Cyclazodone: Difference between revisions

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Cyclazodone is an approximately 3x - 5x more potent N-cyclopropyl derivative of [[pemoline]]. Pemoline is considered to be [[dopamine|dopaminergic]], but its precise method of action has not been fully determined.<ref>"Cylert (Pemoline)" (PDF). FDA. December 2002.</ref> Pemoline has minimal affinity for [[noradrenaline]] receptors and thus has minimal sympathomimetic side effects compared with typical dopaminergic central nervous system stimulants such as methylphenidate and [[Isomer|dextro]]-amphetamine.

According to patents filed by the inventors, cyclazodone exhibited central nervous system stimulating properties and anorexigenic properties much more potent than those of pemoline, and more potent than those of various other N-lower-alkyl-substituted pemoline derivatives. At the time cyclazodone also offered a much more favorable therapeutic index and margin of safety than pemoline and other N-lower-alkyl-substituted pemoline derivatives.<ref>~~Val De Marne~~, ~~Don Pierre~~ R. L. ~~Guidicelli~~, ~~and Henry~~ Najer. 5-~~Phenyl~~-2-~~Cyclopropylamino~~-4-~~Oxazolidinone. Les Laboratoires Dausse~~, ~~assignee. Patent US3609159. 28 Sept~~. ~~1971~~.</ref>

According to patents filed by the inventors, cyclazodone exhibited central nervous system stimulating properties and anorexigenic properties much more potent than those of pemoline, and more potent than those of various other N-lower-alkyl-substituted pemoline derivatives. At the time cyclazodone also offered a much more favorable therapeutic index and margin of safety than pemoline and other N-lower-alkyl-substituted pemoline derivatives.<ref name="GuidicelliPatent">{{Citation | vauthors=((Guidicelli, D. P. R. L.)), ((Najer, H.)) | title=5-phenyl-2-cyclopropylamino-4-oxazolinone, and process for making the same | url=https://patents.google.com/patent/US3609159A/en}}</ref>

In animal models, cyclazodone exhibits central nervous system stimulant and antidepressant efficacy and potency at least equal to that of [[Isomer|dextro]]-amphetamine. The duration of maximum activity spanned 180 minutes, and the total duration of excitation was in excess of 6 hours.<ref~~>Val De Marne, Don Pierre R. L. Guidicelli, and Henry Najer. 5-Phenyl-2-Cyclopropylamino-4-Oxazolidinone. Les Laboratoires Dausse, assignee. Patent US3609159. 28 Sept. 1971.<~~/~~ref~~> Furthermore, according to the inventor's patents, cyclazodone also possessed anorexic efficacy and potency at least equal to that of [[Isomer|dextro]]-amphetamine in animal models, yet the toxicity of cyclazodone was found to be low in comparison with the activity thereof.<ref~~>Val De Marne, Don Pierre R. L. Guidicelli, and Henry Najer. 5-Phenyl-2-Cyclopropylamino-4-Oxazolidinone. Les Laboratoires Dausse, assignee. Patent GB1005738A. 29 Sept. 1965.<~~/~~ref~~>

In animal models, cyclazodone exhibits central nervous system stimulant and antidepressant efficacy and potency at least equal to that of [[Isomer|dextro]]-amphetamine. The duration of maximum activity spanned 180 minutes, and the total duration of excitation was in excess of 6 hours.<ref name="GuidicelliPatent"/> Furthermore, according to the inventor's patents, cyclazodone also possessed anorexic efficacy and potency at least equal to that of [[Isomer|dextro]]-amphetamine in animal models, yet the toxicity of cyclazodone was found to be low in comparison with the activity thereof.<ref name="GuidicelliPatent"/>

