Cyclazodone

Cyclazodone is a phenyl 4-oxazolidinone that differs from the parent pemoline by an N-cyclopropyl group. Compounds like cyclazodone of the 4-oxazolidinone class can be considered as 4-oxy derivatives of the 2-amino-5-aryloxazoline class including aminorex, fluminorex, and 4-methylaminorex, conformationally restricted analogues of phenethylamines and amphetamines.

Cyclazodone is structurally most closely related, not to pemoline, but rather to two N-substituted derivatives of pemoline — fenozolone (N-ethyl pemoline) and thozalinone (N,N-dimethyl pemoline).

Cyclazodone is an approximately 3x - 5x more potent N-cyclopropyl derivative of pemoline. Pemoline is considered to be dopaminergic, but its precise method of action has not been fully determined.^[1] 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 dextro-amphetamine.

According to patents filed by the inventors, cyclazodone exhibited central nervous system stimulating properties and anorexigenic properties more potent than that of pemoline and 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.^[2]

In animal models, cyclazodone exhibits central nervous system stimulant and antidepressant efficacy and potency at least equal to that of dextro-amphetamine. The duration of maximum activity spanned 180 minutes, and the total duration of excitation was in excess of 6 hours.^[2] Furthermore, according to the inventor's patents, cyclazodone also possessed anorexic efficacy and potency at least equal to that of dextro-amphetamine in animal models, yet the toxicity of cyclazodone was found to be low in comparison with the activity thereof.^[2]

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.^[3][4][5] 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 cognitive and physical stimulation within the user.

The stimulant effects of cyclazodone have been compared to those of amphetamine, but with the addition of a low to moderate affinity for serotonin release comparable to that of methamphetamine and 3-FMA. Additionally, it is noticeably less euphoric than amphetamine and appears to have less sympathomimetic activation.

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 ☠.

Experience reports

There are currently 0 experience reports which describe the effects of this substance in our experience index.

The toxicity and long-term health effects of recreational cyclazodone use do not seem to have been studied in any scientific context and the 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^[6]; 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.^[7]

In rodents and primates, sufficiently high doses of monoamine 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 agents are directly neurotoxic in humans. However, large doses of releasing agents may cause indirect neurotoxicity as a result of increased oxidative stress from reactive oxygen species and autoxidation of dopamine.^{[citation needed]}

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

Tolerance and addiction potential

Addiction is a serious risk with heavy recreational stimulant use but is unlikely to arise from typical long-term medical use at therapeutic doses. Notably, the structurally related compound pemoline fails to demonstrate a potential for self-administration in primates and is considered to have reduced risk of dependence relative to those more typical dopaminergic stimulants. Caution is nonetheless advised, as with other monoamine releasing agents.

Tolerance to many of the effects of cyclazodone develops with prolonged and repeated use. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). Cyclazodone presents cross-tolerance with all dopaminergic stimulants, meaning that after the consumption of cyclazodone all stimulants will have a reduced effect.

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, hallucinations, or delusions).^[8][9] A review on the treatment for amphetamine and methamphetamine abuse-induced psychosis states that about 5–15% of users fail to recover completely.^[9][10] The same review asserts that based upon at least one trial, antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis.^[9] 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

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.

• 25x-NBOMe & 25x-NBOH - 25x compounds are highly stimulating and physically straining. Combinations with Cyclazodone should be strictly avoided due to the risk of excessive stimulation and heart strain. This can result in increased blood pressure, vasoconstriction, panic attacks, thought loops, seizures, and heart failure in extreme cases.
• Alcohol - Combining alcohol with stimulants can be dangerous due to the risk of accidental over-intoxication. Stimulants mask alcohol's depressant effects, which is what most people use to assess their degree of intoxication. Once the stimulant wears off, the depressant effects will be left unopposed, which can result in blackouts and severe respiratory depression. If mixing, the user should strictly limit themselves to only drinking a certain amount of alcohol per hour.
• DXM - Combinations with DXM should be avoided due to its inhibiting effects on serotonin and norepinephrine reuptake. There is an increased risk of panic attacks and hypertensive crisis, or serotonin syndrome with serotonin releasers (MDMA, methylone, mephedrone, etc.). Monitor blood pressure carefully and avoid strenuous physical activity.
• MDMA - Any neurotoxic effects of MDMA are likely to be increased when other stimulants are present. There is also a risk of excessive blood pressure and heart strain (cardiotoxicity).
• MXE - Some reports suggest combinations with MXE may dangerously increase blood pressure and increase the risk of mania and psychosis.
• Dissociatives - Both classes carry a risk of delusions, mania and psychosis, and these risk may be multiplied when combined.
• Stimulants - Cyclazodone may be dangerous to combine with other stimulants like cocaine as they can increase one's heart rate and blood pressure to dangerous levels.
• Tramadol - Tramadol is known to lower the seizure threshold^[11] and combinations with stimulants may further increase this risk.

Cyclazodone is currently a gray area compound within all parts of the world, meaning its regulation lies in a legal gray area and that it is not known to be specifically illegal ("scheduled") within any country. However, people may still be charged for its possession under certain circumstances such as under analogue laws and with intent to sell or consume. It is a banned stimulant under the World Anti-Doping Agency prohibited list.

• Germany: Cyclazodone is not a controlled substance under the BtMG (Narcotics Act)^[12] or the NpSG (New Psychoactive Substances Act).^[13] According to §2 AMG (Medicines Act) it would fall under the definition of a medicine because it induces pharmacological effect.^[14] By a decision of the European Court of Justice, this definition was declared ineffective because it was not compatible with EU law.^[15] Cyclazodone can be considered legal.
• Switzerland: Cyclazodone is not controlled under Buchstabe A, B, C and D. It could be considered legal.^[16]
• 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^[17] when intended for human consumption.

• Responsible use
• Research chemicals
• Stimulants
• Releasing agent
• Amphetamine
• 4-Methylaminorex

• Cyclazodone (Wikipedia)
• Cyclazodone (Isomer Design)

• Segal, D. S., Cox Jr, R. H., Stern, W. C., & Maickel, R. P. (1967). Stimulatory effects of pemoline and cyclopropylpemoline on continuous avoidance behavior: similarity to effects of D-amphetamine. Life Sciences, 6(23), 2567-2572. https://doi.org/10.1016/0024-3205(67)90322-0