Abstract
Endocannabinoid signaling is implicated in an array of psychopathologies ranging from anxiety to psychosis and addiction. In recent years, radiotracers targeting the endocannabinoid system have been used in positron emission tomography (PET) studies to determine whether individuals with psychiatric disorders display altered endocannabinoid signaling. We comprehensively reviewed PET studies examining differences in endocannabinoid signaling between individuals with psychiatric illness and healthy controls. Published studies evaluated individuals with five psychiatric disorders: cannabis use disorder, alcohol use disorder, schizophrenia, post-traumatic stress disorder, and eating disorders. Most studies employed radiotracers targeting cannabinoid receptor 1 (CB1). Cannabis users consistently demonstrated decreased CB1 binding compared to controls, with normalization following short periods of abstinence. Findings in those with alcohol use disorder and schizophrenia were less consistent, with some studies demonstrating increased CB1 binding and others demonstrating decreased CB1 binding. Evidence of aberrant CB1 binding was also found in individuals with anorexia nervosa and post-traumatic stress disorder, but limited data have been published to date. Thus, existing evidence suggests that alterations in endocannabinoid signaling are present in a range of psychiatric disorders. Although recent efforts have largely focused on evaluating CB1 binding, the synthesis of new radiotracers targeting enzymes involved in endocannabinoid degradation, such as fatty acid amide hydrolase, will allow for other facets of endocannabinoid signaling to be evaluated in future studies.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Glass M, Dragunow M, Faull RL. Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience. 1997;77:299–318.
Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, et al. Cannabinoid receptor localization in brain. Proc Natl Acad Sci U S A. 1990;87:1932–6.
Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, et al. The endogenous cannabinoid system controls extinction of aversive memories. Nature. 2002;418:530–4.
Hill MN, McLaughlin RJ, Pan B, Fitzgerald ML, Roberts CJ, Lee TT, et al. Recruitment of prefrontal cortical endocannabinoid signaling by glucocorticoids contributes to termination of the stress response. J Neurosci. 2011;31:10506–15.
Zangen A, Solinas M, Ikemoto S, Goldberg SR, Wise RA. Two brain sites for cannabinoid reward. J Neurosci. 2006;26:4901–7.
Le Foll B, Goldberg SR. Cannabinoid CB1 receptor antagonists as promising new medications for drug dependence. J Pharmacol Exp Ther. 2005;312:875–83.
Hungund BL, Szakall I, Adam A, Basavarajappa BS, Vadasz C. Cannabinoid CB1 receptor knockout mice exhibit markedly reduced voluntary alcohol consumption and lack alcohol-induced dopamine release in the nucleus accumbens. J Neurochem. 2003;84:698–704.
Cohen C, Perrault G, Voltz C, Steinberg R, Soubrie P. SR141716, a central cannabinoid (CB(1)) receptor antagonist, blocks the motivational and dopamine-releasing effects of nicotine in rats. Behav Pharmacol. 2002;13:451–63.
Hillard CJ, Liu QS. Endocannabinoid signaling in the etiology and treatment of major depressive illness. Curr Pharm Des. 2014;20:3795–811.
Patel S, Hill MN, Cheer JF, Wotjak CT, Holmes A. The endocannabinoid system as a target for novel anxiolytic drugs. Neurosci Biobehav Rev. 2017;76:56–66.
Sloan ME, Gowin JL, Ramchandani VA, Hurd YL, Le Foll B. The endocannabinoid system as a target for addiction treatment: Trials and tribulations. Neuropharmacology. 2017;124:73–83.
Goffin K, Van Paesschen W, Van Laere K. In vivo activation of endocannabinoid system in temporal lobe epilepsy with hippocampal sclerosis. Brain. 2011;134:1033–40.
Van der Schueren BJ, Van Laere K, Gerard N, Bormans G, De Hoon JN. Interictal type 1 cannabinoid receptor binding is increased in female migraine patients. Headache. 2012;52:433–40.
