A normal average dose of DOC ranges from 0.2–7.0 mg[20] the former producing threshold effects, and the latter producing extremely strong effects. Onset of the drug is 1–3 hours, peak and plateau at 4–8 hours, and a gradual come down with residual stimulation at 9-20h. After effects can last well into the next day.[20][21]
Unlike simple amphetamines, DOC is considered a chemical that influences cognitive and perception processes of the brain. The strongest supposed effects include open and closed eye visuals, increased awareness of sound and movement, and euphoria. In the autobiography PiHKAL, Alexander Shulgin included a description of DOC as "an archetypalpsychedelic" (#64); its presumed full-range visual, audio, physical, and mental effects show exhilarating clarity, and some overwhelming, humbling, and "composting"/interweaving effects.[21]
Very little data exists about the toxicity of DOC. In April 2013, a case of death due to DOC was reported. The source does not specify whether the drug alone caused the death.[22] In 2014, a death was reported in which DOC was directly implicated as the sole causative agent in the death of a user. The autopsy indicated pulmonary edema and a subgaleal hemorrhage.[23]
DOC may be quantitated in blood, plasma or urine by gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalized patients or to provide evidence in a medicolegal death investigation. Blood or plasma DOC concentrations are expected to be in a range of 1–10 μg/L in persons using the drug recreationally, >20 μg/L in intoxicated patients and >100 μg/L in victims of acute overdosage.[24]
Although rare on the black market, it has been available in bulk and shipped worldwide by select elite "Grey Market" Research Chemical suppliers for several years. Sales of DOC on blotting paper and in capsules was reported in late 2005 and again in late 2007. According to the DEA's Microgram from December 2007, the Concord Police Department in Contra Costa County, California, in the US, seized "a small piece of crudely lined white blotter paper without any design, suspected LSD 'blotter acid'". They added "Unusually, the paper appeared to be hand-lined using two pens, in squares measuring approximately 6 x 6 millimeters. The paper displayed fluorescence when irradiated at 365 nanometers; however, color testing for LSD with para-dimethylaminobenzaldehyde (Ehrlich's reagent) was negative. Analysis of a methanol extract by GC/MS indicated not LSD but rather DOC (not quantitated but a high loading based on the TIC)".[25] DOC is sometimes misrepresented as LSD by unscrupulous dealers. This is particularly dangerous, as DOC is not known to have the safety profile of LSD. It can be particularly unsafe, in comparison to LSD, for those suffering from hypertension, as amphetamine compounds are known to cause sharp increases in systolic blood pressure.
Listed as a Schedule 1[26] as it is an analogue of amphetamine.[27] The CDSA was updated as a result of the Safe Streets Act changing amphetamines from Schedule 3 to Schedule 1.[28]
Sveriges riksdag added DOC to schedule I ("substances, plant materials and fungi which normally do not have medical use") as narcotics in Sweden as of Aug 30, 2007, published by Medical Products Agency in their regulation LVFS 2007:10 listed as DOC, 4-klor-2,5-dimetoxi-amfetamin.[31]
DOC was first classified by Sveriges riksdags health ministry Statens folkhälsoinstitut as "health hazard" under the act Lagen om förbud mot vissa hälsofarliga varor (translated Act on the Prohibition of Certain Goods Dangerous to Health) as of Jul 1, 2004, in their regulation SFS 2004:486 listed as 4-klor-2,5-dimetoxiamfetamin (DOC).[32]
^Cha HJ, Jeon SY, Jang HJ, Shin J, Kim YH, Suh SK (May 2018). "Rewarding and reinforcing effects of 4-chloro-2,5-dimethoxyamphetamine and AH-7921 in rodents". Neurosci Lett. 676: 66–70. doi:10.1016/j.neulet.2018.04.009. PMID29626650.
^Kim YJ, Ma SX, Hur KH, Lee Y, Ko YH, Lee BR, et al. (April 2021). "New designer phenethylamines 2C-C and 2C-P have abuse potential and induce neurotoxicity in rodents". Arch Toxicol. 95 (4): 1413–1429. doi:10.1007/s00204-021-02980-x. PMID33515270.
^Custodio RJ, Sayson LV, Botanas CJ, Abiero A, You KY, Kim M, et al. (November 2020). "25B-NBOMe, a novel N-2-methoxybenzyl-phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential". Addict Biol. 25 (6): e12850. doi:10.1111/adb.12850. PMID31749223.
