Details of Disease

Disease Name

Substance withdrawal syndrome

withdrawal disorder; substance withdrawal disorder; substance withdrawal; withdrawal syndrome; drug withdrawal syndrome; drug withdrawal; substance withdrawal syndrome

Definition

A substance-specific organic brain syndrome that follows the discontinuation of administration or use, or reduction in intake of a substance (including alcohol, prescribed medications and recreational drugs). Syndrome manifests with diverse, often painful physical and psychological symptoms, which include but not limited to intense drug craving, anxiety, depression, insomnia, nausea, perspiration, body aches, tremors, hallucinations, and convulsions.

Disease Hierarchy

DIS6SVEE: Syndromic disease

:

DISTT24U: Substance withdrawal syndrome

Disease Identifiers

MONDO ID

MONDO_0005567

MESH ID

D013375

UMLS CUI

C0038587

MedGen ID

20990

SNOMED CT ID

1254795002

General Information of Disease (ID: DISTT24U)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 46 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CREB1	TTH4AN3	Limited	Biomarker	[1]
CRH	TTA7YIZ	Limited	Biomarker	[1]
NCOA4	TT8OY02	Limited	Biomarker	[2]
RHOA	TTP2U16	Limited	Biomarker	[3]
RUNX2	TTD6SZ8	Limited	Biomarker	[3]
SMAD1	TT9GR53	Limited	Biomarker	[3]
ADCY1	TTV1ZSQ	Strong	Biomarker	[4]
ADORA1	TTK25J1	Strong	Biomarker	[5]
ADORA2A	TTM2AOE	Strong	Biomarker	[6]
AVP	TTJ8EWH	Strong	Biomarker	[7]
BDNF	TTSMLOH	Strong	Biomarker	[8]
CCKBR	TTVFO0U	Strong	Biomarker	[9]
CHRM5	TTH18TF	Strong	Biomarker	[10]
CHRNA5	TTH2QRX	Strong	Biomarker	[11]
CHRNA7	TTLA931	Strong	Biomarker	[11]
CHRNB2	TT5KPZR	Strong	Biomarker	[11]
CHRNB4	TTTVAFQ	Strong	Biomarker	[12]
CNR1	TT6OEDT	Strong	Biomarker	[13]
CRP	TTWRN6M	Strong	Biomarker	[14]
DRD2	TTEX248	Strong	Genetic Variation	[15]
FOS	TTOM5AU	Strong	Biomarker	[16]
GNAI1	TTL1HWR	Strong	Biomarker	[17]
GNAO1	TTAXD8Z	Strong	Biomarker	[17]
GRIA1	TTVPQTF	Strong	Biomarker	[18]
GRIA2	TTWM461	Strong	Biomarker	[18]
GRIN2A	TTKJEMQ	Strong	Biomarker	[19]
HCRT	TTU5HJP	Strong	Biomarker	[20]
HCRTR1	TT60Q8D	Strong	Biomarker	[20]
HRH1	TTTIBOJ	Strong	Biomarker	[21]
HRH2	TTQHJ1K	Strong	Biomarker	[21]
HTR2C	TTWJBZ5	Strong	Biomarker	[22]
IFNA2	TTSIUJ9	Strong	Therapeutic	[23]
MAPK1	TT4TQBX	Strong	Biomarker	[24]
MAPK3	TT1MG9E	Strong	Biomarker	[24]
NPTX2	TTNJ5A6	Strong	Biomarker	[25]
NPY	TT64REZ	Strong	Biomarker	[26]
NPY2R	TTJ6WK9	Strong	Biomarker	[27]
OPRD1	TT27RFC	Strong	Biomarker	[28]
OPRK1	TTQW87Y	Strong	Biomarker	[29]
OPRL1	TTNT7K8	Strong	Biomarker	[30]
POMC	TT21AKM	Strong	Biomarker	[31]
PRL	TTJ2TSA	Strong	Biomarker	[32]
REN	TTB2MXP	Strong	Biomarker	[33]
SLC6A1	TTPRKM0	Strong	Therapeutic	[34]
SLC6A4	TT3ROYC	Strong	Biomarker	[35]
TACR1	TTZPO1L	Strong	Biomarker	[36]
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⏷ Show the Full List of 46 DTT(s)

