Chronic Pain as Seen by a Clinic Dedicated to Medical Cannabis – Part 2

Part 1 of this blog post showed some real-world data from the Santé Cannabis observational study and quickly went over chronic pain classification; next came a summary of chronic pain management and the importance of a global treatment, ending with a section on the stigma of chronic pain and pain expression. 

This sequel focuses on medical cannabis, from its role regarding opioid substitution to the evidence supporting cannabinoids and features of a cannabis treatment. 



Chronic pain treatment generally consists of pharmacologic and non-pharmacologic approaches. In certain cases, pain and other symptoms are not successfully controlled, which can be difficult to manage, and it’s challenging to return to a pain-free state. Several non-opioid analgesics are available, but many have low efficacy, poor tolerability and significant adverse effects. [1] Opioids are widely prescribed to relieve chronic non-cancer pain, [2] but their prolonged use is problematic due to their addictive potential, the development of tolerance, the hyperalgesia they can induce and their adverse effects. [1]  

The ongoing opioid epidemic (and human deaths) is linked to habitual partiality in opioid prescriptions for chronic pain, [1] and has prompted a search for other analgesic options. Fuelled by public interest, medical cannabis makes a distinguished mark as a new yet centuries old option.  

Safety is the keyword in the case for cannabinoid-based medicines substitution for opioids: the predominant cannabinoid in cannabis, delta-9-tetrahydrocannabinol (THC), has a very low toxicity (“absence of mortality”—World Health Organization). [3] Cannabidiol (CBD), which is gaining in use, has a favourable safety profile as well. [4, 5] 

A recent Canadian initiative produced a consensus-based algorithm on the safe introduction of cannabinoid-based medicines and opioids taper in chronic pain patients. According to this algorithm, cannabinoid-based medicines can be considered in patients with chronic pain taking opioids and not reaching treatment goals, having opioid-related adverse effects and/or at risk of opioid-related harm. [6] 

But what about the evidence supporting the use of cannabinoid-based medicines for chronic pain? Contrary to what some politicians and uninformed healthcare professionals may say, there is evidence. The subject of debate should rather be: is there sufficient evidence  


Person looking through documents of evidence


Cannabinoid-based medicines still carry an important stigma in the research and medical fields.  

Interpretation of clinical trial results can vary between authors, but the variation is especially high when judging the evidence for cannabinoids’ efficacy. Indeed, depending on reviews, low to substantial evidence support cannabinoid-based treatments use to manage chronic non-cancer pain. [7-19]  

This is understandable since chronic non-cancer pain is an umbrella term that combines various pain conditions that have not been studied to the same extent (see Part 1 for pain classification). Also, reviews may obtain different results based on article design, such as inclusion vs. exclusion of non-randomized controlled trials, analysis per condition vs. “chronic pain” as a single condition, analysis per cannabinoid vs. pooled cannabinoids, etc.  

However, the fact remains that for some conditions like multiple sclerosis-related neuropathic pain, “the current literature has provided more reliable data for cannabinoids than for any other drugs”. [20] 

The following subsections cover the evidence in chronic neuropathic pain, fibromyalgia, and chronic pain with an inflammatory component – since those are common pain types seen at our clinic. 



Chronic neuropathic pain is the best studied type of pain in clinical trials assessing cannabinoids and medical cannabis, [10, 19] with at least 23 published randomized controlled trials (RCTs). [21-46] 

The level and quality of the evidence is highly impacted by the quality of trials (questionable blinding to the treatment, small sample size, short trial duration, etc.). Despite the contribution of numerous trials, the evidence that cannabinoids and medical cannabis are effective in chronic neuropathic pain is limited or modest, depending on authors. [9-11, 15, 17, 47]  

The following table summarizes study results and shows the supporting evidence for pain reduction with cannabinoid-based medicines (in chronic neuropathic pain), with a modest effect size.  

