This post was updated Nov. 1, 2018.
By Dr. Karen Keough, Chief Medical Officer
Determining a patient’s ideal dose and formulation for cannabis-based medications is actually fairly similar to the process for dosing any new pharmaceutical medications that hit the market.
Like most new medications, dosage recommendations and guidelines for cannabidiol (CBD) medicines are best established according to existing scientific research, anecdotal evidence, and individual patient outcomes. The biggest difference is that CBD medicines don’t start out with a dosing range approved by the FDA. Although newly FDA approved drugs include dose ranges approved in clinical trials, the real-world dosing ranges become apparent as more patients use the medication and as both prescribers and patients get a better sense of the dosing they need.
General guidelines for CBD dosing
The dose-finding process will be different for each patient. Because the Texas program is in its infancy, there is a limited knowledge base for physicians at this time; it will grow as more patients join the program and prescribers gain a better understanding of what is working and how patients tolerate CBD treatment. Each patient will need to discover the dosing amount that works best for them. This is what the titration process is all about.
As with every new medication, conservative initial titration and slow dosage increases will minimize the chance of severe side effects, and avoid reaching a dose beyond that necessary to gain control of seizures.
Medically sensitive patients, such as those who are under two years of age or who are taking multiple concomitant seizure medications, should be started at a lower dose and titrated more slowly. Less sensitive patients can be started at a somewhat higher initial dosage.
I devised these guidelines based on available research and clinical trial results, and have refined the approach based on experience with nearly 100 patients I have written prescriptions for since February 2018. They are a starting point, with the expectation that a small portion of patients may require higher doses.
Dosing Recommendations
For each patient, CBD dosing will depend on the following:
- Formulation of product (e.g. CBD concentration, THC concentration). Compassionate Cultivation’s Lone Star product is 100 mg/ml CBD with 5 mg/ml THC (0.5%).
- Patient characteristics, including weight, age and the number and type of medications the patient is already taking.*
- Initial dose and rate of titration both need to be considered.
* It is important to note that one common seizure medication often used in refractory patients that has a strong interaction with CBD is clobazam (Onfi). Patients taking Onfi should be started on lower CBD doses and titrated more gradually even if Onfi is the only other seizure medication the patient is taking when initiating CBD treatment.
Low dose initiation in children
- 0.5 mg/kg/day, minimum dose 10 mg = 0.1 ml.
- Increase every 1-2 weeks by 0.5-1 mg/kg/day, rounding to nearest 10 mg (0.1 ml increments) as long as side effects don’t interfere.
- Target dose 2-10 mg/kg/day; average is 2-6 mg/kg/day; higher doses may be tolerated, but we will need more experience with the Lone Star product to understand the ranges our patients need for optimal response with minimal side effects
Low dose in adults (or children weighing >50 kg)
- 25 mg twice daily.
- Increase every 1-2 weeks by 25 mg/dose.
- Target dose 100-300 mg twice daily if tolerated, or stop sooner if seizures stop or side effects prevent further dose increases. Higher doses have been utilized in some clinical trials, but may not be necessary to achieve good seizure control in all patients.
Higher dose initiation in children
- 1 mg/kg/day, minimum 10 mg = 0.1 ml.
- Increase every 1-2 weeks by 1 mg/kg/day, as long as side effects do not interfere.
- If side effects are a problem, go up more gradually with more time between dose increases.
- Target dose 2-10 mg/kg/day, average is 2-6 mg/kg/day. As noted above, higher doses might be tolerated, but we need more experience with the Lone Star product to understand the ranges our patients need for optimal response with minimal side effects.
Higher dose in adults (or children weighing >50 kg)
- 50 mg twice daily.
- Increase every 1-2 weeks by 50 mg/dose.
- Target dose 100-300 mg twice daily if tolerated, or stop sooner if seizures stop or side effects prevent further dose increases. Higher doses have been utilized in some clinical trials, but may not be necessary to achieve good seizure control in all patients.
Other factors to consider for the patient treatment plan
Dose increments of <0.1 ml are not feasible to measure, so round to 0.1 ml instead of 0.05 ml increments. The half-life is long, so once/day dosing is fine for small doses; split to twice/day if volume makes oral absorption difficult or if the dose starts to cause sleepiness.
