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CC BY-NC-ND 4.0 · Pharmacopsychiatry
DOI: 10.1055/a-2231-6630
Review

Overview: Chronic Pain and Cannabis-Based Medicines

Matthias Karst
1   Anesthesiology, Pain Clinic, Hannover Medical School, Hannover, Germany
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Abstract

Chronic pain is primarily conceptualized as a disease in its own right when it is associated with emotional distress and functional impairment. Pathophysiologically, dysfunction of the cortico-mesolimbic connectome is of major importance, with overlapping signals in the nociceptive and stress systems. The endocannabinoid system plays an important role in the central processing of nociceptive signals and regulates the central stress response. Clinically, there is moderate evidence that cannabis-based medicines (CBM) can contribute to a significant reduction in pain, especially the associated pain affect, and improvement in physical function and sleep quality in a proportion of patients with chronic pain. The analgesic effect appears to be largely independent of the cause of pain. In this context, CBM preferentially regulates stress-associated pain processing.

Key words

cannabis-based medicines - chronic pain - chronic stress - central sensitization - nociplastic pain


Publication History

Received: 14 September 2023
Received: 03 December 2023

Accepted: 07 December 2023

Article published online:
10 January 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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  • References

  • 1 Treede R-D, Rief W, Barke A. et al. Chronic pain as a symptom or a disease: The IASP classification of chronic pain for the international classification of disease (ICD-11). Pain 2019; 160: 19-27
    CrossrefPubMedGoogle Scholar
  • 2 Häuser W, Schmutzer G, Henningsen P. et al. Chronische schmerzen, schmerzkrankheit und zufriedenheit der betroffenen mit der schmerzbehandlung in Deutschland. Schmerz 2014; 28: 483-492
    CrossrefPubMedGoogle Scholar
  • 3 Barke A, Korwisi B, Rief W. Chronic pain in the ICD-11: New diagnoses that clinical psychologist should know about. Clin Psychol Eur 2022; 4: e9933
    CrossrefPubMedGoogle Scholar
  • 4 Nicolson KP, Mills AEE, Senaratne DNS. et al. What is the association between childhood adversity and subsequent chronic pain in adulthood? A systematic review. BJA Open 2023; 6: 100139
    CrossrefPubMedGoogle Scholar
  • 5 Kodila ZN, Shultz SR, Yamakawa GR. et al. Critical windows: Exploring the association between perinatal trauma, epigenetics, and chronic pain. Neuroscientist 2023; DOI: 10.1177/10738584231176233.
    CrossrefPubMedGoogle Scholar
  • 6 Nelson S, Burns M, McEwen B. et al. Stressful experiences in youth: “Set-up” for diminished resilience to chronic pain. Brain Behav Immun Health 2020; 5: 100095
    CrossrefPubMedGoogle Scholar
  • 7 Agorastos A, Pervanidou P, Chrousos GP. et al. Development trajectories of early life stress and trauma: A narrative review on neurobiological aspects beyond stress system dysregulation. Front Psychiatry 2019; 10: 118
    CrossrefPubMedGoogle Scholar
  • 8 McGowan PO, Sasaki A, D’Alessio AC. et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 2009; 12: 342-348
    CrossrefPubMedGoogle Scholar
  • 9 Morena M, Patel S, Bains JS. et al. Neurobiological interactions between stress and the endocannabinoid system. Neuropsychopharmacology 2016; 41: 80-102
    CrossrefPubMedGoogle Scholar
