Benzodiazepines (“Benzos”) are commonly prescribed drugs for anxiety disorders and psychedelics are being studied to treat anxiety amongst other psychiatric conditions. Due to psychedelic-assisted psychotherapies (PAP) being poised to enter the clinician’s armamentarium in the near future, it stands to reason that the question of how to manage benzodiazepines in the context of psychedelic therapies will be relevant clinically. Outside clinical settings, benzodiazepines and psychedelics are already being used and combined in a variety of contexts, thus from a harm reduction perspective it’s already relevant to understand more about how these two classes of drug interact. In this article, we’ll explore how benzodiazepines interface with psychedelic healing as well as potential strategies to minimize risks and maximize benefits.

Benzo Background

What are benzodiazepines?

Benzodiazepines are a group of substances that facilitate GABA neurotransmission. GABA is the major inhibitory neurotransmitter in the brain, thus benzodiazepines have a globally calming effect on brain function. Examples of benzodiazepines include diazepam (Valium), lorazepam (Ativan), alprazolam (Xanax), clonazepam (Klonopin), oxazepam (Serax), temazepam (Restoril) as well as several others. Benzodiazepines are regulated as controlled substances in the United States due to their euphoric and sedative effects as well as their potential for dependence, tolerance, and development of benzodiazepine use disorders (addiction).

How are benzodiazepines used?

The calming properties of benzodiazepines on the brain are leveraged in both acute (emergency) and non-acute clinical situations. For example, benzodiazepines have been used to manage seizures, provide sedation for patients undergoing surgery or in Intensive Care Units, and provide calming effects for persons that are agitated and combative. In non-emergent clinical settings they are prescribed for the management of anxiety disorders and are either taken on an ‘as needed’ or ‘scheduled’ basis. Clinical guidelines for anxiety disorders recommend short courses of use to manage severe symptoms and recommend against the long term use of benzodiazepines due to risks associated with withdrawal and addiction as well as short and long term side effect burdens [1]. Clinical guidelines for PTSD recommend against the use of benzodiazepines due to harm generally outweighing benefits [2]. Nevertheless, due to their fast onset of action and propensity for habituation, it is common to encounter persons that have been using benzodiazepines daily for long periods of time.

In non-clinical contexts benzodiazepines are often used for their sedative and euphoric effects. Benzodiazepines, especially when combined with other sedatives like alcohol, are notorious for being able to produce anterograde amnesia (blackout), and have gained a reputation as date rape agents. For example, the benzodiazepine flunitrazepam is commonly known as a ‘roofie’ [3]. They have also been implicated as contributing to rising overdose deaths, especially in combination with other sedatives like opioids [4]. Due their cross-tolerance and longer lasting effects on GABA neurotransmission compared to alcohol, they are also used in alcohol detoxification protocols.

Benzodiazepine Interactions with Psychedelics

Generally, benzodiazepines will diminish effects of psychedelics and are have been known to be ‘trip killers’ in the psychedelic community (See DMT nexus, Reddit, or Blue Light Forum for more info). Psychedelics have been conceptualized as non-specific amplifiers of emotion while benzodiazepines have dampening effects on emotion, creating a theoretical rationale for counterproductive therapeutic effects [5]. Additionally, chronic benzodiazepine use has been associated with reduced efficacy of cognitive behavioral therapy and reduced gains of exposure therapy in persons with PTSD [6, 7]. Benzodiazepines have cognitive dulling effects that may increase the difficulty of participation in the therapeutic process or prevent them from remembering covered materials. It may therefore be reasonable to think that benzodiazepines could hinder PAP either by pharmacologic interaction or interference with psychotherapy elements of the intervention.

Beyond taking the edge off of subjective effects of psychedelics, benzodiazepines are not dangerous to combine with psychedelics. It is not uncommon in recreational environments for users of psychedelic amphetamines such as MDMA to use a benzo during the comedown phase of the experience to decrease anxiety or facilitate sleep or to ‘abort’ bad trips with LSD [8]. Benzodiazepines have also been administered in emergent situations involving psychedelics to reduce combative behaviors or abort seizures [9]. Guidelines for psychedelic clinical research recommend the use of benzodiazepines in the last resort situation in which acute psychological distress is insufficiently managed by non-drug supportive means [10].

