25CN-NBOH

Last updated
25CN-NBOH
NBOH-2CCN structure.png
Clinical data
Other namesNBOH-2C-CN
Legal status
Legal status
Identifiers
  • 4-[2-[(2-hydroxyphenyl)methylamino]ethyl]-2,5-dimethoxybenzonitrile
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C18H20N2O3
Molar mass 312.369 g·mol−1
3D model (JSmol)
  • COc1cc(C#N)c(OC)cc1CCNCc2ccccc2O
  • InChI=1S/C18H20N2O3/c1-22-17-10-15(11-19)18(23-2)9-13(17)7-8-20-12-14-5-3-4-6-16(14)21/h3-6,9-10,20-21H,7-8,12H2,1-2H3
  • Key:VWEDZTZAXHMZIL-UHFFFAOYSA-N

25CN-NBOH (sometimes also referred to as NBOH-2C-CN) [1] is a compound indirectly derived from the phenethylamine series of hallucinogens, which was discovered in 2014 at the University of Copenhagen. [2] It is a member of the NBOMe family of psychedelics. [3]

Contents

The drug is notable in being one of the most selective agonists of the serotonin 5-HT2A receptor known. [4] [5] [6] [7] [3]

A tritiated version of 25CN-NBOH has also been accessed and used for more detailed investigations of the binding to serotonin 5-HT2 receptors and autoradiography. [8]

Pharmacology

Pharmacodynamics

25CN-NBOH is notable as one of the most selective agonists of the serotonin 5-HT2A receptor yet discovered, with an affinity (pKi) of 8.88 at the human serotonin 5-HT2A receptor, 100-fold selectivity for the serotonin 5-HT2A receptor over the serotonin 5-HT2C receptor, and 46-fold selectivity for the serotonin 5-HT2A receptor over the serotonin 5-HT2B receptor. [4] [5] [6] [7] However, another study found that 25CN-NBOH only had around 25-fold selectivity for the serotonin 5-HT2A receptor over the serotonin 5-HT2B and 5-HT2C receptors. [3] [7] In any case, in 2020, 25CN-NBOH and the related drug (S,S)-DMBMPP were described as the most selective serotonin 5-HT2A receptor agonists discovered to date. [3]

Chemistry

Structure

The structure of 25CN-NBOH in complex with an engineered Gαq heterotrimer of the 5-HT2AR has been determined by cryoelectron microscopy (cryo-EM), showing a distinct binding mode when compared to LSD. [9]

Bindingmode of 25CN-NBOH in 5-HT2AR

Synthesis

25CN-NBOH is readily available from 2C-H in 57% over 4 steps. [10]

Animal studies

25CN-NBOH was found to partially substitute for DOI but was considerably weaker at inducing a head-twitch response (HTR) in mice. [11] [12] Another in vivo evaluation of 25CN-NBOH concluded that "Given its distinct in vitro selectivity for 5-HT2A over non 5-HT2 receptors and its behavioral dynamics, 25CN-NBOH appears to be a powerful tool for dissection of receptor-specific cortical circuit dynamics, including 5-HT2A related psychoactivity." [13]

25CN-NBOH induces the HTRs also referred to as "wet dog shakes" in rodents and the cortical fingerprint of serotonin-2A-receptor-mediated shaking behavior has been investigated in detail. [14]

Additional in vivo investigations with this ligand has emerged. [15] [16] [17] [18] [19] [20] [21] [22] Chronic administration in mice lead to desensitization of the 5-HT2AR (measured via HTR) and increased startle amplitude [23] whereas it does not effect reversal learning in mice. [24] 25CN-NBOH was shown to increase the production of CTGF in chondrocytes. [25] In rats, 25CN-NBOH induce a reduction in conditioned fear that was countered by pretreatment with 5-HT2AR inverse agonist MDL100907. [26]

A bioanalytical method for the detection of 25CN-NBOH has been developed. [27]

Literature

A review covering the literature up to 2020 was published in 2021. [28]

The tendency of the 4-cyano substitution to confer high 5-HT2A selectivity had previously been observed with DOCN, [29] but this was not sufficiently potent to be widely adopted as a research ligand. 25CN-NBOH is still slightly less selective for 5-HT2A than the more complex cyclized derivative 2S,6S-DMBMPP ((2S,6S)-2-(2,5-dimethoxy-4-bromobenzyl)-6-(2-methoxyphenyl)piperidine), [30] in binding assays, however it is also less complex to synthesize and has higher efficacy and selectivity in functional assays as a partial agonist of the 5-HT2A receptor.

