drugset / Trial / NCT06218056
Cannabidiol for Reducing Cigarette Use
Phase 2
Recruiting
120 enrolled
University of California, Los Angeles
Center For Medicinal Cannabis Research at UC San Diego Health · collab
RandomizedParallel-groupQuadruple-blindTreatment
Summary
The goal of this research is to evaluate the efficacy of cannabidiol (CBD) in reducing cigarette smoking. Although there are safe and effective treatments for smoking cessation, not everyone who attempts smoking cessation is successful, even with these treatments. Relapse rates are high, leaving a need for new approaches. Despite justification to evaluate CBD for this indication, human research on the topic is scant. Larger, more extended studies are warranted and essential. The investigators will recruit participants from CRI-Help, Inc., a substance abuse treatment program in North Hollywood, where residents who indicate the desire to stop smoking are prohibited from using other cannabis products which would affect recruitment. The aims of this study are: 1. Evaluate the effects of CBD on nicotine intake. 2. Exploratory Aims. Measure plasma concentrations of CBD, N-arachidonoyl-ethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG) at baseline and day 7. Participants who meet eligibility criteria will take part in a 56-day treatment phase during which they receive the study medication under supervision (CBD or placebo twice daily) and complete questionnaires on side effects, withdrawal, craving and mood symptoms. Blood, breath, and urine tests will also be performed throughout the study. Participants who complete the treatment will also be assessed at 1-month and 3-month follow up visits.
Timeline
- Start
- 2024-10-31
- Primary completion
- 2026-12-31
- Completion
- 2026-12-31
Publications
- Background Fusar-Poli P, Crippa JA, Bhattacharyya S, Borgwardt SJ, Allen P, Martin-Santos R, Seal M, Surguladze SA, O'Carrol C, Atakan Z, Zuardi AW, McGuire PK. Distinct effects of delta9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch Gen Psychiatry. 2009 Jan;66(1):95-105. doi: 10.1001/archgenpsychiatry.2008.519.
- Background Zuardi AW, Morais SL, Guimaraes FS, Mechoulam R. Antipsychotic effect of cannabidiol. J Clin Psychiatry. 1995 Oct;56(10):485-6. No abstract available.
- Background Zuardi AW, Crippa JA, Hallak JE, Moreira FA, Guimaraes FS. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Braz J Med Biol Res. 2006 Apr;39(4):421-9. doi: 10.1590/s0100-879x2006000400001. Epub 2006 Apr 3.
- Background Zuardi AW, Cosme RA, Graeff FG, Guimaraes FS. Effects of ipsapirone and cannabidiol on human experimental anxiety. J Psychopharmacol. 1993 Jan;7(1 Suppl):82-8. doi: 10.1177/026988119300700112.
- Background Zuardi AW. Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Braz J Psychiatry. 2008 Sep;30(3):271-80. doi: 10.1590/s1516-44462008000300015.
- Background Wu P, Wilson K, Dimoulas P, Mills EJ. Effectiveness of smoking cessation therapies: a systematic review and meta-analysis. BMC Public Health. 2006 Dec 11;6:300. doi: 10.1186/1471-2458-6-300.
- Background Wheless JW, Dlugos D, Miller I, Oh DA, Parikh N, Phillips S, Renfroe JB, Roberts CM, Saeed I, Sparagana SP, Yu J, Cilio MR; INS011-14-029 Study Investigators. Pharmacokinetics and Tolerability of Multiple Doses of Pharmaceutical-Grade Synthetic Cannabidiol in Pediatric Patients with Treatment-Resistant Epilepsy. CNS Drugs. 2019 Jun;33(6):593-604. doi: 10.1007/s40263-019-00624-4.
- Background Welty TE, Luebke A, Gidal BE. Cannabidiol: promise and pitfalls. Epilepsy Curr. 2014 Sep;14(5):250-2. doi: 10.5698/1535-7597-14.5.250.
- Background Wakeford AGP, Wetzell BB, Pomfrey RL, Clasen MM, Taylor WW, Hempel BJ, Riley AL. The effects of cannabidiol (CBD) on Delta(9)-tetrahydrocannabinol (THC) self-administration in male and female Long-Evans rats. Exp Clin Psychopharmacol. 2017 Aug;25(4):242-248. doi: 10.1037/pha0000135. Epub 2017 Jul 6.