===Pharmacodynamics===

Cyclazodone is an [[amphetamine]]-like [[agonist]] of the Trace Amine Associated Receptor 1 (TAAR1), which is a key regulator of common and trace brain monoamines such as [[dopamine]], [[serotonin]] and [[noradrenaline]].<ref>The Emerging Role of Trace Amine Associated Receptor 1 in the Functional Regulation of Monoamine Transporters and Dopaminergic Activity ~~(PubMed.gov / NCBI)~~ | ~~http~~://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005101/</ref><ref>~~Drug banks amphetamine targets~~ | ~~http~~://~~www~~.drugbank.ca/drugs~~/DB00182~~#targets</ref><ref>TA1 receptor | http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=364</ref> The agonism of this set of receptors results in the release of increased concentrations of [[dopamine]], [[serotonin]] and [[noradrenaline]] in the [[synaptic cleft]]. This leads to [[Thought acceleration|cognitive]] and [[Stimulation|physical stimulation]] within the user.

Cyclazodone is an [[amphetamine]]-like [[agonist]] of the Trace Amine Associated Receptor 1 (TAAR1), which is a key regulator of common and trace brain monoamines such as [[dopamine]], [[serotonin]] and [[noradrenaline]].<ref>{{cite journal | vauthors=((Miller, G. M.)) | journal=Journal of neurochemistry | title=The Emerging Role of Trace Amine Associated Receptor 1 in the Functional Regulation of Monoamine Transporters and Dopaminergic Activity | volume=116 | issue=2 | pages=164–176 | date= January 2011 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005101/ | issn=0022-3042 | doi=10.1111/j.1471-4159.2010.07109.x}}</ref><ref>{{Citation | title=Amphetamine | url=https://go.drugbank.com/drugs#targets}}</ref><ref>TA1 receptor | http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=364</ref> The agonism of this set of receptors results in the release of increased concentrations of [[dopamine]], [[serotonin]] and [[noradrenaline]] in the [[synaptic cleft]]. This leads to [[Thought acceleration|cognitive]] and [[Stimulation|physical stimulation]] within the user.

==Subjective effects==

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The toxicity and long-term health effects of recreational cyclazodone use do not seem to have been studied in any scientific context and the [[Toxicity::exact toxic dosage is unknown]]. This is because cyclazodone has a very limited history of human usage.

Another compound related in structure, [[4-methylaminorex]], is associated with pulmonary hypertension<ref>~~https://www~~.~~ncbi~~.~~nlm~~.~~nih~~.~~gov~~/~~pubmed/11083709~~</ref>; though, it is reported to induce far stronger stimulation than that of cyclazodone.

Another compound related in structure, [[4-methylaminorex]], is associated with pulmonary hypertension<ref>{{cite journal | vauthors=((Gaine, S. P.)), ((Rubin, L. J.)), ((Kmetzo, J. J.)), ((Palevsky, H. I.)), ((Traill, T. A.)) | journal=Chest | title=Recreational use of aminorex and pulmonary hypertension | volume=118 | issue=5 | pages=1496–1497 | date= November 2000 | issn=0012-3692 | doi=10.1378/chest.118.5.1496}}</ref>; though, it is reported to induce far stronger stimulation than that of cyclazodone.

The structurally related compound pemoline was removed from the market after it was found to cause liver damage in children.<ref>Marotta, P. J., & Roberts, E. A. ~~(1998~~). Pemoline hepatotoxicity in children. ~~The Journal of Pediatrics, 132~~(5)~~, 894~~-~~897.~~</ref>

The structurally related compound pemoline was removed from the market after it was found to cause liver damage in children.<ref>{{cite journal | vauthors=((Marotta, P. J.)), ((Roberts, E. A.)) | journal=The Journal of Pediatrics | title=Pemoline hepatotoxicity in children | volume=132 | issue=5 | pages=894–897 | date= May 1998 | url=https://linkinghub.elsevier.com/retrieve/pii/S0022347698703294 | issn=00223476 | doi=10.1016/S0022-3476(98)70329-4}}</ref>