In contemporary clinical trials of MDMA- and psilocybin-AP, the use of benzodiazepines have been disallowed prior to a psychedelic session. One protocol for MDMA-AP (pages 58-60) in persons with PTSD required taper and discontinuation for 5 half-lives plus an additional week to demonstrate stability for benzodiazepines [11]. Another randomized study of psilocybin-AP (see supplementary materials) for depression and anxiety in persons with cancer excluded persons using benzodiazepines on a daily basis and required those using on an intermittent (PRN or ‘as needed’) basis to refrain from use at least 5 half-lives prior to the psychedelic session [12]. Although not permitted prior to PAP sessions, benzodiazepines have been included in protocols of psychedelic clinical trials as rescue medications in the case of an emergent situation as well as severe anxiety or insomnia in the week after psychedelic use. They were utilized to manage anxiety in the week after (usually not day of) MDMA-AP in 24 of 51 (47%) sessions in one study [13]. In another study of MDMA-AP they were utilized less, although persons exposed to them (and had to taper off) prior to study enrollment appeared more likely to need them after MDMA use [14]. In clinical guidelines for the use of ibogaine constructed by the Global Ibogaine Therapy Alliance (GITA), it is recommended to not discontinue the use of daily benzodiazepines in persons undergoing ibogaine therapy for opioid detoxification due to potential risks of discontinuation and withdrawal seizures complicating the opioid detoxification [15].

There are three conclusions that can be drawn from all this:

Psychedelics and benzodiazepines are not dangerous to combine, although taper and discontinuation of chronic benzo use may optimize therapeutic potential of experience(s) Due to the serious potential risks of withdrawal with benzodiazepines, the risks of discontinuation in chronic users may outweigh benefits of a psychedelic experience in certain situations Intermittent and sparing use of benzodiazepines in the week after PAP sessions may be helpful in managing anxiety or insomnia, especially in persons with previous benzodiazepine exposure

Benzodiazepine Withdrawal

Let’s dive into withdrawal and some of the properties of benzodiazepines next as they will help determine what reasonable and safe management strategies may be.

What are risks of benzo withdrawal?

Benzodiazepines are known to be habit forming and addictive drugs with tolerance and dependence occurring after 3 weeks of consistent use. Due to the calming GABAergic properties of benzodiazepines, they create states of heightened excitatory activity when they are withdrawn, which can lead to things like insomnia, anxiety, panic attacks, hypersensitivity to sensory stimuli, and in severe cases seizures or psychosis. While it is common for psychotropic drugs to have withdrawal or discontinuation syndromes, the withdrawal syndrome for persons taking benzodiazepines can be overwhelming and medically dangerous. It is due to the life-threatening nature of seizures that discontinuation of benzodiazepines should not be done abruptly. It also makes benzodiazepine withdrawal somewhat unique, because while withdrawing from heroin is extremely uncomfortable, there are typically no life threatening complications that occur. Therefore, abrupt discontinuation of daily long term users is dangerous and should be avoided. Other common substance withdrawals that can be complicated by seizures includes alcohol.

What factors increase risk of severe benzodiazepine discontinuation syndromes?

There are a few factors that help guide potential for severe withdrawal:

Dose Higher doses are higher risk

Frequency of use Daily use higher risk than intermittent or ‘as needed’ use

Chronicity of use >8 weeks of consistent use typically requires taper The longer the period of use, the slower the taper should be



In essence, the bigger the dose over the longer period of time, the more difficulty and risk in discontinuation. Age may also play a role as persons aged over 60 years are usually more sensitive to withdrawal [4]. The primary factors that determine potential for severe withdrawal listed above also help to inform tapering schedules, with longer tapers for long time daily users.

By taking these factors in combination we can come up with 3 profiles of different benzodiazepine users: