Depersonalization/derealization disorder:

Epidemiology, pathogenesis, clinical

manifestations, course, and diagnosis
Author: Daphne Simeon, MD
Section Editor: David Spiegel, MD
Deputy Editor: Michael Friedman, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.

Literature review current through: Mar 2023. | This topic last updated: Sep 29, 2022.

INTRODUCTION

Depersonalization/derealization disorder (DDD) is characterized by the

persistence or recurrence of depersonalization and/or derealization that
cause clinically significant distress or impairment in the presence of intact
reality testing [1].

DDD has a prevalence of approximately 2 percent and is associated with

significant morbidity, but often goes undetected or misdiagnosed, leading
to delays in treatment.

This topic discusses the epidemiology, pathogenesis, clinical

manifestations, course, and diagnosis of DDD. Our approach to selecting
among treatments for DDD is discussed separately. Individual medications
and psychotherapies for DDD are also discussed separately. (See "Approach
to treating depersonalization/derealization disorder" and "Psychotherapy
of depersonalization/derealization disorder" and "Pharmacotherapy of
depersonalization/derealization disorder".)
DEFINITIONS

Depersonalization — Depersonalization is a persistent or recurrent feeling

of detachment or estrangement from one’s self. An individual experiencing
depersonalization may report feeling like an automaton or as if in a dream
or as if watching himself or herself in a movie. Depersonalized individuals
may report the sense of being an outside observer of their mental
processes or their body. They often report feeling a loss of control over
their thoughts, perceptions, and actions.

Derealization — Derealization is a subjective sense of detachment or

unreality regarding the world around them (eg, individuals or objects are
experienced as unreal, dreamlike, foggy, lifeless, or visually distorted).

EPIDEMIOLOGY

Prevalence — Transient experiences of depersonalization and

derealization are very common in the general population [2]. In a nonurban
United States sample, the one-year prevalence of depersonalization
symptoms was approximately 20 percent [3]. In a large normative sample
of German adolescents, 12 percent reported clinically significant
depersonalization [4]. Approximately half of college students in another
United States study reported experiencing an episode of depersonalization
in the past year. Adolescents and young adults appear to be at the highest
risk for reporting such symptoms, possibly because their sense of self is
still fluid and developmentally unstable.

Transient depersonalization symptoms, which may be primary or

secondary to another condition, are more common than
depersonalization/derealization disorder (DDD). Studies from several
countries including the United States, Canada, United Kingdom, Turkey,
and Germany have shown a lifetime prevalence for DDD in the range of 0.8
percent to 2.8 percent [5-7], comparable to that of other psychiatric
disorders such as schizophrenia, bipolar disorder, and obsessive-
compulsive disorder.

Risk factors — DDD has been found to be equally common in males and
females in clinical samples [8,9]. In up to half of cases there is no readily
identifiable proximal precipitant [8]. Common risk factors for DDD include
the following:

● Acute and chronic trauma or severe stress.

● Psychiatric conditions, most commonly anxiety or depressive disorders

– Chronic depersonalization and derealization symptoms meeting
diagnostic criteria for the disorder have also been reported to begin
during severe or prolonged episodes of a mood or anxiety disorder,
which may destabilize the sense of usual expected self and in itself act
as a powerful internal stressor [8]. This pattern occurs in approximately
one-third of all patients with DDD. Typically, in this scenario, the
depersonalization and derealization symptoms set in at some point of
escalation of the original disorder, but persist or worsen on a long-
term basis after the precipitating disorder has spontaneously remitted
or been treated, taking on an independent course, a “life of its own.”

● Alexithymia – Additionally, there is evidence of elevated rates of

alexithymia in those suffering from DDD, with nearly half of
participants demonstrating high or moderate alexithymia in one study
[10]. This difficulty in identifying and processing emotions is likely not
simply an outcome of the disorder, but is a risk factor for its genesis, as
alexithymic individuals have greater difficulty with the emotional
processing of traumatic and stressful events.

● Fearful attachment style – There is a high prevalence of insecure

attachment in DDD, with a preponderance of fearful attachment style
[11].