(2S,6S)-2-(2,5-dimethoxy-4-bromobenzyl)-6-(2-methoxyphenyl)piperidine SS9b structure.png
(2S,6S)-2-(2,5-dimethoxy-4-bromobenzyl)-6-(2-methoxyphenyl)piperidine

Legality

Hungary

25CN-NBOH is illegal in Hungary. [31]

United Kingdom

This substance is a Class A drug in the United Kingdom as a result of the N-benzylphenethylamine catch-all clause in the Misuse of Drugs Act 1971 . [32]

See also

Related Research Articles

<span class="mw-page-title-main">Psychedelic drug</span> Hallucinogenic class of psychoactive drug

Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states and a perceived "expansion of consciousness". Also referred to as classic hallucinogens or serotonergic hallucinogens, the term psychedelic is sometimes used more broadly to include various types of hallucinogens, such as those which are atypical or adjacent to psychedelia like salvia and MDMA, respectively.

<span class="mw-page-title-main">5-HT receptor</span> Class of transmembrane proteins

5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand.

5-HT<sub>2A</sub> receptor Subtype of serotonin receptor

The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor (GPCR). The 5-HT2A receptor is a cell surface receptor, but has several intracellular locations.

<span class="mw-page-title-main">Serotonin receptor agonist</span> Neurotransmission-modulating substance

A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin, a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.

5-HT<sub>2B</sub> receptor Mammalian protein found in Homo sapiens

5-Hydroxytryptamine receptor 2B (5-HT2B) also known as serotonin receptor 2B is a protein that in humans is encoded by the HTR2B gene. 5-HT2B is a member of the 5-HT2 receptor family that binds the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Like all 5-HT2 receptors, the 5-HT2B receptor is Gq/G11-protein coupled, leading to downstream activation of phospholipase C.

<span class="mw-page-title-main">25I-NBOH</span> Chemical compound

25I-NBOH is a derivative of the phenethylamine-derived hallucinogen 2C-I that was discovered in 2006 by a team at Purdue University.

<span class="mw-page-title-main">Quipazine</span> Chemical compound

Quipazine, also known as 1-(2-quinolinyl)piperazine, is a serotonergic drug of the arylpiperazine family and an analogue of 1-(2-pyridinyl)piperazine which is used in scientific research. It was first described in the 1960s and was originally intended as an antidepressant but was never developed or marketed for medical use.

<span class="mw-page-title-main">Serotonin releasing agent</span> Class of compounds

A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter efflux at other types of monoamine neurons, including dopamine and norepinephrine neurons.

<span class="mw-page-title-main">25B-NBOMe</span> Chemical compound

25B-NBOMe is a derivative of the phenethylamine psychedelic 2C-B, discovered in 2004 by Ralf Heim at the Free University of Berlin. It acts as a potent full agonist for the 5HT2A receptor. Duration of effects lasts about 3–10 hours, although the parent compound is rapidly cleared from the blood when used in the radiolabeled form in tracer doses. Recently, Custodio et al. (2019) evaluated the potential involvement of dysregulated dopaminergic system, neuroadaptation, and brain wave changes which may contribute to the rewarding and reinforcing properties of 25B-NBOMe in rodents.

<span class="mw-page-title-main">SB-206553</span> Chemical compound

SB-206553 is a drug which acts as a mixed antagonist for the 5-HT2B and 5-HT2C serotonin receptors.

5-HT2C receptor agonists are a class of drugs that activate 5-HT2C receptors. They have been investigated for the treatment of a number of conditions including obesity, psychiatric disorders, sexual dysfunction and urinary incontinence.