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
FAAH	DEUM1EX	Strong	Biomarker	[37]
PER1	DE9HF0I	Strong	Biomarker	[38]
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This Disease Is Related to 14 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
AQP6	OTXS6UYY	Limited	Genetic Variation	[39]
MCF2L	OTEURA8N	Limited	Biomarker	[40]
MLST8	OT8DNJSD	Limited	Biomarker	[41]
SMAD5	OTQNSVCQ	Limited	Biomarker	[3]
SMURF1	OT5UIZR8	Limited	Biomarker	[3]
ANKK1	OT0OM1O0	moderate	Genetic Variation	[15]
ADCY8	OTR1WCZX	Strong	Biomarker	[4]
ARL6IP5	OTYZ6BEQ	Strong	Therapeutic	[42]
CHRNA6	OTT6W86V	Strong	Biomarker	[43]
GNAS	OTMH8BKJ	Strong	Biomarker	[17]
PER2	OTU2B1DJ	Strong	Biomarker	[44]
PER3	OTVKYVJA	Strong	Biomarker	[38]
PNOC	OTJEAADN	Strong	Therapeutic	[45]
PPP1R1B	OTSIJMQ9	Strong	Altered Expression	[46]
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⏷ Show the Full List of 14 DOT(s)

References

1	Evidence for beta1-adrenergic receptor involvement in amygdalar corticotropin-releasing factor gene expression: implications for cocaine withdrawal.Neuropsychopharmacology. 2009 Apr;34(5):1135-48. doi: 10.1038/npp.2008.102. Epub 2008 Jul 2.
2	Functional domain and motif analyses of androgen receptor coregulator ARA70 and its differential expression in prostate cancer.J Biol Chem. 2004 Aug 6;279(32):33438-46. doi: 10.1074/jbc.M401781200. Epub 2004 May 27.
3	E3 Ubiquitin-Protein Ligase SMURF1 in the Nucleus Accumbens Mediates Cocaine Seeking.Biol Psychiatry. 2018 Dec 15;84(12):881-892. doi: 10.1016/j.biopsych.2018.07.013. Epub 2018 Jul 21.
4	Calmodulin-stimulated adenylyl cyclase gene deletion affects morphine responses.Mol Pharmacol. 2006 Nov;70(5):1742-9. doi: 10.1124/mol.106.025783. Epub 2006 Aug 16.
5	Influence of adenosine receptor agonists on benzodiazepine withdrawal signs in mice.Eur J Pharmacol. 2005 Oct 31;523(1-3):71-8. doi: 10.1016/j.ejphar.2005.07.025. Epub 2005 Oct 14.
6	Absence of quasi-morphine withdrawal syndrome in adenosine A2A receptor knockout mice.Psychopharmacology (Berl). 2006 Apr;185(2):160-8. doi: 10.1007/s00213-005-0284-0. Epub 2006 Feb 10.
7	Vasopressin withdrawal produces hypotension in the spontaneously hypertensive rat.Am J Physiol. 1985 Jul;249(1 Pt 2):H193-7. doi: 10.1152/ajpheart.1985.249.1.H193.
8	Time-dependent increases in brain-derived neurotrophic factor protein levels within the mesolimbic dopamine system after withdrawal from cocaine: implications for incubation of cocaine craving.J Neurosci. 2003 Feb 1;23(3):742-7. doi: 10.1523/JNEUROSCI.23-03-00742.2003.
9	Deletion of CCK2 receptor in mice results in an upregulation of the endogenous opioid system.J Neurosci. 2002 Mar 1;22(5):2005-11. doi: 10.1523/JNEUROSCI.22-05-02005.2002.
10	Deletion of the M5 muscarinic acetylcholine receptor attenuates morphine reinforcement and withdrawal but not morphine analgesia.Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11452-7. doi: 10.1073/pnas.162371899. Epub 2002 Aug 1.
11	Differential role of nicotinic acetylcholine receptor subunits in physical and affective nicotine withdrawal signs.J Pharmacol Exp Ther. 2008 Apr;325(1):302-12. doi: 10.1124/jpet.107.132977. Epub 2008 Jan 9.
12	Decreased signs of nicotine withdrawal in mice null for the beta4 nicotinic acetylcholine receptor subunit.J Neurosci. 2004 Nov 10;24(45):10035-9. doi: 10.1523/JNEUROSCI.1939-04.2004.