In rodents and primates, sufficiently high doses of monoamine [[releasing agent|releasing agents]] cause dopaminergic neurotoxicity, or damage to dopamine neurons, which is characterized by reduced transporter and receptor function. There is no evidence that [[releasing agent]]s are directly neurotoxic in humans. However, large doses of [[releasing agent]]s may cause indirect neurotoxicity as a result of increased oxidative stress from reactive oxygen species and autoxidation of dopamine.{{citation needed}}

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===Psychosis===

Based on its pharmacological similarity to other stimulants, it is likely that misuse of this compound can result in state of psychosis marked by a variety of symptoms (e.g., [[Paranoia|paranoia]], [[External hallucinations|hallucinations]], or [[Delusions|delusions]]).<ref>~~http~~://~~www~~.~~drugabuse~~.gov/~~drugs~~-~~abuse~~/emerging-trends</ref><ref name="amppsychosis">Shoptaw, S. J., Kao, U., & Ling, W. (~~2009~~). Treatment for amphetamine psychosis. ~~The Cochrane Library~~.</ref> A review on the treatment for [[amphetamine]] and [[methamphetamine]] abuse-induced psychosis states that about 5–15% of users fail to recover completely.<ref name="amppsychosis" /><ref>Hofmann ~~FG (~~1983). A ~~Handbook~~ on ~~Drug~~ and ~~Alcohol Abuse: The Biomedical Aspects (2nd ed.). New York~~: Oxford University Press~~. p. 329. ISBN 9780195030570.~~</ref> The same review asserts that based upon at least one trial, [[antipsychotic]] medications effectively resolve the symptoms of acute amphetamine psychosis.<ref name="amppsychosis" /> Psychosis very rarely arises from therapeutic use. The combination of the prolonged use of high doses combined with sleep deprivation significantly increases the risk of stimulant psychosis.{{citation needed}}

Based on its pharmacological similarity to other stimulants, it is likely that misuse of this compound can result in state of psychosis marked by a variety of symptoms (e.g., [[Paranoia|paranoia]], [[External hallucinations|hallucinations]], or [[Delusions|delusions]]).<ref>{{Citation | vauthors=((National Institute on Drug Abuse)) | title=Emerging Trends | url=https://nida.nih.gov/research-topics/emerging-trends-alerts}}</ref><ref name="amppsychosis">{{cite book | vauthors=((Shoptaw, S. J.)), ((Kao, U.)), ((Ling, W. W.)) | veditors=((The Cochrane Collaboration)) | date=8 October 2008 | chapter=The Cochrane Database of Systematic Reviews (Complete Reviews) | title=Treatment for amphetamine psychosis | publisher=John Wiley & Sons, Ltd | pages=CD003026.pub2 | url=https://doi.wiley.com/10.1002/14651858.CD003026.pub2 | doi=10.1002/14651858.CD003026.pub2}}</ref> A review on the treatment for [[amphetamine]] and [[methamphetamine]] abuse-induced psychosis states that about 5–15% of users fail to recover completely.<ref name="amppsychosis" /><ref>{{cite book | vauthors=((Hofmann, F. G.)) | date= 1983 | title=A handbook on drug and alcohol abuse: the biomedical aspects | publisher=Oxford University Press | edition=2nd ed | isbn=9780195030563}}</ref> The same review asserts that based upon at least one trial, [[antipsychotic]] medications effectively resolve the symptoms of acute amphetamine psychosis.<ref name="amppsychosis" /> Psychosis very rarely arises from therapeutic use. The combination of the prolonged use of high doses combined with sleep deprivation significantly increases the risk of stimulant psychosis.{{citation needed}}

