide or rufinamide levels | A documented NON-interaction. Recording the negatives is as much a part of an honest screen as recording the positives. | | THC-containing products of any kind | Marinol label §5.3 | "Seizure and seizure-like activity have been reported in patients receiving dronabinol" | See T1-10. This is the row that most often actually applies at a dispensary counter. |

evidence_grade

A for purified pharmaceutical CBD in LGS/Dravet — a grade attached to a product this service does not supply. D — refused — for any dispensary-product recommendation in epilepsy. The supporting numbers, all verified: Lattanzi 2018 (Drugs, PMID 30390221) — "The reduction in all-types seizure frequency by at least 50% occurred in 37.2% of the patients in the CBD 20 mg group and 21.2% of the placebo-treated participants [risk ratio (RR) 1.76, 95% CI 1.07-2.88; p = 0.025]"; Devinsky 2017 (NEJM 376(21):2011–2020, PMID 28538134, Dravet) — "The median frequency of convulsive seizures per month decreased from 12.4 to 5.9 with cannabidiol, as compared with a decrease from 14.9 to 14.1 with placebo (adjusted median difference … -22.8 percentage points; 95% CI, -41.1 to -5.4; P=0.01)", ≥50% responders 43% vs 27% (OR 2.00, P=0.08), seizure-free 5% vs 0%; CFPC 2021 Table 4 pooling the three pivotal RCTs — 17–23% better than placebo, ≥50% reduction 38–44% vs 19–27% — with pooled harms "somnolence in 25 per cent with cannabidiol versus 8 per cent with placebo (NNH = 6)… decreased appetite 20% vs 5% (NNH = 7)… diarrhea 18% vs 9% (NNH = 12)… Elevation of liver enzymes occurs in approximately 16 per cent of cannabidiol users versus approximately 1 per cent of those assigned to placebo," and the honest closing line: "It is important to note that cannabidiol was not adverse event–free as had been hoped."

citations

1. 1. Epidiolex (cannabidiol) FDA label, 2018 — §1 indication, §2.1 pre-treatment labs, §2.2 mg/kg dosing, §5.1 hepatocellular injury and the valproate/clobazam incidence table, §5.5 AED withdrawal, §7.1–7.3 interactions, §12.3 PK — epidiolex_label2018.txt (91,275 bytes; every quotation verified verbatim 2026-09-15).
2. 2. *Geffrey AL et al. 2015, Epilepsia, "Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy," PMID 26114620 — abstract verified in research/pages/geffrey2015_clobazam.json (2,036 bytes, structured abstract, complete). DEFECT: the companion geffrey2015_clobazam.txt (54,355 bytes) is a MIS-SCRAPE — it contains Lukhele & Motadi 2016, BMC Complement Altern Med 16(1):335, on cannabidiol and cervical cancer cells. It is NOT the Geffrey paper and must not be cited. See §Defects.*
3. 3. Grayson L, Vines B, Nichol K, Szaflarski JP 2017, Epilepsy Behav Case Rep 9:10–11, PMID 29387536 — warfarin/CBD case — grayson2018_warfarin.txt (12,100 bytes, verified verbatim). Note the filename says 2018; the paper is 2017.
4. 4. Devinsky O et al. 2017, N Engl J Med 376(21):2011–2020, PMID 28538134 — Dravet RCT — devinsky-28538134.txt (4,142 bytes, abstract verified verbatim).
5. 5. *Lattanzi S et al. 2018, Drugs, PMID 30390221* — meta-analysis. PubMed efetch 2026-09-15; verbatim quote in /home/mike/cannabinoid-evidence-summary.md §4. Full text not staged — PubMed-verifiable review citation.
6. 6. CFPC 2021 — Table 4, pooled adverse events, and the neurologist-referral statement — cfpc-guidance2021.txt, verified verbatim at lines 2661–2727.
7. 7. Marinol FDA label §5.3 — seizure warning for THC-containing products — marinol-label.txt.
8. 8. Antón J et al. 2022, J Clin Med — the documented AED non-interactions — anton2022_clinrelevance.txt.

cannabinoid_ratio

No ratio recommendation is issued from this entry. Its function is a screening gate applied on top of whatever entry the patient qualifies for. The gate exists because of one labelled sentence, Marinol §5.3 verbatim: "Seizure and seizure-like activity have been reported in patients receiving dronabinol. Weigh this potential risk against the benefits before prescribing MARINOL to patients with a history of seizures, including those receiving anti-epileptic medication or with other factors that can lower the seizure threshold." Grade B for the screening action (labelled warning, directly on point); no grade is issued for a product, because no product is selected here.

