Medical Cannabis Condition Guide

Physician Reference

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Purpose and Evidence Grading

This reference summarizes the clinical evidence for cannabis and cannabinoids by indication, current to October 2026. It is written for certifying practitioners and referring physicians. Grades reflect the best available systematic reviews, guidelines, and RCTs, not observational or patient-survey data alone.

Grade Definition
Strong Multiple RCTs with consistent benefit, and usually a regulatory-approved cannabinoid product for the indication.
Moderate RCT evidence of benefit, but effect sizes are small to moderate, or trials are short, heterogeneous, or at risk of bias.
Limited One or few small RCTs, or mixed results. Biologically plausible, not confirmed.
Not established RCTs negative, absent, or limited to surrogate outcomes; or a specialty society recommends against use.

 

Two caveats apply throughout. First, most RCTs used pharmaceutical cannabinoids (dronabinol, nabilone, nabiximols, purified CBD) or standardized research flower . Results do not transfer automatically to dispensary products of differing composition. Second, a negative grade for a disease does not rule out benefit for a related symptom, such as sleep, appetite, or spasticity.

Approved Cannabinoid Medicines

Product Active ingredient Approved indication US status
Epidiolex Purified CBD (oral solution) Seizures in Lennox-Gastaut syndrome, Dravet syndrome, tuberous sclerosis complex; age 1 year and older FDA-approved (2018)
Marinol, Syndros Dronabinol (synthetic THC) Anorexia with weight loss in AIDS; CINV refractory to conventional antiemetics FDA-approved (1985)
Cesamet Nabilone (synthetic THC analogue) CINV refractory to conventional antiemetics FDA-approved (1985)
Sativex Nabiximols (THC:CBD ~1:1 oromucosal spray) Moderate to severe MS spasticity not responding to other antispasticity drugs Approved in Canada and much of Europe; not FDA-approved
Exilby (VER-01) Standardized full-spectrum cannabis extract, oral (2.5 mg THC per unit) Chronic low back pain with a neuropathic component Approved in Germany and Austria (2026); FDA Breakthrough Therapy designation (May 2026), not FDA-approved

 

Sources: CJASN approved-products table; Epidiolex coverage policy citing label.

Regulatory Status

  • Federal. Effective April 28, 2026, on publication in the Federal Register (91 Fed. Reg. 22714); announced April 23, a DOJ/DEA final order placed FDA-approved marijuana-containing products and state-licensed medical marijuana into Schedule III. Adult-use marijuana remains Schedule I pending a separate rescheduling hearing that began June 29, 2026. (Morgan Lewis, Sept 2026; Foley)
  • New York. Practitioners may certify patients for any condition they judge clinically appropriate. Any practitioner licensed to prescribe controlled substances may certify after completing at least a 2-hour OCM-approved course. Practitioners do not prescribe cannabis; they certify. Telehealth evaluations are permitted. (OCM practitioner bundle; OCM patients page)

Pharmacology

The Endocannabinoid System

  • Receptors. CB1 is dense in the basal ganglia, hippocampus, cerebellum, and cortex, and sparse in brainstem respiratory centers. That distribution explains both the psychoactive effects and the absence of opioid-type respiratory depression. CB2 is expressed mainly on immune cells and microglia.
  • Ligands. Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are synthesized on demand and act largely as retrograde messengers that dampen presynaptic neurotransmitter release.
  • Degradation. FAAH (mainly AEA) and MAGL (mainly 2-AG).
  • “Clinical endocannabinoid deficiency” remains a hypothesis. It has not been validated as a diagnosis or a treatment target in controlled studies.

Major phytocannabinoids

Compound Primary mechanism Clinical relevance
Δ9-THC Partial agonist at CB1 and CB2 Analgesia, antiemesis, appetite, spasticity. Dose-dependent psychoactivity, tachycardia, impairment.
CBD Low CB1/CB2 affinity; acts at 5-HT1A, TRPV1, GPR55, and other targets; inhibits FAAH and several CYP450 enzymes Antiseizure at 10 to 20 mg/kg/day (Epidiolex trials). Doses in most dispensary products are far lower. Clinically important drug interactions.
CBG, CBN, CBC, THCV, CBDV, THCA Various, mostly characterized in vitro and in animals Human clinical evidence is minimal. Claims such as “CBN is a strong sedative” or “THCA slows cancer” rest on preclinical data only.

 

Terpenes and The "Entourage Effect"

The entourage effect is the idea that terpenes and minor cannabinoids modify THC and CBD effects. It is plausible but largely untested in human trials. Product labels also mislead: a 2022 PLOS One analysis of about 90,000 samples and a 2021 Nature Plants study found that “indica” and “sativa” labels do not reliably predict chemical composition.

