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Considering abuse liability and neurocognitive effects of cannabis and cannabis-derived products when assessing analgesic efficacy: a comprehensive review of randomized-controlled studies

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Pages 580-595 | Received 16 Feb 2019, Accepted 15 Sep 2019, Published online: 05 Nov 2019

References

  • National Conference of State Legislatures. State Medical Marijuana Laws; 2019.
  • MPP.org. Medical Marijuana Patient Numbers.
  • Chart: No end in sight for Florida’s rapid medical marijuana growth. Available from: https://mjbizdaily.com/chart-no-end-florida-medical-marijuana-market-rapid-growth/ [last accessed 1 Sept 2018].
  • Chart: Montana medical marijuana patient counts skyrocket in revived program. Available from: https://mjbizdaily.com/chart-montana-medical-marijuana-patient-counts-skyrocket-in-revived-program/ [last accessed 1 Sept 2018].
  • Total number of registererd MMJ patients in Hawaii. Available from: https://hawaiicannabis.org/hawaii-medical-cannabis-patient-numbers-2017/ [last accessed 1 Sept 2018].
  • Chart: patient numbers, medical marijuana sales spike in New Jersey. Available from: https://mjbizdaily.com/chart-patient-numbers-medical-marijuana-sales-spike-in-new-jersey/ [last accessed 1 Sept 2018].
  • Bohnert KM, Perron BE, Ashrafioun L, Kleinberg F, Jannausch M, Ilgen MA. Positive posttraumatic stress disorder screens among first-time medical cannabis patients: prevalence and association with other substance use. Addict Behav. 2014;39:1414–17. doi:10.1016/j.addbeh.2014.05.022.
  • Bonn-Miller MO, Boden MT, Bucossi MM, Babson KA. Self-reported cannabis use characteristics, patterns and helpfulness among medical cannabis users. Am J Drug Alcohol Abuse. 2014;40:23–30. doi:10.3109/00952990.2013.821477.
  • Cranford JA, Bohnert KM, Perron BE, Bourque C, Ilgen M. Prevalence and correlates of “Vaping” as a route of cannabis administration in medical cannabis patients. Drug Alcohol Depend. 2016;169:41–47. doi:10.1016/j.drugalcdep.2016.10.024.
  • National Academies of Sciences, Engineering, and Medicine, Health and Medicine Division, Board on Population Health and Public Health Practice, Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda. The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. Washington (DC): National Academies Press (US); 2017.
  • Nugent SM, Morasco BJ, O’Neil ME, Freeman M, Low A, Kondo K, Elven C, Zakher B, Motu’apuaka M, Paynter R, et al. The effects of cannabis among adults with chronic pain and an overview of general harms: a systematic review. Ann Intern Med. 2017;167:319. doi:10.7326/M17-0155.
  • Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, Keurentjes JC, Lang S, Misso K, Ryder S, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015;313:2456.
  • Aviram J, Samuelly-Leichtag G. Efficacy of cannabis-based medicines for pain management: a systematic review and meta-analysis of randomized controlled trials. Pain Physician. 2017;20:E755–E796.
  • U.S. Department of Health And Human Services, Food And Drug Administration, Center For Drug Evaluation And Research (CDER). Assessment of Abuse Potential of Drugs Guidance for Industry; 2017.
  • Wall MM, Liu J, Hasin DS, Blanco C, Olfson M. Use of marijuana exclusively for medical purposes. Drug Alcohol Depend. 2018. December 2018. doi:10.1016/j.drugalcdep.2018.11.009.
  • Ware MA, Martel MO, Jovey R, Lynch ME, Singer J. A prospective observational study of problematic oral cannabinoid use. Psychopharmacology (Berl). 2018;235:409–17. doi:10.1007/s00213-017-4811-6.
  • Spindle TR, Cone EJ, Schlienz NJ, Mitchell JM, Bigelow GE, Flegel R, Hayes E, Vandrey R. Acute effects of smoked and vaporized cannabis in healthy adults who infrequently use cannabis: a crossover trial. JAMA Netw Open. 2018;1:e184841. doi:10.1001/jamanetworkopen.2018.4841.
