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Psilocybin, also known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT), and formerly sold under the brand name Indocybin, is a naturally occurring psychedelic prodrug compound produced by more than 200 species of fungi. Psilocybin is itself biologically inactive but is quickly converted by the body to psilocin, which has mind-altering effects similar, in some aspects, to those of other classical psychedelics. In general, the effects include euphoria, visual and mental hallucinations, changes in perception, a distorted sense of time, and perceived spiritual experiences. It can also cause adverse reactions such as nausea and panic attacks.
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.
Psilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin. Psilocin is a Schedule I drug under the Convention on Psychotropic Substances. Acting on the serotonin 5-HT2A receptors, psilocin's psychedelic effects are directly correlated with the drug's occupancy at these receptor sites. The subjective mind-altering effects of psilocin are highly variable and are said to resemble those of lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DMT).
Norbaeocystin, also known as 4-phosphoryloxytryptamine (4-PO-T), is a psilocybin mushroom alkaloid and analog of psilocybin. It is found as a minor compound in most psilocybin mushrooms together with psilocin, psilocybin, aeruginascin, and baeocystin, from which it is a derivative.
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.
Substituted tryptamines, or serotonin analogues, are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all tryptamines contain an indole ring, joined to an amino (NH2) group via an ethyl (−CH2–CH2−) sidechain. In substituted tryptamines, the indole ring, sidechain, and/or amino group are modified by substituting another group for one of the hydrogen (H) atoms.
Psilocybin therapy is the use of psilocybin in treating a range of mental health conditions, such as depression, anxiety, addictions, obsessive compulsive disorder, and psychosis. It is one of several forms of psychedelic therapy under study. Psilocybin was popularized as a psychedelic recreational drug in the 1970s and was classified as a Schedule I drug by the DEA. Research on psilocybin as a medical treatment was restricted until the 1990s because of the sociocultural fear of dependence on this drug. As of 2022, psilocybin is the most commonly researched psychedelic due to its safety and low potential for abuse and dependence. Clinical trials are being conducted at universities and there is evidence confirming the use of psilocybin in the treatment of depression, PTSD and end of life anxiety.
4-Propionoxy-N,N-dimethyltryptamine is a synthetic psychedelic drug from the tryptamine family with psychedelic effects, and is believed to act as a prodrug for psilocin. It produces a head-twitch response in mice. It has been sold online as a designer drug since May 2019. It was first identified as a new psychoactive substance in Sweden, in July 2019. A number of related derivatives have been synthesized as prodrugs of psilocin for medical applications.
Psychoplastogens are a group of small molecule drugs that produce rapid and sustained effects on neuronal structure and function, intended to manifest therapeutic benefit after a single administration. Several existing psychoplastogens have been identified and their therapeutic effects demonstrated; several are presently at various stages of development as medications including ketamine, MDMA, scopolamine, and the serotonergic psychedelics, including LSD, psilocin, DMT, and 5-MeO-DMT. Compounds of this sort are being explored as therapeutics for a variety of brain disorders including depression, addiction, and PTSD. The ability to rapidly promote neuronal changes via mechanisms of neuroplasticity was recently discovered as the common therapeutic activity and mechanism of action.
FT-104 is a psychedelic tryptamine derivative which is a prodrug ester of the well known designer drug 4-HO-DiPT. It is one of a number of related derivatives developed for potential medical applications, and is in human clinical trials as a possible treatment for postpartum depression and treatment-resistant depression.
4-HO-TMT, or 4-OH-TMT, also known as 4-hydroxy-N,N,N-trimethyltryptamine or as dephosphorylated aeruginascin, is a substituted tryptamine derivative and the active form of aeruginascin (4-PO-TMT), analogously to how psilocin (4-HO-DMT) is the active form of psilocybin (4-PO-DMT). 4-HO-TMT is closely related to bufotenidine, the N-trimethyl analogue of serotonin.