<span class="mw-page-title-main">Head-twitch response</span> Head movement in rodents upon 5-HT2A receptor activation

The head-twitch response (HTR), also sometimes known as wet dog shakes (WDS) in rats, is a rapid side-to-side head movement that occurs in mice and rats when the serotonin 5-HT2A receptor is activated. Serotonergic psychedelics like lysergic acid diethylamide (LSD) and psilocybin consistently induce the HTR in rodents. Because of this, the HTR is widely employed in scientific research as an animal behavioral model of hallucinogen effects and in the discovery of new psychedelic drugs.

<span class="mw-page-title-main">DMBMPP</span> Chemical compound

DMBMPP, or 2-(2,5-dimethoxy-4-bromobenzyl)-6-(2-methoxyphenyl)piperidine, is a 2-benzylpiperidine analog of the hallucinogenic N-benzylphenethylamine 25B-NBOMe and was discovered in 2011 by Jose Juncosa in the group of David E. Nichols at Purdue University. DMBMPP differs from 25B-NBOMe by incorporating the amine within a piperidine ring, making for a more rigid molecular structure than that of the open-chain 25B-NBOMe. The presence of the piperidine ring introduces two stereocenters, thus, four stereoisomers of this compound can be made.

<span class="mw-page-title-main">25N-NBOMe</span> Chemical compound

25N-NBOMe is a derivative of the hallucinogen 2C-N. The pharmacological properties of 25N-NBOMe have not been described in the scientific literature, but it is believed to act in a similar manner to related compounds such as 25I-NBOMe and 25C-NBOMe, which are potent agonists at the 5HT2A receptor. 25N-NBOMe has been sold as a street drug and has only been described in the literature in terms of identification by forensic analysis.

<span class="mw-page-title-main">1-Methylpsilocin</span> Chemical compound

1-Methylpsilocin (developmental code names CMY, CMY-16) is a tryptamine derivative developed by Sandoz which acts as a selective agonist of the serotonin 5-HT2C receptor (IC50Tooltip half-maximal inhibitory concentration of 12 nM, vs. 633 nM at 5-HT2A), and an inverse agonist at 5-HT2B (Ki of 38 nM). While 1-methylpsilocin does have higher affinity for 5-HT2C than 5-HT2A, it does produce a head-twitch response in mice that is dependent on 5-HT2A, so it is not entirely free of effects on 5-HT2Ain vivo. In contrast to psilocin, 1-methylpsilocin did not activate 5-HT1A receptors in mice.

<span class="mw-page-title-main">25B-NBOH</span> Chemical compound

25B-NBOH is a derivative of the phenethylamine derived hallucinogen 2C-B which has been sold as a designer drug. It acts as a potent serotonin receptor agonist with similar affinity to the better-known compound 25B-NBOMe at 5-HT2A and 5-HT2C receptors with pKis values of 8.3 and 9.4, respectively.

<span class="mw-page-title-main">25G-NBOMe</span> Chemical compound

25G-NBOMe (NBOMe-2C-G) is a derivative of the phenethylamine hallucinogen 2C-G, which acts as a highly potent agonist for the human 5-HT2A receptor.

<span class="mw-page-title-main">25-NB</span> Family of serotonergic psychedelics

The 25-NB (25x-NBx) series, or NBOMe series, also known as the N-benzylphenethylamines, is a family of serotonergic psychedelics. They are substituted phenethylamines and were derived from the 2C family. The most commonly encountered NBOMe drugs are 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe.

<span class="mw-page-title-main">LPH-5 (drug)</span> New psychedelic drug

LPH-5 is a psychedelic discovered by Emil Marcher-Rørsted, Jesper L. Kristensen and Anders A. Jensen at Danish biopharmaceutical company Lophora. It is a conformationally-restricted derivative of the phenethylamine 2C-TFM, also a hallucinogen, and acts as a potent agonist of the 5-HT2A receptor (EC50 = 3.2 nM, Emax = 78%). It shows 10- to 100-fold selectivity for the 5-HT2A receptor over the 5-HT2B and 5-HT2C receptors and, along with related compounds like 25CN-NBOH, is said to be one of the few truly selective 5-HT2A receptor agonists. LPH-5 is expected to avoid the cardiac risks of 5-HT2B receptor activation.