● Substance abuse.
Chronic depersonalization and derealization has been reported in as many
as one-third to one-half of individuals experiencing chronic traumatic or
highly stressful situations. Examples of these situations include (see 'Role
of trauma' below):

● Childhood abuse or neglect

● Unexpected death of a loved one
● Growing up with a seriously mentally ill parent or caregiver
● Sexual orientation/identity conflicts in adolescence and young
adulthood
● Serious relationship or work stressors

Comorbid conditions — Based on clinical samples, DDD appears to have

high rates of comorbidity with other psychiatric disorders. As an example,
in a study of 117 United States adults with DDD [8], the lifetime prevalence
of comorbid disorders was as follows:

● Unipolar depression, 73 percent

● Any anxiety disorder, 64 percent
● Obsessive-compulsive disorder, 21 percent
● Avoidant personality disorder, 23 percent
● Borderline personality disorder, 21 percent

PATHOGENESIS

Although the pathogenesis of depersonalization/derealization disorder

(DDD) has not been established, it is generally assumed that the syndrome
becomes manifest in individuals who have an inherent dissociative
diathesis combined with psychological and/or chemical stressors.

Role of trauma — Acute depersonalization and derealization are

quintessential responses to acute trauma (such as a motor vehicle
accident) or other life-threatening experiences [12,13], speculated to be
hardwired into the brain so that a sense of distance and detachment from
the traumatic event can facilitate surviving and negotiating the event
without experiencing overwhelming, disorganizing emotion (ie, “going
through the motions”) [12,13]. However, acute depersonalization and
derealization symptoms occurring in the above circumstances typically
clear within minutes, hours, or days, and do not become chronic. Chronic
depersonalization and derealization symptoms qualifying for the disorder
are more common among persons experiencing chronic traumatic or
highly stressful situations such as verbal or emotional abuse or neglect
during childhood [10,14].

Other traumatic antecedents include growing up with a parent or caregiver

who had severe mental illness, traumatically struggling with sexual
orientation or identity, and experiencing the unexpected death or suicide
of a family member or close friend. Sexual abuse and physical abuse are
less common antecedents of DDD than emotional maltreatment but clearly
occur (see above). Numerous other chronic life stressors (interpersonal,
financial, or occupational) have been associated with onset or exacerbation
of DDD. Examples include loss of a relationship or divorce, or job loss, or
social ostracization. It should be noted, however, that acute, short-lived
traumas or stressors can trigger the onset of the disorder as well. (See 'Risk
factors' above.)

The traumas reported by DDD patients are generally of a different nature

than those typically reported by patients with other dissociative disorders
such as dissociative identity disorder [10,14], centering on emotional
maltreatment rather than sexual abuse. (See "Dissociative identity disorder:
Epidemiology, pathogenesis, clinical manifestations, course, assessment,
and diagnosis".)

In a cumulative sample of 93 adults with DDD compiled across several

research studies, application of established clinically significant childhood
maltreatment cutoff scores for the Childhood Trauma Questionnaire
revealed that 63 percent of participants had experienced at least one form
of maltreatment, predominantly emotional abuse and/or neglect (55
percent). Additionally, physical neglect was endorsed by 40 percent,
physical abuse by 27 percent, and sexual abuse 20 percent [15].

Organic precursors — Common organic risk factors for depersonalization

and derealization include seizures, mild to moderate head injury, brain
tumors, and sleep apnea [16]. In such cases the diagnosis of the disorder is
not made, as it requires the exclusion of such “organic” underpinnings.

Substance abuse is known to precipitate chronic depersonalization in some

people [17]. (See 'Differential diagnosis' below.)

These individuals can thus be conceptualized as having a neurobiological

or genetic vulnerability to the onset of chronic depersonalization and
derealization (ie, DDD), after drug use. A large survey study has shown that
the characteristics and course of the condition do not differ between drug-
induced and non-drug-induced cases [17].

Neurobiology — Several neurotransmitter systems, brain regions, and

functional circuits have been associated with depersonalization and
derealization symptoms with some consistency and are summarized below
[18].

● NMDA (N-methyl-D-aspartate) system – NMDA receptors are widely

distributed in the cortex, hippocampus, and amygdala, and mediate
associative processes. The NMDA antagonist ketamine induces a
profound dissociative state in healthy subjects that is distinct, both
phenomenologically and in the implicated brain pathways, from the
psychotomimetic effects of ketamine [19,20]. Ketamine has complex
pharmacodynamics and effects on other neurotransmitter systems,
including Kappa opioid receptors that could relate to the acute
induction of depersonalization and derealization [21].