^Seo JY, Hur KH, Ko YH, Kim K, Lee BR, Kim YJ, et al. (October 2019). "A novel designer drug, 25N-NBOMe, exhibits abuse potential via the dopaminergic system in rodents". Brain Res Bull. 152: 19–26. doi:10.1016/j.brainresbull.2019.07.002. PMID31279579.
^Lee JG, Hur KH, Hwang SB, Lee S, Lee SY, Jang CG (August 2023). "Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System". ACS Chem Neurosci. 14 (15): 2658–2666. doi:10.1021/acschemneuro.3c00196. PMID37463338.
^Kim YJ, Kook WA, Ma SX, Lee BR, Ko YH, Kim SK, et al. (April 2024). "The novel psychoactive substance 25E-NBOMe induces reward-related behaviors via dopamine D1 receptor signaling in male rodents". Arch Pharm Res. 47 (4): 360–376. doi:10.1007/s12272-024-01491-4. PMID38551761.
^Fantegrossi WE, Murnane KS, Reissig CJ (January 2008). "The behavioral pharmacology of hallucinogens". Biochem Pharmacol. 75 (1): 17–33. doi:10.1016/j.bcp.2007.07.018. PMC2247373. PMID17977517. Despite the reasonably constant recreational use of hallucinogens since at least the early 1970s [44], the reinforcing effects of hallucinogens have not been widely investigated in laboratory animals. Indeed, one of the earliest studies on the reinforcing effects of drugs using the intravenous self-administration procedure in rhesus monkeys found that no animal initiated self-injection of mescaline either spontaneously or after one month of programmed administration [45]. Likewise, the phenethylamine hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM) was not effective in maintaining self-administration in rhesus monkeys [46]. Nevertheless, the hallucinogen-like phenethylamine 3,4-methylenedioxymethamphetamine (MDMA) has been shown to act as a reinforcer in intravenous self-administration paradigms in baboons [47], rhesus monkeys [48 – 50], rats [51] and mice [52].
^Canal CE, Murnane KS (January 2017). "The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens". J Psychopharmacol. 31 (1): 127–143. doi:10.1177/0269881116677104. PMC5445387. PMID27903793. One of the earliest studies on the reinforcing effects of drugs using the intravenous self-administration procedure in rhesus monkeys found that no animal initiated self-injection of mescaline either spontaneously or after one month of programmed administration, [...] (Deneau et al., 1969). The lack of mescaline self-administration stood in contrast to positive findings of self-administration of morphine, codeine, cocaine, amphetamine, pentobarbital, ethanol, and caffeine. A subsequent study with rhesus monkeys using 2,5-dimethoxy-4-methylamphetamine (DOM; Yanagita, 1986) provided similar results as the mescaline study. These findings have withstood the test of time, as the primary literature is virtually devoid of any accounts of self-administration of [classical hallucinogens (CH)], suggesting that there are very limited conditions under which laboratory animals voluntarily consume CH.
^Yanagita T (June 1986). "Intravenous self-administration of (-)-cathinone and 2-amino-1-(2,5-dimethoxy-4-methyl)phenylpropane in rhesus monkeys". Drug Alcohol Depend. 17 (2–3): 135–141. doi:10.1016/0376-8716(86)90004-9. PMID3743404.
^Maguire DR (October 2024). "Evaluation of potential punishing effects of 2,5-dimethoxy-4-methylamphetamine (DOM) in rhesus monkeys responding under a choice procedure". Behav Pharmacol. 35 (7): 378–385. doi:10.1097/FBP.0000000000000787. PMID39052019.
^Baselt RC (2014). Disposition of toxic drugs and chemicals in man. Seal Beach, California: Biomedical Publications. p. 2173. ISBN978-0-9626523-9-4.
^"mg1207"(PDF). Archived from the original(PDF) on 2012-10-17. Retrieved 2013-08-13.
^"Schedule I". Controlled Drugs and Substances Act. Canadian Legal Information Institute. 2022-03-31. Archived from the original on 2022-03-31. Retrieved 2022-03-31.
^"关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Archived from the original on 1 October 2015. Retrieved 1 October 2015.