Practical implication: select products by labeled THC and CBD content in milligrams, not by strain name or indica/sativa category.

Pharmacokinetics by route

Route Onset Peak effect Duration Notes
Inhaled (vaporized flower) Minutes ~15 to 30 min 2 to 4 h Variable bioavailability; easiest to titrate; suited to breakthrough symptoms.
Oral (capsule, oil, edible) 30 min to 2 h 1 to 5 h, may be later 6 to 8 h or more Low, variable bioavailability; first-pass metabolism to 11-OH-THC; most ED visits for intoxication involve edibles.
Oromucosal (spray, sublingual) As early as 10 min Variable Up to about 10 h Partly swallowed; nabiximols is the studied example.
Topical Local Local Variable Minimal systemic absorption; little controlled evidence.

 

Approximate values. Sources: Bhaskar et al. 2021 and the pharmacokinetic literature it cites (Huestis 2007; Grotenhermen 2003; Schlienz 2020).

Evidence by Indication

Evidence is graded by indication, outcome, and product type, because results differ sharply on all three. The strongest support is for refractory CINV , MS spasticity , CBD in three epilepsy syndromes, and, as of 2025–2026, a standardized THC extract in chronic low back pain and dronabinol for PTSD nightmares. Oral CBD alone has consistently failed in pain trials.

