CBD Oil Dose For Neuropathic Pain

CBDISTILLERY

Buy CBD Oil Online

Navigating cannabinoid choices for chronic neuropathic pain in older adults Associate Clinical Professor for Academic Family Medicine at the University of Saskatchewan in Regina. Approximately The combination of CBD and THC is a powerful treatment for nerve damage and neuropathic pain. Here is what you need to know about CBD:THC ratios for neuropathy. Globally, medical cannabis legalization has increased in recent years and medical cannabis is commonly used to treat chronic pain. However, there are few randomized control trials studying medical cannabis indicating expert guidance on how to dose and administer medical cannabis safely and effectively is needed. Using a multistage modified Delphi process, twenty global experts across nine countries developed consensus-based recommendations on how to dose and administer medical cannabis in patients with chronic pain. There was consensus that medical cannabis may be considered for patients experiencing neuropathic, inflammatory, nociplastic, and mixed pain. Three treatment protocols were developed. A routine protocol where the clinician 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. At a CBD-predominant dose of 40 mg/day, 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. A conservative protocol where the clinician initiates the patient on a CBD-predominant variety at a dose of 5 mg once 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. At a CBD-predominant dose of 40 mg/day, clinicians may consider adding THC at 1 mg/day and titrate by 1 mg every 7 days until a maximum daily dose of 40 mg/day of THC. A rapid protocol where the clinician initiates the patient on a balanced THC:CBD variety at 2.5–5 mg of each cannabinoid once or twice daily and titrates by 2.5–5 mg of each cannabinoid every 2 to 3 days until the patient reaches his/her goals or to a maximum THC dose of 40 mg/day. In summary, using a modified Delphi process, expert consensus-based recommendations were developed on how to dose and administer medical cannabis for the treatment of patients with chronic pain.

Navigating cannabinoid choices for chronic neuropathic pain in older adults

Associate Clinical Professor for Academic Family Medicine at the University of Saskatchewan in Regina.

Approximately 18% of Canadian adults use cannabis, which has increased from 14% since the legalization of recreational marijuana. 1 However, less than 2% of Canadians are registered medical cannabis users. 2 , 3 Chronic pain is a common reason for using cannabis. 4 , 5 Because neuropathic pain, a subset of chronic pain, affects approximately 8% of patients and is challenging for physicians and patients to manage adequately, an understanding of cannabinoid therapies (ie, prescription cannabinoids or cannabis) is important (Box 1). 6 – 9 This article will review the evidence for cannabinoids in refractory neuropathic pain and highlight tools to assist family physicians who seek practical guidance in advising, authorizing, prescribing, and monitoring cannabinoids. We acknowledge that there are various viewpoints on the role of cannabinoids and we offer multiple considerations.

Box 1.

Overview and definitions

The following provides an overview of relevant terminology

Cannabinoid: Any compound that activates a cannabinoid receptor (eg, prescription cannabinoid and cannabis). The most studied, although still poorly understood, are THC and CBD

Cannabinoid receptors: CB1 receptors (primarily in the central and peripheral nervous system) and CB2 receptors (primarily in the immune system) are part of the endocannabinoid system

Table 1.

Comparison of cannabinoids for treating neuropathic pain: The full version of the RxFiles cannabinoid treatment chart is available online from CFPlus. *

Licensed producer: Regulated by Health Canada; requires prescribers to authorize medical cannabis via a medical document

Licensed retailer: A regulated retailer or licensed dispensary; regulated by each province and territory, as government-operated, privately licensed stores, or online. Medical oversight is not required

Case description: Mr Wilson

Mr Wilson, an 81-year-old who lives independently with his wife, has been a patient of yours for a long time. Three weeks ago he had an emergency department (ED) visit owing to dizziness and a near fall, and was told to follow up with his family physician if he continued to feel dizzy.

His medical history includes neuropathic pain secondary to long-standing type 2 diabetes mellitus, spinal osteoarthritis, and chronic insomnia. He is an ex-smoker. The discharge summary indicates that findings of the computed tomography scan of his brain were normal and that laboratory test results revealed that complete blood count, renal panel findings, extended electrolyte levels, and random blood glucose level were within normal range. His recent hemoglobin A1c measurement was 7.5%. His blood pressure was 128/84 mm Hg, with no orthostatic drop, and his heart rate was 72 beats/min. Neurologic and cardiac assessments were done, and no evidence of underlying disease was found. Findings of Dix-Hallpike maneuvers were negative.

According to your records, Mr Wilson is currently taking 75 mg of pregabalin twice daily, 60 mg of duloxetine daily, 850 mg of metformin twice daily, 40 units of insulin glargine at night, 20 mg of rosuvastatin daily, 5 mg of ramipril daily, 7.5 mg of zopiclone at night as required (2 or 3 times per week), and 1000 units of vitamin D daily. You recall that nortriptyline was trialed without success a few years ago (it had caused drowsiness and constipation at a dose of 100 mg at night), but after he was switched to pregabalin, Mr Wilson reported some improvement. About a year ago, duloxetine was added, and Mr Wilson reported further improvements in his diabetic neuropathy. Furthermore, Mr Wilson has previously expressed that he wants to avoid opioids “at all costs.”

Mr Wilson is still experiencing dizziness, and on today’s examination, his blood pressure and heart rate are 120/70 mm Hg and 68 beats/min, respectively, with no orthostasis. You confirm his current medication regimen, with no changes made over the past several months. However, upon routine cannabinoid screening, you discover that Mr Wilson was given cannabidiol (CBD) oil 3 months ago by his son to try to help with his nerve pain. You ask Mr Wilson to complete a Cannabis Use Disorder Identification Test–Revised (https://bpac.org.nz/BPJ/2010/June/docs/addiction_CUDIT-R.pdf), on which he scores 4, indicating no hazardous cannabis use. 10

Importance of cannabinoid screening

Screening for cannabinoid use, even in older adults, is important given the prevalence of cannabis use. Patients might contemplate self-medicating with cannabis for various reasons, including viewing cannabis as a “natural” (and therefore “safe”) alternative, or for managing medical conditions not adequately controlled by their current drug therapy. 9 Prescription cannabinoids (ie, nabiximols and nabilone), when dispensed by a community pharmacy, are captured by provincial or territorial electronic prescription databases. Cannabis is not captured by these databases, which makes it easy to miss unless it is specifically asked about, as was the case with Mr Wilson. When screening, it might be helpful to ask patients separately about medical and recreational (or nonmedical) cannabis or marijuana. Also, prompting patients by asking about specific products such as “CBD oil” or “topical cannabis” might be useful, as these products are not always viewed as medications by patients.

Back to Mr Wilson

Physician: I’m sorry that your nerve pain is still causing problems. I didn’t realize how much it was bothering you. Thank you for sharing about your CBD oil though, as it is helpful for your assessment. Did you bring the CBD oil with you?

Mr Wilson: I have a picture of it on my phone. It’s really helping me. I started at 1 drop at night and now I take 16 drops. I think my son said it was safe to go up to 40 drops, but I didn’t need that much. He picked this one because it just has CBD in it. (The label reads CBD 100 mg/mL.)

Physician: May I make a suggestion about what I think could be the possible cause of your dizziness? [Mr Wilson nods.] I’m concerned that this CBD oil might be contributing to this.