titration_steps

None issued. The gate's operation: (1) ask the question — seizure history, febrile seizures, head injury, withdrawal states, any seizure-threshold-lowering co-medication; (2) if positive, do not proceed to the underlying entry's THC titration without prescriber contact. The labelled instruction is to weigh risk against benefit before prescribing, and this consult does not prescribe — so the weighing belongs to the certifying practitioner and must be documented as having happened (DERIVED — the label states the weighing, the routing of it to the prescriber is our inference); (3) if the prescriber approves, the underlying entry's conservative protocol is used, never the routine or rapid one (CAMH: "patients with comorbidity or polypharmacy may only tolerate 2.5 mg CBD or 1 mg THC"); (4) the Marinol monitoring instruction is carried across verbatim — "Monitor patients with a history of seizure disorders for worsened seizure control."

route + onset_profile

Where the underlying entry proceeds with prescriber approval, oral only — the CAMH inhaled delivered-dose band (7.5–25 mg THC from a 0.5 g joint of 10% flower) is incompatible with a population in which a dose-related threshold effect is the specific concern (DERIVED: the label documents the seizure signal, the route inference is ours).

contraindications

Active, poorly controlled seizure disorder → this is a neurology question, and the correct action is referral (T1-09), not a modified protocol. Any patient in whom the prescriber has not documented the risk-benefit weighing that Marinol §5.3 calls for.

interaction_flags

The full T1-09 antiepileptic panel applies to any patient on an AED — clobazam (3-fold N-desmethylclobazam), valproate (hepatic, 21–30% ALT >3× ULN in the labelled-dose setting), phenytoin (CYP2C9), lamotrigine/lorazepam/morphine (UGT2B7), diazepam (CYP2C19), and the documented non-interactions (topiramate, zonisamide, rufinamide). Plus warfarin (Grayson 2017), the consolidated V1 screen, and the CNS-depressant row.

evidence_grade

B (screening action; labelled warning directly on point)

citations

1. 1. Marinol FDA label §5.3 — the seizure warning, the risk-weighing instruction, the monitoring instruction, the discontinuation instruction — marinol-label.txt (verified verbatim).
2. 2. Epidiolex FDA label §5.5 — never withdraw an AED abruptly; §7.1–7.3 — the interaction panel — epidiolex_label2018.txt.
3. 3. CAMH Appendix 5 — conservative floors; inhaled delivered-dose band — camh-appendix.txt.
4. 4. Grayson L et al. 2017, PMID 29387536 — warfarin/CBD in an epilepsy patient on lamotrigine and levetiracetam — grayson2018_warfarin.txt.

cannabinoid_ratio

None recommended. Grade D for the indication. The evidence base has since been extended and it did not improve: Rodas 2024 (J Clin Psychiatry, PMID 38353645) — "This review did not find major benefits of cannabinoids in improving overall PTSD symptoms," and, critically, "Some risks with regard to worsening suicidal ideation and violent behavior were also reported." Aviram 2026 (J Cannabis Res, PMID 42210342) — "The current evidence from high-quality RCTs remains insufficient to support clinical use of cannabinoids in treating PTSD." Black 2019 (Lancet Psychiatry, PMID 31672337) — "There is scarce evidence to suggest that cannabinoids improve … post-traumatic stress disorder." And the guideline position, verbatim: CFPC 2021 Recommendation 4 — "We recommend that until further research clarifies the effectiveness and harms in treating anxiety, post-traumatic stress disorder (PTSD), or insomnia, cannabis is not an appropriate therapy for these conditions (level ii)." This is the one refusal in the library with a documented harm signal attached, not merely absent benefit.

titration_steps

1. 01 None. Where the treating clinician is already managing a cannabinoid trial — a common arrival pattern in PA — the consultant's role narrows to:
2. 02 the full consolidated interaction screen;
3. 03 dose-measurability counselling (oral over inhaled, so quantity is numerable);
4. 04 documenting and reporting back to the treating clinician. No initiation, no titration advice, no dose suggestion. (DERIVED posture, carried from V1 — flagged.)

route + onset_profile

n/a — no product, no route. Counselling only: oral over inhaled for dose accountability if a trial is already under way under someone else's care.

contraindications

Initiating or titrating any cannabinoid for PTSD is out of scope. Russo 2011 (russo-2011-taming-thc.txt) discusses endocannabinoid-system involvement in PTSD — mechanistic plausibility only, explicitly not an indication, and not to be presented to a patient as encouraging.