  • 10 Schaffer J, Fogelman N, Seo D. et al. Chronic pain, chronic stress and substance use: Overlapping mechanisms and implications. Front Pain Res 2023; 4: 1145934
    CrossrefPubMedGoogle Scholar
  • 11 Vachon-Presseau E, Centeno MV, Ren W. et al. The emotional brain as a predictor and amplifier of chronic pain. J Dent Res 2016; 95: 605-612
    CrossrefPubMedGoogle Scholar
  • 12 Timmers I, Quaedflieg CWEM, Hsu C. et al. The interaction between stress and chronic pain through the lens of threat learning. Neurosci Biobehav Rev 2019; 107: 641-655
    CrossrefPubMedGoogle Scholar
  • 13 Achenbach J, Rhein M, Gombert S. et al. Childhood traumatization is associated with differences in TRPA1 promoter methylation in female patients with multisomatoform disorder with pain as the leading bodily symptom. Clin Epigenetics 2019; 11: 126
    CrossrefPubMedGoogle Scholar
  • 14 Burke NN, Fan CY, Trang T. Microglia in health and pain: Impact of noxious early life events. Exp Physiol 2016; 101: 1003-1021
    CrossrefPubMedGoogle Scholar
  • 15 Burke NN, Finn DP, McGuire BE. et al. Psychological stress in early life as a predisposing factor for the development of chronic pain: Clinical and preclinical evidence and neurobiological mechanisms. J Neurosci Res 2017; 95: 1257-1270
    CrossrefPubMedGoogle Scholar
  • 16 Nijs J, Lahousse A, Kapreli E. et al. Nociplastic pain criteria or recognition of central sensitization? Pain phenotyping in the past, present and future. J Clin Med 2021; 10: 3203
    CrossrefPubMedGoogle Scholar
  • 17 Schrepf A, Williams DA, Gallop R. et al. Sensory sensitivity and symptom severity represent unique dimensions of chronic pain: A MAPP research network study. Pain 2018; 159: 2002-2011
    CrossrefPubMedGoogle Scholar
  • 18 Schuttert I, Timmerman H, Petersen KK. et al. The definition, assessment, and prevalence of (human assumed) central sensitisation in patients with chronic low back pain: A systematic review. J Clin Med 2021; 10: 5931
    CrossrefPubMedGoogle Scholar
  • 19 Afari N, Ahumada SM, Wright LJ. et al. Psychological trauma and functional somatic syndromes: A systematic review and meta- analysis. Psychosom Med 2014; 76: 2-11
    CrossrefPubMedGoogle Scholar
  • 20 Janssen J, Abou-Assaly E, Rasic N. et al. Trauma and pain sensitization in youth with chronic pain. Pain Reports 2022; 7: e992
    CrossrefPubMedGoogle Scholar
  • 21 McKernan LC, Johnson BN, Crofford LJ. et al. Posttraumatic stress symptoms mediate the effects of trauma exposure on clinical indicators of central sensitization in patients with chronic pain. Clin J Pain 2019; 35: 385-393
    CrossrefPubMedGoogle Scholar
  • 22 Moeller-Bertram T, Strigo IA, Simmons AN. et al. Evidence for acute central sensitization to prolonged experimental pain in post- traumatic stress disorder. Pain Med 2014; 15: 762-771
    CrossrefPubMedGoogle Scholar
  • 23 Manuel J, Rudolph L, Beissner F. et al. Traumatic events, posttraumatic stress disorder, and central sensitization in chronic pain patients of a German university outpatient clinic. Psychosom Med 2023; 85: 351-357
    CrossrefPubMedGoogle Scholar
  • 24 Campos RMP, Aguiar AF, Paes-Collu Y. et al. Cannabinoid therapeutics in chronic neuropathic pain: From animal research to human treatment. Front Physiol 2021; 12: 785176
    CrossrefPubMedGoogle Scholar
  • 25 Velho RV, Sehouli J, Mechsner S. Mechanisms of peripheral sensitization in endometriosis patients with peritoneal lesions and acyclical pain. Arch Gynecol Obstet 2023; 308: 1327-1340 DOI: 10.1007/s00404-023-07110-9.
