Does variation in trait schizotypy and frequency of cannabis use influence the acute subjective,cognitive and psychotomimetic effects of delta-9-tetrahydrocannabinol? A mega-analysis
Restricted accessResearch articleFirst published online July, 2021
Does variation in trait schizotypy and frequency of cannabis use influence the acute subjective,cognitive and psychotomimetic effects of delta-9-tetrahydrocannabinol? A mega-analysis
While the acute effects of cannabis are relatively benign for most users, some individuals experience significant adverse effects. This study aimed to identify whether variation in schizotypal personality traits and frequency of cannabis use influence the acute effects of delta-9-tetrahydrocannabinol (THC).
Methods:
Individual participant data from four double-blind, randomised, placebo-controlled, acute crossover studies involving 128 cannabis users were combined for a mega-analysis. Using multilevel linear models and moderation analyses, frequency of cannabis use and schizotypal personality traits were investigated as potential moderators of the subjective, cognitive and psychotomimetic effects of acute THC.
Results:
There was evidence of a moderating effect where increased frequency of cannabis use was associated with reduced intensity of subjective (changes in alertness and feeling stoned) and psychosis-like effects following THC when compared with placebo. Moderating effects of cannabis use frequency on acute memory impairment were weak. Trait schizotypy did not moderate the acute psychosis-like effects of THC compared with placebo.
Conclusions:
Our results suggest that a pattern of domain-specific tolerance develops to the acute effects of THC. Tolerance to the alertness-reducing effects occurred more readily than tolerance to psychotomimetic effects. Only partial tolerance to feeling stoned was found, and there was weak evidence for tolerance to memory impairment. Trait schizotypy did not moderate THC’s effects on psychotomimetic symptoms.
AmeriA (1999) The effects of cannabinoids on the brain. Prog Neurobiol58: 315–348.
2.
American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders. Washington, DC: APA.
3.
BarkusELewisS (2008) Schizotypy and psychosis-like experiences from recreational cannabis in a non-clinical sample. Psychol Med38: 1267–1276.
4.
BarkusEMorrisonPDDi FortiM, et al. (2016) Are deficits in cognition associated with psychotic-like experiences after cannabis?Hum Psychopharmacol Clin Exp31: 402–411.
5.
BarkusEStirlingJHopkinsR, et al. (2006) Cannabis-induced psychosis-like experiences are associated with high schizotypy. Psychopathol39: 175–178.
6.
BhattacharyyaSAtakanZMartin-SantosR, et al. (2015) Impairment of inhibitory control processing related to acute psychotomimetic effects of cannabis. Euro Neuropsychopharmacol25: 26–37.
7.
BloomfieldMAHindochaCGreenSF, et al. (2018) The neuropsychopharmacology of cannabis: a review of human imaging studies. Pharmacol Therapeut195: 132–161.
8.
BroydSJvan HellHHBealeC, et al. (2016) Acute and chronic effects of cannabinoids on human cognition: A systematic review. Biol Psychiatry79: 557–567.
9.
CohenPCohenJAikenLS, et al. (1999) The problem of units and the circumstance for POMP. Multivar Behav Res34: 315–346.
10.
ColizziMBhattacharyyaS (2018) Cannabis use and the development of tolerance: a systematic review of human evidence. Neuroscience & Biobehavioral Reviews. 93: 1–25.
11.
ColizziMMcGuirePGiampietroV, et al. (2018) Modulation of acute effects of delta-9-tetrahydrocannabinol on psychotomimetic effects, cognition and brain function by previous cannabis exposure. Euro Neuropsychopharmacol28: 850–862.
12.
CurranHV (1991) Benzodiazepines, memory and mood: A review. Psychopharmacol105: 1–8.
13.
CurranHVFreemanTPMokryszC, et al. (2016) Keep off the grass? Cannabis, cognition and addiction. Nat Rev Neurosci17: 293–306.
14.
CurranHVHindochaCMorganCJ, et al. (2018) Which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like effects?Psychol Med49: 1574–1580.
15.
D’SouzaDCAbi-SaabWMMadonickS, et al. (2005) Delta-9-tetrahydrocannabinol effects in schizophrenia: Implications for cognition, psychosis, and addiction. Biol Psychiatry57: 594–608.
16.
D’SouzaDCFridbergDJSkosnikPD, et al. (2012) Dose-related modulation of event-related potentials to novel and target stimuli by intravenous Δ 9-THC in humans. Neuropsychopharmacol37: 1632–1646.
