Cannabis-Induced Depersonalization-Derealization Disorder

An association between cannabis use and the emergence of psychotic disorders among susceptible individuals is increasingly being described in the medical literature (1). However, little is known about how cannabis use relates to other psychiatric sequelae (2). Moreover, there is a dearth of literature on the clinical characteristics of and risk factors for depersonalization-derealization disorder as precipitated by cannabis use (3).

The principal clinical features of depersonalization-derealization disorder are persistent or recurrent experiences of depersonalization or derealization (4). Depersonalization is a dissociative symptom in which one feels like an outside observer with respect to one's thoughts, body, and sensations (3). Derealization is marked by feelings of unreality and detachment from one's surroundings (4), such that one's environment is experienced as remote or unfamiliar (5). Both symptoms may be a cause of significant distress and functional impairment (4–6).

Transient episodes of depersonalization or derealization have been known to occur across a broad range of psychiatric disorders, including schizophrenia (7). However, persons with depersonalization-derealization are distinguished from those with psychotic disorders by the presence of intact reality testing regarding the dissociative disturbance (4). Whereas an individual with schizophrenia may believe that he or she is actually outside of his or her body, persons with depersonalization-derealization are aware that the dissociation is merely an uncanny sensation (5). Persons with depersonalization-derealization do not appear to be at risk for developing psychotic disorders (2, 3).

The lifetime prevalence of depersonalization-derealization disorder is approximately 2% both in the United States and worldwide (4). The average age at onset is 16 years (8), and women and men are equally affected (5). Persons with the disorder may present with comorbid psychiatric disorders, including personality disorders (8). However, it is uncommon for an individual with depersonalization-derealization disorder to have schizotypal or schizoid personality disorder (8). Personality disorders do not appear to predict symptom severity (8).

Several precipitants have been implicated in depersonalization-derealization disorder, including panic attacks (3) and recreational drugs (5). The most common psychoactive drug precipitant of the disorder is cannabis (3, 5). Although depersonalization and derealization symptoms may occur as part of a panic attack (5), persons with depersonalization-derealization disorder continue to experience symptoms following resolution of the panic attack (3). A cognitive model suggests that those predisposed to anxiety may develop fears regarding episodes of depersonalization and derealization (e.g., fear of "going mad"), which may contribute to the emergence of the symptoms following panic attacks or substance intoxication (9).

Cannabis-induced depersonalization-derealization disorder has been described in the literature for many years (10, 11). However, this type of dissociative disorder is not typically addressed in contemporary reviews focusing on the implications of cannabis use (2). Here, we examine data on prolonged experiences of depersonalization and derealization following cannabis use to provide insight into the clinical features of and risk factors for cannabis-induced depersonalization-derealization disorder.

Pathogenesis

Some individuals who use cannabis will never experience depersonalization or derealization during or after cannabis use (5). However, depersonalization and derealization remain potential side effects of cannabis (12), of which many clinicians are unaware (5). In general, cannabis-induced symptoms of depersonalization and derealization are time-locked to the period of intoxication, peaking approximately 30 minutes after ingestion and subsiding within 120 minutes of exposure to the drug (12, 13). However, among a subgroup of persons who use cannabis, symptoms of depersonalization or derealization persist for weeks, months, or years (3, 5), even after discontinuation of the substance (2, 11). Those who experience prolonged symptoms may have cannabis-induced depersonalization-derealization disorder (2, 10).

The pathogenesis of cannabis-induced depersonalization-derealization disorder can be marked by an initial dissociative disturbance with a severity that subsides but later returns in episodes that eventually become chronic (3). In other cases, onset can be more abrupt, with symptoms emerging during intoxication and persisting unremittingly for months or years (5). For other individuals, symptoms do not occur until hours or days following an episode of cannabis use (3).

Risk Factors

Several factors appear to be associated with risk for cannabis-induced depersonalization-derealization disorder (see box). Most affected individuals have a prior history of an anxiety disorder (6), such as panic disorder (11) or social phobia (2). Additionally, males (6) and adolescents (2) may be disproportionately affected by cannabis-induced symptoms, perhaps due to the higher rates of cannabis use among these groups (14) or to biological predisposing factors (6). Use of cannabis during periods of marked distress (11) or after exposure to trauma (10) may increase risk for cannabis-induced symptoms. Other risk factors may include sudden withdrawal from regular cannabis use (15), severe intoxication (10), and history of prior cannabis-induced symptoms (3) or prior transient substance-induced symptoms (11).