interaction_flags

Full consolidated V1 screen. The CNS-depressant row is the actionable clinical value here — benzodiazepine, opioid and alcohol co-use rates in this cohort are the real, screenable risk. SSRIs: no corpus evidence of a clinically significant PK interaction (Antón 2022, anton2022_clinrelevance.txt) — counsel additive sedation only; do not cite SSRI-PK numbers, they do not exist.

evidence_grade

D for the indication (screening/referral posture; administrative, recommended as the honest handling of an unsupported request)

citations

1. 1. CFPC 2021 (Moulin et al.), Recommendation 4 — cfpc-guidance2021.txt (verified verbatim at lines 514–517).
2. 2. *Rodas JD et al. 2024, J Clin Psychiatry, PMID 38353645* — no major benefit; suicidality and violent-behaviour signals. PubMed efetch 2026-09-15; verbatim quote in /home/mike/pubmed_cannabinoid/cannabinoid_evidence_by_family.md §1.
3. 3. *Aviram J et al. 2026, J Cannabis Res, PMID 42210342* — insufficient RCT evidence. Same source.
4. 4. *Black N et al. 2019, Lancet Psychiatry, PMID 31672337* — scarce evidence. Same source.
5. 5. Russo EB 2011, Br J Pharmacol 163(7):1344–1364 — endocannabinoid mechanism, plausibility only — russo-2011-taming-thc.txt (134,409 bytes).
6. 6. Antón J et al. 2022, J Clin Med — absence of psychiatric-class PK evidence — anton2022_clinrelevance.txt.

cannabinoid_ratio

None recommended. Grade D for the indication. The highest-authority review is negative: Black 2019 (Lancet Psychiatry, PMID 31672337), verbatim — "There is scarce evidence to suggest that cannabinoids improve depressive disorders and symptoms, anxiety disorders, … or psychosis. There is very low quality evidence that pharmaceutical THC (with or without CBD) leads to a small improvement in symptoms of anxiety among individuals with other medical conditions." Note precisely what that last clause concedes and what it does not: a very-low-quality signal for pharmaceutical THC in people whose primary problem is something else. That is not a treatment for an anxiety disorder. The guideline agrees — CFPC 2021 Recommendation 4 names anxiety in its "not an appropriate therapy" list, and its evidence section records that for anxiety the reviews "identified only one RCT… 24 patients over one simulated speaking exercise" (cfpc-guidance2021.txt line 2733). A contrary signal exists and is disclosed: Han 2024 (Psychiatry Research, PMID 38924898) — "this meta-analysis revealed a substantial significant impact of CBD on anxiety with a considerable effect size (Hedges' g = -0.92, 95% CI -1.80 to -0.04). However, caution should be exercised in interpreting our findings due to the limited size of the clinical sample." CONTESTED — and the refusal stands on the higher-authority review, with the disagreement disclosed rather than hidden.

titration_steps

None. And the dose-direction problem is why this refusal is firmer than a simple "no evidence": THC is anxiolytic at low doses and anxiogenic at high doses (Sexton & Ziskind 2013, sexton-ziskind-2013-psychoactive-agents.txt — MECH/CONTESTED). A titration ladder whose direction of effect can reverse as you climb it is not a titration ladder. The inhaled delivered-dose band (7.5–25 mg THC from a 0.5 g joint, CAMH) makes that reversal impossible to control by route. Where the certifying practitioner has already authorised a trial, the consult's role is the interaction screen, dose-measurability counselling, and reporting back.

route + onset_profile

n/a — no product recommended. If a trial is under way under someone else's care: oral only, for the dose-control reason above; inhaled is excluded outright.

contraindications

Psychosis history or family history (the Sativex SmPC §4.3 contraindication is categorical, and this population is where it bites); any prior paradoxical anxiety response; a patient seeking primarily euphoric or anxiolytic THC effect.

interaction_flags

Full consolidated V1 screen. SSRIs/SNRIs and most antidepressants: no corpus evidence of clinically significant PK interaction (Antón 2022) — additive sedation counselling only, and no SSRI-PK numbers are to be quoted, because none exist on disk. Benzodiazepines: the CNS-depressant row is material — a large share of this cohort carries one.

evidence_grade

D for the indication. (Sub-syndromal anxiety-adjacent distress remains C under V1 ANX-ADJ-01 — the thinnest entry in either library, and stated as such to patients.)

citations

1. 1. *Black N et al. 2019, Lancet Psychiatry, PMID 31672337* — the governing negative review. PubMed efetch 2026-09-15; verbatim in /home/mike/pubmed_cannabinoid/cannabinoid_evidence_by_family.md §2.
2. 2. *Han C et al. 2024, Psychiatry Research, PMID 38924898 — the contrary CBD meta-analysis and its own sample-size caveat. Same source. Disclosed as CONTESTED.*
3. 3. CFPC 2021, Recommendation 4 and the anxiety evidence section (the single 24-patient simulated-speaking RCT) — cfpc-guidance2021.txt, verified verbatim.
4. 4. Sexton M & Ziskind J 2013 — THC dose-dependent anxiolysis/anxiogenesis — sexton-ziskind-2013-psychoactive-agents.txt (146,029 bytes).
5. 5. Antón J et al. 2022, J Clin Med — absence of psychiatric-class PK evidence — anton2022_clinrelevance.txt.
6. 6. CAMH Appendix 5 — inhaled delivered-dose band — camh-appendix.txt.

cannabinoid_ratio

None recommended. Grade D for the indication, and for opioid-dose reduction as an effect claim. The evidence position is unusually clean: no systematic review supporting cannabis or cannabinoids as OUD substitution or taper therapy was findable on PubMed in the 2026-09-15 evidence pass (searches covering opioid substitution and reduction terms — /home/mike/pubmed_cannabinoid/cannabinoid_evidence_by_family.md §9). Black 2019 (PMID 31672337), covering substance-use disorders: "There remains insufficient evidence to provide guidance on the use of cannabinoids for treating mental disorders within a regulatory framework." And the trap to avoid: Bilbao & Spanagel 2022 (BMC Medicine, PMID 35982439) does report "moderate evidence for nabiximols on … SUDs (-0.48[CI -0.92, -0.04])" — but that signal is for cannabis-use-disorder substitution, NOT opioid substitution. Misreading that one row is the single most likely way this refusal gets breached, so it is named here explicitly. Busse 2021 on opioid-sparing: the V1 finding stands — opioid-sparing "remain[s] uncertain due to very low certainty evidence."

titration_steps

None from this consult, ever. The one adjacent thing that does exist is prescriber-owned, and the distinction is the whole entry. Sihota 2021's Delphi consensus does publish an opioid-tapering schedule — verbatim: "Initiate opioid tapering when the patient reports a minor/major improvement in function, seeks less as-needed medication to control pain and/or the cannabis dose has been optimised. The opioid tapering schedule may be 5%-10% of the morphine equivalent dose (MED) every 1 to 4 weeks", with success defined as "an improvement in function/quality of life, a ≥30% reduction in pain intensity, a ≥25% reduction in opioid dose, a reduction in opioid dose to <90 mg MED and/or reduction in opioid-related adverse events" (clinther-dosing-pubmed.txt, verified verbatim). This schedule is reproduced for one reason only: so the consultant recognises it when a prescriber is running it, and can support it. It is expert consensus for a PRESCRIBER tapering opioids in a chronic-pain patient. It is NOT evidence that cannabis treats opioid use disorder, it is NOT a taper this consult may initiate, suggest, or pace, and it does NOT apply to a patient on buprenorphine or methadone for OUD.

route + onset_profile

n/a — no product recommended for this indication.

contraindications

Presenting cannabis as a substitution or taper therapy, in any wording, to any patient, is contraindicated as a matter of policy. Marinol §5.4, verbatim: "Patients with a history of substance abuse or dependence, including marijuana or alcohol, may be more likely to abuse MARINOL as well" — relevant, and to be handled without stigma but not skipped.

interaction_flags

The real clinical value of this entry. Buprenorphine — LEVEL 2 (moderate/probable) in the V1 consolidated screen (Antón 2022); dose-adjust and monitor. Methadone — CNS-depressant row; no corpus-specific PK magnitude exists — UNVERIFIED, and no number is quoted. CNS depressants generally — Marinol §7.1, verbatim: "Additive CNS effects (e.g., dizziness, confusion, sedation, somnolence) may occur when MARINOL is taken concomitantly with drugs that have similar effects on the central nervous system"; Cesamet: "Additive drowsiness and CNS depression", and for the diazepam combination the Cesamet label goes further — "This combination should be avoided." Benzodiazepines co-prescribed with opioid agonist therapy are the highest-consequence row in the entire library, and this is the entry where it is screened.

