Elsevier

Psychiatry Research

Volume 228, Issue 3, 30 August 2015, Pages 907-912
Psychiatry Research

MDMA, cannabis, and cocaine produce acute dissociative symptoms

https://doi.org/10.1016/j.psychres.2015.04.028Get rights and content

Highlights

  • We explore the dissociative potential of MDMA, cannabis, and cocaine during intoxication.

  • We compare their effects to dissociative states in clinical and nonclinical samples.

  • Dissociation increased significantly under the influence of MDMA and cannabis.

  • Dissociation increased under the influence of cocaine, but to a lesser degree.

  • MDMA and cannabis can produce dissociative symptoms resembling dissociative pathology.

Abstract

Some drugs of abuse may produce dissociative symptoms, but this aspect has been understudied. We explored the dissociative potential of three recreational drugs (3,4-methylenedioxymethamphetamine (MDMA), cannabis, and cocaine) during intoxication and compared their effects to literature reports of dissociative states in various samples. Two placebo-controlled studies were conducted. In Study 1 (N=16), participants received single doses of 25, 50, and 100 mg of MDMA, and placebo. In Study 2 (N=21), cannabis (THC 300 µg/kg), cocaine (HCl 300 mg), and placebo were administered. Dissociative symptoms as measured with the Clinician-Administered Dissociative States Scale (CADSS) significantly increased under the influence of MDMA and cannabis. To a lesser extent, this was also true for cocaine. Dissociative symptoms following MDMA and cannabis largely exceeded those observed in schizophrenia patients, were comparable with those observed in Special Forces soldiers undergoing survival training, but were lower compared with ketamine-induced dissociation. Cocaine produced dissociative symptoms that were comparable with those observed in schizophrenia patients, but markedly less than those in Special Forces soldiers and ketamine users. Thus, MDMA and cannabis can produce dissociative symptoms that resemble dissociative pathology. The study of drug induced dissociation is important, because it may shed light on the mechanisms involved in dissociative psychopathology.

Introduction

Dissociative symptoms form a heterogeneous class of experiences varying from absent-mindedness, excessive daydreaming, and memory problems to confusion about one׳s own identity. In their most radical form, such symptoms define conditions like dissociative amnesia and depersonalization/derealization disorder (American Psychiatric Association, 2013). Furthermore, dissociative symptoms may accompany a range of psychiatric disorders, such as borderline personality disorder, post-traumatic stress disorder (PTSD), obsessive compulsive disorder, and schizophrenia (Holmes et al., 2005).

Dissociative symptoms have also been shown to occur during intoxication with drugs that cover a broad range of pharmacological profiles (Medford et al., 2003, Morgan et al., 2004, Somer et al., 2010). For example, administration of subanaesthetic doses of the NMDA antagonist ketamine to healthy participants produced subjective experiences of depersonalization and derealization that closely resembled dissociative symptoms such as an altered perception of the environment (Hallak et al., 2011, Krystal et al., 1994, Pomarol-Clotet et al., 2006). Regular use of 3,4-methyldioxymethamphetamine (MDMA) has been associated with a various psychopathological symptoms (e.g., anxiety, depression; Parrott et al., 2000), including mild symptoms of depersonalization and derealization experiences (Vollenweider et al., 1998). MDMA primarily acts as a releasing agent of the monoamines (serotonin, noradrenaline and dopamine) through inhibition and reversal of the monoamine transporters (Bogen et al., 2003, Fleckenstein et al., 2007).

Cocaine also blocks the reuptake of monoamines (Rothman, 2001). It has a similar psychomotor stimulant effect to that of amphetamine and related compounds, and likewise produces euphoria, tachycardia, hypertension, and appetite suppression.

Another drug that is frequently associated with dissociative symptoms is cannabis (Martin-Santos et al., 2012), particularly in individuals with a predisposition to schizophrenia (Bhattacharyya et al., 2009, Bugra et al., 2012). Cannabis exerts its central effects through activation of CB1 receptors, particularly in mediotemporal and anterocingulate areas of the brain (Iversen, 2003).

