In Western societies a considerable percentage of young people expose themselves to the combination of 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy’) and cannabis. 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. We performed a four-way, double blind, randomized, crossover, placebo-controlled study in 16 healthy volunteers (12 male, four female) between the ages of 18 and 27. MDMA (100 mg) was given orally, THC (4, 6, and 6 mg, interval of 90 min) was vaporized and inhaled. THC induced more robust cognitive impairment compared with MDMA, and co-administration did not exacerbate single drug effects on cognitive function. However, co-administration of THC with MDMA increased desired subjective drug effects and drug strength compared with the MDMA condition, which may explain the widespread use of this combination.
AbramsDIVizosoHPShadeSBJayCKellyMEBenowitzNL (2007) Vaporization as a smokeless cannabis delivery system: a pilot study. Clin Pharmacol Ther82: 572–578.
2.
AmeriA (1999) The effects of cannabinoids on the brain. Prog Neurobiol58: 315–348.
3.
AmmonsRB (1951) Effect of distribution of practice on rotary pursuit hits. J Exp Psychol41: 17–22.
4.
BondAJJamesDCLaderMH (1974) Physiological and psychological measures in anxious patients. Psychol Med4: 364–373.
5.
BowdleTARadantADCowleyDSKharaschEDStrassmanRJRoy-ByrnePP (1998) Psychedelic effects of ketamine in healthy volunteers: relationship to steady-state plasma concentrations. Anesthesiology88: 82–88.
6.
BoysAMarsdenJStrangJ (2001) Understanding reasons for drug use amongst young people: a functional perspective. Health Educ Res16: 457–469.
7.
ChoiYHHazekampAPeltenburg-LoomanAMFrederichMErkelensCLefeberAW (2004) NMR assignments of the major cannabinoids and cannabiflavonoids isolated from flowers of Cannabis sativa. Phytochem Anal15: 345–354.
8.
ColadoMIO’SheaEGreenAR (2004) Acute and long-term effects of MDMA on cerebral dopamine biochemistry and function. Psychopharmacology (Berl)173: 249–263.
9.
CurranHVBrignellCFletcherSMiddletonPHenryJ (2002) Cognitive and subjective dose–response effects of acute oral delta 9-tetrahydrocannabinol (THC) in infrequent cannabis users. Psychopharmacology (Berl)164: 61–70.
10.
D’SouzaDCPerryEMacDougallLAmmermanYCooperTWuYT (2004) The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology29: 1558–1572.
11.
D’SouzaDCRanganathanMBraleyGGueorguievaRZimoloZCooperT (2008) Blunted psychotomimetic and amnestic effects of delta-9-tetrahydrocannabinol in frequent users of cannabis. Neuropsychopharmacology33: 2505–2516.
12.
DumontGJValkenbergMMSchoemakerRBuitelaarJKvan GervenJMVerkesRJ (2007) Acute MDMA and ethanol interaction effects on psychomotor performance. Br J Clin Pharmacol63: 503–503.
13.
DumontGJVerkesRJ (2006) A review of acute effects of 3,4-methylenedioxymethamphetamine in healthy volunteers. J Psychopharmacol20: 176–187.
14.
DumontGJWezenbergEValkenbergMMGJde JongCAJBuitelaarJKvan GervenJMA (2008) Acute neuropsychological effects of MDMA and ethanol (co-)administration in healthy volunteers. Psychopharmacology (Berl)197: 465–474.
15.
DumontGJKramersCSweepFCTouwDJvan HasseltJGde KamM (2009) Cannabis co-administration potentiates ecstasy effects on heart rate and temperature in humans. Clin Pharm & Ther86: 160–166.
16.
FirstMBFrancesAJPincusHAVettorelloNDavisWW (1994) DSM-IV in progress. Changes in substance-related, schizophrenic, and other primarily adult disorders. Hosp Community Psychiatry45: 18–20.
17.
GijsmanHJvan GervenJMVerkesRJSchoemakerRCPietersMSPenningsEJ (2002) Saccadic peak velocity and EEG as end-points for a serotonergic challenge test. Hum Psychopharmacol17: 83–89.
18.