Indication / outcome Product studied Grade Key evidence Clinical note
CINV, refractory Dronabinol, nabilone; oral THC:CBD 1:1 Strong FDA-approved. ASCO 2024: may help when added to guideline antiemetics. Grimison 2020: complete response 14% → 25%. Add-on. Not compared with olanzapine.
MS spasticity Nabiximols (oromucosal) Strong Kleiner 2023 meta-analysis: responder OR 2.41 (95% CI 1.39–4.18) in refractory spasticity. Patient-reported > Ashworth. 4-week trial, continue responders.
MS central neuropathic pain Oral cannabinoids Moderate Utah CRRB 2023.
MS bladder, sleep, gait Nabiximols Limited Kleiner 2026 exploratory meta-analysis: signals of benefit; low to very low certainty.
Epilepsy: LGS, Dravet, TSC Purified CBD (Epidiolex) 10–20 mg/kg/day Strong GWPCARE4: LGS drop seizures −43.9% vs −21.8%. Dravet convulsive seizures −39% vs −13% (summary). LFTs; clobazam and valproate interactions. Not established for other epilepsies or dispensary products.
Chronic non-cancer pain, by product THC-only; comparable THC:CBD; low THC:CBD; CBD Moderate (small effect) Chou et al., Ann Intern Med 2026 (RCTs to July 2025): THC-only −0.78, comparable-ratio oromucosal −0.54 points (0–10). Nabilone −1.59; dronabinol −0.23 (no effect). Low THC:CBD may not improve outcomes. CBD alone may not increase harms. Product matters: THC-containing products drive both benefit and AEs.
Chronic low back pain VER-01, standardized full-spectrum oral extract (2.5 mg THC/unit) Moderate Karst et al., Nat Med 2025: n = 820, 12 weeks. NRS MD −0.6 (95% CI −0.9 to −0.3); ≥30% relief 54.1% vs 39.5% (NNT 6.8); neuropathic subgroup MD −1.5. AE discontinuation 17.3% vs 3.5%. No dependence or withdrawal on abrupt stop. Approved Germany and Austria 2026; FDA Breakthrough designation May 2026; US phase 3 under way (report). Sponsor-funded. Results do not transfer to dispensary products.
Chronic neuropathic pain Mixed THC, THC:CBD, CBD Moderate Cochrane 2018: ≥50% relief 21% vs 17%. Cochrane 2026 (21 RCTs, n = 2,187): no clear ≥50% effect for any ratio. Minority of strong responders.
HIV sensory neuropathy Smoked cannabis 3.56% THC Moderate Abrams 2007: pain −34% vs −17%; ≥30% relief 52% vs 24%. Small, 5-day inpatient.
Localized pain: topical CBD CBD cream/oil Limited Heineman 2022, J Hand Surg: thumb CMC OA, n = 18 crossover, VAS 5 → 2 vs 5 → 5. Xu 2020: lower-extremity neuropathy, n = 29, improved. AAHS 2026 abstract: CBD vs diclofenac gel crossover, n = 17, preliminary: comparable or greater QuickDASH gains. Minimal systemic exposure. Small, short, single-center.
Osteoarthritis pain: oral CBD CBD 600 mg/day; CBD-rich oils Not established Pramhas 2023, Lancet Reg Health Eur: knee OA, n = 86, 8 weeks; WOMAC pain −2.5 vs −2.4 (p = 0.80). CANOA 2025: negative. Hand OA/PsA trial (Vela 2022): negative. Liver enzyme rise at 600 mg/day (review). A positive 2024 topical “hemp seed oil” trial used a product with negligible cannabinoids; not CBD evidence.
Rheumatoid arthritis Nabiximols; others Limited Fitzcharles 2016: 4 short RCTs, n = 203 across RA, FM, OA. No evidence of disease modification.
Cancer pain, opioid-refractory Nabiximols, THC Not established Cochrane 2023 (Häuser): SMD −0.19 (−0.40 to 0.02); no effect on opioid maintenance or breakthrough doses.
Cancer-directed therapy Any Not established ASCO 2024: recommend against outside trials.
Anorexia/weight loss in AIDS Dronabinol Moderate FDA-approved indication.
Cancer cachexia THC, cannabis Not established ASCO 2024: uncertain.
Cannabis vs opioids, CLBP VER-01 vs commercial opioids Limited Meissner et al., Pain Ther 2025 (summary): open-label RCT, n = 384, 27 weeks. Primary: constipation, 4× less with VER-01. Pain −2.50 vs −2.16. Open-label; single product.
Cannabis vs opioids, chronic non-cancer pain Various Limited BMJ Open 2024 network meta-analysis, 90 RCTs, >22,000 patients: similar small benefits; fewer AE discontinuations with cannabis. Mostly ≤6-month trials.
Opioid dose reduction Various Limited Nielsen 2022: RCTs show no sparing; observational 85% reduce, 39% stop. Noori 2021: RCTs held opioid doses fixed. New York PMP cohorts: Nguyen 2023 (n = 8,165 on long-term opioids): >30 days of cannabis associated with 47–51% daily MME reduction vs 4–14%; Slawek 2026 (n = 204, prospective, Bronx, 18 months): each 30-day cannabis supply associated with −3.53 MME/day (95% CI −6.68 to −0.04). Both observational; no taper protocol. Taper trial with structured support registered, not reported.
Opioid use disorder: cue-induced craving Oral CBD 400–800 mg × 3 days Limited Hurd 2019, Am J Psychiatry: n = 42; reduced in-session craving and anxiety; at-home craving unchanged. Adjunct concept only; not a MOUD substitute.
PTSD nightmares Dronabinol 2.5–15 mg at bedtime Moderate Roepke et al., Nat Med 2026: n = 171, 10 weeks; CAPS-IV B2 difference −1.50 (95% CI −2.28 to −0.71), d = 0.65. SAEs 8.0% vs 0%. No effect on overall PTSD or depression. Jetly 2015: nabilone, n = 10, positive. Industry grant (Bionorica). Long-term data lacking.
PTSD global symptoms Smoked cannabis; CBD Not established VA/DoD 2023 strong against (commentary); VA NCPTSD 2024. Screen for CUD.
Insomnia (primary) THC, CBD, combinations Limited Cochrane 2026: 9 RCTs, n = 537, little to no effect, very low certainty. Sleep Med 2026: 10 RCTs, benefit. CBT-I first.
Sleep in chronic pain THC-containing analgesics Moderate (small) VER-01: sleep NRS MD −0.7 (−1.0 to −0.3). 2025 meta-analysis: small gain at or above MID.
ALS/MND spasticity Nabiximols Limited CANALS 2019: n = 59, 6 weeks, positive.
Alzheimer’s agitation Nabilone; dronabinol Limited Nabilone RCT 2019, n = 39. Dronabinol RCT, n = 75, ~30% reduction (presented 2024). Falls, sedation.
Migraine, acute Vaporized 6% THC/11% CBD Limited Schuster 2025: 247 attacks; superior at 2 h; CBD alone not. Single center.
Tourette tics Oral THC:CBD 1:1 Limited Mosley 2023, NEJM Evid: n = 22.
Anxiety disorders CBD Limited Wang 2024: g −0.92 (−1.80 to −0.04), 8 small studies. THC anxiogenic.
Crohn’s: symptoms / remission Inhaled THC-rich cannabis; CBD oil Limited / Not established Cochrane: 3 RCTs, n = 93; symptom response without remission or marker change.
Ulcerative colitis CBD-rich extract Not established Cochrane: remission 24% vs 26%.
Fibromyalgia Nabilone Limited Cochrane 2016: 2 RCTs, n = 72.
IBS — Not established No adequately powered RCTs identified. Consider CHS.
Parkinson’s disease CBD, THC Not established AAN 2026 meta-analysis: 10 RCTs, n = 719, no benefit; placebo favored for anxiety.
Glaucoma THC Not established AAO: not recommended.

