Serotonin 5-HT2A receptor antagonists Serotonergic psychedelics, such as
psilocybin (found in
psilocybin mushrooms),
lysergic acid diethylamide (LSD),
mescaline (found in
peyote cacti), and
dimethyltryptamine (DMT) (found in
ayahuasca), mediate their hallucinogenic effects by acting as
agonists of the
serotonin 5-HT2A receptor. This includes the effects of psilocybin, LSD, mescaline, and ayahuasca. Ketanserin is under formal clinical investigation as a "neutralizer" or "off-switch" for psychedelics.
Eplivanserin/volinanserin, a
combination of
eplivanserin and
volinanserin, is being studied for such uses as well. (Seroquel) is an
antipsychotic used as a trip killer. is an
antidepressant used as a trip killer. Other
potent serotonin 5-HT2A receptor antagonists that may block or reduce the effects of serotonergic psychedelics besides the above-listed drugs include other antipsychotics like
quetiapine,
olanzapine,
aripiprazole, and
pipamperone, antidepressants like
trazodone,
mirtazapine,
mianserin,
nefazodone, and
etoperidone, and the
antimigraine agent pizotifen, among others. The
typical antipsychotic chlorpromazine, which has significant but less-potent serotonin 5-HT2A receptor antagonism than many other antipsychotics, has shown incomplete and inconsistent effects in reversing psychedelic effects in clinical studies, A
positron emission tomography (PET) study found 85 to 95% blockade of serotonin 5-HT2 receptors with cyproheptadine at a total dose of 12 to 18mg/day. Certain other serotonin receptor antagonists, like chlorpromazine, have also been used to treat serotonin syndrome. Cyproheptadine might be useful as a serotonergic psychedelic antidote. However, a few small studies on cyproheptadine as an antagonist of the hallucinogenic effects of DMT have been inconsistent and inconclusive, as well as complicated by the drug's pronounced
antihistamine sedative effects. Serotonin 5-HT2A receptor antagonists that have been found to block the psychedelic-like effects of serotonergic psychedelics in animals but have not necessarily been tested for such purposes in humans include
cinanserin,
clozapine,
loxapine,
metergoline,
metitepine (methiothepin),
mianserin,
pirenperone,
pizotifen,
ritanserin, and
seganserin, among others. Non-hallucinogenic partial agonists of the serotonin 5-HT2A receptor with sufficiently low
intrinsic activity, such as
2-bromo-LSD (bromolysergide; BOL-148) and
lisuride, are effective in blocking the hallucinogenic-related effects of psychedelics in animals and/or humans as well. However, it has been argued that lisuride may actually be a psychedelic or hallucinogen itself at sufficiently high doses in humans. Serotonergic psychedelics are being developed as novel treatments for
psychiatric disorders and other conditions such as
depression. A practical limitation in terms of clinical use of many major psychedelics, for instance psilocybin, LSD, and mescaline, is their long
durations of action (4–12hours), which may require a whole day of clinical monitoring. In relation to this, shorter-acting psychedelics, like DMT,
5-MeO-DMT (mebufotenin), and
bretisilocin (5-fluoro-MET; GM-2505), are also being investigated for potential therapeutic use. However, an alternative approach that is being investigated is use of serotonin 5-HT2A receptor antagonists like ketanserin as trip killers to shorten the experiences of psychedelics.
Alcohol, which is also a GABAA receptor positive allosteric modulator with similar effects, has been used for such purposes as well. The reduced effects of psychedelics in the case of concomitant drugs that elevate serotonin levels may be due to
desensitization of serotonin 5-HT2A receptors. Instead, in one study, escitalopram resulted in greater
mystical experience,
emotional breakthrough, and
ego dissolution scores with DMT than in people not on escitalopram. High-dose
nicotinic acid (niacin, a B3
vitamer) was reported to reduce and block the effects of LSD in one early clinical study. However, a subsequent clinical study attempting to
replicate the findings found that it was not effective for this purpose. Some drugs that have been reported to potentiate rather than inhibit the effects of serotonergic psychedelics include
lithium,
reserpine,
pindolol, and
methysergide. Methysergide has also been reported to greatly potentiate the effects of DMT. This drug was originally thought to be a
potent serotonin antagonist, but is actually a
serotonin receptor agonist and produces psychedelic effects itself at supratherapeutic doses. A high rate of
seizures has been reported with the combination of lithium and psychedelics.
Use by recreational psychedelic users Recreational psychedelic users sometimes employ trip killers to abort psychedelic trips. Others used less frequently included the benzodiazepines
lorazepam,
clonazepam, and
etizolam, the antipsychotic
olanzapine, and the antidepressant
mirtazapine, among others. While employed by recreational users for harm-reduction purposes, the use of trip killers to abort the effects of psychedelics is not fully characterized and could pose medical risks. In addition, doses of trip killers used by recreational psychedelic users may be non-optimal or excessive and increase risks. ==Antidotes of other hallucinogens==