Ahmad R, Goffin K, Van den Stock J, De Winter FL, Cleeren E, Bormans G, et al. In vivo type 1 cannabinoid receptor availability in Alzheimer’s disease. Eur Neuropsychopharmacol. 2014;24:242–50.
Van Laere K, Casteels C, Lunskens S, Goffin K, Grachev ID, Bormans G, et al. Regional changes in type 1 cannabinoid receptor availability in Parkinson’s disease in vivo. Neurobiol Aging. 2012;33:e1–8.
Horti AG, Van Laere K. Development of radioligands for in vivo imaging of type 1 cannabinoid receptors (CB1) in human brain. Curr Pharm Des. 2008;14:3363–83.
Hirvonen J. In vivo imaging of the cannabinoid CB1 receptor with positron emission tomography. Clin Pharmacol Ther. 2015;97:565–7.
Heurling K, Leuzy A, Jonasson M, Frick A, Zimmer ER, Nordberg A, et al. Quantitative positron emission tomography in brain research. Brain Res. 2017;1670:220–34.
Terry GE, Hirvonen J, Liow JS, Zoghbi SS, Gladding R, Tauscher JT, et al. Imaging and quantitation of cannabinoid CB1 receptors in human and monkey brains using (18)F-labeled inverse agonist radioligands. J Nucl Med. 2010;51:112–20.
Burns HD, Van Laere K, Sanabria-Bohorquez S, Hamill TG, Bormans G, Eng WS, et al. [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor. Proc Natl Acad Sci U S A. 2007;104:9800–5.
Normandin MD, Zheng MQ, Lin KS, Mason NS, Lin SF, Ropchan J, et al. Imaging the cannabinoid CB1 receptor in humans with [11C]OMAR: assessment of kinetic analysis methods, test-retest reproducibility, and gender differences. J Cereb Blood Flow Metab. 2015;35:1313–22.
Wong DF, Kuwabara H, Horti AG, Raymont V, Brasic J, Guevara M, et al. Quantification of cerebral cannabinoid receptors subtype 1 (CB1) in healthy subjects and schizophrenia by the novel PET radioligand [11C]OMAR. Neuroimage. 2010;52:1505–13.
Terry GE, Liow JS, Zoghbi SS, Hirvonen J, Farris AG, Lerner A, et al. Quantitation of cannabinoid CB1 receptors in healthy human brain using positron emission tomography and an inverse agonist radioligand. Neuroimage. 2009;48:362–70.
Wilson AA, Garcia A, Parkes J, Houle S, Tong J, Vasdev N. [11C]CURB: evaluation of a novel radiotracer for imaging fatty acid amide hydrolase by positron emission tomography. Nucl Med Biol. 2011;38:247–53.
Boileau I, Rusjan PM, Williams B, Mansouri E, Mizrahi R, De Luca V, et al. Blocking of fatty acid amide hydrolase activity with PF-04457845 in human brain: a positron emission tomography study with the novel radioligand [(11)C]CURB. J Cereb Blood Flow Metab. 2015;35:1827–35.
Dincheva I, Drysdale AT, Hartley CA, Johnson DC, Jing D, King EC, et al. FAAH genetic variation enhances fronto-amygdala function in mouse and human. Nat Commun. 2015;6:6395.
Chiang KP, Gerber AL, Sipe JC, Cravatt BF. Reduced cellular expression and activity of the P129T mutant of human fatty acid amide hydrolase: evidence for a link between defects in the endocannabinoid system and problem drug use. Hum Mol Genet. 2004;13:2113–9.
Boileau I, Tyndale RF, Williams B, Mansouri E, Westwood DJ, Le Foll B, et al. The fatty acid amide hydrolase C385A variant affects brain binding of the positron emission tomography tracer [11C]CURB. J Cereb Blood Flow Metab. 2015;35:1237–40.
Vandrey R, Stitzer ML, Mintzer MZ, Huestis MA, Murray JA, Lee D. The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users. Drug Alcohol Depend. 2013;128:64–70.
Trigo JM, Lagzdins D, Rehm J, Selby P, Gamaleddin I, Fischer B, et al. Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings. Drug Alcohol Depend. 2016;161:298–306.
Haney M, Cooper ZD, Bedi G, Vosburg SK, Comer SD, Foltin RW. Nabilone decreases marijuana withdrawal and a laboratory measure of marijuana relapse. Neuropsychopharmacology. 2013;38:1557–65.
Allsop DJ, Copeland J, Lintzeris N, Dunlop AJ, Montebello M, Sadler C, et al. Nabiximols as an agonist replacement therapy during cannabis withdrawal: a randomized clinical trial. JAMA Psychiatry. 2014;71:281–91.
Levin FR, Mariani JJ, Brooks DJ, Pavlicova M, Cheng W, Nunes EV. Dronabinol for the treatment of cannabis dependence: a randomized, double-blind, placebo-controlled trial. Drug Alcohol Depend. 2011;116:142–50.
Levin FR, Mariani JJ, Pavlicova M, Brooks D, Glass A, Mahony A, et al. Dronabinol and lofexidine for cannabis use disorder: a randomized, double-blind, placebo-controlled trial. Drug Alcohol Depend. 2016;159:53–60.
Trigo JM, Soliman A, Quilty LC, Fischer B, Rehm J, Selby P, et al. Nabiximols combined with motivational enhancement/cognitive behavioral therapy for the treatment of cannabis dependence: a pilot randomized clinical trial. PLoS ONE. 2018;13:e0190768.
Schindler CW, Redhi GH, Vemuri K, Makriyannis A, Le Foll B, Bergman J, et al. Blockade of nicotine and cannabinoid reinforcement and relapse by a cannabinoid CB1-receptor neutral antagonist AM4113 and inverse agonist rimonabant in squirrel monkeys. Neuropsychopharmacology. 2016;41:2283–93.
Justinova Z, Munzar P, Panlilio LV, Yasar S, Redhi GH, Tanda G, et al. Blockade of THC-seeking behavior and relapse in monkeys by the cannabinoid CB(1)-receptor antagonist rimonabant. Neuropsychopharmacology. 2008;33:2870–7.
Marshall K,Gowing L,Ali R,Le Foll B. Pharmacotherapies for cannabis dependence. Cochrane Database Syst Rev. 2014;(12): CD008940.
Hirvonen J, Goodwin RS, Li CT, Terry GE, Zoghbi SS, Morse C, et al. Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers. Mol Psychiatry. 2012;17:642–9.
D’Souza DC, Cortes-Briones JA, Ranganathan M, Thurnauer H, Creatura G, Surti T, et al. Rapid changes in CB1 receptor availability in cannabis dependent males after abstinence from cannabis. Biol Psychiatry Cogn Neurosci Neuroimaging. 2016;1:60–7.
Ceccarini J, Kuepper R, Kemels D, van Os J, Henquet C, Van Laere K. [18F]MK-9470 PET measurement of cannabinoid CB1 receptor availability in chronic cannabis users. Addict Biol. 2015;20:357–67.
Boileau I, Mansouri E, Williams B, Le Foll B, Rusjan P, Mizrahi R, et al. Fatty acid amide hydrolase binding in brain of cannabis users: imaging with the novel radiotracer [(11)C]CURB. Biol Psychiatry. 2016;80:691–701.
Morgan CJ, Page E, Schaefer C, Chatten K, Manocha A, Gulati S, et al. Cerebrospinal fluid anandamide levels, cannabis use and psychotic-like symptoms. Br J Psychiatry. 2013;202:381–2.
Sloan ME, Gowin JL, Yan J, Schwandt ML, Spagnolo PA, Sun H, et al. Severity of alcohol dependence is associated with the fatty acid amide hydrolase Pro129Thr missense variant. Addict Biol.2018;23:474–84.
Colombo G, Serra S, Brunetti G, Gomez R, Melis S, Vacca G, et al. Stimulation of voluntary ethanol intake by cannabinoid receptor agonists in ethanol-preferring sP rats. Psychopharmacology (Berl). 2002;159:181–7.