Additional conditions (added October 2026)

Condition Intervention Key data Grade
Autism: disruptive behavior 20:1 CBD:THC whole-plant extract; purified CBD Aran 2021 (n = 150, crossover): CGI-I improved, HSQ-ASD not. Trauner 2025: purified CBD up to 20 mg/kg/day, no benefit on primary outcomes. Meta-analysis 2025: social responsiveness SMD −0.75, disruptive behavior SMD −0.36 Limited
Depression Any cannabinoid No RCTs (2026 Lancet Psychiatry review, 54 RCTs, 2,477 participants, 1980–May 2025). Observational data link heavier use with more depression Not established
Endometriosis pain Inhaled THC; oral CBD No completed RCT: Australian 3-arm feasibility trial and Penn State CBD pilot (NCT04527003) terminated for poor recruitment; ENDOCAN-1 (UK, CBD) started 2025. Scoping review 2025: observational only Not established
Huntington’s: chorea, behavior Nabilone; nabiximols Nabilone 1–2 mg crossover (Curtis 2009, n = 44): improved UHDRS motor and chorea. Nabiximols up to 12 sprays/day (López-Sendón Moreno 2016, n = 24): safe, no symptomatic benefit. Dystonia case series (Saft 2018, n = 7): UHDRS motor −10.3 Limited
Palliative care THC, cannabis extracts Mücke 2018: HIV weight SMD 0.57 and appetite SMD 0.57; no convincing benefit for cancer anorexia-cachexia; megestrol superior (n = 469). MASCC 2022: insufficient evidence for nausea of advanced cancer or cachexia Not Established
Spinal cord injury: spasticity Dronabinol; nabilone; nabiximols Dronabinol (Hagenbach 2007) and nabilone crossover (Pooyania 2010, n = 12, Ashworth improved) positive but small; nabiximols mixed (SCIRE; Utah review) Limited
Cannabis use disorder Nabiximols plus counseling Lintzeris 2019, JAMA Intern Med (n = 128, 12 weeks, mean ~18 sprays/day): 35 vs 53 days of illicit use; withdrawal and craving not different (summary). 2026 Lancet Psychiatry review: THC/CBD reduced withdrawal and use Limited
Opioid use disorder Cannabis; CBD 2026 Lancet Psychiatry review: no benefit. NYSDOH AI guideline: insufficient evidence; any role would augment, not replace, buprenorphine or methadone Not established
Muscular dystrophy: myotonia, myalgia Oral THC/CBD oil Compassionate-use series (Montagnese 2020, n = 6; DM1, DM2, CLCN1 myotonia): Myotonia Behaviour Scale improved ≥2 points in all, hand-opening time in 5 of 6; new constipation in 4. Duchenne: mdx mouse data only (Iannotti 2019). Cardiac conduction disease in DM1 and cardiomyopathy in DMD warrant caution with THC Limited
PTSD: veterans, observational Self-selected medical cannabis Bonn-Miller 2021 smoked-cannabis RCT (n = 80, 3 weeks): all arms improved, none beat placebo. Bonn-Miller 2022 prospective observational (n = 150, 1 year): larger PCL-5 reductions in cannabis users. VA/DoD 2023 guideline recommends against; VA clinicians cannot certify (October 2026) Not established (nightmares: Moderate)

 

Mental health update. The 2026 Lancet Psychiatry review (54 RCTs) found no significant benefit for anxiety disorders, PTSD , psychotic disorders, depression, or opioid use disorder , and low-certainty support for cannabis use disorder , insomnia, Tourette syndrome, and autism. The Anxiety entry was downgraded to Not established for anxiety disorders accordingly .

Opioid Tapering Alongside Medical Cannabis

No published trial has tested a specific taper protocol paired with medical cannabis. In both New York cohorts, opioid changes were made by patients’ own prescribers, with cannabis dispensed monthly through pharmacist-directed dispensaries.