17.
D’SouzaDCPerryEMacDougallL, et al. (2004) The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacol29: 1558–1572.
18.
D’SouzaDCRanganathanMBraleyG, et al. (2008) Blunted psychotomimetic and amnestic effects of Δ-9-tetrahydrocannabinol in frequent users of cannabis. Neuropsychopharmacol33: 2505–2016.
19.
De VryJJentzschKKuhlE, et al. (2004) Behavioral effects of cannabinoids show differential sensitivity to cannabinoid receptor blockade and tolerance development. Behav Pharmacol15: 1–12.
20.
DeRubeisRJGelfandLATangTZ, et al. (1999) Medications versus cognitive behavior therapy for severely depressed outpatients: mega-analysis of four randomized comparisons. Am J Psychiatry156: 1007–1013.
21.
DesrosiersNARamaekersJGChauchardE, et al. (2015) Smoked cannabis’ psychomotor and neurocognitive effects in occasional and frequent smokers. J Anal Toxicol39: 251–261.
ElbourneDRAltmanDGHigginsJPT, et al. (2002) Meta-analyses involving cross-over trials: methodological issues. Int J Epidemiol31: 140–149.
24.
FreemanTPLorenzettiV (2019) ‘Standard THC units’: A proposal to standardize dose across all cannabis products and methods of administration. Addiction115: 1207–1216.
25.
FreemanAMMokryszCSaundersR, et al. (2018) Do trait schizotypy and drug use factors predict vulnerability and/or resilience to the acute effects of cannabis? Available at: https://osf.io/82r3g (accessed 6 January 2021).
26.
GaneshSCortes-BrionesJRanganathanM, et al. (2020) Psychosis-relevant effects of intravenous delta-9-tetrahydrocannabinol-A mega analysis of individual participant-data from human laboratory studies. Int J Neuropsychopharmacol. Epub ahead of print 9May2020. DOI: 10.1093/ijnp/pyaa031.
27.
GreenBKavanaghDYoungR (2003) Being stoned: a review of self-reported cannabis effects. Drug Alcohol Rev22: 453–460.
28.
HammersleyRLeonV (2006) Patterns of cannabis use and positive and negative experiences of use amongst university students. Addict Res Theory14: 189–205.
29.
HartCLVan GorpWHaneyM, et al. (2001) Effects of acute smoked marijuana on complex cognitive performance. Neuropsychopharmacol25: 757–765.
30.
HayesAF (2017) Introduction to Mediation, Moderation, and Conditional Process Analysis: A Regression-Based Approach. Guilford Publications.
31.
HenquetCRosaAKrabbendamL, et al. (2006) An experimental study of catechol-O-methyltransferase Val158Met moderation of Δ-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacol31: 2748–2757.
32.
HigginsJPTAltmanDGGøtzschePC, et al. (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. Br Med J343: d5928.
33.
HigginsJPTGreenS (2008) Cochrane Handbook for Systematic Reviews of Interventions. England: The Cochrane Collaboration and John Wiley & Sons Ltd.
34.
HindochaCFreemanTPSchaferG, et al. (2015) Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: A randomised, double-blind, placebo-controlled study in cannabis users. Euro Neuropsychopharmacol25: 325–334.
35.
HindochaCFreemanTPXiaJX, et al. (2017) Acute memory and psychotomimetic effects of cannabis and tobacco both ‘joint’ and individually: A placebo-controlled trial. Psychol Med47: 2708–2719.
36.
HoriHMatsuoJTeraishiT, et al. (2013) Moderating effect of schizotypy on the relationship between smoking and neurocognition. Euro Psychiatry28: 457–462.
37.
LawnWFreemanTPPopeRA, et al. (2016) Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: An evaluation of the cannabis ‘amotivational’hypotheses. Psychopharmacol233: 3537–3552.
38.
LichtmanAMartinB (2005) Cannabinoid tolerance and dependence. In: Handbook of Experimental Pharmacology. Springer, pp. 691–717.
39.
MasonOJMorganCJADhimanS, et al. (2009) Acute cannabis use causes increased psychotomimetic experiences in individuals prone to psychosis. Psychol Med39: 951–956.
40.
MasonOJMorganCJAStefanovicA, et al. (2008) The psychotomimetic states inventory (PSI): measuring psychotic-type experiences from ketamine and cannabis. Schizophr Res103: 138–142.
41.
MassRBardongCKindlK, et al. (2001) Relationship between cannabis use, schizotypal traits, and cognitive function in healthy subjects. Psychopathology34: 209–214.
42.
MetrikJKahlerCWReynoldsB, et al. (2012) Balanced placebo design with marijuana: pharmacological and expectancy effects on impulsivity and risk taking. Psychopharmacol223: 489–499.
43.
MokryszCFreemanTPKorkkiS, et al. (2016) Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males. Transl Psychiatry6: e961.
44.
MontoyaAK (2019) Moderation analysis in two-instance repeated measures designs: Probing methods and multiple moderator models. Behav Res Methods51: 61–82.
45.
MorganCJAFreemanTPHindochaC, et al. (2018b) Individual and combined effects of acute delta-9-tetrahydrocannabinol and cannabidiol on psychotomimetic symptoms and memory function. Transl Psychiatry8.
46.
MorganCReininghausUReichenbergA, et al. (2018a) Adversity, cannabis use and psychotic experiences: evidence of cumulative and synergistic effects. Br J Psychiatry204: 346–353.
47.
MorrisonPStoneJ (2011) Synthetic delta-9-tetrahydrocannabinol elicits schizophrenia-like negative symptoms which are distinct from sedation. Hum PsychopharmClin Exp26: 77–80.
48.
MorrisonPDZoisVMcKeownD, et al. (2009) The acute effects of synthetic intravenous Δ9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychol Med39: 1607–1616.
49.
MurrayRMQuigleyHQuattroneD, et al. (2016) Traditional marijuana, high-potency cannabis and synthetic cannabinoids: Increasing risk for psychosis. World Psychiatry15: 195–204.
50.
NunnJARizzaFPetersER (2001) The incidence of schizotypy among cannabis and alcohol users. J Nerv Ment Dis189: 741–748.
51.
OlkinI (1995) Keynote addresses. Meta-analysis: Reconciling the results of independent studies. Stat Med14: 457–472.
52.
PertweeR (2008) The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. Br J Pharmacol153: 199–215.
53.
RafteryAE (1995) Bayesian model selection in social research. Sociol Methodol25: 111–164.
54.
RaineA (1991) The SPQ: a scale for the assessment of schizotypal personality based on DSM-III-R criteria. Schizophr Bull17: 555–564.
55.
RamaekersJTheunissenELDe BrouwerM, et al. (2011) Tolerance and cross-tolerance to neurocognitive effects of THC and alcohol in heavy cannabis users. Psychopharmacol214: 391–401.
56.
RamaekersJVan WelJSpronkD, et al. (2016) Cannabis and tolerance: acute drug impairment as a function of cannabis use history. Sci Rep6: 26843.
57.
SchiffmanJNakamuraBEarleywineM, et al. (2005) Symptoms of schizotypy precede cannabis use. Psychiatry Res134: 37–42.
58.
SchoelerTPetrosNDi FortiM, et al. (2016) Effects of continuation, frequency, and type of cannabis use on relapse in the first 2 years after onset of psychosis: an observational study. Lancet Psychiatry3: 947–953.
59.
SpriggensLHidesL (2015) Patterns of cannabis use, psychotic-like experiences and personality styles in young cannabis users. Schizophr Res165: 3–8.
60.
StirlingJBarkusENabosiL, et al. (2008) Cannabis-induced psychotic-like experiences are predicted by high schizotypy: Confirmation of preliminary results in a large cohort. Psychopathology41: 371–378.
61.
VadhanNPCorcoranCMBediG, et al. (2017) Acute effects of smoked marijuana in marijuana smokers at clinical high-risk for psychosis: A preliminary study. Psychiatry Res257: 372–374.
62.
Van WelJKuypersKTheunissenE, et al. (2013) Single doses of THC and cocaine decrease proficiency of impulse control in heavy cannabis users. Br J Pharmacol170: 1410–1420.
63.
VerdouxHGindreCSorbaraF, et al. (2003) Effects of cannabis and psychosis vulnerability in daily life: an experience sampling test study. Psychol Med33: 23–32.
64.
WilliamsJHWellmanNARawlinsJNP (1996) Cannabis use correlates with schizotypy in healthy people. Addiction91: 869–877.
65.
WilsonBA (1993) Ecological validity of neuropsychological assessment: Do neuropsychological indexes predict performance in everyday activities?Appl Prev Psychol2: 209–215.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