Colombo G, Agabio R, Fa M, Guano L, Lobina C, Loche A, et al. Reduction of voluntary ethanol intake in ethanol-preferring sP rats by the cannabinoid antagonist SR-141716. Alcohol Alcohol. 1998;33:126–30.
Arnone M, Maruani J, Chaperon F, Thiebot MH, Poncelet M, Soubrie P, et al. Selective inhibition of sucrose and ethanol intake by SR 141716, an antagonist of central cannabinoid (CB1) receptors. Psychopharmacology (Berl). 1997;132:104–6.
Femenia T, Garcia-Gutierrez MS, Manzanares J. CB1 receptor blockade decreases ethanol intake and associated neurochemical changes in fawn-hooded rats. Alcohol Clin Exp Res. 2010;34:131–41.
George DT, Herion DW, Jones CL, Phillips MJ, Hersh J, Hill D, et al. Rimonabant (SR141716) has no effect on alcohol self-administration or endocrine measures in nontreatment-seeking heavy alcohol drinkers. Psychopharmacology (Berl). 2010;208:37–44.
Soyka M, Koller G, Schmidt P, Lesch OM, Leweke M, Fehr C, et al. Cannabinoid receptor 1 blocker rimonabant (SR 141716) for treatment of alcohol dependence: results from a placebo-controlled, double-blind trial. J Clin Psychopharmacol. 2008;28:317–24.
Neumeister A, Normandin MD, Murrough JW, Henry S, Bailey CR, Luckenbaugh DA, et al. Positron emission tomography shows elevated cannabinoid CB1 receptor binding in men with alcohol dependence. Alcohol Clin Exp Res. 2012;36:2104–9.
Hirvonen J, Zanotti-Fregonara P, Umhau JC, George DT, Rallis-Frutos D, Lyoo CH, et al. Reduced cannabinoid CB1 receptor binding in alcohol dependence measured with positron emission tomography. Mol Psychiatry. 2013;18:916–21.
Ceccarini J, Hompes T, Verhaeghen A, Casteels C, Peuskens H, Bormans G, et al. Changes in cerebral CB1 receptor availability after acute and chronic alcohol abuse and monitored abstinence. J Neurosci. 2014;34:2822–31.
Marconi A, Di Forti M, Lewis CM, Murray RM, Vassos E. Meta-analysis of the association between the level of cannabis use and risk of psychosis. Schizophr Bull. 2016;42:1262–9.
Di Forti M, Marconi A, Carra E, Fraietta S, Trotta A, Bonomo M, et al. Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study. Lancet. Psychiatry. 2015;2:233–8.
Linszen DH, Dingemans PM, Lenior ME. Cannabis abuse and the course of recent-onset schizophrenic disorders. Arch Gen Psychiatry. 1994;51:273–9.
Manrique-Garcia E, Zammit S, Dalman C, Hemmingsson T, Andreasson S, Allebeck P. Prognosis of schizophrenia in persons with and without a history of cannabis use. Psychol Med. 2014;44:2513–21.
D’Souza DC, Perry E, MacDougall L, Ammerman Y, Cooper T, Wu YT, et al. The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology. 2004;29:1558–72.
Cortes-Briones JA, Cahill JD, Skosnik PD, Mathalon DH, Williams A, Sewell RA, et al. The psychosis-like effects of Delta(9)-tetrahydrocannabinol are associated with increased cortical noise in healthy humans. Biol Psychiatry. 2015;78:805–13.
Laprairie RB, Bagher AM, Kelly ME, Denovan-Wright EM. Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br J Pharmacol. 2015;172:4790–805.
Leweke FM, Piomelli D, Pahlisch F, Muhl D, Gerth CW, Hoyer C, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012;2:e94.
McGuire P, Robson P, Cubala WJ, Vasile D, Morrison PD, Barron R, et al. Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: a multicenter randomized controlled trial.Am J Psychiatry. 2018;175:225–31.
Meltzer HY, Arvanitis L, Bauer D, Rein W. Placebo-controlled evaluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorder. Am J Psychiatry. 2004;161:975–84.