Mr Wilson: But I thought CBD is safe because it doesn’t get you high.

Bringing evidence to practice: cannabinoid adverse effects

Cannabinoids can cause many adverse effects that are often underappreciated by patients or their families, such as with Mr Wilson and his son ( Table 2 ). 9 Most cannabinoid trials enrol experienced users and exclude older adults and those with comorbidities common among aging patients. 11 , 12 Interestingly, the risk of adverse effects might even be higher in older adults owing to greater cannabinoid exposure (eg, slower cannabis metabolism and increased fat tissue) compared with younger adults. 11 Cannabis also appears to increase the risk of ED visits. A survey of 14 715 individuals aged 50 years or older found that 30.9% of cannabis users visited the ED compared with 23.5% of nonusers (P < .001). 13 Patients, especially older adults, are at risk of cannabinoid-related adverse effects and should be educated about and monitored for these effects.

Table 2.

Adverse effects of cannabinoids to assess or monitor

ADVERSE EFFECT CANNABINOID EVENT RATE, % PLACEBO EVENT RATE, % NUMBER NEEDED TO HARM
Overall adverse effects 81 62 6
Withdrawal due to adverse effects 11 Approximately 3 14
“Feeling high” 35 3 4
Sedation 50 30 5
Dizziness 32 11 5
Speech disorders 32 7 5
Ataxia or muscle twitching 30 11 6
Hypotension 25 11 8

Data from Allan et al. 9

Cannabinoid therapies can cause dizziness. A systematic review found 3 systematic reviews of cannabinoids versus placebo assessing this adverse effect. 12 The largest systematic review included 41 randomized controlled trials (RCTs) comprising 4243 participants and found an increased risk of dizziness (odds ratio of 5.09, 95% CI 4.10 to 6.32). 14 Increased dizziness with cannabinoid therapy was also found by Wade et al (3 RCTs including 666 participants; 32% vs 11% experienced dizziness; number needed to harm of 5) and by Mücke et al (4 RCTs including 823 patients), who found a numerical, although not statistical, increase in dizziness (risk difference of 3%, 95% CI −2% to 8%). 15 , 16 Furthermore, cannabinoid therapy is active in the central nervous system (CNS) and it can interact with other CNS-active drugs. The American Geriatric Society Beers criteria recommend avoiding the use of 3 or more CNS-active drugs. 17 Mr Wilson is currently taking 4 CNS-active drugs (ie, pregabalin, zopiclone, duloxetine, cannabis oil), which increases his risk of harm, including dizziness.

Whether CBD alone causes dizziness is unstudied; however, all cannabis oil purchased from a legal source in Canada (ie, licensed producers or licensed retailers) will provide labeled concentrations for both CBD and tetrahydrocannabinol (THC) (see Box 2 for cannabis oil considerations). 18 Therefore, it is likely that Mr Wilson was given illegal cannabis oil, as the label only listed the concentration for CBD, and that Mr Wilson’s cannabis oil does contain an unspecified amount of THC despite no labeled concentration. In addition, products purchased from a legal source will have an excise stamp on the packaging and a standardized cannabis symbol (if the product contains greater than 10 μg of THC per gram), which can be another clue about the source of cannabis. 19 , 20 To date, all legal cannabis products in Canada contain both CBD and THC.

Box 2.

Cannabis oil considerations

Most patients will report cannabis oil dose in drops or millilitres per day. However, it is important to know the milligram dose of CBD and THC. The concentration (ie, mg/mL) of CBD and THC should be reported on the product’s label

– Mr Wilson is taking 16 drops per day, which is about 0.8 mL/d (rule of thumb: approximately 20 drops per mL)

Back to Mr Wilson

Physician: There really is no such thing as a safe type of cannabis. In fact, about 1 in 5 patients taking a cannabinoid medication will become dizzy. I am especially concerned when the cannabis is combined with your other medications that put you at risk of falling.

Mr Wilson: So, you want me to stop the CBD oil? But, won’t my pain come back? I don’t feel very good about that.

Bringing evidence to practice: diabetic neuropathic pain management and cannabinoid therapy

Before considering cannabinoid therapy, it is important to discuss goals of therapy with Mr Wilson and assess his previous medication trials. An understanding of Mr Wilson’s perceived benefit with cannabis oil is essential. Focusing on functional goals—that is, goals where success is measured by improvements in activities of daily life (eg, ability to play with grandchildren, garden, get groceries)—versus relying solely on pain scores is central to managing chronic pain. 6 , 21 It is also important to set realistic expectations regarding benefits that can be achieved pharmacologically. For example, a 30% or 50% reduction in pain are common efficacy outcomes assessed in chronic pain RCTs to indicate success; however, some patients might believe that drug therapy will reduce their pain to zero. Because Mr Wilson reported some improvement with both pregabalin and duloxetine, but still pursued self-medicating with cannabis, it would be worthwhile to discuss and set functional goals while emphasizing that complete elimination of pain is unrealistic. In addition, even for patients who might feel as though they have “tried everything,” there is often still an opportunity to optimize therapies. Guidelines recommend nonpharmacologic treatment such as exercise, physiotherapy, and psychological therapies in all patients. 7 Furthermore, many patients perceive a drug therapy to have failed, but have not undergone an adequate trial. For example, most medications need to be titrated to an effective dose and used for at least 6 weeks (and likely 3 months) to realize benefit. 9 Of note, older adults usually require lower doses and slower medication titration than younger adults do (see Geri-RxFiles available at www.RxFiles.ca for further dosing information). 22

Currently, cannabinoids are considered a third- or fourth-line treatment alternative for chronic neuropathic pain after patients fail tricyclic antidepressants, gabapentinoids, and selective norepinephrine reuptake inhibitor antidepressants. 7 , 9 For Mr Wilson, cannabinoids might be a reasonable alternative, as he has trialed nortriptyline, pregabalin, and duloxetine. A 2018 Cochrane meta-analysis of 10 RCTs of patients (1586 participants) experiencing chronic neuropathic pain found that cannabinoids compared with placebo increased the number of patients achieving a 30% or greater reduction in pain with a number needed to treat of 11 (moderate quality of evidence). 23 However, there was no difference in patients with diabetic neuropathy based on a subgroup analysis of 2 RCTs (327 participants). 23 In addition, the review attempted to meta-analyze a functional outcome—patient reported global impression of pain—but the quality of evidence was low and further study is required. 23

Although cannabinoids have been studied in chronic neuropathic pain as outlined above, important limitations exist. Most RCTs included fewer than 100 participants (range 20 to 339), between the ages of approximately 25 to 60 years (up to 70 years), and assessed the prescription cannabinoid nabiximols. 23 None of the RCTs assessed cannabis oil. 23 Two RCTs assessed nabilone (but were not included in the meta-analysis). 23 Most RCTs were 12 weeks in duration (up to 26 weeks), and long-term benefit is unknown. 23 This was further assessed in a systematic review by Allan et al, in which short RCTs (up to 5 weeks) found positive results and longer RCTs (9 to 15 weeks) found neutral results. 12 Thus, cannabinoid effects, especially long-term, remain unknown in older adults, such as Mr Wilson.