    CrossrefPubMedGoogle Scholar
  • 26 Muller C, Morales P, Reggio PH. Cannabinoid ligands targeting TRP channels. Front Mol Neurosci 2019; 11: 487
    CrossrefPubMedGoogle Scholar
  • 27 Zygmunt PM, Petersson J, Andersson DA. et al. Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 1999; 400: 452-457
    CrossrefPubMedGoogle Scholar
  • 28 Pace MC, Passavanti MB, De Nardis L. et al. Nociceptor plasticity: A closer look. J Cell Physiol 2017; 9999: 1-15
    PubMedGoogle Scholar
  • 29 De Petrocellis L, Starowicz K, Moriello AS. et al. Regulation of transient receptor potential channels of melastin type 8 (TRPM8): Effect of cAMP, cannabinoid CB(1) receptors and andovanilloids. Exp Cell Res 2007; 313: 1911-1920
    CrossrefPubMedGoogle Scholar
  • 30 De Petrocellis L, Ligresti A, Moriello AS. et al. Effects of cannabinoids and cannabinoid-enriched cannabis extracts on TRP channels and endocannabinoid metabolomic enzymes. Br J Pharmacol 2011; 163: 1479-1494
    CrossrefPubMedGoogle Scholar
  • 31 Hohmann AG, Suplita RL, Bolton NM. et al. An endocannabinoid mechanism for stress-induced analgesia. Nature 2005; 435: 1108-1112
    CrossrefPubMedGoogle Scholar
  • 32 Carlino E, Benedetti F. Different contexts, different pains, different experiences. Neuroscience 2016; 338: 19-26
    CrossrefPubMedGoogle Scholar
  • 33 Deutsch DG. A personal retrospective: Elevating anandamide (AEA) by targeting fatty acid amide hydrolase (FAAH) and the fatty acid binding proteins (FABPs). Front Pharmacol 2016; 7: 370
    CrossrefPubMedGoogle Scholar
  • 34 Marsicano G, Wotjak CT, Azad SC. et al. The endogenous cannabinoid system controls extinction of aversive memories. Nature 2002; 418: 530-534
    CrossrefPubMedGoogle Scholar
  • 35 Fattore L, Melis M, Fadda P. et al. The endocannabinoid system and nondrug rewarding behaviors. Exp Neurol 2010; 224: 23-36
    CrossrefPubMedGoogle Scholar
  • 36 Walker JM, Huang SM, Strangman NM. et al. Pain modulation by release of the endogenous cannabinoid anandamide. PNAS 1999; 96: 12198-12203
    CrossrefPubMedGoogle Scholar
  • 37 Valverde O, Ledent C, Beslot F. et al. Reduction of stress-induced analgesia but not of exogenous opioid effects in mice lacking CB1 receptors. Eur J Neurosci 2000; 12: 533-539
    CrossrefPubMedGoogle Scholar
  • 38 Cichewicz DL. Synergistic interactions between cannabinoid and opioid analgesics. Life Sci 2004; 74: 1317-1324
    CrossrefPubMedGoogle Scholar
  • 39 Smith PA, Selley DE, Sim-Selley LJ. et al. Low dose combination of morphine and delta9-tetrahydrocannabinol circumvents antinociceptive tolerance and apparent desensitization of receptors. Eur J Pharmacol 2007; 571: 129-137
    CrossrefPubMedGoogle Scholar
  • 40 Nielsen S, Sabioni P, Trigo JM. et al. Opioid-sparing effect of cannabinoids: A systematic review and meta-analysis. Neuropsychopharmacology 2017; 42: 1752-1765
    CrossrefPubMedGoogle Scholar
  • 41 Piper BJ, DeKeuster RM, Beals ML. et al. Substitution of medical cannabis for pharmaceutical agents for pain, anxiety, and sleep. J Psychopharmacol 2017; 31: 569-575
    CrossrefPubMedGoogle Scholar
  • 42 Egle UT, Egloff N, von Känel R. Stress-induced hyperalgesia (SIH) as a consequence of emotional deprivation and psychosocial traumatization in childhood: Implications for the treatment of chronic pain. Schmerz 2016; 30: 526-536
    PubMedGoogle Scholar
  • 43 Löffler M, Schneider P, Schuh-Hofer S. et al. Stress-induced hyperalgesia instead of analgesia in patients with chronic musculoskeletal pain. Neurobiol Pain 2023; 13: 100110
    CrossrefPubMedGoogle Scholar
  • 44 Tsou K, Brown S, Sanudo-Pena MC. et al. Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience 1998; 83: 393-411
    CrossrefPubMedGoogle Scholar
  • 45 De Vita MJ, Moskal D, Maisto SA. et al. Association of cannabinoid administration with experimental pain in healthy adults. JAMA Psychiatry 2018; 75: 1118
    CrossrefPubMedGoogle Scholar
  • 46 Aviram J, Pud D, Gershoni T. et al. Medical cannabis treatment for chronic pain: Outcomes and prediction of response. Eur J Pain 2021; 25: 359-374
    CrossrefPubMedGoogle Scholar
  • 47 Hill MN, Lee FS. Endocannabinoids and stress resilience: Is deficiency sufficient to promote vulnerability?. Biol Psychiatry 2016; 79: 792-793
    CrossrefPubMedGoogle Scholar
  • 48 Karhson DS, Hardan AY, Parker KJ. Endocannabinoid signaling in social functioning: An RDoC perspective. Transl Psychiatry 2016; 6: e905
    CrossrefPubMedGoogle Scholar
  • 49 Lee MC, Ploner M, Wiech K. et al. Amygdala activity contributes to the dissociative effect of cannabis on pain perception. Pain 2013; 154: 124-134
    CrossrefPubMedGoogle Scholar
  • 50 Weizman L, Dayan L, Brill S. et al. Cannabis analgesia in chronic neuropathic pain is associated with altered brain connectivity. Neurology 2018; 91: e1285-e1294
    CrossrefPubMedGoogle Scholar
  • 51 La Porta C, Bura SA, Llorente-Onaindia J. et al. Role of the endocannabinoid system in the emotional manifestations of osteoarthritis pain. Pain 2015; 156: 2001-2012
    CrossrefPubMedGoogle Scholar
  • 52 Azim S, Nicholson J, Rebecci MJ. et al. Endocannabinoids and acute pain after total knee arthroplasty. Pain 2015; 156: 341-347
    CrossrefPubMedGoogle Scholar
  • 53 Neumeister A, Normandin MD, Pietrzak RH. et al. Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: A positron emission tomography study. Mol Psychiatry 2013; 18: 1034-1040
    CrossrefPubMedGoogle Scholar
  • 54 Eisenberg E, Morlion B, Brill S. et al. Medicinal cannabis for chronic pain: The Bermuda triangle of low-quality studies, countless meta-analyses and conflicting recommendations. Eur J Pain 2022; 26: 1183-1185
    CrossrefPubMedGoogle Scholar
  • 55 Chou R, Wagner J, Ahmed AY. et al. Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain: Surveillance Report 4: Literature update period: Mid-January 2022 Through March 2022. In: Living systematic review on cannabis and other plant-based treatments for chronic pain: Interim progress and surveillance reports [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US).
    PubMedGoogle Scholar
  • 56 Campbell G, Stockings E, Nielsen S. Understanding the evidence for medical cannabis and cannabis-based medicines for the treatment of chronic non-cancer pain. Eur Arch Psychiatry Clin Neurosci 2019; 269: 135-144
    CrossrefPubMedGoogle Scholar
  • 57 Ioannidis JPA. The mass production of redundant, misleading, and conflicted systematic reviews and meta-analyses. Milbank Q 2016; 94: 485-514
    CrossrefPubMedGoogle Scholar
  • 58 Greiner T. Subjective bias of the clinical pharmacologist. JAMA 1962; 181: 120-121
    CrossrefPubMedGoogle Scholar
  • 59 Karst M, Wippermann S, Ahrens J. Role of cannabinoids in the treatment of pain and (painful) spasticity. Drugs 2010; 70: 2409-2438
    CrossrefPubMedGoogle Scholar
  • 60 Bilbao A, Spanagel R. Medical cannabinoids: A pharmacology-based systematic review and meta-analysis for all relevant medical indications. BMC Med 2022; 20: 259
    CrossrefPubMedGoogle Scholar
  • 61 Andreae MH, Carter GM, Shaparin N. et al. Inhaled cannabis for chronic neuropathic pain: A meta-analysis of individual patient data. J Pain 2015; 16: 1221-1232
    CrossrefPubMedGoogle Scholar
  • 62 Raz N, Eyal AM, Davidson EM. Optimal treatment with cannabis extracts formulations is gained via knowledge of their terpene content and via enrichment with specifically selected monoterpenes and monoterpenoids. Molecules 2022; 27: 6920
    CrossrefPubMedGoogle Scholar
  • 63 Wang L, Hong PJ, May C. et al. Medical cannabis or cannabinoids for chronic non-cancer and cancer related pain: A systematic review and meta-analysis of randomised clinical trials. BMJ 2021; 374: n1034
    CrossrefPubMedGoogle Scholar
  • 64 Busse JW, Vankrunkelsven P, Zeng L. et al. Medical cannabis or cannabinoids for chronic pain: A clinical practice guideline. BMJ 2021; 374: n2040
    CrossrefPubMedGoogle Scholar
  • 65 Zeng L, Lytvyn L, Wang X. et al. Values and preferences towards medical cannabis among people living with chronic pain: A mixed-methods systematic review. BMJ Open 2021; 11: e050831
    CrossrefPubMedGoogle Scholar
  • 66 Boehnke KF, Scott JR, Litinas E. et al. Cannabis use preferences and decision-making among a cross-sectional cohort of medical cannabis patients with chronic pain. J Pain 2019; 20: 1362-1372
    CrossrefPubMedGoogle Scholar
  • 67 Bialas P, Fitzcharles M-A, Klose P. et al. Long-term observational studies with cannabis-based medicines for chronic non-cancer pain: A systematic review and meta-analysis of effectiveness and safety. Eur J Pain 2022; 26: 1221-1233
    CrossrefPubMedGoogle Scholar
  • 68 Inglet S, Winter B, Yost SE. et al. Clinical data for the use of cannabis-based treatments: A comprehensive review of the literature. Ann Pharmacother 2020; 54: 1109-1143
    CrossrefPubMedGoogle Scholar
  • 69 Fordjour E, Manful CF, Sey AA. et al. Cannabis: A multifaceted plant with endless potentials. Front Pharmacol 2023; 14: 1200269
    CrossrefPubMedGoogle Scholar
  • 70 Nutt DJ, Phillips LD, Barnes MP. et al. A multicriteria decision analysis comparing pharmacotherapy for chronic neuropathic pain, including cannabinoids and cannabis-based medical products. Cannabis Cannabinoid Res 2022; 7: 482-500
    CrossrefPubMedGoogle Scholar