Gouzoulis-MayfrankEDaumannJ (2006) The confounding problem of polydrug use in recreational ecstasy/MDMA users: a brief overview. J Psychopharmacol20: 188–193.
19.
HartCLvan GorpWGHaneyMFoltinRWFischmanMW (2001) Effects of acute smoked marijuana on complex cognitive performance. Neuropsychopharmacology25: 757–765.
20.
HazekampAChoiYHVerpoorteR (2004) Quantitative analysis of cannabinoids from Cannabis sativa using 1H-NMR. Chem Pharm Bull (Tokyo)52: 718–721.
21.
HazekampARuhaakRZuurmanLvan GervenJVerpoorteR (2006) Evaluation of a vaporizing device (Volcano) for the pulmonary administration of tetrahydrocannabinol. J Pharm Sci95: 1308–1317.
22.
HeishmanSJArastehKStitzerML (1997) Comparative effects of alcohol and marijuana on mood, memory, and performance. Pharmacol Biochem Behav58: 93–101.
23.
Hernandez-LopezCFarreMRosetPNMenoyoEPizarroNOrtunoJ (2002) 3,4-methylenedioxymethamphetamine (ecstasy) and alcohol interactions in humans: psychomotor performance, subjective effects, and pharmacokinetics. J Pharmacol Exp Ther300: 236–244.
24.
IlanABGevinsAColemanMElSohlyMAde WitH (2005) Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids. Behav Pharmacol16: 487–496.
25.
IlanABSmithMEGevinsA (2004) Effects of marijuana on neurophysiological signals of working and episodic memory. Psychopharmacology (Berl)176: 214–222.
26.
KuypersKPRamaekersJG (2005) Transient memory impairment after acute dose of 75mg 3.4-methylene-dioxymethamphetamine. J Psychopharmacol19: 633–639.
27.
KuypersKPRamaekersJG (2007) Acute dose of MDMA (75 mg) impairs spatial memory for location but leaves contextual processing of visuospatial information unaffected. Psychopharmacology (Berl)189: 557–563.
28.
LiechtiMEVollenweiderFX (2000) The serotonin uptake inhibitor citalopram reduces acute cardiovascular and vegetative effects of 3,4-methylenedioxymethamphetamine (‘ecstasy’) in healthy volunteers. J Psychopharmacol14: 269–274.
29.
LiechtiMEVollenweiderFX (2001) Which neuroreceptors mediate the subjective effects of MDMA in humans? A summary of mechanistic studies. Hum Psychopharmacol – Clin Exp16: 589–598.
30.
MeerenHKVan LuijtelaarELCoenenAM (1998) Cortical and thalamic visual evoked potentials during sleep–wake states and spike–wave discharges in the rat. Electroencephalogr Clin Neurophysiol108: 306–319.
31.
Meyer-LindenbergAPolineJBKohnPDHoltJLEganMFWeinbergerDRBermanKF (2001) Evidence for abnormal cortical functional connectivity during working memory in schizophrenia. Am J Psychiatry158: 1809–1817.
32.
MlinarBCorradettiR (2003) Endogenous 5-HT, released by MDMA through serotonin transporter- and secretory vesicle-dependent mechanisms, reduces hippocampal excitatory synaptic transmission by preferential activation of 5-HT1B receptors located on CA1 pyramidal neurons. Eur J Neuroscience18: 1559–1571.
33.
MorrisonPDZoisVMcKeownDALeeTDHoltDWPowellJF (2009) The acute effects of synthetic intravenous Delta9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychol Med39: 1607–1616.
34.
Orban de XivryJJLefevreP (2007) Saccades and pursuit: two outcomes of a single sensorimotor process. J Physiol584: 11–23.
35.
ParrottACGouzoulis-MeyfrankERodgersJSolowijN (2004) Ecstasy/MDMA and cannabis: the complexities of their interactive neuropsychobiological effects. J Psychopharmacol18: 572–575.
36.
ParrottACMilaniRMGouzoulis-MayfrankEDaumannJ (2007) Cannabis and ecstasy/MDMA (3,4-methylenedioxymethamphetamine): an analysis of their neuropsychobiological interactions in recreational users. J Neural Transm114: 959–968.
37.