Potential management approaches for Mr Wilson

Managing refractory chronic neuropathic pain is challenging; however, there are a few interventions that Mr Wilson would likely benefit from. Goals of care, with an emphasis on function, should be discussed, and Mr Wilson should be reminded that drug therapy is unlikely to reduce his pain level to zero. Nonpharmacologic therapy is helpful and should be explored (eg, psychotherapy, physiotherapy, supervised activity program). An outline of many nonpharmacologic therapies is available online at www.RxFiles.ca/painlinks.

See also  Rachel Ray CBD Gummies

Various drug therapy approaches for refractory chronic neuropathic pain are reasonable and depend on many variables such as patient characteristics and values. For Mr Wilson, it might be reasonable to trial an increased dose of either 90 mg of duloxetine daily or 75 mg of pregabalin in the morning and 150 mg at night for 3 months while weighing the potential for benefits and adverse effects. 24 , 25

Given that Mr Wilson’s cannabis oil is likely illicit and associated with the onset of his dizziness, he should be encouraged to stop using it, or at least to decrease the dose (although it is important to note that Mr Wilson might not follow medical advice). Tapering is advised when stopping, as withdrawal symptoms (eg, anxiety, sweating, and sleep disturbances) have been reported when cannabinoids are used daily for a few weeks to months. 26 While the optimal tapering regimen is unknown, in non-frail elderly patients like Mr Wilson, decreasing the dose by 25% every 1 to 2 weeks as tolerated is reasonable while monitoring for dizziness resolution, cannabis withdrawal symptoms, and effects on function. 27 You might choose to provide Mr Wilson with a cannabis patient booklet, which highlights some cannabis myths and adverse effects (available at www.RxFiles.ca). 28

If alternative cannabinoid therapy is explored (see Table 1 for cannabinoid product details 9 and the full version of the RxFiles cannabinoid treatment chart available online from CFPlus * ), Mr Wilson should likely be titrated off or given a reduced dose of duloxetine or pregabalin to minimize additive CNS adverse effects. 9 Prescription cannabinoids are preferred over cannabis, as most RCTs assessed these products, dosing guidance is available, provincial and territorial electronic prescription databases capture these products aiding in cannabinoid screening, and the products meet prescription-level quality standards. However, cost might be prohibitive, especially with nabiximols. It would be important to initiate the cannabinoid at a low dose and increase it every few days or weekly, and a reasonable trial duration would be approximately 3 months. In general, the best approach will be patient-centred.

Conclusion

Overall, there are many unknowns and uncertainties about the optimal role of cannabinoids in older adults for refractory neuropathic pain. Until more robust data are available, ensure other nonpharmacologic and pharmacologic therapies are optimized and that patients have failed at least 3 other agents before initiating cannabinoid therapy. Patients might be curious and want to explore cannabinoid therapy, so it is important to screen for cannabinoid use, monitor for potential adverse effects, and engage with patients. In addition, cannabinoid-related tools for practice exist to assist family physicians who seek practical guidance for delivering patient care.

Acknowledgments

We thank Lynette Kosar and Loren Regier for their review of this article.

Footnotes

* The RxFiles Cannabinoid Drug Comparison Chart is available at www.cfp.ca. Go to the full text of the article online and click on the CFPlus tab.

Competing interests

RxFiles and contributing authors do not have any commercial competing interests. RxFiles Academic Detailing Program is funded through a grant from Saskatchewan Health to the University of Saskatchewan; additional “not for profit; not for loss” revenue is obtained from sales of books and online subscriptions. No financial assistance was obtained for this publication.

This article is eligible for Mainpro+ certified Self-Learning credits. To earn credits, go to www.cfp.ca and click on the Mainpro+ link.

La traduction en français de cet article se trouve à www.cfp.ca dans la table des matières du numéro de novembre 2019 à la page e469.

References

1. National Cannabis Survey 1st quarter, 2019. Ottawa, ON: Statistics Canada; 2019. Available from: https://www150.statcan.gc.ca/n1/pub/11-627-m/11-627-m2019032-eng.htm. Accessed 2019 Jul 1. [Google Scholar]

2. National Cannabis Survey, fourth quarter 2018. Ottawa, ON: Statistics Canada; 2018. Available from: https://www150.statcan.gc.ca/n1/daily-quotidien/190207/dq190207b-eng.htm. Accessed 2018 Apr 26. [Google Scholar]

3. National Cannabis Survey, third quarter 2018. Ottawa, ON: Statistics Canada; 2018. Available from: https://www150.statcan.gc.ca/n1/daily-quotidien/181011/dq181011b-eng.htm. Accessed 2018 Apr 26. [Google Scholar]

4. Baron EP, Lucas P, Eades J, Hogue O. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort. J Headache Pain. 2018; 19 (1):37. [PMC free article] [PubMed] [Google Scholar]

5. Boehnke KF, Gangopadhyay S, Clauw DJ, Haffajee RL. Qualifying conditions of medical cannabis license holders In the United States. Health Aff (Millwood) 2019; 38 (2):295–302. Erratum in: Health Aff (Millwood) 2019;38(3):511. [PMC free article] [PubMed] [Google Scholar]

6. Grinzi P. The inherited chronic pain patient. Aust Fam Physician. 2016; 45 (12):868–72. [PubMed] [Google Scholar]

7. Moulin D, Boulanger A, Clark AJ, Clarke H, Dao T, Finley GA, et al. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Res Manag. 2014; 19 (6):328–35. [PMC free article] [PubMed] [Google Scholar]

8. Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain. 2006; 7 (4):281–9. [PubMed] [Google Scholar]

9. Allan GM, Ramji J, Perry D, Ton J, Beahm NP, Crisp N, et al. Simplified guideline for prescribing medical cannabinoids in primary care. Can Fam Physician. 2018; 64 :111–20. (Eng), e64–75 (Fr). [PMC free article] [PubMed] [Google Scholar]

10. Adamson SJ, Kay-Lambkin FJ, Baker AL, Lewin TJ, Thornton L, Kelly BJ, et al. An improved brief measure of cannabis misuse: the Cannabis Use Disorders Identification Test–Revised (CUDIT-R) Drug Alcohol Depend. 2010; 110 (1–2):137–43. Epub 2010 Mar 26. [PubMed] [Google Scholar]

11. Minerbi A, Häuser W, Fitzcharles MA. Medical cannabis for older patients. Drugs Aging. 2019; 36 (1):39–51. [PubMed] [Google Scholar]

12. Allan GM, Finley CR, Ton J, Perry D, Ramji J, Crawford K, et al. Systematic review of systematic reviews for medical cannabinoids. Pain, nausea and vomiting, spasticity, and harms. Can Fam Physician. 2018; 64 :e78–94. Available from: www.cfp.ca/content/cfp/64/2/e78.full.pdf. Accessed 2019 Sep 23. [PMC free article] [PubMed] [Google Scholar]

13. Choi NG, Marti CN, DiNitto DM, Choi BY. Older adults’ marijuana use, injuries, and emergency department visits. Am J Drug Alcohol Abuse. 2018; 44 (2):215–23. Epub 2017 May 8. [PubMed] [Google Scholar]

14. Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015; 313 (24):2456–73. Errata in: JAMA 2015;314(5):520, JAMA 2015;314(8):837, JAMA 2015;314(21):2308, JAMA 2016;315(14):1522. [PubMed] [Google Scholar]