===Dangerous interactions===

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*'''Germany''': Cyclazodone is not a controlled substance under the BtMG (''Narcotics Act'')<ref>{{cite web|url=https://www.gesetze-im-internet.de/btmg_1981/BJNR106810981.html|title=Gesetz über den Verkehr mit Betäubungsmitteln (Betäubungsmittelgesetz - BtMG)|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 28, 2019|language=de}}</ref> or the NpSG (''New Psychoactive Substances Act'').<ref>{{cite web|url=https://www.gesetze-im-internet.de/npsg/BJNR261510016.html|title=Neue-psychoaktive-Stoffe-Gesetz (NpSG)|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 28, 2019|language=de}}</ref> According to §2 AMG (''Medicines Act'') it would fall under the definition of a medicine because it induces pharmacological effect.<ref>{{cite web|url=https://www.gesetze-im-internet.de/amg_1976/__2.html|title=§ 2 AMG|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 28, 2019|language=de}}</ref> By a decision of the European Court of Justice, this definition was declared ineffective because it was not compatible with EU law.<ref>{{cite news|url=https://www.lto.de/recht/hintergruende/h/eugh-urteil-c35813-c18114-legal-highs-kein-arzneimittel-strafbar-amg-btmg/|title= Cannabinoide Kräutermischungen vor dem EuGH: Legal Highs bleiben legal|publisher=LTO|author=Prof. Dr. Helmut Pollähne|trans-title=Cannabinoid herbal mixtures at the ECJ: Legal highs stay legal|date=July 11, 2014|access-date=December 28, 2019|language=de}}</ref> Cyclazodone can be considered legal.

*'''Switzerland''': Cyclazodone is not controlled under Buchstabe A, B, C and D. It could be considered legal.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>

* '''United States''': Cyclazodone being an analogue of [[pemoline]], a Schedule IV controlled substance in the US, may fall under Federal Analogue Act, 21 U.S.C. § 813<ref>https://www.law.cornell.edu/uscode/text/21/813</ref> when intended for human consumption.

* '''United States''': Cyclazodone being an analogue of [[pemoline]], a Schedule IV controlled substance in the US, may fall under Federal Analogue Act, 21 U.S.C. § 813<ref>{{Citation | title=21 U.S. Code § 813 - Treatment of controlled substance analogues | url=https://www.law.cornell.edu/uscode/text/21/813}}</ref> when intended for human consumption.