Ceccarini J, De Hert M, Van Winkel R, Peuskens J, Bormans G, Kranaster L, et al. Increased ventral striatal CB1 receptor binding is related to negative symptoms in drug-free patients with schizophrenia. Neuroimage. 2013;79:304–12.
Ranganathan M, Cortes-Briones J, Radhakrishnan R, Thurnauer H, Planeta B, Skosnik P, et al. Reduced brain cannabinoid receptor availability in schizophrenia. Biol Psychiatry. 2016;79:997–1005.
De Marchi N, De Petrocellis L, Orlando P, Daniele F, Fezza F, Di Marzo V. Endocannabinoid signalling in the blood of patients with schizophrenia. Lipids Health Dis. 2003;2:5.
Leweke FM, Giuffrida A, Wurster U, Emrich HM, Piomelli D. Elevated endogenous cannabinoids in schizophrenia. Neuroreport. 1999;10:1665–9.
Dlugos A, Childs E, Stuhr KL, Hillard CJ, de Wit H. Acute stress increases circulating anandamide and other N-acylethanolamines in healthy humans. Neuropsychopharmacology. 2012;37:2416–27.
Hill MN, Miller GE, Carrier EJ, Gorzalka BB, Hillard CJ. Circulating endocannabinoids and N-acyl ethanolamines are differentially regulated in major depression and following exposure to social stress. Psychoneuroendocrinology. 2009;34:1257–62.
Gunduz-Cinar O, MacPherson KP, Cinar R, Gamble-George J, Sugden K, Williams B, et al. Convergent translational evidence of a role for anandamide in amygdala-mediated fear extinction, threat processing and stress-reactivity. Mol Psychiatry. 2013;18:813–23.
Hariri AR, Gorka A, Hyde LW, Kimak M, Halder I, Ducci F, et al. Divergent effects of genetic variation in endocannabinoid signaling on human threat- and reward-related brain function. Biol Psychiatry. 2009;66:9–16.
Spagnolo PA, Ramchandani VA, Schwandt ML, Kwako LE, George DT, Mayo LM, et al. FAAH gene variation moderates stress response and symptom severity in patients with posttraumatic stress disorder and comorbid alcohol dependence. Alcohol Clin Exp Res. 2016;40:2426–34.
Hill MN, Bierer LM, Makotkine I, Golier JA, Galea S, McEwen BS, et al. Reductions in circulating endocannabinoid levels in individuals with post-traumatic stress disorder following exposure to the World Trade Center attacks. Psychoneuroendocrinology. 2013;38:2952–61.
Neumeister A, Normandin MD, Pietrzak RH, Piomelli D, Zheng MQ, Gujarro-Anton A, et al. Elevated brain cannabinoid CB1 receptor availability in post-traumatic 5stress disorder: a positron emission tomography study. Mol Psychiatry. 2013;18:1034–40.
Wilker S, Pfeiffer A, Elbert T, Ovuga E, Karabatsiakis A, Krumbholz A, et al. Endocannabinoid concentrations in hair are associated with PTSD symptom severity. Psychoneuroendocrinology. 2016;67:198–206.
Pietrzak RH, Huang Y, Corsi-Travali S, Zheng MQ, Lin SF, Henry S, et al. Cannabinoid type 1 receptor availability in the amygdala mediates threat processing in trauma survivors. Neuropsychopharmacology. 2014;39:2519–28.
Jetly R, Heber A, Fraser G, Boisvert D. The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: A preliminary randomized, double-blind, placebo-controlled cross-over design study. Psychoneuroendocrinology. 2015;51:585–8.
D’Souza DC, Ranganathan M. Medical marijuana: is the cart before the horse? JAMA. 2015;313:2431–2.
Steenkamp MM, Blessing EM, Galatzer-Levy IR, Hollahan LC, Anderson WT. Marijuana and other cannabinoids as a treatment for posttraumatic stress disorder: a literature review. Depress Anxiety. 2017;34:207–16.