15. Wade DT, Collin C, Stott C, Duncombe P. Meta-analysis of the efficacy and safety of Sativex (nabiximols), on spasticity in people with multiple sclerosis. Mult Scler. 2010; 16 (6):707–14. [PubMed] [Google Scholar]

16. Mücke M, Carter C, Cuhls H, Prüẞ M, Radbruch L, Häuser W. Cannabinoids in palliative care: systematic review and meta-analysis of efficacy, tolerability and safety [article in German] Schmerz. 2016; 30 (1):25–36. [PubMed] [Google Scholar]

17. 2019 American Geriatrics Society Beers Criteria Update Expert Panel American Geriatrics Society 2019 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019; 67 (4):674–94. Epub 2019 Jan 29. [PubMed] [Google Scholar]

18. Perry D, Ton J, Allan GM. Evidence for THC versus CBD in cannabinoids. Can Fam Physician. 2018; 64 :519. [PMC free article] [PubMed] [Google Scholar]

19. Canada Revenue Agency . EDN54 general overview of the cannabis excise stamps. Ottawa, ON: Government of Canada; 2018. Available from: www.canada.ca/en/revenue-agency/services/forms-publications/publications/edn54/general-overview-cannabis-excise-stamps.html. Accessed 2019 Jul 1. [Google Scholar]

21. Rosenquist EWK. Evaluation of chronic pain in adults. Waltham, MA: UpToDate; 2018. Available from: www.uptodate.com/contents/evaluation-of-chronic-pain-in-adults. Accessed 2019 Jul 1. [Google Scholar]

23. Mücke M, Phillips T, Radbruch L, Petzke F, Häuser W. Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2018;(3):CD012182. [PMC free article] [PubMed] [Google Scholar]

24. Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev. 2014;(1):CD007115. [PubMed] [Google Scholar]

25. Geri-RxFiles. 3rd ed. Saskatoon, SK: University of Saskatchewan; 2019. Pain management in older adults. [Google Scholar]

26. Budney AJ, Hughes JR. The cannabis withdrawal syndrome. Curr Opin Psychiatry. 2006; 19 (3):233–8. [PubMed] [Google Scholar]

27. Geri-RxFiles. 3rd ed. Saskatoon, SK: University of Saskatchewan; 2019. Tapering medications in older adults. [Google Scholar]

28. RxFiles . Cannabis. Questions about cannabis, and the answers that may surprise you. A booklet for people thinking about starting medical cannabis. Saskatoon, SK: University of Saskatchewan; 2019. Available from: www.rxfiles.ca/RxFiles/uploads/documents/Cannabis-Medical-Patient-Booklet.pdf. Accessed 2019 Sep 25. [Google Scholar]

Articles from Canadian Family Physician are provided here courtesy of College of Family Physicians of Canada

Best CBD:THC Ratio For Neuropathy

Learn how to use CBD & THC together for neuropathy and which ratio is best.

Article By

The main active compounds in cannabis, cannabidiol (CBD) and delta 9 tetrahydrocannabinol (THC), offer pain relief and comfort to those suffering from nerve pain.

Nerve pain or neuropathy is often treated with medications made for other disorders like seizures and depression. CBD and THC make great alternatives with less side effects, less risk for tolerance and addiction, and better efficacy.

While each cannabinoid has its own benefits as an anti-inflammatory, analgesic, and muscle relaxant, research suggests that they offer more potent effects towards supporting neuropathic conditions when combined.

The best CBD:THC ratio for neuropathy is 1:1 — where there is an equal amount of these cannabinoids in each dose.

Here’s everything you need to know about the best CBD: THC ratio for nerve pain based on recent studies.

Table of Contents

What is Neuropathy? What Causes It?

Neuropathy refers to nerve pinching, compression, and damage resulting in pain.

There are many different causes of neuropathy, ranging from traumatic injuries to degenerative disorders like multiple sclerosis or cerebral palsy.

The condition leaves patients with significant pain, numbness, and, in severe cases, a reduction in autonomy and paralysis.

Neuropathic pain is especially difficult to treat. Conventional painkillers like acetaminophen don’t normally work that well for this type of pain because they target inflammation. Because the pain originates from the neurons themselves, reducing inflammation has little impact on pain.

Benefits of CBD & THC For Neuropathy

CBD has been widely studied for addressing neuropathy or nerve pain.

CBD on its own may be helpful for peripheral neuropathy, with patients reporting less pain after taking CBD.

CBD has been observed to reduce inflammation in neuropathy patients by interacting with the α3-glycine receptors, which are responsible for our sense of pain [1].

The Benefits of THC and CBD For Neuropathy Include:

  • Reducing inflammation
  • Managing chronic pain
  • Relieving symptoms of depression
  • Supporting healthy sleep quality
  • Promoting nerve regeneration

Will CBD & THC Interact With My Neuropathy Medications?

Neuropathy is often treated with prescription medications — many of which may interact negatively with CBD.

Make sure to always ask your doctor about interactions with any other medications you take to treat your neuropathy, especially antidepressants.

Common neuropathy medications and their potential interaction with CBD:

1. Opiate Painkillers

Opiates are commonly used to treat nerve pain. They’re considered to be one of the strongest classes of prescription painkillers available. They work by targeting the opiate receptors in the central nervous system. This effect blocks the transmission of pain heading from the body to the brain.

CBD may interact with opioid pain medications. This supplement has a similar effect as opiates on inhibiting neurological function and may compete for metabolism in the liver. Both of these effects could lead to an increased risk of side effects and overdose.

Always speak to your doctor about using CBD if you’ve been prescribed an opioid medication.

Common opiates used for neuropathic pain include:

  • Buprenorphine (Cizdol & Brixadi)
  • Codeine
  • Pethidine (Meperidine & Demerol)
  • Fentanyl (Abstral & Actiq)
  • Hydrocodone (Hysingla ER, Zohydro ER & Hycodan)
  • Hydromorphone (Dilaudid)
  • Methadone (Methadose & Dolophine)
  • Morphine (Kadian & Roxanol)
  • Oxycodone (Percodan, Endodan, Roxiprin, Percocet, Endocet, Roxicet & OxyContin)
  • Tramadol (Ultram, Ryzolt & ConZip)

2. Antidepressants

Long-term neuropathic pain often leads to depression. Lowered quality of life, poor sleep, and job loss all contribute further to this effect.

If you’ve been prescribed antidepressants, it’s important to speak with your prescribing doctor about CBD and THC first. Both compounds can interfere with the metabolism of drugs like SSRIs and SNRIs and lead to negative side effects.

THC is especially likely to interact with these substances in a negative way.

Common prescription antidepressants include:

  • Citalopram (Cipramil & Celexa)
  • Dapoxetine (Priligy)
  • Escitalopram (Cipralex & Lexapro)
  • Fluoxetine (Prozac, Rapiflux, Sarafem, Selfemra & Oxactin)
  • Fluvoxamine (Faverin)
  • Paroxetine (Seroxat)
  • Sertraline (Lustral)
  • Vortioxetine (Brintellix)
  • Atomoxetine (Strattera)
  • Desvenlafaxine (Pristiq, Khedezla)
  • Duloxetine (Cymbalta, Irenka)
  • Levomilnacipran (Fetzima)
  • Milnacipran (Savella)
  • Venlafaxine (Effexor XR)

CBD & THC Ratios: What Dose Should I Take?

