Acute effects of cannabinoids on addiction endophenotypes are moderated by genes encoding the CB1 receptor and FAAH enzyme

Journal article

Hindocha, Chandni, Freeman, Tom P., Schafer, Grainne, Gardner, Chelsea, Bloomfield, Michael A. P., Bramon, Elvira, Morgan, Celia J.A. and Curran, Helen Valerie. (2020). Acute effects of cannabinoids on addiction endophenotypes are moderated by genes encoding the CB1 receptor and FAAH enzyme. Addiction Biology. 25(3), pp. 1 - 11. https://doi.org/10.1111/adb.12762
AuthorsHindocha, Chandni, Freeman, Tom P., Schafer, Grainne, Gardner, Chelsea, Bloomfield, Michael A. P., Bramon, Elvira, Morgan, Celia J.A. and Curran, Helen Valerie
Abstract

Understanding genetic factors that contribute to cannabis use disorder (CUD) is important, but to date, findings have been equivocal. Single‐nucleotide polymorphisms (SNPs) in the cannabinoid receptor 1 gene (CNR1; rs1049353 and rs806378) and fatty acid amide hydrolase (FAAH) gene (rs324420) have been implicated in CUD. Their relationship to addiction endophenotypes such as cannabis‐related state satiety, the salience of appetitive cues, and craving after acute cannabinoid administration has not been investigated. Forty‐eight cannabis users participated in a double‐blind, placebo‐controlled, four‐way crossover experiment where they were administered treatments in a randomized order via vaporization: placebo, Δ9‐tetrahydrocannabinol (THC) (8 mg), THC + cannabidiol (THC + CBD) (8 + 16 mg), and CBD (16 mg). Cannabis‐related state satiety, appetitive cue salience (cannabis and food), and cannabis craving were assessed each day. Participants were genotyped for rs1049353, rs806378, and rs324420. Results indicated that CNR1 rs1049353 GG carriers showed increased state satiety after THC/THC + CBD administration in comparison with placebo and reduced the salience of appetitive cues after THC in comparison with CBD administration; A carriers did not vary on either of these measures indicative of a vulnerability to CUD. CNR1 rs806378 CC carriers showed greater salience to appetitive cues in comparison with T carriers, but there was no evidence for changes in state satiety. FAAH rs324420 A carriers showed greater bias to appetitive cues after THC, in comparison with CC carriers. FAAH CC carriers showed reduced bias after THC in comparison with CBD. No SNPs modulated craving. These findings identify candidate neurocognitive mechanisms through which endocannabinoid system genetics may influence vulnerability to CUD.