Chronic Pain Table

A group of pain specialists and psychiatrists, researchers, and patient representatives compared 12 pharmacological treatments (including THC-rich, CBD-rich and THC:CBD 1:1 treatments) for the management of chronic neuropathic pain. In agreement with several reviews, cannabinoids (especially CBD) scored modestly in pain relief rates as compared to other medications (such as duloxetine, gabapentin, pregabalin, amitriptyline). [48] However, cannabinoids scored higher than all other medications when combining benefits and safety scores, with the benefits on quality-of-life contributing heavily to the cannabinoids scores. [48] 



Fibromyalgia is being more and more investigated in recent years and patients frequently turn to medical cannabis in the hope of getting some relief from their symptoms. [49, 50] Four published RCTs can be found, [51-54] as well as several observational and retrospective studies. [49, 50, 55-63] 

  • Two RCTs assessed nabilone in fibromyalgia: one found improvement in pain, [51] while the other found no effect on pain but superior improvement in sleep as compared to amitriptyline. [52] 
  • THC-rich cannabis oil decreased pain and improved functionality, mood and fatigue in a small all-female RCT. [54] 
  • Medical cannabis (three dried cannabis formulations: THC-rich, THC:CBD in similar ratio and CBD-rich) was also assessed in one RCT. Cannabis with THC:CBD in similar ratio decreased pain significantly and THC-rich cannabis showed an analgesic effect in some measures. CBD-rich cannabis failed to show an analgesic effect. [53] 

CBD’s analgesic effect has yet to be evaluated in RCTs, but data from observational and cross-sectional studies show that fibromyalgia patients using CBD-rich products report improvement in pain, sleep and anxiety. [49] Patients report similar benefits from medical cannabis. [56-61] Patients also substitute medical cannabis (including CBD-rich products) for medications such as NSAIDs, opioids, gabapentinoids and benzodiazepines [58-61] due to fewer adverse effects and better symptom management. [63] 



Chronic pain with an inflammatory component can be a characteristic of several chronic conditions, such as rheumatoid arthritis, osteoarthritis, cancer, inflammatory bowel disease, and more. [64] 

Evidence suggests the endocannabinoid system is involved in the response to inflammation and cartilage degradation; patients with rheumatoid arthritis or osteoarthritis (but not healthy controls) present measurable levels of two endocannabinoids (anandamide and 2-Arachidonoylglycerol) in their synovial fluid. [65] Based on preclinical evidence, cannabinoids possess anti-inflammatory properties and could be useful to treat rheumatic conditions. [66-68]  

At this time, only one randomized controlled trial supports cannabinoid-based medicines potential.  

  • Nabiximols was studied in patients with rheumatoid arthritis and demonstrated significant analgesic effect. [69]  

The review of the evidence about cannabinoids and pain would be incomplete without something about the difference between men and women. Current research frequently lacks sex-related reporting and analysis, but we are motivated to provide the best patient care – and that implies getting informed and promoting this important topic. 


Sex-related differences with cannabinoids and pain


Since women with chronic pain outnumber men, [70] and women count for over 60% of Santé Cannabis patients, we need to address the biological difference between women and men and its impact on cannabinoid-mediated analgesia and pain itself. Only a few clinical trials exist on this topic, and they provide initial evidence that women could be more sensitive to cannabis (or THC) than men. 

  • Women experience the same acute effects as men despite lower THC blood concentrations, [71] and are more sensitive to a low THC dose (5 mg oral dose) as compared to men. [72]  
  • Considering adverse effects, women are more likely to experience greater subjective anxiety or nervousness, restlessness, and racing heart after THC intake as compared to men (oral or inhaled intake, doses ranging from 5 to 25 mg THC, and controlling for weight and blood concentration). [73] 

Furthermore, preclinical evidence indicates hormones (like estrogen [74]) modulate pain perception, but the evidence is limited and mixed in clinical trials. [75-77] Preclinical evidence also shows that hormones influence the endocannabinoid system, from receptors’ expression to ligands affinity. [78] More research is greatly needed to better understand these complex interactions and their implication in clinical practice. 

In this last section, we teased out practical information from the scientific evidence to clarify some aspects of medical cannabis treatment. 


Questions about treatment plans 


Disclaimer: this section is intended to explain the rationale behind some elements of a treatment plan, and is not meant to be a medical counsel nor a guide to self-medication. In all cases, it’s best to discuss your questions regarding medical cannabis with a healthcare professional. 



CBD possesses a favourable safety profile [4] and is often recommended at the beginning of the treatment. [79, 80] This is a prudent choice regarding adverse events, precautions/relative contraindications, and it is easier than starting patients on both THC and CBD products at once.  