The best-specified model is the Massachusetts General Hospital pragmatic RCT (NCT04827992; results not yet published). Adults 18–75 on stable opioid doses of 25 MME/day or more for over 90 days are randomized to cannabis plus Prescription Opioid Taper Support (POTS) or waitlist plus POTS:

  • POTS: a manualized behavioral program (Sullivan and T urner) delivered weekly by a trained clinician, covering pain self-management and the pros and cons of tapering.
  • Taper rate: at monthly visits in weeks 4 to 20, a voluntary reduction of about 10% of the baseline dose, with the patient free to decline or choose a smaller step.
  • Prescriber control: every dose change is approved by the patient’s opioid prescriber.
  • Safety: naloxone recommended for all participants; withdrawal tracked with the Clinical and Short Opiate Withdrawal Scales; opioid misuse, CUD , and suicidality screened at each visit.
  • Outcomes: daily PEG scores and PMP-verified median daily MME, the same co-primary measures used in the NYSOM registry protocol.

Practical approach until trial results are available: agree on a written plan with the opioid prescriber; reduce by about 10% of the starting dose per month or slower; hold or reverse a step if pain, function, or withdrawal worsens; co-prescribe naloxone; and recheck interactions and sedation at each step.

Product Selection by Indication

The recommendations follow the product, ratio, route, and dose range used in the positive trials. Minor cannabinoid and terpene choices are labeled as expert opinion unless a human trial supports them. Dispensary products are not equivalent to the trial products; match the ratio and route, then titrate (see Clinical practice).

Indication Ratio / product (trial basis) Route Dose range in trials Minor cannabinoids, terpenes
CINV THC; or THC:CBD 1:1 Oral THC 2.5 mg/CBD 2.5 mg capsules, 1–4 three times daily, day −1 to day 5 (Grimison) —
AIDS anorexia THC Oral, before meals Dronabinol per label —
MS spasticity THC:CBD ~1:1 Oromucosal Nabiximols self-titrated sprays (2.7 mg THC/2.5 mg CBD per spray) —
ALS spasticity THC:CBD ~1:1 Oromucosal Nabiximols (CANALS) —
Rheumatoid arthritis THC:CBD ~1:1 Oromucosal Nabiximols, 5 weeks (Blake): pain on movement −0.95, at rest −1.04, sleep +1.17, DAS28 −0.76 (2026 review) —
Chronic neuropathic / mixed pain THC-containing (comparable or high THC:CBD) Oral; inhaled for breakthrough Bhaskar protocols; typical effective THC ~10 mg/day Low THC:CBD not supported (Chou 2026)
Chronic low back pain THC-dominant full-spectrum extract Oral VER-01 2.5 mg THC/unit, titrated to max 13 units/day Product contains trace CBG and CBD
HIV neuropathy THC flower Smoked/vaporized 3.56% THC, three times daily (Abrams) —
Osteoarthritis, localized CBD Topical 6.2 mg/mL cream twice daily (Heineman); 8 mg/mL lotion three times daily (AAHS 2026) Oral CBD not supported
Peripheral neuropathy, feet CBD Topical 250 mg CBD per 3 fl oz oil (Xu) —
Migraine, acute THC + CBD (6% / 11%) Vaporized flower at onset Single treatment (Schuster) CBD alone ineffective
Tourette THC:CBD 1:1 Oral oil Titrated to 20 mg THC/20 mg CBD daily over 6 weeks (Mosley) —
PTSD nightmares THC Oral, bedtime Dronabinol 2.5–15 mg (Roepke); nabilone 0.5–3 mg (Jetly) —
Alzheimer’s agitation THC Oral Nabilone 1–2 mg (Herrmann); dronabinol 5 mg (Hopkins trial, per report) —
Anxiety CBD-dominant Oral CBD 25–600 mg/day in social anxiety studies (Skelley 2020 review, cited by Bhaskar); chronic dosing undefined Limonene reduced THC-induced anxiety, vaporized, n = 20 (Spindle 2024)
Sleep maintenance CBN Oral, bedtime CBN 20 mg × 7 nights reduced awakenings; CBD add-on did not help (2024 RCT) Myrcene, linalool: no human data. A larger industry-sponsored, remote, self-reported CBN trial (FloraWorks/Radicle, 2023) reported benefit; treat as low quality.
OUD craving CBD Oral 400–800 mg daily × 3 days (Hurd) Research setting only
Epilepsy (LGS, Dravet, TSC) Purified CBD Oral Epidiolex 10–20 mg/kg/day Avoid substituting dispensary CBD

 

Terpenes overall: a 2024 systematic review found terpene “entourage” effects unproven in humans (André et al., Pharmaceuticals). Use terpene profile as a secondary consideration only, and only for tolerability .

Pharmacogenomics and EndoDNA

Genetic variation explains part of the wide inter-individual response to cannabinoids. A few associations are well replicated; most are not yet clinically actionable.

