MDMA THERAPY

Bad trip on psychedelics: what do we mean by that?

A “bad trip” is a popular term for an experience with psychedelics that escalates into intense fear, panic, confusion, or disorientation. This can range from a few minutes of shock and loss of control to a situation where someone becomes dangerously impulsive, appears unresponsive, or requires medical attention. Such episodes occur primarily at higher dosages, with an unfavorable set and setting, in combinations with other substances, with sleep deprivation, or when underlying vulnerability is involved, such as previous psychoses or severe anxiety disorders.

As psychedelics are increasingly being studied in a therapeutic context as well as being used recreationally, attention to safety and harm reduction is also growing. A practical question that arises is: do medications exist that can mitigate or even “stop” a severe psychedelic disorder?

First the basics: de-escalation before medication

In most protocols, as well as in acute care, non-pharmacological support takes priority. Examples include a calm environment, reducing stimuli, safe contact, reassurance, gentle guidance on breathing and posture, and preventing escalation through conflict or physical restraint. This is not merely “soft,” but often effective: many difficult experiences subside on their own when someone feels safe and is not rushed further.

Medication primarily comes into play when someone is at acute risk to themselves or others, is severely agitated, or when anxiety and delusions become so intense that conversation and the environment are no longer sufficient. That is an important distinction: the existence of potential “trip killers” does not mean that they should be used as a standard or low-threshold measure.

What does science say so far about “trip killers”?

A recent scientific review article discusses candidate drugs that could theoretically and pharmacologically attenuate or terminate the psychedelic state. Important: this is a critical review, not a clinical trial. Therefore, no new patient data are presented and no proven effect sizes are provided. The value of such a review lies primarily in organizing plausible options, mechanisms of action, and safety questions, and in exposing the lack of systematic research.

The review examines, among other things, receptor activity (particularly the 5-HT2A receptor, which plays a central role in classic psychedelics such as LSD and psilocybin), pharmacokinetics (how quickly it works and how long it lasts), side effects, and practical applicability in acute situations. Those wishing to read the summary and context of this overview can do so via this source: Trip killers: which medications can potentially weaken or stop a bad trip.

Which middle groups are discussed?

The authors describe several groups of substances. It is useful to understand this classification, because “stopping a trip” is different from “dampening anxiety” or “sedating someone”. Broadly speaking, they mention:

1) Selective 5-HT2A antagonists
This includes substances such as ketanserin, pimavanserin, pirenperone, pizotifen, and ritanserin. The idea is logical: if classic psychedelics largely drive their effects via 5-HT2A, then blocking that receptor could diminish the experience. In the review, ketanserin and pirenperone are mentioned as pharmacologically plausible candidates, but availability, side effects, and practical applicability are limitations.

2) Antipsychotics
A broad list is discussed, including risperidone, paliperidon, olanzapine, quetiapine, and others. The authors conclude that risperidone is a practical “first choice” when ketanserin is unavailable, with paliperidon as an alternative. At the same time, they cite haloperidol specifically as an example of a drug that may be less suitable, because it might not effectively attenuate the psychedelic state and could exacerbate anxiety. That is an important nuance: not every drug used “for psychosis” is automatically appropriate for a psychedelic crisis.

3) Remedies for anxiety and depression
The review discusses trazodone, mirtazapine, buspirone, and mianserin, among others, and also mentions broader classes such as SSRIs and tricyclic antidepressants. The authors view trazodone and mirtazapine in particular as candidates that could be helpful in practice, often partly due to sedation. This does not automatically mean that they end the core of the trip, but rather that they can reduce overstimulation and restlessness.

4) Antihistamines
Cyproheptadine receives relatively much attention because, in addition to antihistaminergic effects, it also has 5-HT2A antagonistic properties. Additionally, diphenhydramine and promethazine are mentioned. Here too, the principle applies: sedation can provide calm, but it is not the same as a targeted “off switch” for psychedelic effects.

5) Benzodiazepines
Benzodiazepines (such as diazepam, lorazepam, and midazolam) are specifically mentioned as agents that usually do not actually stop the trip, but can dampen anxiety and agitation. In acute care, they are known as anxiolytic and sedative, but they also carry risks, such as respiratory depression when combined with other depressants, and the risk of dependence with repeated use.

6) Other and less sensible “strategies”
Niacin is mentioned as historical and speculative. Alcohol and cannabis are cited as examples that can be awkward or risky rather than helpful, because they can turn out unpredictable and cloud the situation.

Why this is not a manual for self-medication

It is tempting to distill a simple “this works” list from such a review. But that would be going too far. First: the overview provides a provisional pharmacological framework, not a proven clinical guideline. Second: drugs such as antipsychotics and benzodiazepines are prescription-only and have serious side effects and interactions. Third: in real crises, context plays a role, such as physical parameters, other medications taken, medical history, and the degree of danger.

In harm reduction, this usually means focusing on prevention (dosage, set and setting, fasting sitter, no risky combinations), and making a plan for emergencies in advance. If someone becomes unwell, loses consciousness, experiences severe chest pain, overheats, has epileptic seizures, or is no longer safe, calling for professional help is the appropriate course of action.

What does this mean for therapy and guided sessions?

In research settings involving psychedelics, there is a strong emphasis on screening, preparation, guidance, and aftercare, precisely to prevent severe dysregulation and to detect it early. Moreover, in the Netherlands, MDMA sessions can currently only be discussed and approached within scientific research or in clinical practice in a harm-reduction context. This makes safety, boundaries, and transparency all the more important: no promises, but realistic information, and clear agreements regarding guidance and emergency procedures.

Anyone considering a guided session would often do well to ask how anxiety peaks are handled, which de-escalation skills are used, how aftercare is structured, and how they act if escalation is necessary. That is generally more sensible than relying on the idea that medication can “switch everything off.”.

Conclusion

Plausible candidate drugs have been described in science that could potentially mitigate or terminate severe dysregulation caused by psychedelics, particularly agents that block the 5-HT2A receptor and certain antipsychotics. At the same time, the substantiation remains provisional: it primarily concerns pharmacological logic and limited evidence, not hard efficacy data from clinical trials. From a harm reduction perspective, therefore, the core remains: good preparation, a safe setting, timely de-escalation, and calling in professional help if the situation becomes dangerous.

If you would like to carefully explore a guided MDMA session within the boundaries of what is currently possible and open for discussion, you can register via https://mdmatherapie.nl/aanmelden-mdma-sessie/.