However, the analgesic (pain relief) effects of CBD have yet to be demonstrated with the same level of evidence that is supporting the modest (but significant)[10] analgesic effects of THC and THC:CBD formulations. [81] Some patients may respond well to CBD-rich products (and/or to trace amounts of THC in these products), [79] but others may need more THC to obtain adequate pain relief. [81]  



Baseline pain-relief treatment with medical cannabis uses oral administration, exploiting the long-lasting effects [82] and accurate dosing of ingested products. [81] Administration frequency varies according to pain frequency, from once daily to two or three times a day. [81] 

Inhalation administration can be helpful to quickly relieve breakthrough pain, [79, 80] with its onset of effects within minutes of inhalation [82-84]. Smoking is common but generally thought inadequate to deliver medication; [85, 86] in comparison, dried cannabis vapourization, which does not burn cannabis, is safer and preferred for treatment delivery. [79, 80, 82] 



That depends on the patient and should be done under medical supervision. 

Chronic pain patients frequently seek medical cannabis treatment for symptoms not adequately relieved by their current treatment and/or when their current treatment causes intolerable adverse effects. Some patients on a medical cannabis treatment report reducing or stopping other medications, [87] but this has not been reproduced in controlled clinical trials [88, 89]. 

Consensus recommendations do not recommend stopping other pain medications before starting a medical cannabis treatment. [6, 80] With appropriate medical monitoring, it’s possible to gradually taper other medications when the pain or function improves, when the medical cannabis treatment is stable, and/or when the patient requires less as-needed medication (like opioids) for pain relief. [6] 

This concludes our short series of chronic pain blog articles that we hope will be useful for our chronic pain patients, caregivers, healthcare professionals and all other interested readers. At Santé Cannabis, we advocate for patients’ right to access medical cannabis, but we are also committed to our patients’ safety – so we are much aware of the limits of the current evidence supporting medical cannabis use. In this light, it’s essential for us to first, share our knowledge on medical cannabis, and second, to correct misconceptions abounding around cannabis. 

For this new yet centuries old therapeutic option, do you agree that there is still no evidence whatsoever? Or should the public discourse evolve to be more nuanced and reflect the advances of modern research? 

Author: Charlotte Bastin  

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.



Find everything there is to know about our clinic.  

Click here



We have more for you! Check out our Modules written specifically for healthcare professionals participating in our Prescriber Training Program. 