==See also==

@@ Line 19: / Line 19: @@
 Cyclazodone is an approximately 3x - 5x more potent N-cyclopropyl derivative of [[pemoline]]. Pemoline is considered to be [[dopamine|dopaminergic]], but its precise method of action has not been fully determined.<ref>"Cylert (Pemoline)" (PDF). FDA. December 2002.</ref> Pemoline has minimal affinity for [[noradrenaline]] receptors and thus has minimal sympathomimetic side effects compared with typical dopaminergic central nervous system stimulants such as methylphenidate and [[Isomer|dextro]]-amphetamine.
-According to patents filed by the inventors, cyclazodone exhibited central nervous system stimulating properties and anorexigenic properties much more potent than those of pemoline, and more potent than those of various other N-lower-alkyl-substituted pemoline derivatives. At the time cyclazodone also offered a much more favorable therapeutic index and margin of safety than pemoline and other N-lower-alkyl-substituted pemoline derivatives.<ref>Val De Marne, Don Pierre R. L. Guidicelli, and Henry Najer. 5-Phenyl-2-Cyclopropylamino-4-Oxazolidinone. Les Laboratoires Dausse, assignee. Patent US3609159. 28 Sept. 1971.</ref>
+According to patents filed by the inventors, cyclazodone exhibited central nervous system stimulating properties and anorexigenic properties much more potent than those of pemoline, and more potent than those of various other N-lower-alkyl-substituted pemoline derivatives. At the time cyclazodone also offered a much more favorable therapeutic index and margin of safety than pemoline and other N-lower-alkyl-substituted pemoline derivatives.<ref name="GuidicelliPatent">{{Citation | vauthors=((Guidicelli, D. P. R. L.)), ((Najer, H.)) | title=5-phenyl-2-cyclopropylamino-4-oxazolinone, and process for making the same | url=https://patents.google.com/patent/US3609159A/en}}</ref>
-In animal models, cyclazodone exhibits central nervous system stimulant and antidepressant efficacy and potency at least equal to that of [[Isomer|dextro]]-amphetamine. The duration of maximum activity spanned 180 minutes, and the total duration of excitation was in excess of 6 hours.<ref>Val De Marne, Don Pierre R. L. Guidicelli, and Henry Najer. 5-Phenyl-2-Cyclopropylamino-4-Oxazolidinone. Les Laboratoires Dausse, assignee. Patent US3609159. 28 Sept. 1971.</ref> Furthermore, according to the inventor's patents, cyclazodone also possessed anorexic efficacy and potency at least equal to that of [[Isomer|dextro]]-amphetamine in animal models, yet the toxicity of cyclazodone was found to be low in comparison with the activity thereof.<ref>Val De Marne, Don Pierre R. L. Guidicelli, and Henry Najer. 5-Phenyl-2-Cyclopropylamino-4-Oxazolidinone. Les Laboratoires Dausse, assignee. Patent GB1005738A. 29 Sept. 1965.</ref>
+In animal models, cyclazodone exhibits central nervous system stimulant and antidepressant efficacy and potency at least equal to that of [[Isomer|dextro]]-amphetamine. The duration of maximum activity spanned 180 minutes, and the total duration of excitation was in excess of 6 hours.<ref name="GuidicelliPatent"/> Furthermore, according to the inventor's patents, cyclazodone also possessed anorexic efficacy and potency at least equal to that of [[Isomer|dextro]]-amphetamine in animal models, yet the toxicity of cyclazodone was found to be low in comparison with the activity thereof.<ref name="GuidicelliPatent"/>
 ===Pharmacodynamics===
-Cyclazodone is an [[amphetamine]]-like [[agonist]] of the Trace Amine Associated Receptor 1 (TAAR1), which is a key regulator of common and trace brain monoamines such as [[dopamine]], [[serotonin]] and [[noradrenaline]].<ref>The Emerging Role of Trace Amine Associated Receptor 1 in the Functional Regulation of Monoamine Transporters and Dopaminergic Activity (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005101/</ref><ref>Drug banks amphetamine targets | http://www.drugbank.ca/drugs/DB00182#targets</ref><ref>TA1 receptor | http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=364</ref> The agonism of this set of receptors results in the release of increased concentrations of [[dopamine]], [[serotonin]] and [[noradrenaline]] in the [[synaptic cleft]]. This leads to [[Thought acceleration|cognitive]] and [[Stimulation|physical stimulation]] within the user.
