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Summary sheet: Clonidine
Chemical Nomenclature
Common names Catapres, Catapres-TTS, Kapvay, Nexiclon XR
Substitutive name Clonidine
Systematic name N-(2,6-dichlorophenyl)-4,5-dihydro-1H-imidazol-2-amine
Class Membership
Psychoactive class Depressant
Chemical class Imidazoline
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.

Threshold 25 μg
Light 50 - 75 μg
Common 75 - 100 μg
Strong 100 - 300 μg
Heavy 300 μg +
Total 6 - 8 hours
Onset 15 - 45 minutes
Peak 60 - 90 minutes
Offset 6 - 8 hours

DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.


Clonidine (known by the trade names Catapres, Kapvay, Nexiclon, Clophelin, and others) is a depressant substance of the imidazoline class. It is primarily used to treat high blood pressure, but can also be used for a variety of conditions that include attention deficit hyperactivity disorder, anxiety disorders, tic disorders, substance withdrawal, migraine, diarrhea, and certain pain conditions.[1]

Developed by Boehringer Ingelheim for its blood pressure effects, clonidine first saw clinical use in 1966.[2] As the first anti-hypertensive agent with a clearly identifiable central site of action, clonidine has been an important pharmacological tool in discovering the role of central α-adrenoceptors in the physiology of central blood pressure regulation.[2]

Clonidine is classified as a centrally acting α2 adrenergic agonist and imidazoline receptor agonist.[2][3] Its activity on the α2 receptors in the brainstem inhibits the release of norepinephrine (NE), resulting in decreased sympathetic nervous system tone.[4]

Clonidine has several off-label uses. It has been prescribed to treat psychiatric disorders including stress, sleep disorders, and hyperarousal caused by post-traumatic stress disorder, borderline personality disorder, and other anxiety disorders.[5][6][7][8][9][10][11][12]

History and culture

In the early 1960s, the medicinal chemist Helmut Stähle was tasked by Boehringer Ingelheim with synthesizing a peripherally active a-adrenergic compound that would be useful for nasal decongestion as simple nose drops. A locally acting a-adrenergic vasoconstrictor agent was expected to provide relief from the symptoms of the common cold by shrinking the swollen nasal membranes and producing an unobstructed air passage.[2]

The synthetic design of clonidine was achieved when Stähle had the idea of substituting two chlorine groups on the phenyl group of the imidazoline structure, which most of the newer decongestive agents at the time were derived from. At that time, a double halogen substitution was still unusual for pharmaceuticals, and the prevailing opinion was that compounds with several halogen atoms would at best be useful as pesticides. Despite this, clonidine was pursued and discovered to have a remarkably high vasoconstrictive and decongestive effect at an unusually low dosage level.[2]

The decongestive effects were then determined by nasal cavity tests on anesthetized dogs. After the first trial in humans, it became clear that clonidine's decongestant properties were far less interesting than its potent anti-hypertensive effects. The compound was then developed for this new indication and was introduced into therapy in 1966 under the trade name Catapres, where it saw widespread use.[2]

With the discovery of clonidine, the central a-adrenergic receptors first became known to chemists, pharmacologists and physicians. It has been an important pharmacological tool in researching the role of central α-adrenoceptors in the physiology of central blood pressure regulation and nervous system function.[2]

In the 2010s, the US Food and Drug Administration (FDA) approved clonidine, both alone or with stimulants, for the treatment of attention deficit hyperactivity disorder (ADHD) in pediatric and adult patients. In Australia, clonidine is an accepted but not approved use for ADHD by the TGA.[13]


Clonidine, or 2-[(2,6-Dichlorophenyl)imino]imidazoline, is a compound of the imidazoline chemical class. Imidazolines are substituted amidines in which the amidine function is incorporated into an imidazoline ring. This portion is connected to an aromatic nucleus by way of a methylene bridge.

Additionally, two chlorine atoms are substituted in the 2- and 6-positions of the phenyl ring. This addition has the critical effect of making the molecule sufficiently lipophilic to penetrate the blood-brain barrier.[citation needed]

Other compounds of this class include the a-adrenergic agents tolazoline, naphazoline, and phentolamine. The a-adrenergic effects of clonidine and other imidazolidine compounds may be explained on the basis of a structural overlap between clonidine and norepinephrine.