Click here




  1. Hutchison, K.E., et al., Cannabinoids, Pain, and Opioid Use Reduction: The Importance of Distilling and Disseminating Existing Data. Cannabis and Cannabinoid Research, 2019. 4(3): p. 158-164.
  2. Busse, J.W., et al., Guideline for opioid therapy and chronic noncancer pain. Cmaj, 2017. 189(18): p. E659-e666.
  3. World Health Organization, WHO Expert Committee on Drug Dependence Pre-Review. 2018.
  4. Chesney, E., et al., Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. Neuropsychopharmacology, 2020. 45(11): p. 1799-1806.
  5. Larsen, C. and J. Shahinas, Dosage, efficacy and safety of cannabidiol administration in adults: a systematic review of human trials. Journal of Clinical Medicine Research, 2020. 12(3): p. 129.
  6. Sihota, A., et al., ConsensusBased Recommendations for Titrating Cannabinoids and Tapering Opioids for Chronic Pain Control. International journal of clinical practice, 2020: p. e13871.
  7. National Academies of Sciences Engineering and Medecine, The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. 2017, Washington (DC).
  8. Fisher, E., et al., Cannabinoids, cannabis, and cannabis-based medicine for pain management: a systematic review of randomised controlled trials. Pain, 2020.
  9. Johal, H., et al., Cannabinoids in Chronic Non-Cancer Pain: A Systematic Review and Meta-Analysis. Clin Med Insights Arthritis Musculoskelet Disord, 2020. 13: p. 1179544120906461.
  10. Wong, S.S.C., W.S. Chan, and C.W. Cheung, Analgesic Effects of Cannabinoids for Chronic Non-cancer Pain: a Systematic Review and Meta-Analysis with Meta-Regression. J Neuroimmune Pharmacol, 2020.
  11. Stockings, E., et al., Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: a systematic review and meta-analysis of controlled and observational studies. Pain, 2018. 159(10): p. 1932-1954.
  12. Nugent, S.M., et al., The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Annals of Internal Medicine, 2017. 167(5): p. 319-331.
  13. Aviram, J. and G. Samuelly-Leichtag, Efficacy of Cannabis-Based Medicines for Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Pain Physician, 2017. 20(6).
  14. Meng, H., et al., Selective Cannabinoids for Chronic Neuropathic Pain: A Systematic Review and Meta-analysis. Anesthesia & Analgesia, 2017. 125(5): p. 1638.
  15. Allan, G.M., et al., Systematic review of systematic reviews for medical cannabinoids: Pain, nausea and vomiting, spasticity, and harms. Canadian Family Physician Medecin De Famille Canadien, 2018. 64(2): p. e78-e94.
  16. Häuser, W., F. Petzke, and M.A. Fitzcharles, Efficacy, tolerability and safety of cannabis-based medicines for chronic pain management – An overview of systematic reviews. European Journal of Pain, 2018. 22(3): p. 455-470.
  17. Mücke, M., et al., Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews, 2018.
  18. Yanes, J.A., et al., Effects of cannabinoid administration for pain: A meta-analysis and meta-regression. Experimental and clinical psychopharmacology, 2019. 27(4): p. 370-382.
  19. Campbell, G., E. Stockings, and S. Nielsen, Understanding the evidence for medical cannabis and cannabis-based medicines for the treatment of chronic non-cancer pain. European Archives of Psychiatry and Clinical Neuroscience, 2019.
  20. Chisari, C.G., et al., An update on the pharmacological management of pain in patients with multiple sclerosis. Expert Opin Pharmacother, 2020: p. 1-15.
  21. Wissel, J., et al., Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain – A double-blind placebo-controlled cross-over trial. Journal of neurology, 2006. 253: p. 1337-41.
  22. Novotna, A., et al., A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex®), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. European Journal of Neurology, 2011. 18(9): p. 1122-1131.
  23. Markovà, J., et al., Sativex® as add-on therapy vs. further optimized first-line ANTispastics (SAVANT) in resistant multiple sclerosis spasticity: a double-blind, placebo-controlled randomised clinical trial. The International Journal of Neuroscience, 2019. 129(2): p. 119-128.
  24. van Amerongen, G., et al., Effects on Spasticity and Neuropathic Pain of an Oral Formulation of Δ9-tetrahydrocannabinol in Patients With Progressive Multiple Sclerosis. Clinical Therapeutics, 2018. 40(9): p. 1467-1482.
  25. Wade, D.T., et al., A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clinical Rehabilitation, 2003. 17(1): p. 21-29.
  26. Karst, M., et al., Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial. Jama, 2003. 290(13): p. 1757-62.
  27. Berman, J.S., C. Symonds, and R. Birch, Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain, 2004. 112(3): p. 299-306.
  28. Nurmikko, T.J., et al., Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain, 2007. 133(1-3): p. 210-20.
  29. Wilsey, B., et al., A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. The Journal of Pain: Official Journal of the American Pain Society, 2008. 9(6): p. 506-521.