+Cyclazodone is an [[amphetamine]]-like [[agonist]] of the Trace Amine Associated Receptor 1 (TAAR1), which is a key regulator of common and trace brain monoamines such as [[dopamine]], [[serotonin]] and [[noradrenaline]].<ref>{{cite journal | vauthors=((Miller, G. M.)) | journal=Journal of neurochemistry | title=The Emerging Role of Trace Amine Associated Receptor 1 in the Functional Regulation of Monoamine Transporters and Dopaminergic Activity | volume=116 | issue=2 | pages=164–176 | date= January 2011 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005101/ | issn=0022-3042 | doi=10.1111/j.1471-4159.2010.07109.x}}</ref><ref>{{Citation | title=Amphetamine | url=https://go.drugbank.com/drugs#targets}}</ref><ref>TA1 receptor | http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=364</ref> The agonism of this set of receptors results in the release of increased concentrations of [[dopamine]], [[serotonin]] and [[noradrenaline]] in the [[synaptic cleft]]. This leads to [[Thought acceleration|cognitive]] and [[Stimulation|physical stimulation]] within the user.
 ==Subjective effects==
@@ Line 115: / Line 115: @@
 The toxicity and long-term health effects of recreational cyclazodone use do not seem to have been studied in any scientific context and the [[Toxicity::exact toxic dosage is unknown]]. This is because cyclazodone has a very limited history of human usage.
-Another compound related in structure, [[4-methylaminorex]], is associated with pulmonary hypertension<ref>https://www.ncbi.nlm.nih.gov/pubmed/11083709</ref>; though, it is reported to induce far stronger stimulation than that of cyclazodone.
+Another compound related in structure, [[4-methylaminorex]], is associated with pulmonary hypertension<ref>{{cite journal | vauthors=((Gaine, S. P.)), ((Rubin, L. J.)), ((Kmetzo, J. J.)), ((Palevsky, H. I.)), ((Traill, T. A.)) | journal=Chest | title=Recreational use of aminorex and pulmonary hypertension | volume=118 | issue=5 | pages=1496–1497 | date= November 2000 | issn=0012-3692 | doi=10.1378/chest.118.5.1496}}</ref>; though, it is reported to induce far stronger stimulation than that of cyclazodone.
-The structurally related compound pemoline was removed from the market after it was found to cause liver damage in children.<ref>Marotta, P. J., & Roberts, E. A. (1998). Pemoline hepatotoxicity in children. The Journal of Pediatrics, 132(5), 894-897.</ref>
+The structurally related compound pemoline was removed from the market after it was found to cause liver damage in children.<ref>{{cite journal | vauthors=((Marotta, P. J.)), ((Roberts, E. A.)) | journal=The Journal of Pediatrics | title=Pemoline hepatotoxicity in children | volume=132 | issue=5 | pages=894–897 | date= May 1998 | url=https://linkinghub.elsevier.com/retrieve/pii/S0022347698703294 | issn=00223476 | doi=10.1016/S0022-3476(98)70329-4}}</ref>
 In rodents and primates, sufficiently high doses of monoamine [[releasing agent|releasing agents]] cause dopaminergic neurotoxicity, or damage to dopamine neurons, which is characterized by reduced transporter and receptor function. There is no evidence that [[releasing agent]]s are directly neurotoxic in humans. However, large doses of [[releasing agent]]s may cause indirect neurotoxicity as a result of increased oxidative stress from reactive oxygen species and autoxidation of dopamine.{{citation needed}}
@@ Line 130: / Line 130: @@
 ===Psychosis===
 {{Main|Stimulant psychosis}}
-Based on its pharmacological similarity to other stimulants, it is likely that misuse of this compound can result in state of psychosis marked by a variety of symptoms (e.g., [[Paranoia|paranoia]], [[External hallucinations|hallucinations]], or [[Delusions|delusions]]).<ref>http://www.drugabuse.gov/drugs-abuse/emerging-trends</ref><ref name="amppsychosis">Shoptaw, S. J., Kao, U., & Ling, W. (2009). Treatment for amphetamine psychosis. The Cochrane Library.</ref> A review on the treatment for [[amphetamine]] and [[methamphetamine]] abuse-induced psychosis states that about 5–15% of users fail to recover completely.<ref name="amppsychosis" /><ref>Hofmann FG (1983). A Handbook on Drug and Alcohol Abuse: The Biomedical Aspects (2nd ed.). New York: Oxford University Press. p. 329. ISBN 9780195030570.</ref> The same review asserts that based upon at least one trial, [[antipsychotic]] medications effectively resolve the symptoms of acute amphetamine psychosis.<ref name="amppsychosis" /> Psychosis very rarely arises from therapeutic use. The combination of the prolonged use of high doses combined with sleep deprivation significantly increases the risk of stimulant psychosis.{{citation needed}}