evidence_grade

D for the indication (refusal-and-referral posture; the interaction-screening function is graded B on labelled §7 text)

citations

1. 1. PubMed evidence pass, 2026-09-15 — no positive systematic review located for cannabinoids in OUD substitution or opioid tapering — /home/mike/pubmed_cannabinoid/cannabinoid_evidence_by_family.md §9 and research/08-qualifying-conditions-inventory.md Part B. A documented absence, recorded as an absence.
2. 2. *Black N et al. 2019, Lancet Psychiatry, PMID 31672337* — insufficient evidence for cannabinoids in mental disorders and SUDs. Same source.
3. 3. *Bilbao A & Spanagel R 2022, BMC Medicine, PMID 35982439 — the nabiximols SUD signal, explicitly flagged as cannabis-use-disorder substitution and not opioid substitution.* Same source.
4. 4. Sihota A et al. 2021, Int J Clin Pract 75(8):e13871, PMID 33249713 — the prescriber-owned taper schedule — clinther-dosing-pubmed.txt / sihota-consensus.txt (verified verbatim).
5. 5. Busse JW et al. 2021, BMJ 374:n2040 — opioid-sparing uncertainty — busse-bmj.txt.
6. 6. Marinol FDA label §5.4, §7.1; Cesamet label class table — marinol-label.txt, cesamet-label.txt.
7. 7. Antón J et al. 2022 — buprenorphine row — anton2022_clinrelevance.txt.

cannabinoid_ratio

None recommended. Grade D for the indication. No systematic review supporting a migraine indication was located in the 2026-09-15 evidence pass. What exists is positive-but-weak and observational-weighted: Okusanya BO et al. 2022 (Front Neurol, PMID 35711271) — "There is promising evidence that MC may have a beneficial effect on the onset and duration of migraine headaches in adults. However, well-designed experimental studies … are needed," and the same review flags medication-overuse headache risk. A second paper (Sherpa et al. 2022, Cureus, PMID 36660507) is positive but sits in a low-quality venue and is not load-bearing here. Neither the CFPC guidance nor Allan 2018 nor Busse 2021 addresses migraine at all — checked directly: cfpc-guidance2021.txt contains no migraine content (the only "headache" hits are adverse-event and withdrawal-symptom listings at lines 1882 and 1929). The guideline corpus is silent, and silence is not support.

titration_steps

1. 01 None. And migraine carries a refusal hazard the other Tier 2 entries do not: medication-overuse headache. The pattern that an unsupervised migraine patient naturally falls into — dose at headache onset, dose again when it does not resolve, most days of the month — is the exact pattern that generates MOH. Okusanya 2022 flags the risk; the corpus contains no cannabinoid-MOH incidence figure, and none is invented — UNVERIFIED. The consultant's actions:
2. 02 the honest decline;
3. 03 screen frequency of use explicitly — this is the one Tier 2 entry where "how many days a month?" is a required question (DERIVED, flagged);
4. 04 referral to the treating clinician or neurologist, where triptan, CGRP-antagonist and preventive pathways actually exist;
5. 05 the interaction screen;
6. 06 document.

route + onset_profile

n/a — no product recommended. Counselling note if a trial is under way under someone else's care: inhaled routes are the ones most likely to produce a dose-at-onset, dose-again pattern, and are the least dose-accountable (CAMH's 7.5–25 mg band).

contraindications

Presenting any product as a migraine treatment or preventive. Pregnancy (CFPC: "guidelines strongly recommend against their use in pregnancy"). Any red-flag headache.

interaction_flags

Full consolidated V1 screen. Material rows: triptans — no corpus evidence of a PK interaction; UNVERIFIED, and no number is quoted; serotonergic-load counselling is the treating clinician's, not this consult's. TCAs (amitriptyline is a common migraine preventive) — Cesamet class table: "Additive tachycardia, hypertension, drowsiness." Beta-blockers and antihypertensives — V1 records no corpus evidence of clinically relevant interaction, but Marinol §7.2 additive cardiac effects ("hypotension, hypertension, syncope, tachycardia") is a live counselling row. CNS depressants; butalbital-containing combinations sit squarely in the Cesamet barbiturate row ("Additive drowsiness and CNS depression").