ParrottAC (2001) Human psychopharmacology of ecstasy (MDMA): a review of 15 years of empirical research. Hum Psychopharmacol16: 557–577.
38.
PiflCDrobnyHReitherHHornykiewiczOSingerEA (1995) Mechanism of the dopamine-releasing actions of amphetamine and cocaine – plasmalemmal dopamine transporter versus vesicular monoamine transporter. Mol Pharmacol47: 368–373.
39.
PlonerCJTschirchAOstendorfFDickSGaymardBMRivaud-PechouxS (2002) Oculomotor effects of delta-9-tetrahydrocannabinol in humans: implications for the functional neuroanatomy of the brain cannabinoid system. Cereb Cortex12: 1016–1023.
40.
RamaekersJGRobbeHWO’HanlonJF (2000) Marijuana, alcohol and actual driving performance. Hum Psychopharmacol15: 551–558.
41.
RanganathanMD’SouzaDC (2006) The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology (Berl)188: 425–444.
42.
RonenAGershonPDrobinerHRabinovichABar-HamburgerRMechoulamR (2008) Effects of THC on driving performance, physiological state and subjective feelings relative to alcohol. Accid Anal Prev40: 926–934.
43.
SewellARPolingJSofuogluM (2009) The effect of cannabis compared with alcohol on driving. Am J Addictions18: 185–219.
44.
SpragueJEBrutcherREMillsEMCadenDRusyniakDE (2004) Attenuation of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)-induced rhabdomyolysis with alpha1- plus beta3-adrenoreceptor antagonists. Br J Pharmacol142: 667–670.
45.
StrougoAZuurmanLRoyCPinquierJvan GervenJCohenA (2008) Modelling of the concentration–effect relationship of THC on central nervous system parameters and heart rate – insight into its mechanisms of action and a tool for clinical research and development of cannabinoids. J Psychopharmacol22: 717–726.
46.
SumnallHRColeJCJeromeL (2006) The varieties of ecstatic experience: an exploration of the subjective experiences of ecstasy. J Psychopharmacol20: 670–682.
47.
SundstromIBackstromT (1998) Citalopram increases pregnanolone sensitivity in patients with premenstrual syndrome: an open trial. Psychoneuroendocrinology23: 73–88.
48.
SvrakicDMWhiteheadCPrzybeckTRCloningerCR (1993) Differential diagnosis of personality disorders by the seven-factor model of temperament and character. Arch Gen Psychiatry50: 991–999.
van SteveninckALvan BerckelBNSchoemakerRCBreimerDDvan GervenJMCohenAF (1999) The sensitivity of pharmacodynamic tests for the central nervous system effects of drugs on the effects of sleep deprivation. J Psychopharmacol13: 10–17.
51.
WachtelSRElSohlyMARossSAAmbreJdeWitH (2002) Comparison of the subjective effects of delta(9)-tetrahydrocannabinol and marijuana in humans. Psychopharmacology (Berl)161: 331–339.
52.
WeinsteinABricknerOLermanHGreemlandMBlochMLesterH (2008) Brain imaging study of the acute effects of delta9-tetrahydrocannabinol (THC) on attention and motor coordination in regular users of marijuana. Psychopharmacology (Berl)196: 119–131.
53.
WinstockARGriffithsPStewartD (2001) Drugs and the dance music scene: a survey of current drug use patterns among a sample of dance music enthusiasts in the UK. Drug Alcohol Depend64(1): 9–17.
54.
WrightBM (1971) A simple mechanical ataxia-meter. J Physiol218: 27P–28P.
55.
YoungJMMcGregorISMalletPE (2005) Co-administration of THC and MDMA (‘ecstasy’) synergistically disrupts memory in rats. Neuropsychopharmacology30: 1475–1482.
56.
ZuurmanLRoyCSchoemakerRCHazekampAden HartighJBenderJC (2008) Effect of intrapulmonary tetrahydrocannabinol administration in humans. J Psychopharmacol22: 707–716.
57.
ZuurmanLIppelAEMoinEvan GervenJM (2009) Biomarkers for the effects of cannabis and THC in healthy volunteers. Br J Clin Pharmacol67: 5–21.