● Endogenous cannabinoid system – Cannabis has been

experimentally shown to induce depersonalization in healthy
 volunteers, with a pronounced component of temporal disintegration,
and particular brain regions have been implicated [22]. Cannabinoids
block NMDA receptors at sites distinct from other noncompetitive
NMDA antagonists [23] and therefore their dissociative effect may be
partly mediated via NMDA antagonism, as well as by the endogenous
cannabinoid system.

● Kappa opioid agonists – The illicit drug salvia, which acts as a selective
kappa opioid agonist, has been found to precipitate chronic
depersonalization [17,24]. Nonselective antagonists such as naloxone,
naltrexone, and nalmefene, which have varying affinity for the kappa
receptor, have been reported to diminish dissociative symptoms.

● Serotonin agonists – Hallucinogens act as agonists at serotonin

5HT2A and especially 5HT2C receptors. Experimental challenge studies
with the partial 5HT2A and C agonist m-CPP have demonstrated the
induction of depersonalization in a mixed group of social phobia,
borderline personality disorder, and obsessive-compulsive disorder
participants [25], the induction of flashbacks and dissociative
symptoms in a subgroup of posttraumatic stress disorder patients [26],
and the induction of dissociation in healthy volunteers [27].

● Autonomic hypo-reactivity – There is some evidence for autonomic

hypo-reactivity in DDD [28,29].

● Hypothalamic-pituitary-adrenal (HPA) axis – The HPA axis has been

investigated in DDD with conflicting findings. While one study reported
nonsignificantly lower basal salivary cortisol in DDD subjects compared
to healthy ones [30,31].

● Neuroimaging – Neuroimaging studies show evidence for the

following in DDD:

• Sensory integration occurring in the temporoparietal junction, in

particular in the right hemisphere, has been implicated in out-of-
 body experiences [32]. Altered activity in this area has been shown
by positron emission tomography scans [33].

• Functional magnetic resonance imaging studies have implicated

hypoactivation of the limbic system, in particular the insula, driven
by heightened prefrontal inhibition, in the hypoemotionality and
overthinking of DDD [34-36].

• Deficient representation of visceral-afferent neural signals at the

brainstem level [37].

• Evidence of less effective arousal suppression under cognitive stress

[38] and a higher sympathetic tone [39].

• Distinct brain correlates for anxiety, depression, somatization, and

dissociation symptoms [40].

• Grey matter alterations [41,42].

• Heightened activation in several brain areas associated with self-

processing [43].

The relationship between genes and DDD is not known. An analysis of

proband-based family history data in 117 subjects with DDD found a
heritability rate of only 5 percent [8].

Psychotherapeutic models — Conceptual models for DDD have been

developed from cognitive-behavioral and psychodynamic perspectives;
these are described separately. (See "Psychotherapy of
depersonalization/derealization disorder", section on 'Psychodynamic
therapy' and "Psychotherapy of depersonalization/derealization disorder".)

CLINICAL MANIFESTATIONS

Patients experiencing depersonalization and derealization often have great

difficulty putting their impalpable experiences into words. Unfamiliarity
with these symptoms may lead individuals to fear that they may be taken
for “crazy” or will become crazy. This is especially common in those raised
in homes with mental illness, those prone to hypochondriasis and
ruminations, and those who fear that a drug ingestion has caused
irreversible brain damage. Clinicians’ typical focus on comorbid symptoms
such as mood and anxiety often contributes to underdiagnosis or
misdiagnosis of depersonalization/derealization disorder (DDD).

Symptoms, although quite specific, may sound vague or metaphorical

rather than clear subjective experiences, such as “feeling dead,” “everything
is unreal,” “I don’t feel I’m the one doing anything,” “it’s like I’m watching a
movie,” etc. The symptoms are typically extremely distressing, at times
crippling, and are associated with major morbidity and some mortality. The
affectively flattened and robotic demeanor that these patients often
demonstrate can also fool the clinician into not recognizing the extreme
emotional pain of the condition. It is not uncommon, for example, for
patients to wonder whether it would really matter if they died as they
already feel dead. Suicide attempts are associated with DDD; however,
given the high rates of comorbid depression and other psychiatric
disorders in DDD, the relationship between suicidality and DDD remains
unclear [8,17]. (See 'Comorbid conditions' above.)

