4.1 The “A GUIDE” Mnemonic for Patient-Specific Dosing

A = Age , Weight, & Allergies

1. Age & Developmental Status

   • Pediatric and geriatric cohorts often exhibit reduced metabolic clearance, heightened pharmacodynamic sensitivity, and increased risk of polypharmacy, necessitating conservative titration and vigilant monitoring.

   • In pediatric cases, neurodevelopmental and endocrine factors may further complicate cannabinoid metabolism and warrant specialized clinical oversight.

2. Weight & Body Habitus

   • Body composition (e.g., adipose to lean mass ratio) can influence cannabinoid distribution volume and resultant pharmacokinetics.

   • Observing ideal body weight vs. actual body weight can assist in calculating more precise starting doses.

3. Allergic Profiles

   • Ascertain any hypersensitivities to cannabis plant constituents (cannabinoids, terpenes) or common excipients such as carrier oils and flavoring agents.

   • A thorough allergen screening is imperative to avoid anaphylactic or dermatologic reactions, especially with topical or sublingual formulations.

   
   

Clinical Recommendation: Elicit detailed patient history on age-specific considerations, weight-based dosing, and allergies to preempt adverse events and inform initial therapeutic strategies.

G = Goals & Diagnosis

1. Clinical Objectives

   • Collaborate with the patient to define measurable and functional targets: e.g., reducing pain from 9/10 to 6/10, improving daily activity levels by a specified percentage, or decreasing seizure frequency by a quantifiable margin.

   • Strive for SMART goals (Specific, Measurable, Achievable, Relevant, Time-bound), fostering clear benchmarks of therapeutic success.

2. Differential Diagnosis & Cannabis Applicability

   • Map the patient’s primary and secondary diagnoses (chronic pain syndromes, anxiety disorders, epilepsy, oncologic or palliative diagnoses) to the relevant cannabinoid profiles.

   • Recognize the distinct pathophysiological underpinnings (e.g., neuropathic vs. nociceptive pain) that may influence dosing regimens or THC:CBD ratios.

Clinical Recommendation: Integrate formalized outcome measures (e.g., validated pain scales, seizure diaries) to track goal attainment and guide iterative treatment modifications.

U = Underlying Conditions & Medications

1. Comorbidity Assessment

   • Identify cardiovascular, hepatic, renal, or psychiatric comorbid conditions that could restrict the use of higher-THC products or dictate a more cautious titration timeline.

   • In hepatic or renal compromise, monitor markers of organ function and adjust dosing intervals to mitigate accumulation or toxicity.

2. Pharmacologic Interactions

   • Scrutinize medication lists for CYP450 substrates or inducers (e.g., anticoagulants, antiepileptics, CNS depressants).

   • Consider how polypharmacy may increase the likelihood of drug-drug interactions or synergistic sedation.

   • Implement a precision-medicine ethos by factoring genetic polymorphisms (e.g., CYP2C9, CYP2C19) that may affect cannabinoid metabolism.

3. Risk-Benefit Analysis

   • Weigh the contraindications (e.g., recent myocardial infarction, severe arrhythmias, acute psychosis) against the potential therapeutic gains of cannabinoid therapy.

   • Implement a multidisciplinary approach (e.g., involving pharmacists, psychologists, physiatrists) to form an integrative plan addressing comorbid factors comprehensively.

Clinical Recommendation: Prior to initiating therapy, consult robust drug-interaction databases and incorporate collaborative care models to navigate complex medical profiles safely. For THC, enter THC and/or Marinol. For CBD, enter CBD and/or Epidiolex.

I = Integrated Care

1. Integrated Therapeutic Framework

   • Align cannabis-based interventions with concurrent treatments (e.g., physical therapy, psychotherapy, occupational therapy), optimizing global outcomes.

   • Outline interventions for side-effect management (e.g., antiemetics, anxiolytics) to mitigate potential adverse events and boost adherence.

2. Monitoring of all therapies

   • Recommend and review the patient’s diary of concurrent ongoing treatments.

   • Employ iterative data collection (e.g., standardized diaries, wearable devices) to refine dosing intervals and formulations on an ongoing basis.

Clinical Recommendation: Maintain robust follow-up schedules (telehealth or in-person) to capture evolving patient needs, adjusting cannabinoid ratios and doses in real time.

D – Diet, Exercise, & Social Hx/Support

1. Nutritional & Metabolic Considerations

   • High-fat meals can enhance oral bioavailability of cannabinoids, possibly necessitating dose adjustments or timing modifications.

   • Evaluate overall nutritional status—malnourished or cachectic patients (e.g., cancer) may experience altered pharmacodynamics.

2. Exercise & Routine

   • Ascertain daily activity patterns: higher-activity patients might require alternative dosing intervals to accommodate performance and recovery cycles.

   • Incorporate physiologic feedback (heart rate, blood pressure) to ensure safety in comorbid states (e.g., cardiovascular disease).

3. Lifestyle & Social Determinants

   • Explore sleep habits, shift-work scheduling, or significant stressors that can affect cannabinoid metabolism or therapeutic efficacy.

   • Recognize the impact of social support systems (caregivers, family) on adherence and safety—especially pivotal in older adults or cognitively impaired patients.

4. Route Preference & Patient Autonomy

   • You can match the route of administration—oral, sublingual, inhalation, topical—to patient lifestyle and comfort, considering onset and duration of action.

   • Using shared decision-making, empowering patients in selecting the method that aligns best with their routine and symptom intensity.

Clinical Recommendation: Emphasize a holistic approach, integrating diet, exercise, and psychosocial dynamics into the cannabis treatment plan for optimal, sustained results.

E – Experience with Cannabis

1. Prior Cannabis Exposure

   • Determine previous medical or recreational cannabis use, side-effect thresholds, and preference for specific ‘strains’ (which are more accurately called “chemical varieties” or ‘chemovars’ rather than ‘strains’).

   • Cannabis-naïve individuals benefit from an ultra-low initial dose and cautious titration—“start low and go slow.” (ex 1-5 mg THC or CBN and 10-25 mg CBD)

2. Complexity of the Condition

   • Chronic pain, neurodegenerative conditions, and palliative scenarios may demand higher cannabinoid thresholds or unique titration trajectories.

   • Co-existing mental health conditions (e.g., anxiety, PTSD) might benefit from specific CBD-dominant formulations.

3. Patient Education & Self-Monitoring

   • Instruct patients on safe usage, potential impairment, and signs of excessive THC (e.g., paranoia, psychological effects, etc ).

   • Promote self-reporting (journals, symptom trackers) for real-time feedback, enabling proactive dose recalibrations.

Clinical Insight: Consider using the “A GUIDE” mnemonic or some other method to help you and your staff members be systematic and comprehensive. I like this one but at times I have used other mnemonics and switched to “A GUIDE”, in order to be more comprehensive in preparation to give recommendations.

A = Age , Weight, & Allergies

G = Goals & Diagnosis

U = Underlying Conditions & Medications

I = Integrated Care

D = Diet, Exercise, Lifestyle, & Social Support E = Experience with Cannabis

References & Further Reading

• MacCallum CA, Russo EB. Practical considerations in medical cannabis administration and dosing. Eur J Intern Med. 2018 Mar;49:12-19. doi: 10.1016/j. ejim.2018.01.004. Epub 2018 Jan 4. PMID: 29307505.

• Christensen C, Allesø M, Rose M, Cornett C. Clinical Research Evidence Supporting Administration and Dosing Recommendations of Medicinal Cannabis as Analgesic in Cancer Patients. J Clin Med. 2022 Dec 30;12(1):307. doi: 10.3390/ jcm12010307. PMID: 36615107; PMCID: PMC9821014.

• Bell AD, MacCallum C, Margolese S, Walsh Z, Wright P, Daeninck PJ, Mandarino E, Lacasse G, Kaur Deol J, de Freitas L, St Pierre M, Belle-Isle L, Gagnon M, Bevan S, Sanchez T, Arlt S, Monahan-Ellison M, O’Hara J, Boivin M, Costiniuk C. Clinical Practice Guidelines for Cannabis and Cannabinoid-Based Medicines in the Management of Chronic Pain and Co-Occurring Conditions. Cannabis Cannabinoid Res. 2024 Apr;9(2):669-687. doi: 10.1089/can.2021.0156. Epub 2023 Mar 27. PMID: 36971587; PMCID: PMC10998028.

These references provide additional depth on evidence-based dosing, safety considerations, and the evolving landscape of medical cannabis research. For more see resources see the REFERENCE section at the end of this book and resources like Pubmed.gov

4.2 Pharmacogenomics and Patient Variability

• CYP2C9 Variants: May slow THC metabolism, increasing psychoactive effects.

• Endocannabinoid System Polymorphisms: Genetic differences in CB1 receptor or FAAH enzyme activity can shift therapeutic response.

Clinical Insight: Leveraging pharmacogenomic data ensures clinicians can adjust cannabinoid ratios and routes of administration to optimize efficacy and minimize adverse effects.

4.3 Common Delivery Methods

4.3 Pros, Cons and Dosing in Clinical Practice

• Inhalation: Best for acute relief (e.g., breakthrough pain, severe nausea). For inhalation 1 dose may range from 1-5 mg of THC based on concentration, depth of inhalation, lung health, physiologic dead space and other factors.