References

  1. ↑ "25CN-NBOH". Chemical Probes.
  2. ↑ "CNS Medicinal Chemistry in the Kristensen Group". Department of Drug Design and Pharmacology. University of Copenhagen. 25 March 2019.
  3. 1 2 3 4 Poulie CB, Jensen AA, Halberstadt AL, Kristensen JL (December 2020). "DARK Classics in Chemical Neuroscience: NBOMes". ACS Chem Neurosci. 11 (23): 3860–3869. doi:10.1021/acschemneuro.9b00528. PMC   9191638 . PMID   31657895.
  4. 1 2 Hansen M, Phonekeo K, Paine JS, Leth-Petersen S, Begtrup M, Bräuner-Osborne H, Kristensen JL (March 2014). "Synthesis and structure-activity relationships of N-benzyl phenethylamines as 5-HT2A/2C agonists". ACS Chemical Neuroscience. 5 (3): 243–249. doi:10.1021/cn400216u. PMC   3963123 . PMID   24397362.
  5. 1 2 Jensen AA, McCorvy JD, Leth-Petersen S, Bundgaard C, Liebscher G, Kenakin TP, et al. (June 2017). "Detailed Characterization of the In Vitro Pharmacological and Pharmacokinetic Properties of N-(2-Hydroxybenzyl)-2,5-Dimethoxy-4-Cyanophenylethylamine (25CN-NBOH), a Highly Selective and Brain-Penetrant 5-HT2A Receptor Agonist". The Journal of Pharmacology and Experimental Therapeutics. 361 (3): 441–453. doi: 10.1124/jpet.117.239905 . PMID   28360333.
  6. 1 2 Hansen M (2011). Design and Synthesis of Selective Serotonin Receptor Agonists for Positron Emission Tomography Imaging of the Brain (Ph.D. thesis). University of Copenhagen.
  7. 1 2 3 Halberstadt AL, Sindhunata IS, Scheffers K, Flynn AD, Sharp RF, Geyer MA, Young JW (August 2016). "Effect of 5-HT2A and 5-HT2C receptors on temporal discrimination by mice". Neuropharmacology. 107: 364–375. doi:10.1016/j.neuropharm.2016.03.038. PMC   5403251 . PMID   27020041.
  8. ↑ Jensen AA, Halberstadt AL, Märcher-Rørsted E, Odland AU, Chatha M, Speth N, et al. (July 2020). "The selective 5-HT2A receptor agonist 25CN-NBOH: Structure-activity relationship, in vivo pharmacology, and in vitro and ex vivo binding characteristics of [3H]25CN-NBOH". Biochemical Pharmacology. 177: 113979. doi:10.1016/j.bcp.2020.113979. PMID   32298690. S2CID   215802376.
  9. ↑ Kim K, Che T, Panova O, DiBerto JF, Lyu J, Krumm BE, et al. (September 2020). "Structure of a Hallucinogen-Activated Gq-Coupled 5-HT2A Serotonin Receptor". Cell. 182 (6): 1574–1588.e19. doi:10.1016/j.cell.2020.08.024. PMC   7593816 . PMID   32946782.
  10. ↑ Märcher-Rørsted E, Nykodemová J, Kristensen JL (2021-06-08). "An improved, scalable synthesis of the selective serotonin 2A receptor agonist 25CN-NBOH". SynOpen. 05 (2): a–1524–4439. doi: 10.1055/a-1524-4439 . ISSN   2509-9396.
  11. ↑ Fantegrossi WE, Gray BW, Bailey JM, Smith DA, Hansen M, Kristensen JL (March 2015). "Hallucinogen-like effects of 2-([2-(4-cyano-2,5-dimethoxyphenyl) ethylamino]methyl)phenol (25CN-NBOH), a novel N-benzylphenethylamine with 100-fold selectivity for 5-HT₂A receptors, in mice". Psychopharmacology. 232 (6): 1039–1047. doi:10.1007/s00213-014-3739-3. PMC   4339409 . PMID   25224567.
  12. ↑ Halberstadt AL, van der Zee JV, Chatha M, Geyer MA, Powell SB (February 2019). "Chronic treatment with a metabotropic mGlu2/3 receptor agonist diminishes behavioral response to a phenethylamine hallucinogen". Psychopharmacology. 236 (2): 821–830. doi:10.1007/s00213-018-5118-y. PMC   6778591 . PMID   30448990.
  13. ↑ Buchborn T, Lyons T, Knöpfel T (2018). "Tolerance and Tachyphylaxis to Head Twitches Induced by the 5-HT2A Agonist 25CN-NBOH in Mice". Frontiers in Pharmacology. 9: 17. doi: 10.3389/fphar.2018.00017 . PMC   5808243 . PMID   29467649.
  14. ↑ Buchborn T, Lyons T, Song C, Feilding A, Knöpfel T (May 2023). "Cortical Correlates of Psychedelic-Induced Shaking Behavior Revealed by Voltage Imaging". International Journal of Molecular Sciences. 24 (11): 9463. doi: 10.3390/ijms24119463 . ISSN   1422-0067. PMC   10253917 . PMID   37298417.
  15. ↑ Harmon JL, Wills LP, McOmish CE, Demireva EY, Gingrich JA, Beeson CC, Schnellmann RG (April 2016). "5-HT2 Receptor Regulation of Mitochondrial Genes: Unexpected Pharmacological Effects of Agonists and Antagonists". The Journal of Pharmacology and Experimental Therapeutics. 357 (1): 1–9. doi:10.1124/jpet.115.228395. PMC   4809314 . PMID   26787771.
  16. ↑ Odland AU, Jessen L, Kristensen JL, Fitzpatrick CM, Andreasen JT (February 2021). "The 5-hydroxytryptamine 2A receptor agonists DOI and 25CN-NBOH decrease marble burying and reverse 8-OH-DPAT-induced deficit in spontaneous alternation". Neuropharmacology. 183: 107838. doi:10.1016/j.neuropharm.2019.107838. PMID   31693871. S2CID   207831116.
  17. ↑ Yang GE, Tae HJ, Lee TK, Park YE, Cho JH, Kim DW, et al. (September 2019). "Risperidone Treatment after Transient Ischemia Induces Hypothermia and Provides Neuroprotection in the Gerbil Hippocampus by Decreasing Oxidative Stress". International Journal of Molecular Sciences. 20 (18): 4621. doi: 10.3390/ijms20184621 . PMC   6770640 . PMID   31540405.
  18. ↑ Amodeo DA, Hassan O, Klein L, Halberstadt AL, Powell SB (October 2020). "Acute serotonin 2A receptor activation impairs behavioral flexibility in mice". Behavioural Brain Research. 395: 112861. doi: 10.1016/j.bbr.2020.112861 . PMID   32814148.
  19. ↑ Xing L, Kalebic N, Namba T, Vaid S, Wimberger P, Huttner WB (December 2020). "Serotonin Receptor 2A Activation Promotes Evolutionarily Relevant Basal Progenitor Proliferation in the Developing Neocortex". Neuron. 108 (6): 1113–1129.e6. doi: 10.1016/j.neuron.2020.09.034 . PMID   33080227. S2CID   224775595.
  20. ↑ Elsilä LV, Korhonen N, Hyytiä P, Korpi ER (2020). "Acute Lysergic Acid Diethylamide Does Not Influence Reward-Driven Decision Making of C57BL/6 Mice in the Iowa Gambling Task". Frontiers in Pharmacology. 11: 602770. doi: 10.3389/fphar.2020.602770 . PMC   7745734 . PMID   33343373.
  21. ↑ Liu X, Zhu H, Gao H, Tian X, Tan B, Su R (April 2022). "Gs signaling pathway distinguishes hallucinogenic and nonhallucinogenic 5-HT2AR agonists induced head twitch response in mice". Biochemical and Biophysical Research Communications. 598: 20–25. doi:10.1016/j.bbrc.2022.01.113. PMID   35149433. S2CID   246548173.
  22. ↑ Ilchibaeva T, Tsybko A, Zeug A, Müller FE, Guseva D, Bischoff S, et al. (August 2022). "Serotonin Receptor 5-HT2A Regulates TrkB Receptor Function in Heteroreceptor Complexes". Cells. 11 (15): 2384. doi: 10.3390/cells11152384 . PMC   9368268 . PMID   35954229.