Two factor analytic studies of the core symptomatology have reported five
discrete symptom clusters common in patients with DDD [44,45]:

● Unreality of self, defined as feeling detached from one’s physical body,

mind and thoughts

● Perceptual alterations, which encompasses visual, tactile, and

somatosensory distortions

● Emotional numbing, characterized by blunted affect, pain and volition

● Anomalous subjective recall, which consists of disrupted experiences

of time and related imagery
 ● Alienation from surroundings, which comprises symptoms of
derealization

COURSE

Depersonalization/derealization disorder (DDD) can have an episodic,

relapsing/remitting, or chronic course. In a series of 117 cases of patients
with DDD, approximately one-third of individuals had an episodic course;
one-third had a continuous course from time of onset; and one-third
initially had an episodic course that over time became continuous [8].

Many patients with chronic depersonalization and derealization experience

marked impairment in occupational, social, and personal functioning. In a
study comparing 223 patients with DDD with a sample of patients with
depressive disorders without comorbid depersonalization/derealization,
the two groups differed markedly in clinical presentation and course. DDD
patients were younger, significantly more male, had a longer illness
duration, earlier age of onset, and tended to show greater functional
impairment [46].

Available research suggests that onset is most commonly in late

adolescence or early adulthood, with onset of the disorder rarely occurring
as late as the fourth or fifth decade of life [8]. Onset may be very sudden or
insidious. Most patients with DDD are initially treated for secondary anxiety
and mood disorder symptoms; the primary nature of the DDD may not be
recognized until later. Once chronic depersonalization has set in, new
traumatic or stressful events or episodes of other illness may lead to
exacerbations of the symptoms.

Depersonalization or derealization that follows acute traumatic or stressful

experiences or intoxication is often transient and remits spontaneously [3].
In our clinical experience, depersonalization accompanying mood or
anxiety disorder episodes commonly remits with timely treatment of these
conditions, but runs the risk of becoming more chronic and difficult to treat
over time. In some cases, dissociation persists long after the initial
precipitants and can become more refractory to treatment.

ASSESSMENT AND DIAGNOSIS

Assessment — We undertake a diagnostic assessment including detailed

psychiatric history, medical history, and mental status examination and
cursory physical examination in all individuals with suspected
depersonalization/derealization disorder (DDD). A thorough medical and
neurologic evaluation is not routinely necessary; however, we conduct
these evaluations in all patients presenting with atypical symptoms or
illness course, of older age, or a general medical status or history that
raises concerns about the differential diagnosis. (See 'Differential diagnosis'
below.)

We obtain brain imaging (eg, computed tomography or magnetic

resonance imaging) and ambulatory electroencephalogram (EEG) in cases
of diagnostic ambiguity or in the presence of atypical symptoms (eg,
blackouts, unexplained subtle motor or sensory symptoms, intermittent
episodes that are difficult to correlate with any precipitants), seizures, or a
family history of epilepsy. For example, we obtain brain imaging, EEG, and
basic metabolic panel in individuals.

● Age of 40 or greater; onset is unusual at this age (see 'Risk factors'

above)

● Focal findings on neurologic examination

● History of head injury, seizure disorder, or any brain lesions

● History of any medical illness that could be associated with altered

brain structure and function (eg, autoimmune disease)

● Suspicion of sleep apnea

 ● Suspicion of Lyme disease or other infectious processes

● Family history of neurologic or related diseases

● Any typical symptoms such as numbness, tingling, or head pressure

sensations

We obtain urine toxicology screening if history or examination suggests the

possibility of substance abuse, although patients with DDD will typically
refrain from any further substance use once the disorder sets in and even
become phobic of such drug use [17].

Rating scales — We typically use the Dissociative Experiences Scale

( table 1). The scale has several items pertaining to
depersonalization/derealization experiences whereas the endorsement of
other items pertaining to amnesia and identity alteration should be
essentially very low or absent [47-49]. More specific to the disorder, the
Cambridge Depersonalization Scale is a self-report questionnaire
comprised of 29 items which rate both frequency and duration of
depersonalization/derealization experiences ( table 2). A total score of 70
has been shown to reliably differentiate DDD patients from those with
various mood, anxiety, or neurologic disorders [50].