+Based on its pharmacological similarity to other stimulants, it is likely that misuse of this compound can result in state of psychosis marked by a variety of symptoms (e.g., [[Paranoia|paranoia]], [[External hallucinations|hallucinations]], or [[Delusions|delusions]]).<ref>{{Citation | vauthors=((National Institute on Drug Abuse)) | title=Emerging Trends | url=https://nida.nih.gov/research-topics/emerging-trends-alerts}}</ref><ref name="amppsychosis">{{cite book | vauthors=((Shoptaw, S. J.)), ((Kao, U.)), ((Ling, W. W.)) | veditors=((The Cochrane Collaboration)) | date=8 October 2008 | chapter=The Cochrane Database of Systematic Reviews (Complete Reviews) | title=Treatment for amphetamine psychosis | publisher=John Wiley & Sons, Ltd | pages=CD003026.pub2 | url=https://doi.wiley.com/10.1002/14651858.CD003026.pub2 | doi=10.1002/14651858.CD003026.pub2}}</ref> A review on the treatment for [[amphetamine]] and [[methamphetamine]] abuse-induced psychosis states that about 5–15% of users fail to recover completely.<ref name="amppsychosis" /><ref>{{cite book | vauthors=((Hofmann, F. G.)) | date= 1983 | title=A handbook on drug and alcohol abuse: the biomedical aspects | publisher=Oxford University Press | edition=2nd ed | isbn=9780195030563}}</ref> The same review asserts that based upon at least one trial, [[antipsychotic]] medications effectively resolve the symptoms of acute amphetamine psychosis.<ref name="amppsychosis" /> Psychosis very rarely arises from therapeutic use. The combination of the prolonged use of high doses combined with sleep deprivation significantly increases the risk of stimulant psychosis.{{citation needed}}
 ===Dangerous interactions===
@@ Line 141: / Line 141: @@
 *'''Germany''': Cyclazodone is not a controlled substance under the BtMG (''Narcotics Act'')<ref>{{cite web|url=https://www.gesetze-im-internet.de/btmg_1981/BJNR106810981.html|title=Gesetz über den Verkehr mit Betäubungsmitteln (Betäubungsmittelgesetz - BtMG)|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 28, 2019|language=de}}</ref> or the NpSG (''New Psychoactive Substances Act'').<ref>{{cite web|url=https://www.gesetze-im-internet.de/npsg/BJNR261510016.html|title=Neue-psychoaktive-Stoffe-Gesetz (NpSG)|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 28, 2019|language=de}}</ref> According to §2 AMG (''Medicines Act'') it would fall under the definition of a medicine because it induces pharmacological effect.<ref>{{cite web|url=https://www.gesetze-im-internet.de/amg_1976/__2.html|title=§ 2 AMG|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 28, 2019|language=de}}</ref> By a decision of the European Court of Justice, this definition was declared ineffective because it was not compatible with EU law.<ref>{{cite news|url=https://www.lto.de/recht/hintergruende/h/eugh-urteil-c35813-c18114-legal-highs-kein-arzneimittel-strafbar-amg-btmg/|title= Cannabinoide Kräutermischungen vor dem EuGH: Legal Highs bleiben legal|publisher=LTO|author=Prof. Dr. Helmut Pollähne|trans-title=Cannabinoid herbal mixtures at the ECJ: Legal highs stay legal|date=July 11, 2014|access-date=December 28, 2019|language=de}}</ref> Cyclazodone can be considered legal.
 *'''Switzerland''': Cyclazodone is not controlled under Buchstabe A, B, C and D. It could be considered legal.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>
-* '''United States''': Cyclazodone being an analogue of [[pemoline]], a Schedule IV controlled substance in the US, may fall under Federal Analogue Act, 21 U.S.C. § 813<ref>https://www.law.cornell.edu/uscode/text/21/813</ref> when intended for human consumption.
+* '''United States''': Cyclazodone being an analogue of [[pemoline]], a Schedule IV controlled substance in the US, may fall under Federal Analogue Act, 21 U.S.C. § 813<ref>{{Citation | title=21 U.S. Code § 813 - Treatment of controlled substance analogues | url=https://www.law.cornell.edu/uscode/text/21/813}}</ref> when intended for human consumption.
 ==See also==