  23. ↑ Tsybko AS, Ilchibaeva TV, Filimonova EA, Eremin DV, Popova NK, Naumenko VS (December 2020). "The Chronic Treatment With 5-HT2A Receptor Agonists Affects the Behavior and the BDNF System in Mice". Neurochemical Research. 45 (12): 3059–3075. doi:10.1007/s11064-020-03153-5. PMID   33095437. S2CID   225052555.
  24. ↑ Odland AU, Kristensen JL, Andreasen JT (August 2021). "The selective 5-HT2A receptor agonist 25CN-NBOH does not affect reversal learning in mice". Behavioural Pharmacology. 32 (5): 448–452. doi:10.1097/FBP.0000000000000626. PMID   33595957. S2CID   231953516.
  25. ↑ Hori A, Nishida T, Takashiba S, Kubota S, Takigawa M (2017-11-16). "Regulatory mechanism of CCN2 production by serotonin (5-HT) via 5-HT2A and 5-HT2B receptors in chondrocytes". PLOS ONE. 12 (11): e0188014. Bibcode:2017PLoSO..1288014H. doi: 10.1371/journal.pone.0188014 . PMC   5690650 . PMID   29145495.
  26. ↑ Hagsäter SM, Pettersson R, Pettersson C, Atanasovski D, Näslund J, Eriksson E (September 2021). "A Complex Impact of Systemically Administered 5-HT2A Receptor Ligands on Conditioned Fear". The International Journal of Neuropsychopharmacology. 24 (9): 749–757. doi: 10.1093/ijnp/pyab040 . PMC   8453278 . PMID   34228806.
  27. ↑ Breusova K, Ernstsen KG, Palner M, Linnet K, Kristensen JL, Kretschmann AC (May 2021). "A quantitative method for the selective 5-HT2A agonist 25CN-NBOH in rat plasma and brain". Journal of Pharmaceutical and Biomedical Analysis. 199: 114016. doi:10.1016/j.jpba.2021.114016. PMID   33784574. S2CID   232431316.
  28. ↑ Märcher Rørsted E, Jensen AA, Kristensen JL (November 2021). "25CN-NBOH: A Selective Agonist for in vitro and in vivo Investigations of the Serotonin 2A Receptor". ChemMedChem. 16 (21): 3263–3270. doi:10.1002/cmdc.202100395. PMID   34288515. S2CID   236157499.
  29. ↑ Nelson DL, Lucaites VL, Wainscott DB, Glennon RA (January 1999). "Comparisons of hallucinogenic phenylisopropylamine binding affinities at cloned human 5-HT2A, -HT(2B) and 5-HT2C receptors". Naunyn-Schmiedeberg's Archives of Pharmacology. 359 (1): 1–6. doi:10.1007/PL00005315. PMID   9933142. S2CID   20150858.
  30. ↑ Juncosa JI, Hansen M, Bonner LA, Cueva JP, Maglathlin R, McCorvy JD, et al. (January 2013). "Extensive rigid analogue design maps the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin receptor agonist ligands". ACS Chemical Neuroscience. 4 (1): 96–109. doi:10.1021/cn3000668. PMC   3547484 . PMID   23336049.
  31. ↑ "A Magyarországon megjelent, a Kábítószer és Kábítószer-függőség Európai Megfigyelő Központjának Korai Jelzőrendszerébe (EMCDDA EWS) 2005 óta bejelentett ellenőrzött anyagok büntetőjogi vonatkozású besorolása" [The criminal law-related classification of controlled substances announced in 2005 in the Early Warning System of the European Monitoring Center for Drugs and Drug Addiction (EMCDDA EWS) in Hungary](PDF) (in Hungarian). September 2015.
  32. ↑ "The Misuse of Drugs Act 1971 (Ketamine etc.) (Amendment) Order 2014". UK Statutory Instruments 2014 No. 1106. www.legislation.gov.uk.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.