Gene / variant Finding Strength
CYP2C9*3 After oral THC, *3/*3 homozygotes had threefold higher THC AUC and 70% lower THC-COOH than *1/*1, with a trend toward more sedation; *2 had no effect (n = 43) (Sachse-Seeboth 2009) Pharmacokinetic, small
AKT1 rs2494732 C/C carriers who used cannabis had about twice the odds of psychotic disorder, rising to about seven times with daily use (489 cases, 278 controls) (Di Forti 2012). The journal’s editor noted it does not yet work as a clinical risk test Replicated association
COMT, FAAH, CNR1 variants Associations with psychotomimetic response, pain sensitivity, and mood reported; a larger study found AKT1, COMT, and FAAH did not modulate acute cannabis experiences (Hindocha) Inconsistent

 

EndoDNA. NYSOM works with EndoDNA (Endocanna Health) and integrates its results into the patient matching platform.

  • Test: buccal swab or upload of existing raw genotype data; analyzed in a CLIA-certified, CAP-accredited lab for about 672,000 SNPs associated with the endocannabinoid system and cannabinoid metabolism (GenomeWeb).
  • Report: about 57 trait reports in 12 categories (Nebula review), covering cannabinoid metabolism, predisposition to adverse effects, and traits such as mood, sleep, pain, and inflammation, plus a medication management report flagging drugs that may interact with THC or CBD . Each reported association is tied to peer-reviewed vb literature.
  • Physician access: ordering physicians view results through a physician portal.
  • Patents: US 11,612,582 (server-based genotype analysis and cannabinoid formulation recommendations) and US 12,288,603 (machine-learning efficacy prediction that groups patients by outcome, genetic, and biometric data).
  • How NYSOM uses it: genetic results are one input to the matching platform alongside history, medications, and observed response. They never override the safety rules or pharmacist review. Consented outcomes feed the shared EndoDNA registry for IRB-approved analysis.
  • Evidence status: individual associations come from published studies, but no prospective trial has yet shown that genotype-guided product selection improves efficacy or safety . Treat results as hypothesis-generating support for clinical judgment.
  • Consent: New York Civil Rights Law §79-l requires dated, signed written informed consent before testing.

NYSOM has a business partnership with EndoDNA.

Endo DNA

Cannabinoid and Terpene Reference by Condition

This table lists each compound, the conditions where it has been studied, the strongest type of evidence, and the source. Evidence type matters more than the finding: a positive animal study is not evidence of benefit in patients, and several compounds with strong lab data have failed in human trials.

Evidence types: RCT-P = randomized trial in patients · RCT-H = randomized experimental study in healthy volunteers · Pre = animal or lab only · Neg = negative or null human trial.

Major cannabinoids

Compound Condition / outcome Evidence Finding Source
THC (incl. dronabinol, nabilone) Chemotherapy nausea RCT-P; FDA-approved Effective as add-on for refractory CINV ASCO 2024
THC AIDS anorexia RCT-P; FDA-approved Dronabinol approved indication CJASN table
THC Chronic, mainly neuropathic pain RCT-P THC-only −0.78 points; nabilone −1.59, dronabinol −0.23 (0–10) Chou 2026
THC-dominant extract Chronic low back pain RCT-P NRS −0.6 vs placebo; ≥30% relief 54% vs 40% Karst 2025
THC PTSD nightmares RCT-P Dronabinol d = 0.65, n = 171; nabilone positive, n = 10 Roepke 2026; Jetly 2015
THC Alzheimer’s agitation RCT-P Nabilone and dronabinol reduced agitation Herrmann 2019; Hopkins 2024
THC Glaucoma Physiologic only IOP falls 3–4 h only; not recommended AAO
THC:CBD ~1:1 MS spasticity RCT-P Responder OR 2.41 Kleiner 2023
THC:CBD ~1:1 ALS/MND spasticity RCT-P Improved, n = 59 CANALS 2019
THC:CBD ~1:1 Rheumatoid arthritis RCT-P Pain −0.95 to −1.04, sleep +1.17, DAS28 −0.76; n = 58 2026 scoping review
THC:CBD 1:1 Tourette tics RCT-P Reduced tic scores, n = 22 Mosley 2023
THC + CBD (6% / 11% flower) Acute migraine RCT-P Superior to placebo at 2 h; CBD-only flower was not Schuster 2025
CBD (purified) LGS, Dravet, TSC seizures RCT-P; FDA-approved LGS drop seizures −44% vs −22% GWPCARE4 summary
CBD Anxiety disorders RCT-P (small) Hedges g −0.92 across 8 studies Wang 2024
CBD Opioid use disorder: cue-induced craving RCT-P Reduced craving and anxiety, n = 42 Hurd 2019
CBD (topical) Thumb OA; foot neuropathy RCT-P (small) Pain reduced; n = 18 and n = 29 Heineman 2022; Xu 2020
CBD (oral) Knee and hand OA pain Neg 600 mg/day no better than placebo, n = 86 Pramhas 2023
CBD Ulcerative colitis remission Neg 24% vs 26% Cochrane
CBD Parkinson’s: induced anxiety and tremor RCT-P (single dose) Reduced, n = 24; overall PD meta-analysis negative de Faria 2020; AAN 2026
CBD Type 2 diabetes glycemic control Neg No effect vs placebo (100 mg twice daily, 13 weeks) Jadoon 2016