evidence_grade

D for the indication (refusal-and-referral posture)

citations

1. 1. *Okusanya BO et al. 2022, Front Neurol, PMID 35711271* — promising-but-inadequate; MOH risk flagged. PubMed efetch 2026-09-15; verbatim in /home/mike/pubmed_cannabinoid/cannabinoid_evidence_by_family.md §11.
2. 2. *Sherpa ML et al. 2022, Cureus, PMID 36660507 — positive, low-quality venue; disclosed and explicitly not relied upon.* Same source.
3. 3. CFPC 2021 — checked and confirmed to contain no migraine guidance — cfpc-guidance2021.txt (absence verified by direct search 2026-09-15).
4. 4. Cesamet FDA label class interaction table; Marinol §7.2 — cesamet-label.txt, marinol-label.txt.
5. 5. CAMH Appendix 5 — inhaled delivered-dose band — camh-appendix.txt.

cannabinoid_ratio

No product recommendation is issued for IBD as a disease. Grade D for disease treatment. The reviews converge and they are recent: Doeve BH et al. 2021 (J Clin Gastroenterol, PMID 32675631), verbatim — "Cannabi(noid)s do not induce clinical remission or affect inflammation in IBD patients. However, cannabi(noid)s significantly improve patient-reported symptoms and QoL." Kafil TS et al. 2018 (Cochrane, PMID 30407616) — "no firm conclusions regarding the efficacy and safety of cannabis and cannabis oil in adults with active Crohn's disease can be drawn." The Doeve sentence is the entry in miniature — symptoms and quality of life improve; remission and inflammation do not. A patient who hears the first half and not the second may delay or de-prioritise disease-modifying therapy, and that is the specific harm this entry is written to prevent. Where the treating gastroenterologist has authorised a symptom-directed trial, the supportable route is through an existing graded entry — abdominal pain via the V1 chronic-pain ladder, nausea only within its own (narrow, largely negative) evidence boundary per T1-08 — never as an IBD protocol. Grade C for the symptom-support function, borrowed entirely from the adjacent entries and earning nothing of its own; Grade D for anything disease-directed.

titration_steps

None originating here. Any titration is the adjacent entry's (V1 chronic-pain ladder; MacCallum & Russo or Sihota schedules, both CONTESTED and both disclosed), applied to a patient who happens to have IBD, with the disease-treatment refusal stated out loud at the start of the consult and documented. No IBD-specific dose, ratio, route or schedule exists in the corpus and none is invented.

route + onset_profile

Where an adjacent graded entry applies, its route governs — oral oil, onset 30–60 min, peak 2–4 h, bioavailability 6–20% (CAMH). Suppository/rectal dosing: Grade D, refused — no corpus data, and the rectal THC-hemisuccinate literature is UNVERIFIED and not staged. This matters here because rectal formulations are marketed at exactly this population; the refusal is carried forward from V1 unchanged and is load-bearing.

contraindications

Any framing in which a cannabinoid substitutes for or defers disease-modifying therapy. Active severe flare, obstruction, or any acute abdomen → medical referral, not a consult. Pregnancy.

interaction_flags

Full consolidated V1 screen. Material rows: CNS depressants (opioid analgesia is common in this population and is itself a driver of gut dysmotility — the interaction counselling and the clinical counselling point the same way). Tacrolimus and immunosuppressants — the V1 screen carries tacrolimus at LEVEL 2 with documented plasma increases of +358%, +200%, +77% with CBD; IBD patients on calcineurin inhibitors or azathioprine make this row live, and it is the single most consequential interaction in this entry. Highly protein-bound NTI drugs (Marinol §7.4). Biologics: no corpus evidence of a PK interaction — UNVERIFIED, no number quoted, and the absence is recorded as an absence rather than as reassurance.

evidence_grade

C (symptom-support function only, borrowed from adjacent graded entries) / D (IBD as a disease-treatment indication — refused)

citations

1. 1. *Doeve BH et al. 2021, J Clin Gastroenterol, PMID 32675631* — SR/meta-analysis; the remission-vs-symptoms split. PubMed efetch 2026-09-15; verbatim in /home/mike/pubmed_cannabinoid/cannabinoid_evidence_by_family.md §5.
2. 2. *Kafil TS et al. 2018, Cochrane Database Syst Rev, PMID 30407616* — no firm conclusions in active Crohn's. Same source.
3. 3. Antón J et al. 2022, J Clin Med — citing Kafil et al. (Inflamm Bowel Dis 2020): "evidence is not robust" — anton2022_clinrelevance.txt; carried from the V1 refusal row.
4. 4. Marinol FDA label §5.5 (paradoxical nausea/vomiting/abdominal pain), §7.4 — marinol-label.txt.
5. 5. V1 consolidated interaction screen — tacrolimus magnitudes — build/PROTOCOL-LIBRARY-V1-chronic-pain.md.