Clonidine is an agonist for the α2 adrenergic receptor. When α2 receptors in the brain are stimulated, peripheral vascular resistance decreases, resulting in lowered blood pressure. It has specificity towards the presynaptic α2 receptors in the vasomotor center in the brainstem. This binding decreases presynaptic calcium levels and inhibits the release of norepinephrine (NE). The net effect is a decrease in sympathetic nervous system tone.[14]

Three G-protein coupled α2-receptor subtypes have been identified: α2A, α2B, and α2C. Each subtype has a unique pattern of tissue distribution in the central nervous system and peripheral tissues. The α2A-receptor is widely distributed throughout the central nervous system; it is found in the locus coeruleus, brain stem nuclei, cerebral cortex, septum, hypothalamus, and hippocampus. α2A receptors are also expressed in the kidneys, spleen, thymus, lung and salivary glands. The α2C-receptor is primarily expressed in the central nervous system, including the striatum, olfactory tubercle, hippocampus and cerebral cortex. The α2B receptor is located primarily in the periphery (kidney, liver, lung and heart).[citation needed]

The α2A- and α2C receptors are located presynaptically and inhibit the released of noradrenaline from sympathetic nerves. Stimulation of these receptors decreases sympathetic tone, resulting in decreases in blood pressure and heart rate. Sedation and analgesia is mediated by centrally located α2A receptors, while peripheral α2B receptors mediate constriction of vascular smooth muscle. α2A receptors also mediate essential components of the analgesic effect of nitrous oxide in the spinal cord. Clonidine stimulates all three α2 receptor subtypes with similar potency.[citation needed]

Clonidine also has peripheral α1 agonist activity.[citation needed]

Clonidine is also an agonist for the imidazoline I1 receptor.[15] This has been proposed to be responsible for the antihypertensive effects.[16]

Binding Sites Binding Affinity Ki (nM)[17]
α1A 316.23
α1B 316.23
α1D 125.89
α2A 42.92
α2B 106.31
α2C 233.1


Clonidine is rapidly absorbed from the gastrointestinal tract and has excellent CNS penetration because of lipid solubility.[citation needed] Peak plasma concentrations are reached 3-5 hours after a single oral dose.[citation needed] No known pharmacologically active metabolites exist.[citation needed] Plasma half-life is 12-16 hours, with the antihypertensive effects occurring within 30-60 minutes of ingestion. Clonidine is excreted unchanged in the urine and is metabolized by the liver.[citation needed]

Subjective effects

''Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.''

Physical effects

Cognitive effects

Auditory effects

After effects
Aftereffects (3).svg

Experience reports

There are currently 1 anecdotal reports which describe the effects of this compound within our experience index.

Additional experience reports can be found here:

Toxicity and harm potential

At therapeutic doses (0.2-0.9 mg/d), clonidine is commonly associated with adverse effects such as dry mouth, sedation, dizziness, and constipation. While generally safe, at toxic doses clonidine can cause serious cardiopulmonary instability and central nervous system (CNS) depression in children and adults. Caution should be used when clonidine is taken with other depressants.

It is strongly recommended that one use harm reduction practices when using this substance.

Lethal dosage

The oral LD50 for clonidine in mice is 206 mg/kg and for rats, 465 mg/kg.[citation needed] In humans, lethality is rare with a small number of reported deaths. Morbidity, in terms of cardiorespiratory and CNS dysfunction, generally tends to be more severe in young persons than in adults.[citation needed]


Symptoms of clonidine overdose include constriction of pupils of the eye, drowsiness, high blood pressure followed by a drop in pressure, irritability, low body temperature, slowed breathing, slowed heartbeat, slowed reflexes, and weakness.[citation needed]

There are case reports that show naloxone may be a useful antidote in treating clonidine overdoses. However, this is not in widespread clinical use.[22]

Tolerance and addiction potential

Clonidine is not addictive and has a low potential for abuse. The chronic use of clonidine can produce physical dependence and withdrawal symptoms if one suddenly stops their usage. Clonidine therapy should generally be gradually tapered when discontinuing therapy to avoid rebound hypertension from occurring.