  • Cooper ZD, Bedi G, Ramesh D, Balter R, Comer SD, Haney M. Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability. Neuropsychopharmacology. 2018;5. doi:10.1038/s41386-018-0011-2.
  • Notcutt W, Price M, Miller R, Newport S, Phillips C, Simmons S, Sansom C. Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 ‘N of 1ʹ studies. Anaesthesia. 2004;59:440–52. doi:10.1111/ana.2004.59.issue-5.
  • Wade DT, Makela P, Robson P, House H, Bateman C. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult Scler Houndmills Basingstoke Engl. 2004;10:434–41. doi:10.1191/1352458504ms1082oa.
  • Greenwald MK, Stitzer ML. Antinociceptive, subjective and behavioral effects of smoked marijuana in humans. Drug Alcohol Depend. 2000;59:261–275. doi:10.1016/s0376-8716(99)00117-9.
  • Rog DJ, Nurmikko TJ, Friede T, Young CA. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology. 2005;65:812–19. doi:10.1212/01.wnl.0000176753.45410.8b.
  • Nurmikko TJ, Serpell MG, Hoggart B, Toomey PJ, Morlion BJ, Haines D. Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain. 2007;133:210–20. doi:10.1016/j.pain.2007.03.019.
  • Wilsey B, Marcotte T, Tsodikov A, Millman J, Bentley H, Gouaux B, Fishman S. A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J Pain. 2008;9:506–21. doi:10.1016/j.jpain.2007.12.010.
  • Wilsey B, Marcotte T, Deutsch R, Gouaux B, Sakai S, Donaghe H. Low-dose vaporized cannabis significantly improves neuropathic pain. J Pain. 2013;14:136–48. doi:10.1016/j.jpain.2013.06.004.
  • Wilsey B, Marcotte TD, Deutsch R, Zhao H, Prasad H, Phan A. An exploratory human laboratory experiment evaluating vaporized cannabis in the treatment of neuropathic pain from spinal cord injury and disease. J Pain. 2016;17:982–1000. doi:10.1016/j.jpain.2015.12.006.
  • Cooper ZD, Haney M. Sex-dependent effects of cannabis-induced analgesia. Drug Alcohol Depend. 2016;167:112–20. doi:10.1016/j.drugalcdep.2016.08.001.
  • Cooper ZD, Comer SD, Haney M. Comparison of the analgesic effects of dronabinol and smoked marijuana in daily marijuana smokers. Neuropsychopharmacology. 2013;38:1984–92. doi:10.1038/npp.2013.97.
  • van Amerongen G, Kanhai K, Baakman AC, Heuberger J, Klaassen E, Beumer TL, Strijers RL, Killestein J, van Gerven J, Cohen A, et al. Effects on spasticity and neuropathic pain of an oral formulation of Δ9-tetrahydrocannabinol in patients withprogressive multiple sclerosis. Clin Ther. 2017. February 2017. doi:10.1016/j.clinthera.2017.01.016.
  • Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Potts R, Fallon MT. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symptom Manage. 2010;39:167–79. doi:10.1016/j.jpainsymman.2009.06.008.
  • Portenoy RK, Ganae-Motan ED, Allende S, Yanagihara R, Shaiova L, Weinstein S, McQuade R, Wright S, Fallon MT. Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J Pain. 2012;13:438–49.
  • Wade DT, Robson P, House H, Makela P, Aram J. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin Rehabil. 2003;17:21–29. doi:10.1191/0269215503cr581oa.
  • Corey-Bloom J, Wolfson T, Gamst A, Jin S, Marcotte TD, Bentley H, Gouaux B. Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial. Can Med Assoc J. 2012;184:1143–50.
  • Wallace MS, Marcotte TD, Umlauf A, Gouaux B, Atkinson JH. Efficacy of inhaled cannabis on painful diabetic neuropathy. J Pain. 2015;16:616–27. doi:10.1016/j.jpain.2015.03.008.