Keywordsaddiction; cannabis; CBD; craving; endophenotype; salience; THC
Year2020
JournalAddiction Biology
Journal citation25 (3), pp. 1 - 11
PublisherBlackwell Publishing Ltd
ISSN1355-6215
Digital Object Identifier (DOI)https://doi.org/10.1111/adb.12762
Scopus EID2-s2.0-85064645400
Page range1 - 11
Publisher's version
File Access Level
Controlled
Place of publicationUnited Kingdom
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Tom P. Freeman, Rebecca A. Pope, Matthew B. Wall, James A. Bisby, Maartje Luijten, Chandni Hindocha, Claire Mokrysz, Will Lawn, Abigail Moss, Michael A. P. Bloomfield, Celia J. A. Morgan, David J. Nutt and H. Valerie Curran. (2018). Cannabis Dampens the Effects of Music in Brain Regions Sensitive to Reward and Emotion. International Journal of Neuropsychopharmacology. 21(1), pp. 21-32. https://doi.org/10.1093/ijnp/pyx082
Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal
Chandni Hindocha, Tom P. Freeman, Meryem Grabsk, Jack B. Stroud, Holly Crudgington, Alan C. Davies, Ravi K. Das, William Lawn, Celia Morgan and H. Valerie Curran. (2018). Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal. Addiction. 113(9), pp. 1696-1705. https://doi.org/10.1111/add.14243
Amisulpride for very late-onset schizophrenia-like psychosis: The ATLAS three-arm RCT
Howard, Robert, Cort, Elizabeth, Bradley, Rosie, Harper, Emma, Kelly, Linda, Bentham, Peter, Ritchie, Craig, Reeves, Suzanne, Fawzi, Waleed, Livingston, Gill, Sommerlad, Andrew, Oomman, Sabu, Nazir, Ejaz, Nilforooshan, Ramin, Barber, Robert, Fox, Chris, Macharouthu, Ajay, Ramachandra, Pranathi, Pattan, Vivek, ... Gray, Richard. (2018). Amisulpride for very late-onset schizophrenia-like psychosis: The ATLAS three-arm RCT. Health Technology Assessment. 22(67), pp. 1 - 60. https://doi.org/10.3310/hta22670
Ketamine treatment for depression : Opportunities for clinical innovation and ethical foresight
Singh, Ilina, Morgan, Celia, Curran, Valerie, Nutt, David, Schlag, Anne and McShane, Rupert. (2017). Ketamine treatment for depression : Opportunities for clinical innovation and ethical foresight. The Lancet Psychiatry. 4(5), pp. 419-426. https://doi.org/10.1016/S2215-0366(17)30102-5
Anatomy of a Joint: Comparing Self-Reported and Actual Dose of Cannabis and Tobacco in a Joint, and How These Are Influenced by Controlled Acute Administration
Chandni Hindocha, Tom P. Freeman and H. Valerie Curran. (2017). Anatomy of a Joint: Comparing Self-Reported and Actual Dose of Cannabis and Tobacco in a Joint, and How These Are Influenced by Controlled Acute Administration. Cannabis and Cannabinoid Research. 2(1), pp. 217-223. https://doi.org/10.1089/can.2017.0024
Acute memory and psychotomimetic effects of cannabis and tobacco both 'joint' and individually: A placebo-controlled trial
Hindocha, Chandni, Freeman, T. P., Xia, J. X., Shaban, Natacha D. C. and Curran, Helen V.. (2017). Acute memory and psychotomimetic effects of cannabis and tobacco both 'joint' and individually: A placebo-controlled trial. Psychological Medicine. 47(15), pp. 2708 - 2719. https://doi.org/10.1017/S0033291717001222
Editorial : Reporting guidelines for psychopharmacology
Steckler, Thomas, Curran, H. Valerie, de Wit, Harriet, Howes, Oliver, Hoyer, Daniel, Lucki, Irwin, Miczek, Klaus A., Morrow, A. Leslie, Price, Lawrence H. and Robbins, Trevor W.. (2016). Editorial : Reporting guidelines for psychopharmacology. Psychopharmacology. 233(7), pp. 1131-1134. https://doi.org/10.1007/s00213-016-4252-7
AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers
Morgan, Celia J. A., Freeman, T. P., Powell, J. and Curran, Helen V.. (2016). AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers. Translational Psychiatry. 6(2), pp. 1 - 6. https://doi.org/10.1038/tp.2015.219
Deconstructing the nature of episodic foresight deficits associated with chronic opiate use
Mercuri, Kimberly, Terrett, Gill, Bailey, Phoebe E., Henry, Julie D., Curran, Helen Valerie and Rendell, Peter G.. (2016). Deconstructing the nature of episodic foresight deficits associated with chronic opiate use. British Journal of Clinical Psychology. 55(4), pp. 401 - 413. https://doi.org/10.1111/bjc.12110
Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males
Mokrysz, Claire, Freeman, Tom P., Korkki, S., Griffiths, K. and Curran, Helen V.. (2016). Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males. Translational Psychiatry. 6(11), pp. 1 - 10. https://doi.org/10.1038/tp.2016.225
LSD enhances the emotional response to music
Kaelen, M., Barrett, F. S., Roseman, L., Lorenz, R., Family, N., Bolstridge, M., Curran, Helen V., Feilding, A., Nutt, David J. and Carhart-Harris, R. L.. (2015). LSD enhances the emotional response to music. Psychopharmacology. 232(19), pp. 3607 - 3614. https://doi.org/10.1007/s00213-015-4014-y
Effects of immediate-release opioid on memory functioning: A randomized-controlled study in patients receiving sustained-release opioids
Kamboj, S. K., Conroy, L., Tookman, A., Carroll, E., Jones, L. and Curran, H.. (2014). Effects of immediate-release opioid on memory functioning: A randomized-controlled study in patients receiving sustained-release opioids. European Journal of Pain. 18(10), pp. 1376 - 1384. https://doi.org/10.1002/j.1532-2149.2014.498.x
Effects of ecstasy on cooperative behaviour and perception of trustworthiness: A naturalistic study
Stewart, L. H., Ferguson, B., Morgan, C. J. A., Swaboda, N., Jones, L., Fenton, R., Wall, M. B. and Curran, H.. (2014). Effects of ecstasy on cooperative behaviour and perception of trustworthiness: A naturalistic study. Journal of Psychopharmacology. 28(11), pp. 1001 - 1008. https://doi.org/10.1177/0269881114544775
Prospective memory impairment in long-term opiate users
Terrett, Gillian, McLennan, Skye, Henry, Julie, Biernacki, Kathryn, Mercuri, Kimberly, Curran, Valerie and Rendell, Peter. (2014). Prospective memory impairment in long-term opiate users. Psychopharmacology. 231(13), pp. 2623 - 2632. https://doi.org/10.1007/s00213-014-3432-6
Benzodiazepines: Risks and benefits. A reconsideration
Baldwin, David S., Aitchison, Katherine, Bateson, Alan, Curran, H. Valerie, Davies, Simon, Leonard, Brian, Nutt, David J., Stephens, David N. and Wilson, Sue. (2013). Benzodiazepines: Risks and benefits. A reconsideration. Journal of Psychopharmacology. 27(11), pp. 967 - 971. https://doi.org/10.1177/0269881113503509
Prospective memory and future event simulation in individuals with alcohol dependence
Griffiths, Alison, Hill, Robert, Morgan, Celia, Rendell, Peter Gregory, Karimi, Khashayar, Wanagaratne, Shamil and Curran, Valerie. (2012). Prospective memory and future event simulation in individuals with alcohol dependence. Addiction. 107(10), pp. 1809 - 1816. https://doi.org/10.1111/j.1360-0443.2012.03941.x
Neurocognitive function and schizophrenia-proneness in individuals dependent on ketamine, on high potency cannabis (skunk) or on cocaine
Morgan, Celia, Duffin, S., Hunt, S., Monaghan, L., Mason, O. and Curran, Helen. (2012). Neurocognitive function and schizophrenia-proneness in individuals dependent on ketamine, on high potency cannabis (skunk) or on cocaine. Pharmacopsychiatry. 45(7), pp. 269 - 274. https://doi.org/10.1055/s-0032-1306310