 

Minor cannabinoids

Compound Condition / outcome Evidence Finding Source
CBN Sleep maintenance RCT-P (small) 20 mg nightly × 7 nights reduced awakenings and overall disturbance; no effect on sleep onset or WASO; adding CBD did not help 2024 RCT
CBN Sleep Pre + single-dose human trial Increased NREM and REM sleep in rats; single-dose human insomnia trial reported as promising, presented but not yet published University of Sydney, 2024
CBN Sleep Industry-sponsored remote trial, self-reported 25–100 mg reported to improve sleep; 50 mg best. Low quality FloraWorks release, 2023
CBN Pain, inflammation, appetite — No human trials identified —
CBG Acute anxiety and stress RCT-H 20 mg reduced anxiety and stress vs placebo; improved verbal memory; no impairment; n = 34 healthy adults Cuttler 2024, Sci Rep
CBG Inflammatory bowel disease, glaucoma Pre Animal models only —
THCV Type 2 diabetes RCT-P 5 mg twice daily × 13 weeks lowered fasting glucose 1.2 mmol/L vs placebo and improved beta-cell function; n = 62 Jadoon 2016
THCV Appetite and weight Mixed human data Conflicting metabolic findings across small studies Summary table
THCV Parkinson’s, seizures Pre Animal models only —
CBDV Focal seizures Neg Phase 2, n = 162: ~40% reduction in both CBDV and placebo arms GW topline
CBDV Autism, Rett syndrome Early-phase only No adequately powered efficacy trial Review of CBDV trials
THCA, CBDA Nausea, inflammation Pre Animal models only; no human trials identified —

 

Terpenes

Terpene Condition / outcome Evidence Finding Source
d-Limonene THC-induced anxiety RCT-H Vaporized with 30 mg THC, reduced “anxious” and “paranoid” ratings; other THC effects unchanged; n = 20 Spindle 2024
Linalool Anxiety RCT-P (lavender oil, not cannabis) Silexan lavender oil (~37% linalool), 80 mg/day × 10 weeks, beat placebo in 5 RCTs, n = 1,213. Linalool content of cannabis is far lower; benefit from cannabis-derived linalool is unproven. Silexan meta-analysis; composition
Beta-caryophyllene Pain, inflammation Pre CB2 agonist; analgesic in animal models Liktor-Busa 2021, Pharmacol Rev
Myrcene Relaxation, sedation Pre Exploratory data only; topical myrcene added nothing to CBD André 2024
Pinene, humulene, others Various Pre No human trials identified Alfieri 2025 review
All terpenes “Entourage” enhancement of cannabinoids Not established Unproven in humans André 2024

 

Bottom line for product steering: only THC, CBD , and their fixed ratios have patient trials across multiple conditions. Among minor compounds, CBN (sleep maintenance), CBG (acute anxiety , healthy volunteers), THCV (glycemic control), and limonene (THC-induced anxiety) each have one small human trial. Treat these as reasonable add-on considerations, not primary therapy .

Clinical Practice

Titration

The most widely cited framework is the 2021 international Delphi consensus (Bhaskar et al.) for chronic pain. It is expert opinion, not trial-derived, and was funded by a cannabis producer . It focuses on oral oils and capsules.