We find self-report questionnaires to be helpful in affirming the diagnosis

of DDD. This may be especially useful for clinicians who are not as
extensively familiar with dissociative symptoms.

Diagnostic criteria — DDD is diagnosed using the American Psychiatric

Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth
Edition, Text Revision (DSM-5-TR) diagnostic criteria [1]:

● A. The presence of persistent or recurrent experiences of

depersonalization, derealization, or both:

• 1. Depersonalization – Experiences of unreality, detachment, or

being an outside observer with respect to one's thoughts, feelings,
 sensations, body, or actions (eg, perceptual alterations, distorted
sense of time, unreal or absent self, emotional and/or physical
numbing).

• 2. Derealization – Experiences of unreality or detachment with

respect to surroundings (eg, individuals or objects are experienced
as unreal, dreamlike, foggy, lifeless, or visually distorted).

● B. During the depersonalization or derealization experiences, reality

testing remains intact.

● C. The symptoms cause clinically significant distress or impairment in

social, occupational, or other important areas of functioning.

● D. The disturbance is not attributable to the physiological effects of a

substance (eg, a drug of abuse, medication) or another medical
condition (eg, seizures).

● E. The disturbance is not better explained by another mental disorder

such as schizophrenia, panic disorder, major depressive disorder, acute
stress disorder, posttraumatic stress disorder (PTSD), or another
dissociative disorder. (See 'Differential diagnosis' below.)

Depersonalization and derealization that follow traumatic or stressful

experiences or intoxication commonly remit spontaneously. Our clinical
experience suggests that it may not be useful or effective to diagnose and
treat DDD unless the symptoms continue for a month or possibly longer.
The DSM-5-TR diagnostic criteria for DDD do not specify a minimal duration
of symptoms [8].

Differential diagnosis — A detailed psychiatric history and mental status

examination can distinguish DDD from other mental disorders and medical
conditions. Depersonalization or derealization can present as a symptom of
other mental disorders. We differentiate these by the following symptoms
or symptom patterns:
● Schizophrenia or other psychotic spectrum disorder – Individuals
with DDD have intact reality testing whereas in individuals with
schizophrenia or other psychotic spectrum disorder reality testing is
typically not intact. Additionally in prodromal psychotic syndromes,
perceptual alterations are often accompanied by magical ideation-type
interpretations of the symptoms whereas this is not seen in DDD. For
example, a person with DDD may feel like they are a zombie, but
knows they are not a zombie. A study comparing perceptual alterations
and magical ideation in patients with DDD and healthy volunteers
found that people with the disorder only had elevated perceptual, but
not cognitive, distortions [51]. (See "Schizophrenia in adults: Clinical
manifestations, course, assessment, and diagnosis".)

● Panic disorder – While both panic disorder and DDD may present with
symptoms of derealization or depersonalization, individuals with panic
disorder have recurrent unexpected surges of intense fear or
discomfort that reaches a peak within minutes and are associated with
symptoms such as palpitations, sweating, trembling, chest pain or
dizziness. These are not typically seen in DDD. (See "Panic disorder in
adults: Epidemiology, clinical manifestations, and diagnosis".)

● Major depressive disorder – We differentiate DDD from depressive

disorder by the presence of depressed mood, diminished interest or
pleasure in most or all activities, changes in sleep pattern (insomnia,
hypersomnia), fatigue, feelings of worthlessness or guilt, and
psychomotor changes that are typically seen in major depressive
disorder. These symptoms are not typically seen in DDD.

● Acute stress disorder – While both DDD and acute stress disorder
may have dissociative symptoms, in acute stress disorder the
symptoms last for three days to one month and are associated with
symptoms such as intrusions, avoidance of distressing memories or
external reminders of the traumatic event, and symptoms of altered
 arousal (eg, sleep disturbance, hypervigilance, exaggerated startle
reflex.) These are not commonly seen in DDD. (See "Acute stress
disorder in adults: Epidemiology, pathogenesis, clinical manifestations,
course, and diagnosis".)