  • Wallace M, Schulteis G, Atkinson JH, Wolfson T, Lazzaretto D, Bentley H, Gouaux B, Abramson I. Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers. Anesthesiology. 2007;107:785–96. doi:10.1097/01.anes.0000286986.92475.b7.
  • Ellis RJ, Toperoff W, Vaida F, van Den Brande G, Gonzales J, Gouaux B, Bentley H, Atkinson JH. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology. 2009;34:672–80. doi:10.1038/npp.2008.120.
  • Abrams DI, Vizoso HP, Shade SB, Jay C, Kelly ME, Benowitz NL. Vaporization as a smokeless cannabis delivery system: a pilot study. Clin Pharmacol Ther. 2007;82:572–78. doi:10.1038/sj.clpt.6100200.
  • Berman JS, Symonds C, Birch R. 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;112:299–306. doi:10.1016/j.pain.2004.09.013.
  • Lynch ME, Cesar-Rittenberg P, Hohmann AG. A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. J Pain Symptom Manage. 2014;47:166–73. doi:10.1016/j.jpainsymman.2013.02.018.
  • Selvarajah D, Gandhi R, Emery CJ, Tesfaye S. 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;33:128–30. doi:10.2337/dc09-1029.
  • Serpell M, Ratcliffe S, Hovorka J, Schofield M, Taylor L, Lauder H, Ehler E. A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment: efficacy of THC/CBD spray in peripheral neuropathic pain. Eur J Pain. 2014;18:999–1012. doi:10.1002/ejp.2014.18.issue-7.
  • Conte A, Bettolo CM, Onesti E, Frasca V, Iacovelli E, Gilio F, Giacomelli E, Gabriele M, Aragona M, Tomassini V, et al. Cannabinoid-induced effects on the nociceptive system: a neurophysiological study in patients with secondary progressive multiple sclerosis. Eur J Pain. 2009;13:472–77. doi:10.1016/j.ejpain.2008.05.014.
  • Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A, Thompson A. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. The Lancet. 2003;362:1517–26. doi:10.1016/S0140-6736(03)14738-1.
  • Zajicek JP, Hobart JC, Slade A, Barnes D, Mattison PG, on behalf of the MUSEC Research Group. Multiple Sclerosis and Extract of Cannabis: results of the MUSEC trial. J Neurol Neurosurg Psychiatry. 2012;83:1125–1132.
  • Collin C, Ehler E, Waberzinek G, Alsindi Z, Davies P, Powell K, Notcutt W, O’Leary C, Ratcliffe S, Nováková I, et al. A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis. Neurol Res. 2010;32:451–59. doi:10.1179/016164109X12590518685660.
  • Langford RM, Mares J, Novotna A, Vachova M, Novakova I, Notcutt W, Ratcliffe S. 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. J Neurol. 2013;260:984–97.
  • Fallon MT, Albert Lux E, McQuade R, Rossetti S, Sanchez R, Sun W, Wright S, Lichtman AH, Kornyeyeva E. Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo-controlled phase 3 studies. Br J Pain. 2017;11:119–33. doi:10.1177/2049463717710042.
  • Lichtman AH, Lux EA, McQuade R, Rossetti S, Sanchez R, Sun W, Wright S, Kornyeyeva E, Fallon MT. Results of a double-blind, randomized, placebo-controlled study of nabiximols oromucosal spray as an adjunctive therapy in advanced cancer patients with chronic uncontrolled pain. J Pain Symptom Manage. 2018;55:179–188.e1. doi:10.1016/j.jpainsymman.2017.09.001.
  • Ware MA, Wang T, Shapiro S, Robinson A, Ducruet T, Huynh T, Gamsa A, Bennett GJ, Collet J-P. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. Can Med Assoc J. 2010;182:E694–E701. doi:10.1503/cmaj.091414.
  • de Vries M, van Rijckevorsel DCM, Vissers KCP, Wilder-Smith OHG, van Goor H. Tetrahydrocannabinol does not reduce pain in patients with chronic abdominal pain in a phase 2 placebo-controlled study. Clin Gastroenterol Hepatol. 2017;15:1079–1086.e4. doi:10.1016/j.cgh.2016.09.147.