A trip killer, or hallucinogen antidote, is a drug that aborts or reduces the effects of a hallucinogenic drug experience. As there are different types of hallucinogens that work in different ways, there are different types of trip killers. They can completely block or reduce the effects of hallucinogens or they can simply provide anxiety relief and sedation. Examples of trip killers, in the case of serotonergic psychedelics, include serotonin receptor antagonists, like antipsychotics and certain antidepressants, and benzodiazepines. Trip killers are sometimes used by recreational psychedelic users as a form of harm reduction to manage so-called bad trips, for instance difficult experiences with prominent anxiety. They can also be used clinically to manage effects of hallucinogens, like anxiety and psychomotor agitation, for instance in the emergency department.
ITI-1549 is a putatively non-hallucinogenic serotonin 5-HT2A receptor agonist which is under development for the treatment of mood disorders and other psychiatric disorders. In addition to acting at the serotonin 5-HT2A receptor, it is also an antagonist of the serotonin 5-HT2B receptor and an agonist of the serotonin 5-HT2C receptor. The drug's route of administration has not been specified.
CYB003, or CYB-003, also known as deuterated psilocybin analogue, is a serotonergic psychedelic related to psilocybin which is under development for the treatment of major depressive disorder, alcoholism, and other psychiatric disorders. It is taken by mouth.
BMB-201 is a serotonin 5-HT2A and 5-HT2C receptor agonist described as a non-hallucinogenic psychoplastogen which is under development for the treatment of depression, anxiety, pain, and other indications.
BMB-202 is a serotonin 5-HT2A receptor agonist and psychedelic hallucinogen which is under development for the treatment of depressive disorders and post-traumatic stress disorder (PTSD). It is taken by mouth. However, BMB-202 has also been evaluated by injection in preclinical studies.
LPH-48 is a selective serotonin 5-HT2A receptor agonist and psychedelic hallucinogen which is under development for the treatment of alcoholism. Its route of administration has not been specified.
MYCO-005 is a serotonin 5-HT2A receptor agonist and psychedelic hallucinogen which is under development for the treatment of depressive disorders and anxiety disorders.
References
- 1 2 Mindset Pharma (14 November 2022). "Mindset Pharma Presents Poster at Neuroscience 2022 Highlighting Preclinical Data on MSP-1014, its Psilocybin-like Lead Drug Candidate". GlobeNewswire News Room (Press release). Retrieved 29 October 2024.
- 1 2 3 Araujo JA, Higgins GA, de Lannoy IA, Dean I, Atkinson J, Lanthier J, Slassi M. (2022 November 13). 147.05 / JJ5 - The preclinical safety, behavioural and pharmacokinetics properties of MSP-1014, a novel prodrug of psilocin. Neuroscience 2022. https://www.abstractsonline.com/pp8/#!/10619/presentation/70912
- 1 2 3 4 5 "MSP 1014". AdisInsight. 9 January 2024. Retrieved 29 October 2024.
- 1 2 3 4 "Delving into the Latest Updates on MSP-1014 with Synapse". Synapse. 26 October 2024. Retrieved 29 October 2024.
- 1 2 3 4 "Mindset Pharma Receives Approval for Phase II Clinical Trial Evaluating MSP-1014 for the Treatment of Major Depressive Disorder". BioSpace. 22 June 2023. Retrieved 29 October 2024.
MSP-1014 is a novel and patent-protected prodrug of psilocin, the active metabolite of psilocybin. MSP-1014 is anticipated to exert similar efficacy to psilocybin in improving symptoms of depression. Preclinical studies comparing MSP-1014 to psilocybin suggest that the tolerability of MSP-1014 may be superior to psilocybin.
- ↑ Dodd S, Norman TR, Eyre HA, Stahl SM, Phillips A, Carvalho AF, et al. (July 2022). "Psilocybin in neuropsychiatry: a review of its pharmacology, safety, and efficacy". CNS Spectrums. 28 (4): 416–426. doi: 10.1017/S1092852922000888 . PMID 35811423.
- ↑ US 2022/0289774,Slassi A, Araujo J,"Psilocin derivatives as serotonergic psychedelic agents for the treatment of cns disorders",issued 7 March 2023, assigned to Mindset Pharma Inc.
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