Doses should be given in cheek or under tongue ideally; if swallowed, should be given with some fatty food to increase absorption.
Higher doses have been utilized in some clinical trials, but may not be necessary in all patients to achieve good seizure control. These higher doses may be well tolerated, but we need more experience with the Lone Star product to understand the ranges our patients need for optimal response with minimal side effects.
For the complete Dosing Guidelines document, as well as full references for research and clinical trials on CBD treatment, please visit texasoriginal.com/physicians.
A note on costs
The Lone Star line is available in two quantities: 7.5 mL (containing 750 mg CBD / 37.5 mg THC) for $105; and 15 mL (containing 1,500 mg CBD / 75 mg THC) for $200. Breaking it down further, the retail cost for a single milligram of CBD is approximately 13 cents.
For example, a 25 kg (55 lbs) child who is on a 1.5 mg/kg/day (37.5 mg CBD/day) dose of Lone Star tincture would equate to approximately $146 per month. A 50 kg (110 lbs) adult or child who is taking 3 mg/kg/day (150 mg CBD/day) would equate to approximately $585 per month.
Entering Prescriptions Into the Compassionate Use Registry of Texas (CURT)
The Compassionate Use Program (CUP) allows for research of patient participants in a HIPPA-compliant system. However, the quality of data will depend on how thoroughly prescribers enter prescription information into the system.
Currently the drop-down menus and existing text entry fields have some limitations, so detailed prescriber notes will be important for clearly describing patient histories into the CUP system.
With that in mind, here’s a brief rundown for prescribers of the three-step process for entering patient prescriptions into the CUP system.
The first step is to complete two text entry fields under the patient “Treatment Plan” tab. The following is what I have been utilizing for those fields, but other prescribers may develop their own approaches:
- Monitoring symptoms plan:
- Log number & type of seizures daily
- Monitoring Tolerance/reaction plan:
- Watch for somnolence, nausea & vomiting
- Baseline LFTs were drawn & will be followed serially during treatment
The prescriber must indicate both duration of therapy and the amount prescribed under the patient Treatment Plan. I’ve chosen three months as a standard duration of therapy, but the amount prescribed may or may not last three months. Duration depends on the patient’s personal titration schedule, which can’t be predicted at the time of the first prescription. Once a patient’s ongoing dose is established, the amount prescribed will become more readily predicted. Larger prescription volumes may be especially useful for patients living far away from the dispensary, to help minimize travel times and/or delivery costs.
The prescription can be written “as directed,” but the SIG line is too short to allow for entry of titration instructions, so those specifics will need to be communicated to the patient or their guardian directly, independent of the prescription. The route of administration is not included as a field for entry. The addition of “buccal” or “sublingual” into the dose instruction is possible, but can also be communicated directly to the patient or guardian.
Compassionate Cultivation’s CBD tincture product comes in two sizes, 750 ml or 1500 ml, which I’ve instructed to dose in the buccal pouch. Dosing enterally (e.g. by G tube or swallowed) will result in some absorption by the liver and decrease the amount that enters circulation. But enteral dosing could be done if the volume is too large to instill in the buccal pouch, or for patients prone to aspiration, where buccal delivery could be risky.
The second step for prescribers when entering prescription information into the CUP is to fill out the Prescription section, which will be partially completed by information flowing from the Treatment Plan tab. The Prescription section allows prescribers to designate a dispensary, which will provide patients with specific instructions regarding their prescriptions.
Based on my close association with Compassionate Cultivation throughout their development and my confidence in their products, I specify this dispensary on every prescription. In doing so, I am assured that a quality product with consistent content will be delivered to the patient every time.
The final section for prescribers to fill out is the Safety & Efficacy tab, where they will enter information about seizure type, duration and frequency. The drop-down menu for seizure type does not include an option for epileptic spasms. Categorizing seizure frequency into a single description proved challenging to me, so I used the “Notes” field to add details that I felt would be relevant to research and to tracking response to treatment. I also added notes about concomitant medications when it was pertinent to the patient dosing plan – particularly for patients taking multiple different medications at the same time, or patients taking Onfi as a co-treatment with CBD.
(Top photo: Compassionate Cultivation staff)