The best CBD:THC ratio for neuropathy is 1:1+, meaning equal parts CBD and THC or less CBD than THC.

Keep in mind that dosing and ratio are two very different things.

The dose refers to how much of the compounds you’re taking, and it’s typically measured in milligrams. There is no one-size-fits-all approach to dosing for neuropathic pain, but higher doses (50 mg +) have been shown to provide the most relief towards pain and inflammation.

To determine your doses, you can try our dosage calculator. This will give you a rough estimate of how much CBD you should consume depending on your weight and desired strength, but you can expect to experiment with your doses as cannabinoids affect individuals differently.

CBD and THC gummies and oils are easy to dose using ratios because you can cut the gummies or measure oil in mL. However, you can also buy CBD:THC ratio products that are already mixed for you.

Other CBD:THC Ratios

The best ratio of CBD to THC is a hot topic lately. While we already have a lot of data available for the benefits of both these cannabinoids for certain conditions — there’s very little information about what the optimal ratio of each one is when used in conjunction.

As more research comes to light on the intricate synergy between these two compounds, scientists are uncovering insight into ways we can get even more effectiveness out of cannabis.

Here are some of the other optimal CBD to THC ratios based on the current evidence so far:

Final Thoughts: Best CBD:THC Ratio For Neuropathy

The best CBD:THC ratio for neuropathy is 1:1 with equal parts THC to CBD.

Both THC and CBD are useful in managing pain from this condition. Taken together, the effects become even stronger.

There are several pharmaceutical medications using CBD and THC for treating pain — the majority of which use this same 1:1 ratio.

You can achieve this ratio by taking equal doses of CBD oil and THC oil or by mixing roughly equivalent doses of CBD or THC vape pens, capsules, gummies, or other products. You don’t have to use a premade CBD:THC product to get the benefits of this combination.

Consensus recommendations on dosing and administration of medical cannabis to treat chronic pain: results of a modified Delphi process

Globally, medical cannabis legalization has increased in recent years and medical cannabis is commonly used to treat chronic pain. However, there are few randomized control trials studying medical cannabis indicating expert guidance on how to dose and administer medical cannabis safely and effectively is needed.

See also  Khalifa Sisters CBD Gummies

Methods

Using a multistage modified Delphi process, twenty global experts across nine countries developed consensus-based recommendations on how to dose and administer medical cannabis in patients with chronic pain.

Results

There was consensus that medical cannabis may be considered for patients experiencing neuropathic, inflammatory, nociplastic, and mixed pain. Three treatment protocols were developed. A routine protocol where the clinician 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. At a CBD-predominant dose of 40 mg/day, 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. A conservative protocol where the clinician initiates the patient on a CBD-predominant variety at a dose of 5 mg once 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. At a CBD-predominant dose of 40 mg/day, clinicians may consider adding THC at 1 mg/day and titrate by 1 mg every 7 days until a maximum daily dose of 40 mg/day of THC. A rapid protocol where the clinician initiates the patient on a balanced THC:CBD variety at 2.5–5 mg of each cannabinoid once or twice daily and titrates by 2.5–5 mg of each cannabinoid every 2 to 3 days until the patient reaches his/her goals or to a maximum THC dose of 40 mg/day.

Conclusions

In summary, using a modified Delphi process, expert consensus-based recommendations were developed on how to dose and administer medical cannabis for the treatment of patients with chronic pain.

Background

Cannabis is being legalized and/or decriminalized across the globe and hundreds of thousands of patients are currently being treated with medical cannabis (Abuhasira et al. 2018; Lintzeris et al. 2020). Patient-reported data indicate that chronic pain management is one of the most common reasons for medical cannabis use (Reiman et al. 2017; Boehnke et al. 2019; Kosiba et al. 2019; Azcarate et al. 2020). Chronic pain affects close to 2 billion people worldwide and is associated with impairment in physical and emotional function, reduced participation in social and vocational activities, and lower perceived quality of life (Dueñas et al. 2016; Hylands-White et al. 2017; Vos et al. 2017). In patients with chronic pain, medical cannabis treatment has been associated with an improvement in pain-related outcomes, increased quality of life, improved function, and a reduced requirement for opioid analgesia (Abrams et al. 2011; Haroutounian et al. 2016; National Academies of Sciences 2017; Cooper et al. 2018; Rod 2019; Sagy et al. 2019; Johal et al. 2020; Safakish et al. 2020; Okusanya et al. 2020).

Despite the increased global use of medical cannabis to manage pain, systematic reviews and meta-analyses report low to substantial levels of evidence to support the use of cannabis and cannabinoids for the treatment of chronic pain (Russo 2007; Whiting et al. 2015; Allan et al. 2018; National Academies of Sciences 2017; Stockings et al. 2018; Mücke et al. 2018; Häuser et al. 2018; Johal et al. 2020; Safakish et al. 2020; Okusanya et al. 2020). Explanations as to why some describe the level of evidence is low may include limited availability of investigational products due to legal status, lack of standardization of cannabis products, lack of standardization of product administration, and overemphasis on pain scores to define efficacy. However, despite the low to moderate level of evidence, patients are being treated with medical cannabis across the world.

Therefore, the lack of randomized control trial evidence combined with the practical reality that patients are receiving a pharmaceutically active drug creates an atypical clinical scenario that necessitates expert guidance from experienced clinicians on how to safely and, perhaps, effectively dose and administer medical cannabis.

The recommendations presented herein were developed as practical guidance for clinicians who may have limited experience with prescribing or recommending (if patient is in USA) medical cannabis. It is important to note that every patient is different and medical cannabis treatment, like most other therapies, should be individualized to the patient. Shared treatment decision-making with the patient is important and establishing treatment goals during the initial medical consultation may enhance patient outcomes and adherence to medical cannabis treatment. The intent is to provide clinicians with safe and effective medical cannabis prescribing protocols, which may be considered when a clinician decides to include medical cannabis in a patient’s treatment regimen.

Methods

To address the unmet need for clinical guidance on the safe and effective use of medical cannabis for chronic pain, and to build on previous recommendations from MacCallum and Russo (2018) and Boehnke and Clauw (2019), we developed a modified Delphi process (Dalkey and Helmer 1963; Dalkey 1969; Saad et al. 2019; Oude Voshaar et al. 2019) to establish expert consensus-based recommendations on the dosage and administration of medical cannabis (Fig. 1). The modified Delphi process has been used extensively in health care settings to provide consensus-based recommendations on important clinical questions where randomized control trial data is lacking (Hasson et al. 2000).

Timeline and Flow of modified Delphi process

A global task force of twenty individuals was recruited based on extensive clinical experience and/or high academic interest in prescribing and managing patients on medical cannabis for the treatment of chronic pain (Table 1). The panel was selected based on clinical experience prescribing medical cannabis, research with medical cannabis, and a focus on inclusion of representatives from different countries. Upon recruitment, the task force participants completed a practice patterns survey (Additional file 1) to gain insights into how clinicians around the world were treating patients with medical cannabis. After the practice profile was completed, nine recent articles were provided to the task force (Habib and Artul 2018; Banerjee and McCormack 2019; Crawley et al. 2019; Maher et al. 2019; Boyaji et al. 2020; Johal et al. 2020; Montero-Oleas et al. 2020; Wong et al. 2020; Gulbransen et al. 2020). An initial draft of 37 consensus questions was developed based on the practice patterns survey and reviewed for rationale and applicability to clinical practice by a nine-member scientific committee. After review and scientific committee approval, an updated version was distributed to the other task force participants for their review of its rationale and applicability.