Individuals naive to cannabis or those with little previous exposure to the substance do not appear to be less prone to onset of cannabis-induced depersonalization-derealization disorder. Simeon et al. (16) examined 89 individuals who developed prolonged experiences of depersonalization and derealization following cannabis use, 28% of whom disclosed using cannabis between 100 and 500 times prior to symptom onset. Sudden emergence of the disorder among persons who use cannabis regularly may be due to life stressors that increase sensitivity to cannabis and risk for mental disorders. Moran (11) examined individuals who used cannabis regularly while experiencing periods of marked distress, such as divorce. Cannabis use during such periods of distress appears to contribute to symptom onset among individuals with little or no prior exposure (10).

Association With Acute Anxiety

There appears to be a strong relationship between acute anxiety and symptom onset in both cases of cannabis-induced depersonalization-derealization disorder (3) and depersonalization-derealization disorder unrelated to drug use (8). Persons who experience prolonged depersonalization-derealization symptoms following cannabis use often report experiencing a panic attack during intoxication (16), which may be due to altered hypothalamic-pituitary-adrenal axis functioning (17). However, the emergence of cannabis-induced depersonalization-derealization disorder is not always associated with panic (5), which suggests that cannabis may be a direct cause of symptom onset without mediation of anxiety symptoms (6).

Sierra and Berrios (18) proposed that beyond a specific threshold of anxiety, a "left-sided prefrontal mechanism" inhibits the amygdala and, in turn, the anterior cingulate, leading to blunted autonomic arousal and feelings of detachment from the self. Concurrently, disinhibited amygdala arousal systems may activate the dorsolateral prefrontal cortex, thereby inhibiting the anterior cingulate, giving rise to other experiential features of depersonalization-derealization disorder, including mind emptiness and indifference to pain (18). Although patients with depersonalization-derealization disorder often show attenuated autonomic arousal (3), PET imaging data on transient cannabis-induced symptoms do not support this model (13). Elucidating how cannabis may be associated with symptom onset is challenging, given the varying strains of cannabis and chemical compounds that are currently available (19).

While acute anxiety is known to be involved in the emergence of depersonalization-derealization disorder symptoms, less is known about why such symptoms may persist following cannabis use. Rather than a direct pharmacologic effect, persistent symptoms have been thought to be associated with causal attributions and fears regarding an episode of dissociation (20). Some patients have attributed their symptoms to brain damage (11), while others have refused pharmacological intervention due to the fear of such intervention worsening their symptoms (11). In light of the consistent relationship between anxiety and symptoms of depersonalization-derealization disorder (3, 5), it is possible that such beliefs or fears about symptom episodes may perpetuate otherwise transient substance-induced symptoms (20). It would be less likely that prolonged symptoms are due to residual drug effects, given that tetrahydrocannabinol is typically eliminated from the body within a few weeks (2).

Conclusions

We reviewed data on prolonged experiences of depersonalization or derealization following cannabis use to provide insight into the clinical features of and risk factors for cannabis-induced depersonalization-derealization disorder. Most risk factors were derived from cases of individuals who received a definitive diagnosis of depersonalization-derealization disorder after using cannabis (2, 10, 11). The most significant risk factor appears to be a history of pathological anxiety (3, 5), which may be contributory to both symptom onset (14) and the persistent nature of the syndrome (20). Anxiety-prone young males who use cannabis may be at ultra-high risk for cannabis-induced depersonalization-derealization disorder, particularly when cannabis is used under marked distress.

Depersonalization-derealization disorder has been considered a hardwired coping mechanism through which feelings of unreality and detachment from one's self and one's surroundings help one to cope with acute distress (3). Episodes of depersonalization or derealization associated with cannabis use are typically time-locked to the period of intoxication (12). However, in susceptible individuals who use cannabis, "external stressors and intrapsychic factors may contribute to its continued use as a defense mechanism," as described by Syzmanski (10). Interventions aimed at mitigating anxiety and targeting intrapsychic factors may prove to be useful in treating cannabis-induced depersonalization-derealization disorder (20).

Prolonged symptoms following cannabis use have been associated with psychotic syndromes in some case reports (10, 11). However, persons who meet diagnostic criteria for depersonalization-derealization disorder present with intact reality testing and do not have a psychotic disorder (2, 4). Although symptoms of depersonalization-derealization disorder may occur in the prodrome of schizophrenia (3), validated instruments used in the assessment of early- and late-prodromal schizophrenia have not revealed any evidence of risk for psychosis among patients with cannabis-induced depersonalization-derealization disorder (2). It is noteworthy that in our review, individuals who did not show signs of prodromal schizophrenia reported experiencing some of the more severe clinical features of depersonalization and derealization, including sensations of physical separation from their bodies and agency (2). Prolonged and severe dissociation following cannabis use may, therefore, not always be an indication of evolving psychosis.

Distinguishing cases of cannabis-induced psychosis from cases of cannabis-induced depersonalization-derealization disorder may be critical in guiding appropriate diagnosis and treatment of this distressing dissociative disorder.

Key Points/Clinical Pearls