It is generally assumed that the pharmacological action of drugs of abuse are the prime cause of the dissociative states during drug intoxication and that drug users may actually seek “chemical dissociation” to detach themselves from reality (Somer et al., 2010). Others have shown that dissociative symptoms increase following sleep deprivation or sleep loss, which inspired the sleep-dissociation model (Van Heugten-van der Kloet et al., 2014, Van der Kloet et al., 2012). This model would predict that drugs of abuse that increase sleepiness and sedation (e.g., cannabis) are more likely to induce dissociative symptoms than stimulant drugs (e.g., MDMA, cocaine) that increase wakefulness. On the other hand, the chemical dissociation hypothesis (Somer et al., 2010) would predict that the dissociative properties of both psychostimulants and sedatives are substantial as long as they induce experiences that help people to detach themselves from reality.

With this in mind, we conducted two studies exploring the acute effects of MDMA (Study 1), and cocaine and cannabis (Study 2) on dissociative symptom levels. We anticipated that all drugs would promote dissociative symptoms, but to explore the clinical relevance of these effects; we compared them with dissociative symptom levels found in a variety of clinical and non-clinical samples (Ahn et al., 2011, Bremner et al., 1998, Hallak et al., 2011, Morgan et al., 2001). Bremner et al. (1998) developed the Clinician-Administered Dissociative States Scale (CADSS), and employed this instrument to discriminate patients with dissociative disorders from other patients. We compared our findings with the CADSS scores of their sample of schizophrenia patients (N=22) and with baseline CADSS scores of a more recent sample of patients with schizophrenia (N=13; Ahn et al., 2011).

Furthermore, we compared our findings with acute dissociation during Special Forces survival training in healthy soldiers (N=50; Morgan et al., 2001). These soldiers experienced uncontrollable stress during survival training, as they were subject to semi-starvation, sleep deprivation, lack of control over personal hygiene, and external control over movement, social contact, and communication. Finally, we related our findings to dissociation levels during ketamine intoxication in healthy men (N=10; Hallak et al., 2011).

Section snippets

Measures

Clinician-Administered Dissociative States Scale (CADSS; Cronbach׳s α=0.82; Bremner et al., 1998). The CADSS is an instrument to measure state symptoms of dissociation. The scale consists of 19 self-report items and 8 observation items. An illustrative self-report item is: “Do you feel as if you are watching the situation as an observer?” The intensity of each dissociative symptom can vary from 0 (not present) to 4 (extremely present). Respondents are asked to use the last 3 h as a point of

Results

Table 1 shows lifetime drug use of the participants enrolled in Study 1 and 2. Table 2 shows mean scores on the CADSS in Study 1 and 2, as well as univariate analyses, and statistical comparisons of the state dissociation subscales for both studies. We correlated the history of drug use of the participants from both studies with drug-induced dissociation scores (CADSS), and found a significant negative correlation between duration (in years) of MDMA use and CADSS. Drug induced CADSS scores

Discussion

The present study demonstrates that MDMA and cannabis can induce dissociative symptoms. Cannabis significantly increased subjective ratings of depersonalization, derealization, and amnesia during intoxication. MDMA primarily increased feelings of derealization. The magnitude of total dissociation following cannabis and MDMA, however, was comparable. On the other hand, cocaine only mildly increased the total CADSS score when compared with placebo. CADDS ratings were negatively correlated to MDMA

Acknowledgments

This study was funded by the Dutch Organization for Health Research and Health Care Innovation grant (ZONMw; Number: 40-001812-98-08036) awarded to DHK, EU grant (Number: TREN-05-FP6TR-So7.61320-518404) awarded to JR, and a ZONMw grant (Number: 31160206) awarded to JR and RJV. There are no conflicts of interest.

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