13	Marijuana withdrawal and craving: influence of the cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH) genes.Addiction. 2008 Oct;103(10):1678-86. doi: 10.1111/j.1360-0443.2008.02292.x. Epub 2008 Aug 14.
14	C-reactive protein and depressed mood in a sub-group of smokers during nicotine abstinence.Hum Psychopharmacol. 2003 Jul;18(5):329-37. doi: 10.1002/hup.487.
15	Influence of DRD2 and ANKK1 polymorphisms on the manifestation of withdrawal syndrome symptoms in alcohol addiction.Pharmacol Rep. 2012;64(5):1126-34. doi: 10.1016/s1734-1140(12)70909-x.
16	Anxiety-like symptoms induced by morphine withdrawal may be due to the sensitization of the dorsal periaqueductal grey.Physiol Behav. 2008 Jul 5;94(4):552-62. doi: 10.1016/j.physbeh.2008.03.014. Epub 2008 Apr 1.
17	Changes of the level of G protein alpha-subunit mRNA by tolerance to and withdrawal from pentobarbital in rats.Neurochem Res. 2002 Jun;27(6):527-33. doi: 10.1023/a:1019808905500.
18	Extinction-induced upregulation in AMPA receptors reduces cocaine-seeking behaviour.Nature. 2003 Jan 2;421(6918):70-5. doi: 10.1038/nature01249.
19	Locus-specific rescue of GluRepsilon1 NMDA receptors in mutant mice identifies the brain regions important for morphine tolerance and dependence.J Neurosci. 2003 Jul 23;23(16):6529-36. doi: 10.1523/JNEUROSCI.23-16-06529.2003.
20	Antagonism of orexin type-1 receptors (OX1Rs) attenuates naloxone-precipitated morphine withdrawal syndrome in rat dorsal hippocampus.Pharmacol Biochem Behav. 2017 Jul;158:39-48. doi: 10.1016/j.pbb.2017.06.001. Epub 2017 Jun 3.
21	The role of histaminergic-noradrenergic axis in naloxone-induced withdrawal symptoms in mice.Pharmacol Biochem Behav. 1996 Sep;55(1):49-54. doi: 10.1016/0091-3057(95)02219-8.
22	A potent serotonin-modulating compound AP-267 attenuates morphine withdrawal-induced blood-brain barrier dysfunction in rats.Ann N Y Acad Sci. 2006 Aug;1074:482-96. doi: 10.1196/annals.1369.049.
23	Immune response products alter CNS activity: interferon modulates central opioid functions.J Neurosci Res. 1988;19(1):130-9. doi: 10.1002/jnr.490190118.
24	Activation of the ERK signalling pathway contributes to the adaptive changes in rat hearts during naloxone-induced morphine withdrawal.Br J Pharmacol. 2007 Jul;151(6):787-97. doi: 10.1038/sj.bjp.0707301. Epub 2007 Jun 4.
25	Nicotine and Delta(9)-tetrahydrocannabinol withdrawal induce Narp in the central nucleus of the amygdala.Synapse. 2009 Mar;63(3):252-5. doi: 10.1002/syn.20586.
26	Lack of neuropeptide Y attenuates the somatic signs of opiate withdrawal.Synapse. 2006 Dec 1;60(7):553-6. doi: 10.1002/syn.20328.
27	Neuropeptide Y receptor genes are associated with alcohol dependence, alcohol withdrawal phenotypes, and cocaine dependence.Alcohol Clin Exp Res. 2008 Dec;32(12):2031-40. doi: 10.1111/j.1530-0277.2008.00790.x. Epub 2008 Sep 25.
28	Mu- and delta-opioid receptor-mediated epileptoid responses in morphine-dependent and non-dependent rats.Electroencephalogr Clin Neurophysiol. 1985 Dec;61(6):569-72. doi: 10.1016/0013-4694(85)90976-9.
29	Effect of the selective kappa-opioid receptor antagonist JDTic on nicotine antinociception, reward, and withdrawal in the mouse.Psychopharmacology (Berl). 2010 Jun;210(2):285-94. doi: 10.1007/s00213-010-1803-1. Epub 2010 Mar 16.
