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Serotonergic psychedelics (also known as serotonergic hallucinogens) are a class of hallucinogenic drugs (specifically psychedelic drugs) with a method of action strongly tied to the serotonin neurotransmitter. Serotonin (often referred to as 5-HT, short for its full chemical name 5-Hydroxy Tryptamine) is a naturally occurring neurotransmitter which is tied to positive mood, certain involuntary muscle control, and countless other functions, many of which are not yet fully understood.

Method of actionEdit

While the method of action of serotonergic psychedelics is not fully understood, different serotonergic psychedelics are known to show affinities for different 5-HT receptors in different ways and at different levels, and may be classified by their activity at different 5-HT sub-sites, such as 5-HT1A, 5-HT1B, 5-HT2A, etc. Many serotonergic psychedelics, such as the family of tryptamines, have very strong structural similarities to serotonin itself, which partially explains the affinity for certain 5-HT sites. It is almost unanimously agreed that serotonergic psychedelics produce their effect by acting as strong partial agonists at the 5-HT2A receptors. How this produces the psychedelic experience is unclear, but it is likely that it acts by increasing excitation in the cortex, possibly by specifically facilitating input from the thalamus, the major relay for sensory information input to the cortex [1]. Worth noting is that selective serotonin reuptake inhibitors (a class of antidepressants including Paxil, Prozac, and Zoloft) strongly decrease the hallucinogenic effects of serotonergic psychedelics.[How to reference and link to summary or text] MDMA's effect is also strongly negated by the use of SSRIs, however MDMA is generally not considered a serotonergic psychedelic, as the majority of MDMA's action appears to be through stimulating a release of serotonin, which does not appear to be the method of action of the serotonergic psychedelics.


Examples of Serotonergic psychedelics include LSD, psilocybin, DMT and mescaline. The tryptamines, such as DMT, psilocybin, etc structurally resemble serotonin itself, see's Chem-Compare tool, here shown comparing serotonin and psilocybin. The family of phenethylamines, which includes Mescaline and many of the research chemicals such as 2C-I more strongly resembles dopamine, as shown here in a comparison of dopamine and mescaline.

Recreational usesEdit

The most widely known use of serotonergic psychedelics is as recreational drugs, providing the user with a psychedelic experience known in the common slang as a trip.

Spiritual usesEdit

Serotonergic psychedelics can be used in a religious or spiritual role as entheogens. In some cases (such as mescaline and psilocin) such use has occurred for centuries. Some entheogenic users also engage in or support recreational use, while others deem it irresponsible or sacrilegious.

Medical usesEdit

  • There is substantial anecdotal evidence that serotonergic psychedelics may be helpful in the treatment of cluster headaches.
  • There has been research, largely during the 1960s, suggesting that psychedelic drugs may be able to lead to breakthrough experiences during psychotherapy. Most of this research was centered around serotonergic psychedelics.
  • During the 1960s, some therapists would self-administer LSD in an attempt to gain insight to the nature of Schizophrenia and other psychotic disorders, as the effects of LSD and various other similar psychedelic drugs were believed at the time to be psychotomimetic. However while psychedelic drug therapy is believed to have some therapeutic effect, psychotomimetic action has not been found to be a direct product of LSD or other psychedelic drug use. Sandoz Laboratories provided most of the LSD for this use under the brand-name Delysid. Timothy Leary was a noteworthy individual who initially was performing LSD research along these lines.
  • Also during the 1960s, AMT (Alpha-Methyl-Tryptamine) was prescribed as an antidepressant due to its MAO Inhibitory properties, mostly in the former Soviet Union.
  • Psilocybin and other 5-HT2A receptor agonists appear to have a rapid and often sustained (after the drug has left the body) therapeutic effect on Obsessive-compulsive disorder.


  1. Nichols, David E. (2004). Hallucinogens. Pharmacology & Therapeutics 101 (2): 131–81.

External resourcesEdit

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