Hasin DS, Kerridge BT, Saha TD, Huang B, Pickering R, Smith SM, et al. Prevalence and correlates of DSM-5 cannabis use disorder, 2012-2013: findings from the National Epidemiologic Survey on alcohol and related conditions-iii. Am J Psychiatry. 2016;173:588–99.
Haney M, Ward AS, Comer SD, Foltin RW, Fischman MW. Abstinence symptoms following smoked marijuana in humans. Psychopharmacology (Berl). 1999;141:395–404.
FDA. MARINOL (dronabinol) capsules, for oral use. 2017.
Le Strat Y, Le Foll B. Obesity and cannabis use: results from 2 representative national surveys. Am J Epidemiol. 2011;174:929–33.
Cluny NL, Keenan CM, Reimer RA, Le Foll B, Sharkey KA. Prevention of diet-induced obesity effects on body weight and gut microbiota in mice treated chronically with delta9-tetrahydrocannabinol. PLoS ONE. 2015;10:e0144270.
Le Foll B, Trigo JM, Sharkey KA, Le Strat Y. Cannabis and delta9-tetrahydrocannabinol (THC) for weight loss? Med Hypotheses. 2013;80:564–7.
Gatta-Cherifi B, Matias I, Vallee M, Tabarin A, Marsicano G, Piazza PV, et al. Simultaneous postprandial deregulation of the orexigenic endocannabinoid anandamide and the anorexigenic peptide YY in obesity. Int J Obes (Lond). 2012;36:880–5.
Di Marzo V, Verrijken A, Hakkarainen A, Petrosino S, Mertens I, Lundbom N, et al. Role of insulin as a negative regulator of plasma endocannabinoid levels in obese and nonobese subjects. Eur J Endocrinol. 2009;161:715–22.
Heyman E, Gamelin FX, Goekint M, Piscitelli F, Roelands B, Leclair E, et al. Intense exercise increases circulating endocannabinoid and BDNF levels in humans--possible implications for reward and depression. Psychoneuroendocrinology. 2012;37:844–51.
Koltyn KF, Brellenthin AG, Cook DB, Sehgal N, Hillard C. Mechanisms of exercise-induced hypoalgesia. J Pain. 2014;15:1294–304.
Despres JP, Golay A, Sjostrom L. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005;353:2121–34.
Scheen AJ, Finer N, Hollander P, Jensen MD, Van Gaal LF, Group, R-DS. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet. 2006;368:1660–72.
Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rossner S. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet. 2005;365:1389–97.
Pi-Sunyer FX, Aronne LJ, Heshmati HM, Devin J, Rosenstock J, Group, R-NAS. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA. 2006;295:761–75.
EMA. EUROPEAN PUBLIC ASSESSMENT REPORT (EPAR) ACOMPLIA: EPAR summary for the public. London: European Medicines Agency; 2007.
Rucker D, Padwal R, Li SK, Curioni C, Lau DC. Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ. 2007;335:1194–9.
Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet. 2007;370:1706–13.
Topol EJ, Bousser MG, Fox KA, Creager MA, Despres JP, Easton JD, et al. Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial. Lancet. 2010;376:517–23.
Monteleone AM, Di Marzo V, Aveta T, Piscitelli F, Dalle Grave R, Scognamiglio P, et al. Deranged endocannabinoid responses to hedonic eating in underweight and recently weight-restored patients with anorexia nervosa. Am J Clin Nutr. 2015;101:262–9.
Gerard N, Pieters G, Goffin K, Bormans G, Van Laere K. Brain type 1 cannabinoid receptor availability in patients with anorexia and bulimia nervosa. Biol Psychiatry. 2011;70:777–84.
Brun R, Kuo B. Functional dyspepsia. Ther Adv Gastroenterol. 2010;3:145–64.
Ly HG, Ceccarini J, Weltens N, Bormans G, Van Laere K, Tack J, et al. Increased cerebral cannabinoid-1 receptor availability is a stable feature of functional dyspepsia: a [F]MK-9470 PET study. Psychother Psychosom. 2015;84:149–58.