30	Enhanced spinal nociceptin receptor expression develops morphine tolerance and dependence.J Neurosci. 2000 Oct 15;20(20):7640-7. doi: 10.1523/JNEUROSCI.20-20-07640.2000.
31	Suppression of acute morphine withdrawal syndrome by adenovirus-mediated -endorphin in rats.Brain Res. 2011 Nov 8;1422:13-9. doi: 10.1016/j.brainres.2011.07.063. Epub 2011 Aug 6.
32	Neurobehavioral syndrome induced by H2-receptor blocker withdrawal: possible role of prolactin.Clin Neuropharmacol. 1997 Feb;20(1):49-54. doi: 10.1097/00002826-199702000-00006.
33	Withdrawal of clonidine: effects of varying dosage or duration of treatment on subsequent blood pressure and heart rate responses.J Pharmacol Exp Ther. 1978 Aug;206(2):268-73.
34	Decrease of morphine-induced reward effects and withdrawal symptoms in mice overexpressing gamma-aminobutyric acid transporter I.J Neurosci Res. 2003 Nov 15;74(4):614-21. doi: 10.1002/jnr.10780.
35	Polymorphism in the serotonin transporter gene and moderators of prolactin response to meta-chlorophenylpiperazine in African-American cocaine abusers and controls.Psychiatry Res. 2006 Nov 15;144(2-3):99-108. doi: 10.1016/j.psychres.2006.01.012. Epub 2006 Sep 25.
36	RP 67580, a selective antagonist of neurokinin-1 receptors, modifies some of the naloxone-precipitated morphine withdrawal signs in rats.Neurosci Lett. 1993 Jun 25;156(1-2):135-40. doi: 10.1016/0304-3940(93)90457-v.
37	Intermediate cannabis dependence phenotypes and the FAAH C385A variant: an exploratory analysis.Psychopharmacology (Berl). 2009 Apr;203(3):511-7. doi: 10.1007/s00213-008-1397-z. Epub 2008 Nov 12.
38	Circadian alteration in neurobiology during protracted opiate withdrawal in rats.J Neurochem. 2010 Oct;115(2):353-62. doi: 10.1111/j.1471-4159.2010.06941.x. Epub 2010 Aug 25.
39	Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study.Haematologica. 2016 Jun;101(6):717-23. doi: 10.3324/haematol.2015.139899. Epub 2016 Feb 17.
40	Seventy Years with the Globus Pallidus: Pallidal Surgery for Movement Disorders Between 1947 and 2017.Mov Disord. 2017 Jul;32(7):972-982. doi: 10.1002/mds.27054. Epub 2017 Jun 7.
41	Validation of the Withdrawal Assessment Tool-1 in Adult Intensive Care Patients.Am J Crit Care. 2019 Sep;28(5):361-369. doi: 10.4037/ajcc2019559.
42	JWA regulates chronic morphine dependence via the delta opioid receptor.Biochem Biophys Res Commun. 2011 Jun 10;409(3):520-5. doi: 10.1016/j.bbrc.2011.05.037. Epub 2011 May 11.
43	The role of alpha6-containing nicotinic acetylcholine receptors in nicotine reward and withdrawal.J Pharmacol Exp Ther. 2009 Nov;331(2):547-54. doi: 10.1124/jpet.109.155457. Epub 2009 Jul 30.
44	Development of morphine-induced tolerance and withdrawal: involvement of the clock gene mPer2.Eur Neuropsychopharmacol. 2010 Jul;20(7):509-17. doi: 10.1016/j.euroneuro.2010.03.006.
45	Orphanin FQ/nociceptin inhibits morphine withdrawal.Life Sci. 2000 Jan 14;66(8):PL119-23. doi: 10.1016/s0024-3205(99)00648-7.
46	Nanotherapeutic approach for opiate addiction using DARPP-32 gene silencing in an animal model of opiate addiction.J Neuroimmune Pharmacol. 2015 Mar;10(1):136-52. doi: 10.1007/s11481-015-9585-1. Epub 2015 Jan 22.