Although clonidine is not considered to be addictive, cases of misuse have been documented among certain groups with pre-existing substance use disorders. It is sometimes used in combination with opiates to extend and potentiate their effects.[23] This practice may increase the risk of oversedation and respiratory depression associated with opioid use.

Dangerous interactions

Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).

Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.

  • Depressants (1,4-Butanediol, 2M2B, alcohol, benzodiazepines, barbiturates, GHB/GBL, methaqualone, opioids) - This combination potentiates the muscle relaxation, amnesia, sedation, and respiratory depression caused by one another. At higher doses, it can lead to a sudden, unexpected loss of consciousness along with a dangerous amount of depressed respiration. There is also an increased risk of suffocating on one's vomit while unconscious. If nausea or vomiting occurs before a loss of consciousness, users should attempt to fall asleep in the recovery position or have a friend move them into it.
  • Dissociatives - This combination can unpredictably potentiate the amnesia, sedation, motor control loss and delusions that can be caused by each other. It may also result in a sudden loss of consciousness accompanied by a dangerous degree of respiratory depression. If nausea or vomiting occurs before consciousness is lost, users should attempt to fall asleep in the recovery position or have a friend move them into it.
  • Stimulants - Stimulants mask the sedative effect of depressants, which is the main factor most people use to gauge their level of intoxication. Once the stimulant effects wear off, the effects of the depressant will significantly increase, leading to intensified disinhibition, motor control loss, and dangerous black-out states. This combination can also potentially result in severe dehydration if one's fluid intake is not closely monitored. If choosing to combine these substances, one should strictly limit themselves to a pre-set schedule of dosing only a certain amount per hour until a maximum threshold has been reached.

Legal status


This legality section is a stub.

As such, it may contain incomplete or wrong information. You can help by expanding it.

  • Germany: Clonidine is prescription medicine, according to Anlage 1 AMVV.[24]
  • Switzerland: Clonidine is listed as a "Abgabekategorie B" pharmaceutical, which requires a prescription.[citation needed]
  • United States: Clonidine is only available with a prescription.[25]