- Background Spanagel R. Cannabinoids and the endocannabinoid system in reward processing and addiction: from mechanisms to interventions . Dialogues Clin Neurosci. 2020 Sep;22(3):241-250. doi: 10.31887/DCNS.2020.22.3/rspanagel.
- Background Smith LC, Tieu L, Suhandynata RT, Boomhower B, Hoffman M, Sepulveda Y, Carrette LLG, Momper JD, Fitzgerald RL, Hanham K, Dowling J, Kallupi M, George O. Cannabidiol reduces withdrawal symptoms in nicotine-dependent rats. Psychopharmacology (Berl). 2021 Aug;238(8):2201-2211. doi: 10.1007/s00213-021-05845-4. Epub 2021 Apr 28.
- Background Scheidweiler KB, Newmeyer MN, Barnes AJ, Huestis MA. Quantification of cannabinoids and their free and glucuronide metabolites in whole blood by disposable pipette extraction and liquid chromatography-tandem mass spectrometry. J Chromatogr A. 2016 Jul 1;1453:34-42. doi: 10.1016/j.chroma.2016.05.024. Epub 2016 May 7.
- Background Sasco AJ, Secretan MB, Straif K. Tobacco smoking and cancer: a brief review of recent epidemiological evidence. Lung Cancer. 2004 Aug;45 Suppl 2:S3-9. doi: 10.1016/j.lungcan.2004.07.998.
- Background Roslawski MJ, Remmel RP, Karanam A, Leppik IE, Marino SE, Birnbaum AK. Simultaneous Quantification of 13 Cannabinoids and Metabolites in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry in Adult Epilepsy Patients. Ther Drug Monit. 2019 Jun;41(3):357-370. doi: 10.1097/FTD.0000000000000583.
- Background Rosen LJ, Galili T, Kott J, Goodman M, Freedman LS. Diminishing benefit of smoking cessation medications during the first year: a meta-analysis of randomized controlled trials. Addiction. 2018 May;113(5):805-816. doi: 10.1111/add.14134. Epub 2018 Jan 29.
- Background Perucca E, Bialer M. Critical Aspects Affecting Cannabidiol Oral Bioavailability and Metabolic Elimination, and Related Clinical Implications. CNS Drugs. 2020 Aug;34(8):795-800. doi: 10.1007/s40263-020-00741-5.
- Background Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008 Jan;153(2):199-215. doi: 10.1038/sj.bjp.0707442. Epub 2007 Sep 10.
- Background Paulus V, Billieux J, Benyamina A, Karila L. Cannabidiol in the context of substance use disorder treatment: A systematic review. Addict Behav. 2022 Sep;132:107360. doi: 10.1016/j.addbeh.2022.107360. Epub 2022 May 7.
- Background Notley C, Gentry S, Livingstone-Banks J, Bauld L, Perera R, Hartmann-Boyce J. Incentives for smoking cessation. Cochrane Database Syst Rev. 2019 Jul 17;7(7):CD004307. doi: 10.1002/14651858.CD004307.pub6.
- Background Morgan CJ, Das RK, Joye A, Curran HV, Kamboj SK. Cannabidiol reduces cigarette consumption in tobacco smokers: preliminary findings. Addict Behav. 2013 Sep;38(9):2433-6. doi: 10.1016/j.addbeh.2013.03.011. Epub 2013 Apr 1.
- Background Mitrirattanakul S, Ramakul N, Guerrero AV, Matsuka Y, Ono T, Iwase H, Mackie K, Faull KF, Spigelman I. Site-specific increases in peripheral cannabinoid receptors and their endogenous ligands in a model of neuropathic pain. Pain. 2006 Dec 15;126(1-3):102-14. doi: 10.1016/j.pain.2006.06.016. Epub 2006 Jul 14.
- Background McPherson SM, Burduli E, Smith CL, Herron J, Oluwoye O, Hirchak K, Orr MF, McDonell MG, Roll JM. A review of contingency management for the treatment of substance-use disorders: adaptation for underserved populations, use of experimental technologies, and personalized optimization strategies. Subst Abuse Rehabil. 2018 Aug 13;9:43-57. doi: 10.2147/SAR.S138439. eCollection 2018.