Table 1 Global task force on medical cannabis dosing and administration for treatment of chronic pain

Once the full task force had reviewed all questions and proposed answers, and all comments had been incorporated; the first round of voting took place on 63 questions using an online survey (Qualtrics, Provo, Utah; (Additional file 2) with the following rules in place:

For multiple choice questions, consensus is found if ≥ 75% of the responses support one answer. For ranking questions, consensus is found if ≥ 75% of the responses are agree/strongly agree or disagree/strongly disagree. This consensus threshold is similar to previous studies using a modified Delphi method (Diamond et al. 2014; Gillessen et al. 2018).

There was an “abstain” option for all questions.

For the purposes of this document, medical cannabis refers to CBD and THC extracted from a cannabis plant.

The dosing and administration protocol was focused on oral preparations (oils and gel capsules) to support harm reduction from smoking and/or e-vaping (Tashkin 2013; Sangmo et al. 2020), and to nullify the risk of e-cigarette or vaping product use-associated lung injury (EVALI) (Layden et al. 2019).

It was stressed that clinicians would need to customize the recommendations based on availability and regulations in their region of practice.

The first round of voting established consensus on several topics including the rationale for using medical cannabis, the type of pain medical cannabis could be used to treat, age limitations for CBD, when medical cannabis should be avoided, and what the patient goals of using medical cannabis could be. This first round of voting indicated that the task force members were using medical cannabis for similar patient profiles, but dosing and administration protocols were different. The consensus questions were then revised to focus on key remaining elements, and 55 questions were considered for the second round of voting using online surveys (Additional file 3).

Following analysis of the first two rounds of voting, intended live meeting discussion topics were narrowed down. However, due to the COVID-19 pandemic, the live meeting was converted to a virtual format. Over two virtual meetings, 31 questions were voted on through Zoom Meeting polling software (Zoom Video Communications, San Jose, California, Additional files 4 and 5). The key topics for discussion surrounded the dosing and administration procedures across the different medical cannabis treatment protocols. The other two sections for discussion were breakthrough pain and follow-up recommendations. The task force was encouraged to discuss the question before voting to find common ground if possible.

Phrasing of questions was refined over the rounds of review and voting based on task force feedback. At least 16 members of the task force voted at each of the steps. The reader is directed to Additional file 2, 3, 4 and 5 for all voting results.

Role of funding source

This work was funded by Spectrum Therapeutics. Spectrum Therapeutics is the medical division of Canopy Growth Corporation, which sells both medical and recreational cannabis. The funder influenced the selection of the task force, and all authors declare they have received funding from Spectrum (Additional file 6). However, the funder had no influence on the design and conduct of the voting and discussions; collection, management, analysis, and interpretation of the data; preparation, review, approval of the manuscript; or decision to submit the manuscript for publication. The sponsor was provided the opportunity to review the manuscript for medical and scientific accuracy and did not suggest any changes to the manuscript.

Results

Dosing and administration of medical cannabis to treat patients with chronic pain

During the Delphi voting, three streams of oral dosing and administration recommendations based on patient need evolved: Routine, Conservative, and Rapid (Figs. 2, 3, and 4). The protocols were developed with a focus on safety and what experienced prescribers observe in their practice to be effective. For each protocol, a starting cannabinoid type was voted on, followed by a titration protocol up to a maximum daily dose recommendation. If necessary, the clinician may consider moving a patient between protocols to individualize the patient’s treatment plan. There was a consensus that medical cannabis may be considered for the treatment of neuropathic pain, inflammatory pain, nociplastic pain, and mixed pain (Sihota et al. 2020). Clinicians should titrate and manage the dosing regimen to reach patient treatment goals, which may be varied and therefore individualized (Table 2).

Routine protocol for medical cannabis dosing and administration

Conservative protocol for medical cannabis dosing and administration

Rapid protocol for medical cannabis dosing and administration

Routine protocol for medical cannabis dosing and administration

The routine protocol is recommended for most patients (Fig. 2). The Delphi process led to agreement that a patient may initiate with 5 mg twice daily (bid) of a CBD-predominant strain and up-titrate by 10 mg/day (5 mg CBD bid) every 2–3 days up to 40 mg CBD per day. A key reason for choosing to initiate with a CBD-predominant variety was to prioritize safety as CBD is highly tolerable, does not induce euphoria, and has a low risk for adverse effects (Taylor et al. 2018; Larsen and Shahinas 2020). In addition, many CBD-predominant preparations contain a small percentage of THC (Bonn-Miller et al. 2017; Lachenmeier et al. 2020). It was decided that the maximum amount of THC allowed in a CBD-predominant product to be considered for these protocols would be 1:10 THC to CBD. Many global CBD-predominate products contain 0.–2% THC (Bonn-Miller et al. 2017; Corroon et al. 2020; Lachenmeier et al. 2020).

If 40 mg/day CBD-predominant dose does not reach treatment goals, clinicians may consider initiating 2.5 mg of THC per day and titrate by 2.5 mg THC every 2–7 days up to 40 mg/day while maintaining the same CBD-predominant dose. It is recommended to seek expert consultation if considering going above 40 mg/day THC. The THC titration frequency of 2–7 days is a large range to promote tailoring to the patient’s needs.

Clinicians are encouraged to titrate medical cannabis to the effects desired by each patient, as opposed to a specific CBD or THC dose. During the titration phase, the total daily dose of CBD and/or THC can be divided between two to four administrations.

Conservative protocol for dosing and administration of medical cannabis

The conservative protocol is recommended for patients who may be more sensitive to drug effects (Fig. 3). Clinically frail patients, those with complex comorbidities, polypharmacy, and/or mental health disorders may also be appropriate for the conservative approach. It was agreed a patient may start on a 5 mg once daily dose of a CBD-predominant strain and up-titrate by 5–10 mg every 2–3 days up to 40 mg CBD per day, leveraging twice daily administration when needed. If treatment goals have not been met by 40 mg/day CBD-predominant dose, consider initiating 1 mg of THC and titrating by 1 mg once per week up to 40 mg/day of THC while keeping the same CBD dose. The patient may need a higher THC dose and moving them into the routine stream may be necessary. It is recommended to seek expert consultation if the clinician and patient are considering exceeding 40 mg of THC.

Rapid protocol for dosing and administration of medical cannabis

The rapid treatment protocol may be considered for patients requiring urgent management of severe pain, palliation, and for those with significant prior use of cannabis (Fig. 4). For patients in palliative care, caution is advised when choosing the medical cannabis protocol as these patients may have higher frailty and a higher risk of terminal delirium, which would make them suitable for the conservative approach as well.

It was agreed that a patient should start on a balanced THC:CBD product of 2.5–5 mg of each cannabinoid once or twice daily and up-titrate every 2–3 days by 2.5–5 mg/day of each cannabinoid until patient goals are met, or to 40 mg THC. If choosing to initiate twice daily with a balanced product, the lower doses would be more appropriate to consider at the beginning. The recommendation to seek expert consultation at 40 mg of THC is also present in the rapid protocol. When considering patients with neuropathic pain, products that contain THC may be more suitable (Andreae et al. 2015; Longo et al. 2020).