See also

External links



  1. Soni, H., Brayfield, A., eds. (13 January 2014). ""Clonidine". Martindale: The Complete Drug Reference". Pharmaceutical Press. 22 (5): 12–12. doi:10.7748/en.22.5.12.s13. ISSN 1354-5752. Retrieved 28 June 2014. 
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Stähle, H. (June 2000). "A historical perspective: development of clonidine". Best Practice & Research Clinical Anaesthesiology. 14 (2): 237–246. doi:10.1053/bean.2000.0079. ISSN 1521-6896. 
  3. Neil, M. J. (November 2011). "Clonidine: clinical pharmacology and therapeutic use in pain management". Current Clinical Pharmacology. 6 (4): 280–287. doi:10.2174/157488411798375886. ISSN 2212-3938. 
  4. Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 12. ISBN 1-59541-101-1.
  5. van der Kolk, BA (September–October 1987). "The drug treatment of post-traumatic stress disorder". Journal of Affective Disorders. 13 (2): 203–13. doi:10.1016/0165-0327(87)90024-3. PMID 2960712. 
  6. Sutherland, SM; Davidson, JR (June 1994). "Pharmacotherapy for post-traumatic stress disorder". The Psychiatric Clinics of North America. 17 (2): 409–23. PMID 7937367. 
  7. Southwick, SM; Bremner, JD; Rasmusson, A; Morgan CA, 3rd; Arnsten, A; Charney, DS (November 1999). "Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder". Biological Psychiatry. 46 (9): 1192–204. doi:10.1016/S0006-3223(99)00219-X. PMID 10560025. 
  8. Strawn, JR; Geracioti, TD, Jr (2008). "Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder". Depression and Anxiety. 25 (3): 260–71. doi:10.1002/da.20292. PMID 17354267. 
  9. Boehnlein, JK; Kinzie, JD (March 2007). "Pharmacologic reduction of CNS noradrenergic activity in PTSD: the case for clonidine and prazosin". Journal of Psychiatric Practice. 13 (2): 72–8. doi:10.1097/01.pra.0000265763.79753.c1. PMID 17414682. 
  10. Huffman, JC; Stern, TA (2007). "Neuropsychiatric consequences of cardiovascular medications". Dialogues in Clinical Neuroscience. 9 (1): 29–45. PMC 3181843Freely accessible. PMID 17506224. 
  11. Najjar, F; Weller, RA; Weisbrot, J; Weller, EB (April 2008). "Post-traumatic stress disorder and its treatment in children and adolescents". Current Psychiatry Reports. 10 (2): 104–8. doi:10.1007/s11920-008-0019-0. PMID 18474199. 
  12. Ziegenhorn, AA; Roepke, S; Schommer, NC; Merkl, A; Danker-Hopfe, H; Perschel, FH; Heuser, I; Anghelescu, IG; Lammers, CH (April 2009). "Clonidine improves hyperarousal in borderline personality disorder with or without comorbid posttraumatic stress disorder: a randomized, double-blind, placebo-controlled trial". Journal of Clinical Psychopharmacology. 29 (2): 170–3. doi:10.1097/JCP.0b013e31819a4bae. PMID 19512980. 
  13. Rossi, S., Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, Pharmaceutical Society of Australia, Royal Australian College of General Practitioners (2013). Australian medicines handbook 2013. Australian Medicines Handbook. ISBN 9780980579093. 
  14. Sullivan, P. A., De Quattro, V., Foti, A., Curzon, G. (July 1986). "Effects of clonidine on central and peripheral nerve tone in primary hypertension". Hypertension (Dallas, Tex.: 1979). 8 (7): 611–617. doi:10.1161/01.hyp.8.7.611. ISSN 0194-911X. 
  15. Bricca, G., Greney, H., Zhang, J., Dontenwill, M., Stutzmann, J., Belcourt, A., Bousquet, P. (January 1994). "Human brain imidazoline receptors: further characterization with [3H]clonidine". European Journal of Pharmacology: Molecular Pharmacology. 266 (1): 25–33. doi:10.1016/0922-4106(94)90205-4. ISSN 0922-4106. 
  16. Reis, D. J., Piletz, J. E. (November 1997). "The imidazoline receptor in control of blood pressure by clonidine and allied drugs". The American Journal of Physiology. 273 (5): R1569–1571. doi:10.1152/ajpregu.1997.273.5.R1569. ISSN 0002-9513. 
  17. Roth, BL; Driscol, J (12 January 2011). "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Archived from the original on 8 November 2013. Retrieved 25 November 2013.
  18. Anderson, R. J., Hart, G. R., Crumpler, C. P., Lerman, M. J. (February 1981). "Clonidine overdose: report of six cases and review of the literature". Annals of Emergency Medicine. 10 (2): 107–112. doi:10.1016/s0196-0644(81)80350-2. ISSN 0196-0644. 
  19. Mitchell, A., Bührmann, S., Opazo Saez, A., Rushentsova, U., Schäfers, R. F., Philipp, T., Nürnberger, J. (January 2005). "Clonidine lowers blood pressure by reducing vascular resistance and cardiac output in young, healthy males". Cardiovascular Drugs and Therapy. 19 (1): 49–55. doi:10.1007/s10557-005-6890-6. ISSN 0920-3206. 
  20. Gold, MarkS., Redmond, D. E., Kleber, HerbertD. (September 1978). "CLONIDINE BLOCKS ACUTE OPIATE-WITHDRAWAL SYMPTOMS". The Lancet. 312 (8090): 599–602. doi:10.1016/S0140-6736(78)92823-4. ISSN 0140-6736. 
  21. Hoehn-Saric, R. (1 November 1981). "Effects of Clonidine on Anxiety Disorders". Archives of General Psychiatry. 38 (11): 1278. doi:10.1001/archpsyc.1981.01780360094011. ISSN 0003-990X. 
  22. Niemann, J. T., Getzug, T., Murphy, W. (October 1986). "Reversal of clonidine toxicity by naloxone". Annals of Emergency Medicine. 15 (10): 1229–1231. doi:10.1016/S0196-0644(86)80874-5. ISSN 0196-0644. 
  23. Dennison, S. J. (2001). "Clonidine abuse among opiate addicts". The Psychiatric Quarterly. 72 (2): 191–195. doi:10.1023/a:1010375727768. ISSN 0033-2720. 
  24. AMVV - Verordnung über die Verschreibungspflicht von Arzneimitteln