- Background Maione S, Piscitelli F, Gatta L, Vita D, De Petrocellis L, Palazzo E, de Novellis V, Di Marzo V. Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action. Br J Pharmacol. 2011 Feb;162(3):584-96. doi: 10.1111/j.1476-5381.2010.01063.x.
- Background Leweke FM, Piomelli D, Pahlisch F, Muhl D, Gerth CW, Hoyer C, Klosterkotter J, Hellmich M, Koethe D. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012 Mar 20;2(3):e94. doi: 10.1038/tp.2012.15.
- Background Le Foll B, Forget B, Aubin HJ, Goldberg SR. Blocking cannabinoid CB1 receptors for the treatment of nicotine dependence: insights from pre-clinical and clinical studies. Addict Biol. 2008 Jun;13(2):239-52. doi: 10.1111/j.1369-1600.2008.00113.x.
- Background Kendzor DE, Businelle MS, Poonawalla IB, Cuate EL, Kesh A, Rios DM, Ma P, Balis DS. Financial incentives for abstinence among socioeconomically disadvantaged individuals in smoking cessation treatment. Am J Public Health. 2015 Jun;105(6):1198-205. doi: 10.2105/AJPH.2014.302102. Epub 2014 Nov 13.
- Background Kotlinska-Lemieszek A, Klepstad P, Haugen DF. Clinically significant drug-drug interactions involving opioid analgesics used for pain treatment in patients with cancer: a systematic review. Drug Des Devel Ther. 2015 Sep 16;9:5255-67. doi: 10.2147/DDDT.S86983. eCollection 2015.
- Background Kathmann M, Flau K, Redmer A, Trankle C, Schlicker E. Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors. Naunyn Schmiedebergs Arch Pharmacol. 2006 Feb;372(5):354-61. doi: 10.1007/s00210-006-0033-x. Epub 2006 Feb 18.
- Background Karimi-Haghighi S, Razavi Y, Iezzi D, Scheyer AF, Manzoni O, Haghparast A. Cannabidiol and substance use disorder: Dream or reality. Neuropharmacology. 2022 Apr 1;207:108948. doi: 10.1016/j.neuropharm.2022.108948. Epub 2022 Jan 13.
- Background Jordan CJ, Xi ZX. Discovery and development of varenicline for smoking cessation. Expert Opin Drug Discov. 2018 Jul;13(7):671-683. doi: 10.1080/17460441.2018.1458090. Epub 2018 Mar 28.
- Background Hughes JR, Keely J, Naud S. Shape of the relapse curve and long-term abstinence among untreated smokers. Addiction. 2004 Jan;99(1):29-38. doi: 10.1111/j.1360-0443.2004.00540.x.
- Background Hindocha C, Freeman TP, Grabski M, Crudgington H, Davies AC, Stroud JB, Das RK, Lawn W, Morgan CJA, Curran HV. The effects of cannabidiol on impulsivity and memory during abstinence in cigarette dependent smokers. Sci Rep. 2018 May 15;8(1):7568. doi: 10.1038/s41598-018-25846-2.
- Background Hindocha C, Freeman TP, Grabski M, Stroud JB, Crudgington H, Davies AC, Das RK, Lawn W, Morgan CJA, Curran HV. Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal. Addiction. 2018 May 1;113(9):1696-705. doi: 10.1111/add.14243. Online ahead of print.
- Background Halperin AC, McAfee TA, Jack LM, Catz SL, McClure JB, Deprey TM, Richards J, Zbikowski SM, Swan GE. Impact of symptoms experienced by varenicline users on tobacco treatment in a real world setting. J Subst Abuse Treat. 2009 Jun;36(4):428-34. doi: 10.1016/j.jsat.2008.09.001. Epub 2008 Nov 11.
- Background Garcia-Gomez L, Hernandez-Perez A, Noe-Diaz V, Riesco-Miranda JA, Jimenez-Ruiz C. SMOKING CESSATION TREATMENTS: CURRENT PSYCHOLOGICAL AND PHARMACOLOGICAL OPTIONS. Rev Invest Clin. 2019;71(1):7-16. doi: 10.24875/RIC.18002629.