Protocol For whom Start Titrate Ceiling before specialist input
Routine Most patients CBD-predominant 5 mg twice daily +10 mg/day every 2 to 3 days to 40 mg/day CBD. If goals not met, add THC 2.5 mg/day, +2.5 mg every 2 to 7 days 40 mg/day THC
Conservative Frail, polypharmacy, complex comorbidity, mental health history CBD-predominant 5 mg once daily +5 to 10 mg every 2 to 3 days to 40 mg/day CBD. Then THC 1 mg/day, +1 mg weekly 40 mg/day THC
Rapid Severe pain, palliation, prior cannabis experience Balanced THC:CBD 2.5 to 5 mg each, once or twice daily +2.5 to 5 mg of each every 2 to 3 days 40 mg/day THC
  • The consensus notes that about 10 mg/day THC is a typical therapeutic dose for most patients.
  • Start THC in the evening to limit workplace and driving impairment.
  • For breakthrough symptoms, vaporized dried flower is preferred over smoking or vaping extracts (EVALI risk).
  • Follow up every 2 to 4 weeks during titration, then every 3 months when stable.
  • Stop for moderate or severe adverse effects, lack of benefit at the agreed ceiling, or misuse or diversion.

Contraindications and cautions

  • Avoid: psychotic disorders, unstable cardiovascular disease, pregnancy , planned pregnancy , breastfeeding (Bhaskar consensus).
  • Use caution: age under 25, bipolar disorder , personal or f amily history of psychosis, substance use disorder , older adults with f all risk, hepatic impairment (CBD).

Drug interactions

THC is metabolized mainly by CYP2C9 and CYP3A4; CBD by CYP3A4 and C YP2C19. CBD inhibits several C YP450 and UGT enzymes. A 2024 systematic review of real-world reports found warfarin, valproate, tacrolimus, and sirolimus were the most frequently reported interacting drugs. Penn State hosts a free checker at CANN-DIR.

Drug Interaction Action
Warfarin Increased INR and bleeding Check INR at start and with dose changes
Clobazam CBD raises N-desmethylclobazam via CYP2C19 inhibition; sedation Monitor sedation; consider clobazam reduction
Valproate Transaminase elevation with CBD Baseline and periodic LFTs
Tacrolimus, sirolimus Increased levels Therapeutic drug monitoring
Clopidogrel Possible reduced activation (CYP2C19) Consider alternatives in high-risk patients
DOACs CYP3A4 and P-gp effects Use caution
CNS depressants, alcohol, opioids Additive sedation Counsel; avoid alcohol

 

Adverse effects and risks

  • Common: dizziness, somnolence, dry mouth, nausea, tachycardia, cognitive slowing. In the AHRQ review , these rose moderately to substantially with THC-containing products.
  • Cannabis use disorder: A 2024 meta-analysis estimated CUD prevalence among medical users at 25% (95% CI 18 to 33%), similar to recreational users. A 2025 JAMA Psychiatry analysis of NSDUH found higher CUD prevalence with medical-only than nonmedical-only use, likely reflecting more frequent use. Screen at baseline and follow-up.
  • Cardiovascular: In 434,104 BRFSS respondents, daily use carried adjusted odds ratios of 1.25 for MI and 1.42 for stroke, and 1.49 and 2.16 among never-tobacco users (Jeffers 2024, JAHA). A 2025 meta-analysis in Heart found a positive association with MACE. Cross-sectional data cannot prove causation, but caution is warranted in CAD .
  • Psychosis: In a Danish cohort of 6.9 million, CUD carried adjusted HRs for schizophrenia of 2.42 in men and 2.02 in women. Up to about 30% in men aged 21 to 30; about 15% in males aged 16 to 49 (Hjorthøj 2023). Avoid high-potency THC in patients under 25.
  • Cannabinoid hyperemesis syndrome: cyclic vomiting with compulsive hot bathing in heavy, long-term users. Resolution requires cessation.
  • Withdrawal: irritability , insomnia, vivid dreams, reduced appetite, typically within days of stopping heavy use.
  • Overdose: no confirmed deaths from respiratory depression, because CB1 receptors are sparse in brainstem respiratory centers. Serious harms still occur: pediatric ingestions, edible over-intoxication, falls, motor vehicle crashes, and acute cardiovascular events.

Special Populations

  • Pregnancy and lactation: avoid.
  • Adolescents and young adults: CBD has no consensus age limit; THC has none, but under-25 brain development and psychosis risk argue for caution.
  • Older adults: start with the conservative protocol. Watch for orthostasis, falls, and confusion. Relevant to assisted-living and long-term-care settings.
  • Driving: advise no driving while impaired. Oral THC effects can persist 6 hours or more.

Documentation Checklist

  • Indication and target symptom with a measurable goal
  • Prior treatments tried
  • Psychiatric, cardiovascular , and substance use screen
  • Medication reconciliation for interactions
  • Pregnancy status where relevant
  • Product type, THC/CBD ratio, route, and titration plan
  • Follow-up date and stopping criteria

Guidelines and major reviews

References

Trials and meta-analyses by indication

Safety

Regulatory

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