A trip killer is a drug that aborts or reduces the effects of a hallucinogenic drug experience (or 'trip').[1][2][3][4][5][6][excessive citations] Examples, in the case of serotonergic psychedelics, such as LSD, psilocybin, mescaline, and dimethyltryptamine (DMT), include serotonin receptor antagonists like antipsychotics and certain antidepressants, benzodiazepines, and various other drugs.[4][7] Trip killers are often used by recreational psychedelic users as a form of harm reduction to manage so-called bad trips, for instance difficult experiences with prominent anxiety.[2][4] Although trip killers exist for certain types of hallucinogens, antidotes do not exist for all types of hallucinogens, for instance dissociatives like phencyclidine (PCP).[3]
The most commonly encountered putative trip killers in a 2024 online study of Reddit social media postings were the benzodiazepines alprazolam and diazepam, the antipsychotic quetiapine, the antidepressant trazodone, and alcohol.[4][5][6]
Drugs that have been formally assessed and shown in clinical studies to completely block or reduce the effects of serotonergic psychedelics include the serotonin 5-HT2A receptor antagonists ketanserin and risperidone.[7][8][9][10][11][12][13][excessive citations]
Benzodiazepines are anxiolytics and may be useful in reducing anxiety with hallucinogens, including clinically.[3][14] High-dose niacin (vitamin B3) was reported to reduce and block the effects of LSD in one study, but subsequent research found that it was ineffective.[7][15][16]
While used for harm-reduction purposes, combining hallucinogens with trip killers is not fully characterized and might pose medical risks.[1][2][4][5][6][excessive citations]
When psychedelics are used in recreational contexts without adequate supervision, they can lead to tragic outcomes.20 There are rare reports of serious adverse effects, including psychosis and even suicide, arising from recreational use.21 Methods for subduing socalled "bad trips" in recreational settings include potentially dangerous habits, such as taking benzodiazepines, which are known to be "trip killers."22
Another form of mixing substances involves the use of trip killers; a pharmacological coping strategy aimed to reduce the negative effects of a psychedelic experience by consuming a different substance (Suran, 2024). While this is a new concept and an under researched area, there are reports of trip killers being effective in reducing the negative effects of a psychedelic experience (Suran, 2024). One study gathered research from reddit, an online social media platform, investigating the usage of trip killers during challenging psychedelic experiences (Suran, 2024). The most popular and effective trip killers used were prescription medication, with 47% reporting the use of benzodiazepines as they reduce anxiety, followed by the use of antipsychotic and antidepressant medication (Suran, 2024). However, there are risks in mixing substances with psychedelic drugs, and subjectivity in the effectiveness. As some individuals may experience positive effects, while for others it may lead to negative effects (Suran, 2024). Therefore, it is recommended that before using trip killers, individuals should try other non- pharmacological coping strategies to reduce the negative effects of the psychedelic drug (Gable, 2004; Van Amsterdam et al., 2011). These factors discussed above, demonstrate the effectiveness of protective behaviours and harm reduction practices, in promoting safe psychedelic use and reducing harm.
Reports from clinical trials conclude that the psychedelic effects of psilocybin and LSD are mediated by 5-HT2A receptors, because they are blocked by ketanserin (40 mg, P.O.), typically viewed as a selective 5-HT2A antagonist (Kometer et al. 2012; Kraehenmann et al. 2017; Preller et al. 2017; Quednow et al. 2012). Haloperidol, typically viewed as a selective dopamine D2 antagonist, is much less effective than ketanserin at blocking psilocybin's effects, but risperidone, an antipsychotic with combined D2/5-HT2 activity, is as effective as ketanserin (Vollenweider et al. 1998).
Two 5- HT2A receptor antagonists – ketanserin (an antihypertensive) and risperidone (an atypical antipsychotic) – have been shown to eliminate self-reported psilocybin psychedelic effects in humans.2
In older work, various steroids (Bergen et al., 1960) including progesterone (Krus et aI., 1961) were reported to be effective antagonists. This has not been replicated. In other early work, some compounds initially reported to be effective were not found to be so by other workers. These include azacyclonal (Fabing, 1955) and niacin (Agnew and Hoffer, 1955).