• Oral: Ideal for chronic conditions needing sustained plasma levels; requires careful dose titration. A dose is often considered as 10 mg THC. For medically sensitive patients, consider starting at a fraction of a dose; 1, 2, 2.5 or 5 mg.

• Sublingual: Balances faster onset with ease of administration. Similar to oral.

• Topical: Limited to localized issues (arthritis, minor injury) but spares systemic side effects. Less systemic absorption allows for faster increases of dosing and greater flexibility. May start at 12.5-25 mg THC and/or CBD per dose and gradually increase to 4-6x per day.

4.4 Start Low, Go Slow: Titration Principles

1. Initial Dose: Begin with the lowest plausible effective dose (e.g., 1–5 mg of THC or 10-25 mg CBD for adults via one route of administration and consider adding additional routes gradually over days to weeks, if needed).

   • For more experienced patients, multiple routes can be continued, started, or increased more quickly.

2. Incremental Adjustments: Increase every 2–3 days if needed and as tolerated.

3. Monitor Response: Track symptom relief and any adverse events.

4. Ceiling Effect: Identify the point at which further dose escalations yield minimal additional benefit.

Clinical Insight: Patients often require individualized titration schedules, especially with oral formulations where onset is delayed (30–90 minutes) and peak may not be reached for several hours.

4.5 Guidelines for Effective Titration

Clinical Insight: Advise patients that initial dosing with oral routes (edibles and capsules) can be variable and it is easy to take more than needed when starting. I believe this often occurs when patients consume the medicine as if it were a food (i.e. taking 2-4 small cookies as a snack vs. taking 1⁄4 cookie as a medicine). Remind patients this is a medicine. A 10 mg edible can be started at 1⁄4 the dose 4-6 hours (2.5mg ) for the 1st few doses, then 5mg/dose until the patient becomes more acclimated to the medicine.

Clinical Insight 2: More experienced patients may be started at a higher dose and/or increase to the lowest effective dose more quickly. The key is to take a systematic approach and understand the patients prior and recent experience with cannabis.

1. Use Patient-Reported Outcomes: Pain scales, anxiety inventories, and quality-of- life metrics guide dose adjustments.

2. Allow Time for Physiological Adaptation: Particularly critical for oral cannabinoids with slow onset.

3. Educate Patients on Red-Flag Side Effects: Dizziness, excessive sedation, paranoia— these may warrant dose reduction or THC/CBD ratio adjustments.

4.6 Tailoring Dosing for Specific Conditions

1. Chronic Pain

   • Recommendation: Start at 2.5 - 5 mg THC or CBD; titrate to ~20–50 mg/day total.

   • Rationale: Balanced THC:CBD formulas often outperform single-cannabinoid regimens.

2. Anxiety

   • Recommendation: Initiate 10-25 mg CBD; titrate to 25–200 mg/day.

   • Rationale: Low-THC, high-CBD regimens minimize psychoactive side effects while providing anxiolysis.

3. Epilepsy

   • Recommendation: 10–20 mg/kg/day of CBD (as in CBD Tincture or Epidiolex).

   • Rationale: FDA-approved in the U.S. for Dravet syndrome, Lennox-Gastaut syndrome.

4. Spasticity (e.g., MS)

   • Recommendation: 2.5–5 mg THC/day + 10–20 mg CBD/day titrate up to the lowest effective dose.

   • Rationale: Combination sprays (Sativex) have demonstrated improvements in muscle tone and spasm frequency.

4.7 Dr. Newton’s Tips for Cannabinoid Dosing

1. Onset Timing – The 2-20-2 Rule

   • Inhalation: ~2 minutes for rapid relief

   • Sublingual: ~20 minutes for moderate speed

   • Oral: ~2 hours for extended-release effect

2. Dosing Strategy – The 2-5, 25 Rule

   • Psychoactive Cannabinoids (e.g., THC, CBN): Start at 2–5 mg; escalate in 2–5 mg increments

   • Non-Psychoactive Cannabinoids (e.g., CBD, THC-A): Start at 25 mg; adjust in 25 mg steps

4.8 Clinical Pearls

1. Pearl 1: Liver Impairment

   • Suggest sublingual or topical routes to circumvent extensive first-pass metabolism, reducing systemic load.

2. Pearl 2: Leverage the Entourage Effect

   • Combine THC and CBD to maximize efficacy and minimize side effects; terpenes and other cannabinoids further refine the therapeutic profile.

3. Pearl 3: GAMES-Minded Consults

   • Use the GAMES mnemonic (Goals, Age/Allergies, Medical Hx, Experience, Social Hx) at every visit to recalibrate dosing and therapy.

Key Takeaway

A structured, evidence-informed approach—encompassing GAMES to assess individual patient factors—enables precision in cannabis dosing. Coupled with genomic insights and vigilant titration, clinicians can optimize safety and outcomes across diverse patient populations.