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.
5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), also known as O-methylbufotenin or mebufotenin, is a naturally occurring psychedelic of the tryptamine family. It is found in a wide variety of plant species, and is also secreted by the glands of at least one toad species, the Colorado River toad. It may occur naturally in humans as well. Like its close relatives dimethyltryptamine (DMT) and bufotenin (5-HO-DMT), it has been used as an entheogen in South America. Slang terms include Five-methoxy, the power, bufo, and toad venom.
Functional selectivity is the ligand-dependent selectivity for certain signal transduction pathways relative to a reference ligand at the same receptor. Functional selectivity can be present when a receptor has several possible signal transduction pathways. To which degree each pathway is activated thus depends on which ligand binds to the receptor. Functional selectivity, or biased signaling, is most extensively characterized at G protein coupled receptors (GPCRs). A number of biased agonists, such as those at muscarinic M2 receptors tested as analgesics or antiproliferative drugs, or those at opioid receptors that mediate pain, show potential at various receptor families to increase beneficial properties while reducing side effects. For example, pre-clinical studies with G protein biased agonists at the μ-opioid receptor show equivalent efficacy for treating pain with reduced risk for addictive potential and respiratory depression. Studies within the chemokine receptor system also suggest that GPCR biased agonism is physiologically relevant. For example, a beta-arrestin biased agonist of the chemokine receptor CXCR3 induced greater chemotaxis of T cells relative to a G protein biased agonist.
18-Methoxycoronaridine, also known as zolunicant, is a derivative of ibogaine invented in 1996 by the research team around the pharmacologist Stanley D. Glick from the Albany Medical College and the chemists Upul K. Bandarage and Martin E. Kuehne from the University of Vermont. In animal studies it has proven to be effective at reducing self-administration of morphine, cocaine, methamphetamine, nicotine and sucrose. It has also been shown to produce anorectic effects in obese rats, most likely due to the same actions on the reward system which underlie its anti-addictive effects against drug addiction.
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.
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.
Tebanicline is a potent synthetic nicotinic (non-opioid) analgesic drug developed by Abbott. It was developed as a less toxic analog of the potent poison dart frog-derived compound epibatidine, which is about 200 times stronger than morphine as an analgesic, but produces extremely dangerous toxic side effects. Like epibatidine, tebanicline showed potent analgesic activity against neuropathic pain in both animal and human trials, but with far less toxicity than its parent compound. It acts as a partial agonist at neuronal nicotinic acetylcholine receptors, binding to both the α3β4 and the α4β2 subtypes.
5-Fluoro-N,N-dimethyltryptamine is a tryptamine derivative related to compounds such as 5-bromo-DMT and 5-MeO-DMT. It produces a robust head-twitch response in mice, and hence is a putative serotonergic psychedelic. Fluorination of psychedelic tryptamines either reduces or has little effect on 5-HT2A/C receptor affinity or intrinsic activity, although 6-fluoro-DET is inactive as a psychedelic despite acting as a 5-HT2A agonist, while 4-fluoro-5-methoxy-DMT is a much stronger agonist at 5-HT1A than 5-HT2A.
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, including lysergic acid diethylamide (LSD), induce the HTR, and so the HTR is widely used as an animal behavioral model of hallucinogen effects and to discover new psychedelic drugs. HTR-like effects are also induced by psychedelics in other animal species, for instance cats and stump-tailed macaque monkeys. Other related behaviors to head twitches induced by serotonergic agents include limb jerks and body scratches. The only other behavioral paradigms for assessment of psychedelic-like effects in animals are drug discrimination (DD), prepulse inhibition (PPI), and time perception.
Tabernanthalog is a novel water-soluble, non-toxic azepinoindole analog of the psychoactive drug Tabernanthine first synthesized by Professor David E. Olson at UC Davis.
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.
DM-506 (ibogaminalog) is a drug first invented in the 1960s, which acts as both a partial agonist at the 5-HT2A receptor, and a negative allosteric modulator at the α7 and α9α10 nicotinic acetylcholine receptors. It can be regarded as a structurally simplified derivative of ibogaine and has been researched both for anti-addictive effects and for the treatment of neuropathic pain.
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.
6-MeO-DMT, or 6-methoxy-N,N-dimethyltryptamine, also known as 6-OMe-DMT, is a serotonergic drug of the tryptamine family. It is the 6-methoxy derivative of the serotonergic psychedelic N,N-dimethyltryptamine (DMT) and is a positional isomer of the serotonergic psychedelic 5-MeO-DMT.
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.
6-MeO-isoDMT, or 6-OMe-isoDMT, also known as 6-methoxy-N,N-dimethylisotryptamine, is a serotonin 5-HT2A receptor agonist, putative serotonergic psychedelic, and psychoplastogen of the isotryptamine group. It is the isotryptamine analogue of the psychedelic 5-MeO-DMT and is a positional isomer of the non-hallucinogenic psychoplastogen 5-MeO-isoDMT.
5-MeO-isoDMT, or 5-OMe-isoDMT, also known as 5-methoxy-N,N-dimethylisotryptamine, is a putatively non-hallucinogenic serotonin 5-HT2A receptor agonist and psychoplastogen of the isotryptamine group. It is the isotryptamine analogue of the non-hallucinogenic 6-MeO-DMT and is a positional isomer of the psychedelic 6-MeO-isoDMT.
isoDMT, also known as N,N-dimethylisotryptamine, is a putatively non-hallucinogenic serotonin 5-HT2A receptor agonist and psychoplastogen of the isotryptamine group. It is the isotryptamine homologue of dimethyltryptamine (DMT), a more well-known serotonergic psychedelic of the tryptamine family, and represents a small structural modification of DMT.