  • 71 Zeraatkar D, Cooper MA, Agarwal A. et al. Long-term and serious harms of medical cannabis and cannabinoids for chronic pain: A systematic review of non-randomised studies. BMJ Open 2022; 12: e054282
    CrossrefPubMedGoogle Scholar
  • 72 Lathrop JR, Rosen SN, Heitkemper MN. et al. Cyclic vomiting syndrome and cannabis hyperemesis syndrome: The state of the science. Gastroenterol Nurs 2023; 46: 208-224
    CrossrefPubMedGoogle Scholar
  • 73 Sperber AD, Bangdiwala SI, Drossman DA. et al. Worldwide prevalence and burden of functional gastrointestinal disorders, results of Rome Foundation Global Study. Gastroenterology 2021; 160: 99-114
    CrossrefPubMedGoogle Scholar
  • 74 Package leaflet: Information for the patient Sativex® Oromucosal Spray https://www.medicines.org.uk/emc/files/pil.602.pdf
    PubMed
  • 75 Hasin DS, Wall MM, Alschuler DM. et al. Chronic pain, cannabis legalisation, and cannabis use disorder among patients in the US Veterans Health Administration system, 2005 to 2019: A repeated, cross-sectional study. Lancet Psychiatry 2023; 10: 877-886
    CrossrefPubMedGoogle Scholar
  • 76 Lauff S, Petzke F, Brill S. et al. Face validity of the ICD-10 criteria of substance abuse and dependence for patients prescribed cannabis-based medicines for chronic pain – a survey of pain medicine physicians in Canada, Germany and Israel. Eur J Pain 2023; 27: 588-601
    CrossrefPubMedGoogle Scholar
  • 77 Urits I, Charipova K, Gress K. et al. Adverse effects of recreational and medical cannabis. Psychopharmacol Bull 2021; 51: 94-109
    PubMedGoogle Scholar
  • 78 Feingold D, Brill S. Goor-Aryeh et al. Medical marihuana dependence among chronic pain patients suffering from depression and anxiety. Harfuah 2019; 158: 438-444
    PubMedGoogle Scholar
  • 79 Häuser W, Schubert T, Vogelmann T. et al. All-cause mortality in patients with long-term opioid therapy compared with non-opioid analgesics for chronic non-cancer pain: A database study. BMC Med 2020; 18: 162
    CrossrefPubMedGoogle Scholar
  • 80 Zeng C, Dubreuil M, LaRochelle MR. et al. Association of tramadol with all-cause mortality among patients with osteoarthritis. JAMA 2019; 321: 969-982
    CrossrefPubMedGoogle Scholar
  • 81 Nielsen S, Picco L, Murnion B. et al. Opioid-sparing effect of cannabinoids for analgesia: An updated systematic review and meta-analysis of preclinical and clinical studies. Neuropsychopharmacology 2022; 47: 1315-1330
    CrossrefPubMedGoogle Scholar
  • 82 Wilson J, Mills K, Freeman TP. et al. Weeding out the truth: A systematic review and meta-analysis on the transition from cannabis use to opioid use and opioid disorders, abuse or dependence. Addiction 2022; 117: 284-298
    CrossrefPubMedGoogle Scholar
  • 83 Cohn AM, Elmasry H. First use of cannabis compared to first use of alcohol and tobacco: Associations with single and poly-substance use behavior. Drug Alcohol Depend 2023; 248: 109904
    CrossrefPubMedGoogle Scholar
  • 84 Gorey C, Kroon E, Runia N. et al. Direct effects of cannabis intoxication on motivations for softer and harder drug use. An experimental approach to the gateway hypothesis. Cannabis Cannabinoid Res 2023; DOI: 10.1089/can.2022.0157.
    CrossrefPubMedGoogle Scholar
  • 85 Beaulieu P, Boulanger A, Desroches J. et al. Medical cannabis: Considerations for the anesthesiologist and pain physician. Can J Anaesth 2016; 63: 608-624
    CrossrefPubMedGoogle Scholar
  • 86 Levine A, Clemenza K, Rynn M. et al. Evidence for the risks and consequences of adolescent cannabis exposure. J Am Acad Child Adolesc Psychiatry 2017; 56: 214-225
    CrossrefPubMedGoogle Scholar
  • 87 Tashkin DP. Effects of marijuana smoking on the lung. Ann Am Thorac Soc 2013; 10: 239-247
    CrossrefPubMedGoogle Scholar
  • 88 Chaiton M, Kundu A, Rueda S. et al. Are vaporizers a lower-risk alternative to smoking cannabis?. Can J Public Health 2022; 113: 293-296
    CrossrefPubMedGoogle Scholar
  • 89 Boakye E, El Shahawy O, Obisesan O. et al. The inverse association of state cannabis vaping prevalence with the e-cigarette or vaping product-use associated lung injury. PLoS One 2022; 17: e0276187
    CrossrefPubMedGoogle Scholar
  • 90 Reddy TS, Zomer R, Mantri N. Nanoformulations as a strategy to overcome the delivery limitations of cannabinoids. Phytother Res 2023; 37: 1526-1538
    CrossrefPubMedGoogle Scholar
  • 91 Hill MH, Campolongo P, Yehuda R. et al. Integrating endocannabinoid signaling and cannabinoids into the biology and treatment of posttraumatic stress disorder. Neuropsychopharmacology 2018; 43: 80-102
    CrossrefPubMedGoogle Scholar
  • 92 MacCallum CA, Russo EB. Practical considerations in medical cannabis administration and dosing. Eur J Intern Med 2018; 49: 12-19
    CrossrefPubMedGoogle Scholar
  • 93 Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet 2003; 42: 327-360
    CrossrefPubMedGoogle Scholar
  • 94 Lunn S, Diaz P, O`Hearn S. et al. Human pharmacokinetic parameters of orally administered delta-tetrahydrocannabinol capsules are altered by fed versus fasted conditions and sex differences. Cannabis Cannabinoid Res 2019; 4: 255-264
    CrossrefPubMedGoogle Scholar
  • 95 Petzke F, Karst M, Gastmeier K. et al. Position paper on medical cannabis and cannabis-based medicines in pain medicine. Schmerz 2019; 33: 449-465
    PubMedGoogle Scholar
  • 96 Wall M, Perez-Reyes M. The metabolism of delta9-tetrahydrocannabinol and related cannabinoids in man. J Clin Pharmacol 1981; 21: 178S-189S
    CrossrefPubMedGoogle Scholar
  • 97 Karst M. Cannabinoids for the treatment of chronic neuropathic pain and spasticity. MMW Fortschr Med 2022; 164: 51-60
    PubMedGoogle Scholar
  • 98 Bhaskar A, Bell A, Boivin M. et al. Consensus recommendations on dosing and administration of medical cannabis to treat chronic pain: Results of a modified Delphi process. J Cannabis Res 2021; 3: 22
    CrossrefPubMedGoogle Scholar
  • 99 Christensen C, Rose M, Cornett C. et al. Decoding the postulated entourage effect of medicinal cannabis: What it is and what it isn`t. Biomedicines 2023; 11: 2323
    CrossrefPubMedGoogle Scholar
  • 100 Lawson K. A brief review of the pharmacology of amitriptyline and clinical outcomes in treating fibromyalgia. Biomedicines 2017; 5: 24
    CrossrefPubMedGoogle Scholar
  • 101 Buhck M, Achenbach J, Wiese B. et al. The interplay of chronic stress and genetic traits discriminates between patients suffering from multisomatoform disorder with pain as the leading symptom and matched controls. J Affect Disord 2022; 308: 466-472
    CrossrefPubMedGoogle Scholar
  • 102 Connor JP, Stjepanović D, Le Foll B. et al. Cannabis use and cannabis use disorder. Nat Rev Dis Primers 2021; 7: 16
    CrossrefPubMedGoogle Scholar
  • 103 Ste-Marie PA, Shir Y, Rampakakis E. et al. Survey of herbal cannabis (marijuana) use in rheumatology clinic attenders with a rheumatologist confirmed diagnosis. Pain 2016; 157: 2792-2797
    CrossrefPubMedGoogle Scholar
  • 104 Arkell TR, Downey LA, Hayley AC. et al. Assessment of medical cannabis and health-related quality of life. JAMA Network Open 2023; 6: e2312522
    CrossrefPubMedGoogle Scholar
  • 105 Lavie-Ajavi M, Shvartzman P. Restored self: A phenomenological study of pain relief by cannabis. Pain Med 2018; 20: 2083-2093
    PubMedGoogle Scholar