MDMA, cannabis, and cocaine produce acute dissociative symptoms

This randomized, double-blind, placebo-controlled, four-way, cross-over study (n=37) investigated the acute dissociative effects of MDMA (25, 50, and 100 mg), cannabis (THC 21mg/70kg), and cocaine (300 mg) and compared them to data of schizophrenia patients, Special Forces soldiers, and ketamine users. Results indicate that MDMA, cannabis, and (to a lesser extent) cocaine can produce dissociative symptoms that are similar to dissociative pathology.

Abstract

“Introduction: 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.

Methods: 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.

Results: 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.

Discussion: 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.”

Authors: Dalenavan Heugten-Van der Kloet, Timo Giesbrecht, Janelle van Wel, Wendy M. Bosker, Kim PC Kuypers, Eef L. Theunissen, Desirée B. Spronk, Robbert Jan Verkes, Harald Merckelbach & Johannes G. Ramaekers

Summary

Some drugs of abuse may produce dissociative symptoms, but this aspect has been understudied. MDMA and cannabis can produce dissociative symptoms that resemble dissociative pathology, but cocaine can also produce dissociative symptoms that are less severe than those observed in Special Forces soldiers and ketamine users.

1. Introduction

Dissociative symptoms are a heterogeneous class of experiences varying from absent-mindedness, excessive daydreaming, and memory problems to confusion about one’s own identity.

Intoxication with drugs that cover a broad range of pharmacological profiles can produce subjective experiences of depersonalization and derealization that closely resemble dissociative symptoms. Regular use of 3,4-methyldioxymethamphetamine (MDMA) has been associated with a variety of psychopathological symptoms, including mild symptoms of depersonalization and derealization experiences.

The dissociative states during drug intoxication are generally assumed to be caused by the pharmacological action of drugs of abuse and that drug users may actually seek “chemical dissociation” to detach themselves from reality.

We conducted two studies to explore the acute effects of MDMA, cocaine and cannabis on dissociative symptom levels. We compared our findings with baseline CADSS scores of patients with schizophrenia.

We compared our findings with acute dissociation levels during Special Forces survival training in healthy soldiers and with dissociation levels during ketamine intoxication in healthy men.

2.1. Measures

The Clinician-Administered Dissociative States Scale (CADSS) is a 19-item instrument that measures state symptoms of dissociation. The intensity of each dissociative symptom can vary from 0 (not present) to 4 (extremely present).

The Dissociative Experiences Scale (DES) is a self-report scale that intends to measure trait dissociation. It requires participants to indicate on 100 mm visual analog scales to what extent they experience 28 dissociative experiences in daily life.

2.2. Participants and procedure

Participants for both studies were recruited via advertisements at Maastricht University, The Netherlands. They were medically examined by a physician, and consent was obtained from each participant after complete description of each study to the participants.

In Study 1, participants received single doses of placebo, 25, 50, and 100 mg MDMA orally in identically appearing formulations. The wash-out period between treatments was at least 1 week, and participants were not allowed to drink alcohol or caffeine or smoke tobacco during a 24-h period prior to testing.

In Study 2, we administered single doses of cannabis, cocaine, and a placebo to regular cannabis and cocaine users to explore the effects of these drugs on dissociative experiences.

Three separate tests were conducted with a minimum of 7 days between sessions. Cannabis (300 mg/kg THC) and cocaine (300 mg) were administered using a vaporizer and a double-blind, placebo-controlled, double-dummy procedure.

2.3. Data analysis

Statistical analyses were performed using SPSS 18.0 software. We compared our data with findings from several previous studies that explored the prevalence of acute dissociative symptoms in a variety of groups.

3.1. MDMA Study 1

We found a significant effect of drug dosage on CADSS scores. No significant differences were found between placebo and the 25 mg and 50 mg conditions.

3.2. Cannabis and cocaine Study 2

CADSS scores were skewed to the right and a significant main effect of drug was found. Both cannabis and cocaine treatment significantly increased acute dissociation levels as compared with placebo.

Participants who scored high on trait dissociation showed a higher sensitivity to drug-induced state dissociation. The correlation between trait dissociation and CADSS scores was significant for cannabis but not cocaine.

3.3. Acute dissociation in other samples

We compared our findings with those of patients suffering from schizophrenia, Special Forces soldiers, and healthy male volunteers intoxicated with ketamine.

Our analysis showed that single doses of MDMA and cannabis induced dissociative symptoms that were comparable to those experienced by Special Forces soldiers during their survival training course, but that were significantly higher than those produced by ketamine.

4. Discussion

MDMA and cannabis can induce dissociative symptoms, but the effects are dose dependent. Cocaine only mildly increases the total CADSS score when compared with placebo.

We compared the results of our study with the data of schizophrenia patients, Special Forces soldiers, and ketamine users.

Schizophrenia patients had low CADSS scores, similar to those observed in our participants during placebo treatments. In contrast, CADSS scores were elevated in Special Forces soldiers and ketamine users, and cannabis and MDMA produced severe dissociative symptoms that resembled dissociative pathology.

We measured trait dissociation in participants of Study 2 with the DES. The results suggest that participants did not develop dissociative pathology despite their regular drug use history.

The findings demonstrate that stimulant drugs like MDMA and cocaine may produce dissociative effects, and that these effects are not necessarily due to the sleep-promoting properties of the drugs involved.

Research shows that dissociative disorders and substance abuse disorders are often co-occurring, and that dual diagnoses patients pose serious treatment challenges due to drug abuse, increased risk of suicidal and violent behaviors, and overall poorer functioning.

Our studies had several limitations, such as small samples, history of drug use, and only using 19 self-report items. Therefore, the results may underestimate drug-induced dissociative responses in novice drug users.

MDMA, cannabis, and cocaine all induce acute dissociative symptoms, which are similar to pathological symptomatology. Future studies should include mechanistic designs to further distinguish the neuropharmacology of drug-induced dissociative states.