Medical cannabis treatment for breakthrough pain

In patient scenarios where breakthrough pain is common, inhaled medical cannabis can be considered due to the more rapid onset of action and limited duration of action (Huestis 2007). Dried flower vaporization is the preferred mode of administration as opposed to smoking or vaporization of cannabis extracts in an electronic cigarette device (e-vaping), as smoking and e-vaping carry significant health risks. Smoking cannabis is associated with inflammation of the airways and chronic cannabis smokers may experience a heightened risk for bronchitis, respiratory infections, and pneumonia (Tashkin 2013; Volkow et al. 2014; Owen et al. 2014). E-vaping of THC containing products has been associated with a relatively novel but grave lung disease known as e-cigarette or vaping product use-associated lung injury (EVALI) (Layden et al. 2019; King et al. 2020).

See also  How Long After Taking CBD Oil Can I Drink Water

When using medical cannabis to manage breakthrough pain, a balanced THC:CBD or THC-predominant product may be used as needed (prn). Clinicians could also consider that breakthrough pain may be suppressed by increasing the dose or frequency of the scheduled oral medical cannabis treatment.

Follow-up and discontinuation considerations

At the initiation of medical cannabis treatment, clinicians may consider following the patient every 2–4 weeks (Table 3). In individual patients, more frequent follow-up may be needed, particularly at the beginning of the medical cannabis treatment. Once the patient is at a stable dose or sufficiently knowledgeable with medical cannabis dosing and titration, follow-up may occur once every 3 months or even longer thereafter. However, adherence to local jurisdictional guidance may dictate follow-up frequency. The follow-up and discontinuation recommendations were consistent across the three protocols. Discontinuation of medical cannabis treatment should occur if the patient experiences intolerable, moderate, or severe cannabis-related adverse effects, the maximum agreed upon dose is reached and does not benefit the patient, and/or the patient has misuse or diversion associated with cannabis. Reporting of adverse events should be congruent with regional regulatory requirements.

Additional safety considerations for medical cannabis use

Patients who should avoid medical cannabis

There was consensus that individuals with psychotic disorders, unstable cardiovascular disorders, who are pregnant, who are planning to become pregnant, and/or who are breastfeeding, should avoid medical cannabis, similar to previous guidance documents ([CSL STYLE ERROR: reference with no printed form.]; National Academies of Sciences 2017; Canadian Medical Association 2020). The contraindications associated with medical cannabis are more closely linked to THC, but as discussed, CBD-predominant products may contain THC.

Age ranges

There was consensus for no minimum or maximum age limitation for CBD. Although it was agreed no upper age limit for THC use was necessary, there was debate regarding the minimum age recommendation for THC use, but no consensus was found. It has been reported that the human nervous system is not fully developed until 25 years of age, but different jurisdictions around the world have put varying age limits in place (Arain et al. 2013; Casey et al. 2013). In addition, it is unknown whether treatment with medical cannabis supervised by a physician influences brain development in minors. The recommendation for age limits therefore is to follow the local government regulations and consider the clinical risk-benefit ratio to each individual patient.

Drug-drug interactions

Drug-drug interactions should be considered (Balachandran et al. 2021). THC is a substrate of CYP3A4 and CYP2C9 while CBD is a substrate of CYP3A4 and CYP2C19 (Antoniou et al. 2020) CBD and THC may also inhibit or stimulate drug transporter P-glycoprotein (Zhu et al. 2006). Direct-acting oral anticoagulants all contain warnings to avoid use with drugs that inhibit CYP3A4 and P-glycoprotein. Caution is strongly encouraged when coadministering medical cannabis with direct-acting anticoagulants ( XARELTO® (rivaroxaban), 2020; https://www.pfizer.ca/sites/default/files/201910/ELIQUIS_PM_229267_07Oct2019_Marketed_E.pdf, 2020; https://www.boehringer-ingelheim.ca/sites/ca/files/documents/pradaxapmen.pdf, 2020), warfarin (Yamreudeewong et al. 2009; Yamaori et al. 2012), drugs metabolized by CYP2C19 (e.g., clopidogrel (Kazui et al. 2010) and clobazam (Geffrey et al. 2015; Cox et al. 2019), checkpoint inhibitors (e.g., PD-1 (Taha et al. 2019), and immunotherapy agents (e.g., tacrolimus (Leino et al. 2019). In addition, awareness around the potential reduced efficacy of theophylline and clozapine is important (Cox et al. 2019).

Discussion

The modified Delphi process led to the development of three treatment protocols to support dosing and administration of medical cannabis in patients with chronic pain. The clinician may consider moving patients across the streams as a means to tailor the approach. Patient participation in the treatment decisions may enhance adherence and the likelihood of improved patient outcomes. The clinical success of medical cannabis should not be limited to pain scores and should consider improvements in function and quality of life.

Routine CBD dosing and administration

There was considerable debate around the starting cannabinoid type for routine dosing. It was not until the last round of voting that the group reached consensus to start with a CBD-predominant strain. A deciding factor was ultimately the safety profile of CBD. Purified CBD has been shown to be safe and well tolerated up to 6000 mg (Taylor et al. 2018). CBD at doses ranging from 10 to 20 mg/kg/day is effective as an add-on therapy to reduce refractory seizures in two pediatric populations, Lennox-Gastaut syndrome, and Dravet syndrome (Lattanzi et al. 2018). CBD has also been studied in social anxiety where CBD doses ranging from 25 to 600 mg per day has been shown to be effective, as reviewed in Skelley et al. (2020). Our recommendations are much lower than those used in reducing seizures and are at the lowest end of dosing for social anxiety.

There are some data to suggest that CBD may support pain relief and quality of life. In a recent patient-reported outcomes audit study from New Zealand (n = 400), CBD was well-tolerated and improved pain outcomes and quality of life (Gulbransen et al. 2020). The CBD doses used in this study ranged from 40 to 300 mg/day, but there was no statistical association between CBD dose and patient-reported benefit. In a single-arm prospective cohort study investigating the effect of CBD from hemp on opioid use over 8 weeks, CBD reduced opioid use and improved quality of life (Capano et al. 2019). In this study, over 90% of the participants used a dose of 30 mg/day CBD. In a commissioned review by the Australian government, CBD below 60 mg/day was deemed tolerable and safe (Goods Administration 2020). In line with these publications, our Delphi process with global experts in medical cannabis led to the recommendation that in the absence of achieving treatment goals by 40 mg/day of CBD, THC should be considered.

Another deciding factor in choosing CBD-predominant as the initiating product was the fact that many CBD-predominant preparations contain a small percentage of THC (Bonn-Miller et al. 2017; Lachenmeier et al. 2020). If the ratio of THC to CBD is 1:20, a patient taking 40 mg of a CBD-predominant product is also receiving 2 mg of THC. Two milligrams of THC is close to the recommended initiating dose of 2.5 mg. Unexpectedly, experiencing the psychotropic effects of THC may be undesirable for the patient, and treating clinicians should always be aware of the THC concentration within any given product.