- Background Gamaleddin IH, Trigo JM, Gueye AB, Zvonok A, Makriyannis A, Goldberg SR, Le Foll B. Role of the endogenous cannabinoid system in nicotine addiction: novel insights. Front Psychiatry. 2015 Mar 25;6:41. doi: 10.3389/fpsyt.2015.00041. eCollection 2015.
- Background Elmes MW, Kaczocha M, Berger WT, Leung K, Ralph BP, Wang L, Sweeney JM, Miyauchi JT, Tsirka SE, Ojima I, Deutsch DG. Fatty acid-binding proteins (FABPs) are intracellular carriers for Delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD). J Biol Chem. 2015 Apr 3;290(14):8711-21. doi: 10.1074/jbc.M114.618447. Epub 2015 Feb 9.
- Background Gomez-Coronado N, Walker AJ, Berk M, Dodd S. Current and Emerging Pharmacotherapies for Cessation of Tobacco Smoking. Pharmacotherapy. 2018 Feb;38(2):235-258. doi: 10.1002/phar.2073. Epub 2018 Jan 29.
- Background Dos Santos RG, Hallak JEC, Crippa JAS. Neuropharmacological Effects of the Main Phytocannabinoids: A Narrative Review. Adv Exp Med Biol. 2021;1264:29-45. doi: 10.1007/978-3-030-57369-0_3.
- Background Devinsky O, Marsh E, Friedman D, Thiele E, Laux L, Sullivan J, Miller I, Flamini R, Wilfong A, Filloux F, Wong M, Tilton N, Bruno P, Bluvstein J, Hedlund J, Kamens R, Maclean J, Nangia S, Singhal NS, Wilson CA, Patel A, Cilio MR. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016 Mar;15(3):270-8. doi: 10.1016/S1474-4422(15)00379-8. Epub 2015 Dec 24.
- Background Consroe P, Laguna J, Allender J, Snider S, Stern L, Sandyk R, Kennedy K, Schram K. Controlled clinical trial of cannabidiol in Huntington's disease. Pharmacol Biochem Behav. 1991 Nov;40(3):701-8. doi: 10.1016/0091-3057(91)90386-g.
- Background Businelle MS, Kendzor DE, Kesh A, Cuate EL, Poonawalla IB, Reitzel LR, Okuyemi KS, Wetter DW. Small financial incentives increase smoking cessation in homeless smokers: a pilot study. Addict Behav. 2014 Mar;39(3):717-20. doi: 10.1016/j.addbeh.2013.11.017. Epub 2013 Nov 27.
- Background Burggren AC, Shirazi A, Ginder N, London ED. Cannabis effects on brain structure, function, and cognition: considerations for medical uses of cannabis and its derivatives. Am J Drug Alcohol Abuse. 2019;45(6):563-579. doi: 10.1080/00952990.2019.1634086. Epub 2019 Jul 31.
- Background Borgwardt SJ, Allen P, Bhattacharyya S, Fusar-Poli P, Crippa JA, Seal ML, Fraccaro V, Atakan Z, Martin-Santos R, O'Carroll C, Rubia K, McGuire PK. Neural basis of Delta-9-tetrahydrocannabinol and cannabidiol: effects during response inhibition. Biol Psychiatry. 2008 Dec 1;64(11):966-73. doi: 10.1016/j.biopsych.2008.05.011. Epub 2008 Jun 27.
- Background Bergamaschi MM, Queiroz RH, Zuardi AW, Crippa JA. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr Drug Saf. 2011 Sep 1;6(4):237-49. doi: 10.2174/157488611798280924.
- Background Baker TB, Piper ME, Smith SS, Bolt DM, Stein JH, Fiore MC. Effects of Combined Varenicline With Nicotine Patch and of Extended Treatment Duration on Smoking Cessation: A Randomized Clinical Trial. JAMA. 2021 Oct 19;326(15):1485-1493. doi: 10.1001/jama.2021.15333.
- Background Ananda Scientific (2021). ATL-5 Investigator's Brochure.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Cannabidiol | Other / unclassified | 800 mg | Oral |