  30. Selvarajah, D., et al., Randomized Placebo-Controlled Double-Blind Clinical Trial of Cannabis-Based Medicinal Product (Sativex) in Painful Diabetic Neuropathy: Depression is a major confounding factor. Diabetes Care, 2010. 33(1): p. 128-130.
  31. Toth, C., et al., An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo-controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain. Pain, 2012. 153(10): p. 2073-82.
  32. Wilsey, B., et al., Low-dose vaporized cannabis significantly improves neuropathic pain. The journal of pain : official journal of the American Pain Society, 2013. 14 2: p. 136-48.
  33. Serpell, M., et al., A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. Eur J Pain, 2014. 18(7): p. 999-1012.
  34. Schimrigk, S., et al., Dronabinol Is a Safe Long-Term Treatment Option for Neuropathic Pain Patients. European neurology, 2017. 78(5-6): p. 320-329.
  35. Xu, D.H., et al., The Effectiveness of Topical Cannabidiol Oil in Symptomatic Relief of Peripheral Neuropathy of the Lower Extremities. Current Pharmaceutical Biotechnology, 2019.
  36. Abrams, D.I., et al., Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology, 2007. 68(7): p. 515-521.
  37. Ellis, R.J., et al., Smoked Medicinal Cannabis for Neuropathic Pain in HIV: A Randomized, Crossover Clinical Trial. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2009. 34(3): p. 672-680.
  38. Wilsey, B., et al., An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain From Spinal Cord Injury and Disease. The journal of pain, 2016. 17(9): p. 982-1000.
  39. Almog, S., et al., The pharmacokinetics, efficacy, and safety of a novel selective-dose cannabis inhaler in patients with chronic pain: A randomized, double-blinded, placebo-controlled trial. Eur J Pain, 2020. 24(8): p. 1505-1516.
  40. Svendsen, K.B., T.S. Jensen, and F.W. Bach, Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial. BMJ : British Medical Journal, 2004. 329(7460): p. 253.
  41. Langford, R.M., et al., A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis. Journal of Neurology, 2013. 260(4): p. 984-997.
  42. Turcotte, D., et al., Nabilone as an Adjunctive to Gabapentin for Multiple Sclerosis-Induced Neuropathic Pain: A Randomized Controlled Trial. Pain Medicine, 2015. 16(1): p. 149-159.
  43. Ware, M.A., et al., Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ, 2010. 182(14): p. E694-E701.
  44. Frank, B., et al., Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study. BMJ (Clinical research ed.), 2008. 336(7637): p. 199-201.
  45. Corey-Bloom, J., et al., Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial. CMAJ, 2012. 184(10): p. 1143-1150.
  46. Leocani, L., et al., Sativex® and clinical–neurophysiological measures of spasticity in progressive multiple sclerosis. Journal of Neurology, 2015. 262(11): p. 2520-2527.
  47. Haleem, R. and R. Wright, A Scoping Review on Clinical Trials of Pain Reduction With Cannabis Administration in Adults. 2020. 2020.
  48. Nutt, D.J., et al., A Multicriteria Decision Analysis Comparing Pharmacotherapy for Chronic Neuropathic Pain, Including Cannabinoids and Cannabis-Based Medical Products. Cannabis and Cannabinoid Research, 2021.
  49. Boehnke, K.F., et al., Cannabidiol Use for Fibromyalgia: Prevalence of Use and Perceptions of Effectiveness in a Large Online Survey. The Journal of Pain, 2021.
  50. Fitzcharles, M.A., et al., Use of medical cannabis by patients with fibromyalgia in Canada after cannabis legalisation: a cross-sectional study. Clin Exp Rheumatol, 2021.
  51. Skrabek, R.Q., et al., Nabilone for the treatment of pain in fibromyalgia. J Pain, 2008. 9(2): p. 164-73.
  52. Ware, M.A., et al., The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial. Anesthesia and Analgesia, 2010. 110(2): p. 604-610.
  53. van de Donk, T., et al., An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia. Pain, 2019. 160(4): p. 860-869.
  54. Chaves, C., P.C.T. Bittencourt, and A. Pelegrini, Ingestion of a THC-Rich Cannabis Oil in People with Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Pain Med, 2020. 21(10): p. 2212-2218.
  55. Weber, J., et al., Tetrahydrocannabinol (Delta 9-THC) Treatment in Chronic Central Neuropathic Pain and Fibromyalgia Patients: Results of a Multicenter Survey. Anesthesiol Res Pract, 2009. 2009.
  56. Fiz, J., et al., Cannabis use in patients with fibromyalgia: effect on symptoms relief and health-related quality of life. PLoS One, 2011. 6(4): p. e18440.
  57. Yassin, M., A. Oron, and D. Robinson, Effect of adding medical cannabis to analgesic treatment in patients with low back pain related to fibromyalgia: an observational cross-over single centre study. Clin Exp Rheumatol, 2019. 37 Suppl 116(1): p. 13-20.
  58. Habib, G. and I. Avisar, The Consumption of Cannabis by Fibromyalgia Patients in Israel. Pain Res Treat, 2018. 2018: p. 7829427.
  59. Habib, G. and S. Artul, Medical Cannabis for the Treatment of Fibromyalgia. J Clin Rheumatol, 2018. 24(5): p. 255-258.