● Posttraumatic stress disorder – We distinguish PTSD from DDD by

the presence of intrusion symptoms (ie, flashbacks, persistent
avoidance of stimuli associated with the traumatic event), and
symptoms of altered arousal that are commonly seen in PTSD. (See
"Dissociative aspects of posttraumatic stress disorder: Epidemiology,
clinical manifestations, assessment, and diagnosis".)

● Other dissociative disorders – Individuals with DDD do not have

distinct personality states as in dissociative identity disorder.
Individuals with DDD do not have an inability to recall important
autobiographical information as in dissociative amnesia. (See
"Dissociative identity disorder: Epidemiology, pathogenesis, clinical
manifestations, course, assessment, and diagnosis".)

● Personality disorders – Individuals with personality disorders or DDD

may manifest symptoms such as depersonalization or derealization.
However, in personality disorders, the enduring pattern of inner
experience or behavior is manifested by changes in cognition, affect,
interpersonal functioning, or impulse control. The behaviors are
inflexible and pervasive across a broad range of personal and social
situations, stable and of long duration, and lead to significant distress
or impairment in psychosocial functioning. (See "Borderline personality
disorder: Epidemiology, pathogenesis, clinical features, course,
assessment, and diagnosis".)

● Other medical or neurologic conditions – Chronic depersonalization

and derealization may less commonly result from a medical or
neurologic condition (eg, temporal lobe epilepsy, mild to moderate
brain trauma) [52,53], or be secondary to substance abuse (most
 commonly marijuana, hallucinogens, ketamine, and salvia) [17,54].
Rare cases have been seen with vestibular pathology or sleep apnea as
the underlying cause. (See 'Assessment' above and "Focal epilepsy:
Causes and clinical features", section on 'Seizure semiology' and
"Cannabis use disorder in adults" and "Vestibular neuritis and
labyrinthitis".)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected

countries and regions around the world are provided separately. (See
"Society guideline links: Dissociative disorders".)

SUMMARY
● Introduction and definitions – Depersonalization/derealization
disorder (DDD) is characterized by the persistence or recurrence of
depersonalization and/or derealization that cause clinically significant
distress or impairment in the presence of intact reality testing (see
'Assessment and diagnosis' above):

• Depersonalization is a persistent or recurrent feeling of detachment

or estrangement from one’s self
• Derealization is a subjective sense of detachment or unreality
regarding the world around them

● Epidemiology – Transient experiences of depersonalization and/or

derealization are very common, while DDD has a prevalence of
approximately two percent. DDD has high rates of comorbidity with
depression and anxiety disorders as well as avoidant and borderline
personality disorders. (See 'Epidemiology' above.)

● Role of trauma – While the pathogenesis of DDD has not been

established, chronic depersonalization and derealization symptoms
 qualifying for the disorder are more common among persons
experiencing chronic traumatic or highly stressful situations such as
verbal or emotional abuse or neglect during childhood.

● Organic precursors – Common organic risk factors for

depersonalization include seizures, mild to moderate head injury, and
substance abuse. Several neurotransmitter systems, brain areas, and
functional circuits have been associated with depersonalization with
some consistency in research studies. (See 'Pathogenesis' above.)

● Clinical manifestations – Studies of patients with DDD suggest that

five discrete symptoms clusters commonly appear in the disorder (see
'Clinical manifestations' above):

• Unreality of self
• Perceptual alterations
• Emotional numbing
• Anomalous subjective recall
• Alienation from surroundings

● Assessment – We undertake a diagnostic assessment including

detailed psychiatric history, medical history and mental status
examination and cursory physical examination in all individuals with
suspected DDD. A thorough medical and neurologic evaluation is not
routinely necessary; however, we conduct these evaluations in all
patients presenting with atypical symptoms or illness course, of older
age, or a general medical status or history that raises concerns about
the differential diagnosis. (See 'Assessment and diagnosis' above.)

● Differential diagnosis – We differentiate DDD from other disorders

that may present with symptoms of depersonalization/derealization.
These include (see 'Differential diagnosis' above):

• Schizophrenia or other psychotic spectrum disorders

• Panic disorder
 • Major depression
• Acute stress disorder
• Posttraumatic stress disorder
• Other dissociative disorders
• Personality disorders
• General medical conditions such as temporal lobe epilepsy, mild to
moderate brain trauma, brain tumors
• Substance abuse: marijuana, hallucinogens, ketamine, and salvia
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