  • Blake DR, Robson P, Ho M, Jubb RW, McCabe CS. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatol Oxf Engl. 2006;45:50–52. doi:10.1093/rheumatology/kei183.
  • Buggy DJ, Toogood L, Maric S, Sharpe P, Lambert DG, Rowbotham DJ. Lack of analgesic efficacy of oral delta-9-tetrahydrocannabinol in postoperative pain. Pain. 2003;106:169–72. doi:10.1016/S0304-3959(03)00331-2.
  • Lee MC, Ploner M, Wiech K, Bingel U, Wanigasekera V, Brooks J, Menon DK, Tracey I. Amygdala activity contributes to the dissociative effect of cannabis on pain perception. Pain. 2013;154:124–34. doi:10.1016/j.pain.2012.09.017.
  • Kraft B, Frickey NA, Kaufmann RM, Reif M, Frey R, Gustorff B, Kress HG. Lack of Analgesia by oral standardized cannabis extract on acute inflammatory pain and hyperalgesia in volunteers. Anesthesiology. 2008;109:101–10. doi:10.1097/ALN.0b013e31817881e1.
  • Walter C, Oertel BG, Felden L, Kell CA, Nöth U, Vermehren J, Kaiser J, Deichmann R, Lötsch J. Brain mapping-based model of Δ9-tetrahydrocannabinol effects on connectivity in the pain matrix. Neuropsychopharmacology. 2016;41:1659–69. doi:10.1038/npp.2015.336.
  • Conley KM, Toledano AY, Apfelbaum JL, Zacny JP. Modulating effects of a cold water stimulus on opioid effects in volunteers. Psychopharmacology (Berl). 1997;131:313–20. doi:10.1007/s002130050298.
  • Webb J, Kamali F. Analgesic effects of lamotrigine and phenytoin on cold-induced pain: a crossover placebo-controlled study in healthy volunteers. Pain. 1998;76:357–63. doi:10.1016/S0304-3959(98)00068-2.
  • Kowalczyk WJ, Evans SM, Bisaga AM, Sullivan MA, Comer SD. Sex differences and hormonal influences on response to cold pressor pain in humans. J Pain. 2006;7:151–60. doi:10.1016/j.jpain.2005.10.004.
  • Compton P, Kehoe P, Sinha K, Torrington MA, Ling W. Gabapentin improves cold-pressor pain responses in methadone-maintained patients. Drug Alcohol Depend. 2010;109:213–19. doi:10.1016/j.drugalcdep.2010.01.006.
  • Desrosiers NA, Ramaekers JG, Chauchard E, Gorelick DA, Huestis MA. Smoked cannabis’ psychomotor and neurocognitive effects in occasional and frequent smokers. J Anal Toxicol. 2015;39:251–61. doi:10.1093/jat/bkv012.
  • Gruber SA, Sagar KA, Dahlgren MK, Gonenc A, Smith RT, Lambros AM, Cabrera KB, Lukas SE. The grass might be greener: medical marijuana patients exhibit altered brain activity and improved executive function after 3 months of treatment. Front Pharmacol. 2018;8. doi:10.3389/fphar.2017.00983.
  • Ward SJ, McAllister SD, Kawamura R, Murase R, Neelakantan H, Walker EA. Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT 1A receptors without diminishing nervous system function or chemotherapy efficacy: cannabidiol prevents chemotherapy neuropathic pain. Br J Pharmacol. 2014;171:636–45. doi:10.1111/bph.12439.
  • Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG. Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology (Berl). 1982;76:245–50. doi:10.1007/BF00432554.
  • Nicholson AN, Turner C, Stone BM, Robson PJ. Effect of Delta-9-tetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults. J Clin Psychopharmacol. 2004;24:305–13. doi:10.1097/01.jcp.0000125688.05091.8f.
  • Morgan CJA, Schafer G, Freeman TP, Curran HV. Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study. Br J Psychiatry. 2010;197:285–90. doi:10.1192/bjp.bp.110.077503.
  • Bhattacharyya S. Induction of psychosis byΔ9-tetrahydrocannabinol reflects modulation of prefrontal and striatal function during attentional salience processing. Arch Gen Psychiatry. 2012;69:27. doi:10.1001/archgenpsychiatry.2012.513.
  • Morgan CJA, Gardener C, Schafer G, Swan S, Demarchi C, Freeman TP, Warrington P, Rupasinghe I, Ramoutar A, Tan N, et al. Sub-chronic impact of cannabinoids in street cannabis on cognition, psychotic-like symptoms and psychological well-being. Psychol Med. 2012;42:391–400. doi:10.1017/S0033291711001322.
  • Englund A, Morrison PD, Nottage J, Hague D, Kane F, Bonaccorso S, Stone JM, Reichenberg A, Brenneisen R, Holt D, et al. Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. J Psychopharmacol (Oxf). 2013;27:19–27. doi:10.1177/0269881112460109.
  • Smart R, Caulkins JP, Kilmer B, Davenport S, Midgette G. Variation in cannabis potency and prices in a newly legal market: evidence from 30 million cannabis sales in Washington state: legal cannabis potency and price variation. Addiction. 2017;112:2167–77. doi:10.1111/add.13886.
  • Rog DJ, Nurmikko TJ, Young CA. Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial. Clin Ther. 2007;29:2068–79. doi:10.1016/j.clinthera.2007.09.013.
  • Wade DT, Makela PM, House H, Bateman C, Robson P. Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis. Mult Scler Houndmills Basingstoke Engl. 2006;12:639–45. doi:10.1177/1352458505070618.
  • Comer SD, Sullivan MA, Whittington RA, Vosburg SK, Kowalczyk WJ. Abuse liability of prescription opioids compared to heroin in morphine-maintained heroin abusers. Neuropsychopharmacology. 2008;33:1179–91. doi:10.1038/npp.2008.45.
  • Evoy KE, Morrison MD, Saklad SR. Abuse and misuse of pregabalin and gabapentin. Drugs. 2017;77:403–26. doi:10.1007/s40265-017-0731-3.
  • Mintzer MZ, Lanier RK, Lofwall MR, Bigelow GE, Strain EC. Effects of repeated tramadol and morphine administration on psychomotor and cognitive performance in opioid-dependent volunteers. Drug Alcohol Depend. 2010;111:265–68. doi:10.1016/j.drugalcdep.2010.05.002.
  • Salinsky MC, Binder LM, Oken BS, Storzbach D, Aron CR, Dodrill CB. Effects of gabapentin and carbamazepine on the EEG and cognition in healthy volunteers. Epilepsia. 2002;43:482–90. doi:10.1046/j.1528-1157.2002.22501.x.
  • Schoedel KA, Chen N, Hilliard A, White L, Stott C, Russo E, Wright S, Guy G, Romach MK, Sellers EM. A randomized, double-blind, placebo-controlled, crossover study to evaluate the subjective abuse potential and cognitive effects of nabiximols oromucosal spray in subjects with a history of recreational cannabis use: a study of the abuse potential of nabiximols. Hum Psychopharmacol Clin Exp.2011; n/a-n/a.
  • Arkell TR, Lintzeris N, Kevin RC, Ramaekers JG, Vandrey R, Irwin C, Haber PS, McGregor IS. Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition. Psychopharmacology (Berl). 2019;1. doi:10.1007/s00213-019-05246-8.
  • Perron BE, Holt KR, Yeagley E, Ilgen M. Mental health functioning and severity of cannabis withdrawal among medical cannabis users with chronic pain. Drug Alcohol Depend. 2019;194:401–09. doi:10.1016/j.drugalcdep.2018.09.029.
  • Serpell MG, Notcutt W, Collin C. Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis. J Neurol. 2013;260:285–95. doi:10.1007/s00415-012-6683-3.
  • Notcutt W, Langford R, Davies P, Ratcliffe S, Potts R. A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receiving long-term Sativex® (nabiximols). Mult Scler J. 2012;18:219–28. doi:10.1177/1352458511419700.

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