Unlike THC, the mechanism of action of CBD is not believed to be primarily through its binding to the cannabinoid receptor. CBD is thought to exert its action on G-coupled protein receptors, transient receptor potential (TRP) channels, reducing intracellular transporters of endocannabinoids, and decreasing metabolism of endocannabinoids through its interaction with the enzyme FAAH and the P450 isoenzyme system (Mlost et al. 2020). CBD has a wide spectrum of biological activity, including antioxidant and anti-inflammatory activity (Atalay et al. 2020). Through these mechanisms of action, CBD is thought to improve symptoms in a variety of chronic pain conditions (Mlost et al. 2020). Preclinical trials have demonstrated a potential anti-nociceptive effect of CBD and when combined with other compounds in several pain-related diseases (Atalay et al. 2020; Mlost et al. 2020).

The 40 mg/day dose of a CBD-predominant strain before adding THC is lower than the CBD doses recommended by Boehske and Clauw (2019). However, the cost of CBD may restrict the use of CBD at high doses (Gulbransen et al. 2020). Moving forward, purified isolates of CBD will likely become more available such that the concern around THC inclusion with CBD-predominant product will be unnecessary.

Sihota et al. recently examined how to use medical cannabis to support opioid tapering (Sihota et al. 2020). The modified Delphi process was also applied in this report to pragmatically align on how to titrate medical cannabis while reducing the opioid dose. This report differs from the present report as we did not specifically consider opioid sparing but considered all patients living with chronic pain. However, similar recommendations on how to dose and administer medical cannabis were observed across the two studies, i.e., start with CBD and titrate THC for most patients. The main difference between the two studies is that the medical cannabis recommendations for opioid tapering are larger in range, while we have provided three titration protocols that may be used depending on the patient. It is encouraging that two Delphi processes resulted in similar recommendations.

Routine THC dosing and administration

In line with two previous clinical dosing and administration recommendation documents (MacCallum and Russo 2018; Boehnke and Clauw 2019), it was agreed that an initiating THC dose of 2.5 mg was appropriate. A large number of studies in various indications, including chronic pain, have observed that in most patients, the analgesic effects of THC start between 2 and 2.5 mg THC (Beal et al. 1995). It is important to note that analgesic effects of THC in chronic neuropathic pain in humans have been shown to occur at plasma levels well below those associated with euphoria (Ware et al. 2010; Wallace et al. 2020). Therefore, the patient may not need to experience the psychotropic effects of THC to achieve pain relief. However, before considering THC, clinicians should review local jurisdictional regulations on THC, as local guidance on THC may differ from CBD and require additional attention.

There was consensus that the daily dose of THC should not exceed 40 mg unless coupled with expert consultation. As the initiating dose is 2.5 mg, the clinician should titrate slowly with THC and ensure the patient is comfortable with each increasing dose. If considering THC above 40 mg, a consult with a cannabinoid specialist or an experienced medical cannabis clinician is highly recommended as tolerance to cannabis may be developing (Nguyen et al. 2018; Wilkerson et al. 2019).

When considering the pharmacodynamics of orally ingested THC, a recent crossover study examining 17 healthy adults who had not consumed recreational or medical cannabis for at least 60 days, completed four experimental sessions where they ingested 0, 10, 25, or 50 mg of THC (Schlienz et al. 2020). Subjective effects, vital signs, cognitive/psychomotor performance, and blood THC concentrations were assessed before, and then every 30 min for 8 h post ingestion. The 10 mg THC dose produced subjective drug effects and elevated heart rate but did not impact cognitive/psychomotor performance. The 25 and 50 mg doses of THC elicited pronounced subjective effects and impaired cognitive and psychomotor functioning compared to placebo. Subject-reported “good drug effect” was similar between the three doses, but the risk of “bad drug effect” increased with the 25 and 50 mg of THC doses. Although there is wide variation, when considering the majority of patients, 10 mg of THC per day is a typical therapeutic dose. If necessary, the tentative maximum daily dose of 40 mg is still safe but is unlikely to be needed often.

When orally administering THC, the pharmacodynamic effects may begin as early as 30 min and continue to rise between 1 and 3 h post ingestion (Grotenhermen 2003; Schlienz et al. 2020). This coincides with whole blood THC concentrations peaking at 1 h (Schlienz et al. 2020). The delay of drug effect when orally ingesting THC and duration of effect are important considerations for patients being treated with medical cannabis. Oral cannabis products (e.g., edibles) are responsible for the majority of emergency room visits related to cannabis intoxication, and understanding when and how long to expect a drug effect may help prevent accidental intoxication (Hudak et al. 2015; Barrus et al. 2016; Monte et al. 2019).

Conservative THC dosing and titration

The conservative protocol was developed to be lower and slower than routine with a focus on prevention of side effects and creating comfort with medical cannabis. The initiating and titrating doses of THC are different between the conservative and routine dosing and administration protocols as there may be concern with the psychotropic effects of THC. Our Delphi process led to agreement that 1 mg THC should be considered as the initiating dose, which is consistent with the lowest range set out in the Boehnke and Clauw guidance document (Boehnke and Clauw 2019). The tentative maximum dose of 40 mg THC for conservative regimen is the same as routine. There was discussion on the importance of exercising caution regarding the rate at which THC is titrated, but not the maximum THC dose.

Medical cannabis safety considerations

The predicted median lethal dose (LD50) for THC is > 1000-fold higher than the effective dose (Thompson et al. 1973; World Health Organization 2012). Unlike opioids, there are limited cannabinoid receptors in the brain stem areas that control vital functions such as respiration (Herkenham et al. 1990). Following oral administration, the LD50 of THC is 800 mg/kg in rats, 3000 mg/kg in dogs, and up to 9000 mg/kg in monkeys. A lethal THC dose for a 70-kg human is therefore estimated at approximately 4000 mg/kg of THC, which is a dose of 280,000 mg THC and likely unachievable with oral consumption, smoking, or vaporization (World Health Organization 2012). Clinicians may feel comfortable with tailoring the medical cannabis treatment regimen knowing that patients are not at a significant overdose death risk. However, cannabis-associated health risks including Cannabis Use Disorder and complications resulting from the psychoactive effects of THC need to be considered, even at low doses (Adam et al. 2020). This concept is important for the operation of motor vehicles, as well as occupational and recreational hazardous activity. When adding THC, the clinician may consider starting the first dose in the evening to limit potential issues with workplace functioning and driving. In addition, THC at night may support sleep quality and many patients with chronic pain suffer from sleep disturbances. Patients often experience an improvement in function as a result of improved sleep quality when treated with medical cannabis (Sanford et al. 2008; Bachhuber et al. 2019). However, the role of medical cannabis and sleep is currently being tested in a placebo-controlled randomized control trial (Suraev et al. 2020).

Conclusions

In summary, this modified Delphi process, led by global experts in the field of medical cannabis/cannabinoid medicine, resulted in the development of three protocols for the dosing and administration of medical cannabis to treat chronic pain. We hope that these recommendations will support clinicians and patients in achieving safe and effective dosing and administration of medical cannabis. Future randomized control trials examining the safety and efficacy of medical cannabis compared against current standards of care will be required to elucidate whether the developed protocols result in improved patient outcomes. The recommendations provided will be updated as new clinical trial evidence becomes available to inform on the type of dosing and mode of administration of medical cannabis for the treatment of chronic pain.

How useful was this post?

Click on a star to rate it!

Average rating 5 / 5. Vote count: 1

No votes so far! Be the first to rate this post.