P.1.c.001 Acute psychomotor, memory and subjective effects of MDMA and THC (co-) administration over time in healthy volunteers

Abstract

Introduction: In Western societies a considerable percentage of young people expose themselves to the combination of 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”). Cannabis (main active compound D9-tetrahydrocannabinol or THC) is frequently co-used with ecstasy (Parrott et al., 2007). Despite the prevalence of co-administration of MDMA and THC, the effects of combined use of these substances on behaviour in humans have so far not been investigated. The aim of the present study was to assess the acute effects of (co-) administration of MDMA and THC (the main psychoactive compound of cannabis) on pharmacokinetics, psychomotor performance, memory and subjective experience over time. Methods: We performed a four-way, double blind, randomized, crossover, placebo-controlled study in 16 healthy volunteers (12 male, 4 female) between the ages of 18 and 27. MDMA (100 mg) was given orally, THC (4, 6, and 6 mg, interval of 90 minutes) was vaporized and inhaled. Outcome measures were assessed repeatedly, i.e. before MDMA administration and at 15, 60, 105, 150, 240 and 300 minutes post drug administration, with the exception of the 18 word list memory task, which was performed 120 minutes after drug administration. Repeated measures consisted of blood sampling for analysis of study drug kinetics and assessments of postural stability (body sway), psychomotor function (eye movements and the Rotor Pusuit Task), memory (18 word list and N-back task), and subjective effects (VAS). Results: Body sway was increased, i.e. postural position was impaired, in all drug conditions compared to placebo. THC alone as well as co-administration of THC plus MDMA increased body sway compared to the MDMA alone condition. Eye movements were unaffected by THC, MDMA increased the peak velocity of eye movements. The Rotor Pursuit task (see Figure 1) performance was significantly impaired in the THC condition and the MDMA plus THC condition compared to the placebo and MDMA condition. MDMA alone did not affect the Rotor Pursuit task. Immediate recall of words was impaired in all drug conditions compared to placebo. Delayed recall and delayed recognition did not show a significant main effect of drug administration. The effects of (co-administration) of THC on the N-back working memory task were time- and dose dependent, where THC generally induced a robust but short-lived impairment of working memory. N-back performance was unaffected in the MDMA condition. Co-administration of THC and MDMA enhanced separate subjective drug effects: ratings of 'drug strength', 'internal and external perception', and 'feeling high' were increased compared to the MDMA condition. Conclusion: These results suggest that THC may exert much of its cognitive impairment via a common mechanism of reduced alertness. The stimulant effects of MDMA may attenuate this effect, but could not overcome THC induced impairments in the current study. Overall, THC induced more robust cognitive impairment compared to MDMA. Co-administration of THC with MDMA increased desired subjective drug effects and drug strength compared to the MDMA condition, which may explain the widespread use of this combination.