Ceccarini J, Weltens N, Ly HG, Tack J, Van Oudenhove L, Van Laere K. Association between cerebral cannabinoid 1 receptor availability and body mass index in patients with food intake disorders and healthy subjects: a [(18)F]MK-9470 PET study. Transl Psychiatry. 2016;6:e853.
Ashok AH, Mizuno Y, Volkow ND, Howes OD. Association of stimulant use with dopaminergic alterations in users of cocaine, amphetamine, or methamphetamine: a systematic review and Meta-analysis. JAMA Psychiatry. 2017;74:511–9.
Volkow ND, Fowler JS, Wolf AP, Schlyer D, Shiue CY, Alpert R, et al. Effects of chronic cocaine abuse on postsynaptic dopamine receptors. Am J Psychiatry. 1990;147:719–24.
Mihov Y. Positron emission tomography studies on cannabinoid receptor type 1 in Schizophrenia. Biol Psychiatry. 2016;79:e97–9.
Wiers CE, Towb PC, Hodgkinson CA, Shen PH, Freeman C, Miller G, Lindgren E, Shokri-Kojori E, Demiral ÅžB, Kim SW, Tomasi D. Association of genetic ancestry with striatal dopamine D2/D3 receptor availability. Molecular psychiatry. 2017 Nov 7. https://doi.org/10.1038/mp.2017.208. [Epub ahead of print]
Hirvonen J, Zanotti-Fregonara P, Gorelick D, Rallis-Frutos D, Morse C, Zoghbi S, et al. Decreased brain cannabinoid CB1 receptor binding in tobacco smokers examined with positron emission tomography. J Nucl Med. 2014;55:84.
Wang C, Placzek MS, Van de Bittner GC, Schroeder FA, Hooker JM. A novel radiotracer for imaging monoacylglycerol lipase in the brain using positron emission tomography. ACS Chem Neurosci. 2016;7:484–9.
Van Sickle MD, Duncan M, Kingsley PJ, Mouihate A, Urbani P, Mackie K, et al. Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science. 2005;310:329–32.
Zhang HY, Gao M, Liu QR, Bi GH, Li X, Yang HJ, et al. Cannabinoid CB2 receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice. Proc Natl Acad Sci Usa. 2014;111:E5007–15.
Xi ZX, Peng XQ, Li X, Song R, Zhang HY, Liu QR, et al. Brain cannabinoid CB(2) receptors modulate cocaine’s actions in mice. Nat Neurosci. 2011;14:1160–6.
Ortega-Alvaro A, Aracil-Fernandez A, Garcia-Gutierrez MS, Navarrete F, Manzanares J. Deletion of CB2 cannabinoid receptor induces schizophrenia-related behaviors in mice. Neuropsychopharmacology. 2011;36:1489–504.
Spinelli F, Mu L, Ametamey SM. Radioligands for positron emission tomography imaging of cannabinoid type 2 receptor. J Label Comp Radiopharm. 2018;61:299–308.
Acknowledgements
This study was supported by the NIAAA Division of Intramural Clinical and Biological Research (Z1A AA000466).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Sloan, M.E., Grant, C.W., Gowin, J.L. et al. Endocannabinoid signaling in psychiatric disorders: a review of positron emission tomography studies. Acta Pharmacol Sin 40, 342–350 (2019). https://doi.org/10.1038/s41401-018-0081-z
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/s41401-018-0081-z
Keywords
This article is cited by
-
Effects of acute alcohol administration on endocannabinoids and relation to subjective effects
Psychopharmacology (2025)
-
Peripheral endocannabinoids in major depressive disorder and alcohol use disorder: a systematic review
BMC Psychiatry (2024)
-
Cannabis self-administration in the human laboratory: a scoping review of ad libitum studies
Psychopharmacology (2023)
-
Cannabis use and cannabis use disorder
Nature Reviews Disease Primers (2021)
-
Lower brain fatty acid amide hydrolase in treatment-seeking patients with alcohol use disorder: a positron emission tomography study with [C-11]CURB
Neuropsychopharmacology (2020)