  60. Sagy, I., et al., Safety and Efficacy of Medical Cannabis in Fibromyalgia. Journal of Clinical Medicine, 2019. 8(6).
  61. Giorgi, V., et al., Adding medical cannabis to standard analgesic treatment for fibromyalgia: a prospective observational study. Clin Exp Rheumatol, 2020. 38 Suppl 123(1): p. 53-59.
  62. Anson, P., Marijuana Rated Most Effective for Treating Fibromyalgia, in National Pain Report. 2014: National Pain Report.
  63. Boehnke, K.F., et al., Substituting Cannabidiol for Opioids and Pain Medications Among Individuals With Fibromyalgia: A Large Online Survey. J Pain, 2021.
  64. Vučković, S., et al., Cannabinoids and Pain: New Insights From Old Molecules. Frontiers in Pharmacology, 2018. 9: p. 1259.
  65. Richardson, D., et al., Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis research & therapy, 2008. 10(2): p. R43-R43.
  66. Lowin, T., M. Schneider, and G. Pongratz, Joints for joints: cannabinoids in the treatment of rheumatoid arthritis. Current Opinion in Rheumatology, 2019. 31(3): p. 271-278.
  67. Gonen, T. and H. Amital, Cannabis and Cannabinoids in the Treatment of Rheumatic Diseases. Rambam Maimonides Med J, 2020. 11(1).
  68. Fitzcharles, M.-A., et al., Efficacy, tolerability and safety of cannabinoids in chronic pain associated with rheumatic diseases (fibromyalgia syndrome, back pain, osteoarthritis, rheumatoid arthritis): A systematic review of randomized controlled trials. Schmerz (Berlin, Germany), 2016. 30(1): p. 47-61.
  69. Blake, D.R., et al., Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology (Oxford, England), 2006. 45(1): p. 50-52.
  70. Sorge, R.E. and S.K. Totsch, Sex Differences in Pain. J Neurosci Res, 2017. 95(6): p. 1271-1281.
  71. Matheson, J., et al., Sex differences in the acute effects of smoked cannabis: evidence from a human laboratory study of young adults. Psychopharmacology (Berl), 2020. 237(2): p. 305-316.
  72. Fogel, J.S., et al., Sex differences in the subjective effects of oral Δ(9)-THC in cannabis users. Pharmacology, biochemistry, and behavior, 2017. 152: p. 44-51.
  73. Sholler, D.J., et al., Sex differences in the acute effects of oral and vaporized cannabis among healthy adults. Addiction Biology, 2020. n/a(n/a): p. e12968.
  74. Chen, Q., et al., Estrogen receptors in pain modulation: cellular signaling. Biology of sex differences, 2021. 12(1): p. 22-22.
  75. Piroli, A., et al., Influence of the Menstrual Cycle Phase on Pain Perception and Analgesic Requirements in Young Women Undergoing Gynecological Laparoscopy. Pain Pract, 2019. 19(2): p. 140-148.
  76. Bartley, E.J. and J.L. Rhudy, Comparing pain sensitivity and the nociceptive flexion reflex threshold across the mid-follicular and late-luteal menstrual phases in healthy women. Clin J Pain, 2013. 29(2): p. 154-61.
  77. Hellström, B. and U.M. Anderberg, Pain perception across the menstrual cycle phases in women with chronic pain. Percept Mot Skills, 2003. 96(1): p. 201-11.
  78. Blanton, H.L., et al., Sex differences and the endocannabinoid system in pain. Pharmacol Biochem Behav, 2021. 202: p. 173107.
  79. Bhaskar, A., et al., Consensus recommendations on dosing and administration of medical cannabis to treat chronic pain: results of a modified Delphi process. Journal of Cannabis Research, 2021. 3(1): p. 22.
  80. MacCallum, C.A., L.A. Lo, and M. Boivin, “Is medical cannabis safe for my patients?” A practical review of cannabis safety considerations. European Journal of Internal Medicine, 2021.
  81. MacCallum, C.A., et al., Practical Strategies Using Medical Cannabis to Reduce Harms Associated With Long Term Opioid Use in Chronic Pain. Front Pharmacol, 2021. 12: p. 633168.
  82. MacCallum, C.A. and E.B. Russo, Practical considerations in medical cannabis administration and dosing. European Journal of Internal Medicine, 2018. 49: p. 12-19.
  83. Sharma, P., P. Murthy, and M.M.S. Bharath, Chemistry, Metabolism, and Toxicology of Cannabis: Clinical Implications. Iranian Journal of Psychiatry, 2012. 7(4): p. 149-156.
  84. Grotenhermen, F., Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical pharmacokinetics, 2003. 42(4): p. 327–360.
  85. Zajicek, J., et al., Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. The Lancet, 2003. 362(9395): p. 1517-1526.
  86. Notcutt, W.G., Clinical Use of Cannabinoids for Symptom Control in Multiple Sclerosis. Neurotherapeutics, 2015. 12(4): p. 769-777.
  87. Meng, H., et al., Patient-reported outcomes in those consuming medical cannabis: a prospective longitudinal observational study in chronic pain patients. Can J Anaesth, 2021.
  88. Nielsen, S., et al., Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis. Neuropsychopharmacology, 2017. 42(9): p. 1752-1765.
  89. Noori, A., et al., Opioid-sparing effects of medical cannabis or cannabinoids for chronic pain: a systematic review and meta-analysis of randomised and observational studies. BMJ Open, 2021. 11(7): p. e047717.