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Acute memory and psychotomimetic effects of cannabis and tobacco both ‘joint’ and individually: a placebo-controlled trial

  • C. Hindocha (a1), T. P. Freeman (a1), J. X. Xia (a2), N. D. C. Shaban (a1) and H. V. Curran (a1)...



Cannabis and tobacco have contrasting cognitive effects. Smoking cannabis with tobacco is prevalent in many countries and although this may well influence cognitive and mental health outcomes, the possibility has rarely been investigated in human experimental psychopharmacological research.


The individual and interactive effects of cannabis and tobacco were evaluated in 24 non-dependent cannabis and tobacco smokers in a randomized, placebo-controlled, double-blind, 2 (cannabis, placebo) × 2 (tobacco, placebo) crossover design. Verbal memory (prose recall), working memory (WM) performance including maintenance, manipulation and attention (N-back), psychotomimetic, subjective and cardiovascular measures were recorded on each of four sessions.


Cannabis alone impaired verbal memory. A priori contrasts indicated that tobacco offset the effects of cannabis on delayed recall. However, this was not supported by linear mixed model analysis. Cannabis load-dependently impaired WM. By contrast, tobacco improved WM across all load levels. The acute psychotomimetic effects and ratings of ‘stoned’ and ‘dizzy’ induced by cannabis were not altered by tobacco. Cannabis and tobacco had independent effects on increasing heart rate and interacting effects on increasing diastolic blood pressure.


Relative to placebo, acute cannabis impaired verbal memory and WM. Tobacco enhanced performance on WM, independently of cannabis. Moreover, we found some preliminary evidence that tobacco may offset the effects of cannabis on delayed, but not immediate, verbal recall. In contrast, the psychotomimetic and subjective effects of cannabis were unaffected by tobacco co-administration. By reducing the cognitive impairment from cannabis, tobacco co-administration may perpetuate use despite adverse health consequences.

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This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (, which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

*Address for correspondence: C. Hindocha, Clinical Psychopharmacology Unit, University College London, Gower St, London WC1E 6BT, UK. (Email:


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Agrawal, A, Lynskey, MT, Madden, PA, Pergadia, ML, Bucholz, KK, Heath, AC (2009). Simultaneous cannabis and tobacco use and cannabis-related outcomes in young women. Drug and Alcohol Dependence 101, 812.
Amos, A, Wiltshire, S, Bostock, Y, Haw, S, Mcneill, A (2004). ‘You can't go without a fag… you need it for your hash’ – a qualitative exploration of smoking, cannabis and young people. Addiction 99, 7781.
Beck, AT, Steer, RA, Ball, R, Ranieri, WF (1996). Comparison of Beck Depression Inventories-IA and-II in psychiatric outpatients. Journal of Personality Assessment 67, 588597.
Bossong, MG, Jansma, JM, Van Hell, HH, Jager, G, Oudman, E, Saliasi, E, Kahn, RS, Ramsey, NF (2012). Effects of δ9-tetrahydrocannabinol on human working memory function. Biological Psychiatry 71, 693699.
Broyd, SJ, Van Hell, HH, Beale, C, Yucel, M, Solowij, N (2016). Acute and chronic effects of cannabinoids on human cognition-a systematic review. Biol Psychiatry 79, 557567.
Cohen, C, Kodas, E, Griebel, G (2005). CB 1 receptor antagonists for the treatment of nicotine addiction. Pharmacology Biochemistry and Behavior 81, 387395.
Cooper, ZD, Haney, M (2009). Comparison of subjective, pharmacokinetic, and physiological effects of marijuana smoked as joints and blunts. Drug and Alcohol Dependence 103, 107113.
Crane, NA, Schuster, RM, Fusar-Poli, P, Gonzalez, R (2013). Effects of cannabis on neurocognitive functioning: recent advances, neurodevelopmental influences, and sex differences. Neuropsychology Review 23, 117137.
Curran, HV, Brignell, C, Fletcher, PC, Middleton, P, Henry, J (2002). Cognitive and subjective dose-response effects of acute oral D9-tetrahydrocannabinol (THC) in infrequent cannabis users. Psychopharmacology (Berl) 164, 6170.
Curran, HV, Freeman, TP, Mokrysz, C, Lewis, DA, Morgan, CJ, Parsons, LH (2016). Keep off the grass? Cannabis, cognition and addiction. Nature Reviews Neuroscience 17, 293306.
De Leon, J, Diaz, FJ (2005). A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors. Schizophrenia Research 76, 135157.
De Simoni, S, Schwarz, AJ, O'daly, OG, Marquand, AF, Brittain, C, Gonzales, C, Stephenson, S, Williams, SC, Mehta, MA (2013). Test–retest reliability of the BOLD pharmacological MRI response to ketamine in healthy volunteers. NeuroImage 64, 7590.
D'souza, DC, Ahn, K, Bhakta, S, Elander, J, Singh, N, Nadim, H, Jatlow, P, Suckow, RF, Pittman, B, Ranganathan, M (2012). Nicotine fails to attenuate ketamine-induced cognitive deficits and negative and positive symptoms in humans: implications for schizophrenia. Biological Psychiatry 72, 785794.
D'souza, DC, Perry, E, Macdougall, L, Ammerman, Y, Cooper, T, Wu, Y-t, Braley, G, Gueorguieva, R, Krystal, JH (2004). The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology 29, 15581572.
D'souza, DC, Ranganathan, M, Braley, G, Gueorguieva, R, Zimolo, Z, Cooper, T, Perry, E, Krystal, J (2008). Blunted psychotomimetic and amnestic effects of delta-9-tetrahydrocannabinol in frequent users of cannabis. Neuropsychopharmacology 33, 25052516.
Englund, A, Morrison, PD, Nottage, J, Hague, D, Kane, F, Bonaccorso, S, Stone, JM, Reichenberg, A, Brenneisen, R, Holt, D (2013). Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. Journal of Psychopharmacology 27, 1927.
Faul, F, Erdfelder, E, Lang, AG, Buchner, A (2007). G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behavior Research Methods 39, 175191.
Fernandez-Ruiz, J, Hernandez, M, Ramos, JA (2010). Cannabinoid-dopamine interaction in the pathophysiology and treatment of CNS disorders. CNS Neuroscience & Therapeutics 16, e72e91.
Fletcher, PC, Honey, GD (2006). Schizophrenia, ketamine and cannabis: evidence of overlapping memory deficits. Trends in Cognitive Sciences 10, 167174.
Forget, B, Hamon, M, Thiébot, M-H (2005). Cannabinoid CB1 receptors are involved in motivational effects of nicotine in rats. Psychopharmacology 181, 722734.
Freeman, TP, Morgan, CJ, Vaughn-Jones, J, Hussain, N, Karimi, K, Curran, HV (2012). Cognitive and subjective effects of mephedrone and factors influencing use of a ‘new legal high’. Addiction 107, 792800.
Gage, S, Hickman, M, Heron, J, Munafò, M, Lewis, G, Macleod, J, Zammit, S (2014). Associations of cannabis and cigarette use with psychotic experiences at age 18: findings from the Avon Longitudinal Study of Parents and Children. Psychological Medicine 44, 34353444.
Gamaleddin, I, Wertheim, C, Zhu, AZ, Coen, KM, Vemuri, K, Makryannis, A, Goldberg, SR, Le Foll, B (2012). Cannabinoid receptor stimulation increases motivation for nicotine and nicotine seeking. Addiction Biology 17, 4761.
Gossop, M, Darke, S, Griffiths, P, Hando, J, Powis, B, Hall, W, Strang, J (1995). The Severity of Dependence Scale (SDS): psychometric properties of the SDS in English and Australian samples of heroin, cocaine and amphetamine users. Addiction 90, 607614.
Gray, R, Rajan, AS, Radcliffe, KA, Yakehiro, M, Dani, JA (1996). Hippocampal synaptic transmission enhanced by low concentrations of nicotine. Nature 383, 713716.
Gurillo, P, Jauhar, S, Murray, RM, Maccabe, JH (2015). Does tobacco use cause psychosis? Systematic review and meta-analysis. Lancet Psychiatry 2, 718725.
Hart, CL, Ilan, AB, Gevins, A, Gunderson, EW, Role, K, Colley, J, Foltin, RW (2010). Neurophysiological and cognitive effects of smoked marijuana in frequent users. Pharmacology Biochemistry and Behavior 96, 333341.
Hautus, MJ (1995). Corrections for extreme proportions and their biasing effects on estimated values ofd′. Behavior Research Methods, Instruments, & Computers 27, 4651.
Heatherton, TF, Kozlowski, LT, Frecker, RC, Fagerstrom, KO (1991). The fagerstrom test for nicotine dependence: a revision of the fagerstrom tolerance questionnaire. British Journal of Addiction 86, 11191127.
Heishman, SJ, Kleykamp, BA, Singleton, EG (2010). Meta-analysis of the acute effects of nicotine and smoking on human performance. Psychopharmacology (Berl) 210, 453469.
Herkenham, M, Lynn, AB, Little, MD, Johnson, MR, Melvin, LS, De Costa, BR, Rice, KC (1990). Cannabinoid receptor localization in brain. Proceedings of the National Academy of Sciences of the United States of America 87, 19321936.
Hindocha, C, Freeman, TP, Ferris, JA, Lynskey, MT, Winstock, AR (2016). No smoke without tobacco: a global overview of cannabis and tobacco routes of administration and their association with intention to quit. Frontiers in Psychiatry 7, 19.
Hindocha, C, Freeman, TP, Schafer, G, Gardener, C, Das, RK, Morgan, CJ, Curran, HV (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. European Neuropsychopharmacology 25, 325334.
Hunault, CC, Mensinga, TT, Bocker, KB, Schipper, CM, Kruidenier, M, Leenders, ME, De Vries, I, Meulenbelt, J (2009). Cognitive and psychomotor effects in males after smoking a combination of tobacco and cannabis containing up to 69 mg delta-9-tetrahydrocannabinol (THC). Psychopharmacology (Berl) 204, 8594.
Jacobsen, LK, Pugh, KR, Constable, RT, Westerveld, M, Mencl, WE (2007). Functional correlates of verbal memory deficits emerging during nicotine withdrawal in abstinent adolescent cannabis users. Biological Psychiatry 61, 3140.
Jarvik, ME, Madsen, DC, Olmstead, RE, Iwamoto-Schaap, PN, Elins, JL, Benowitz, NL (2000). Nicotine blood levels and subjective craving for cigarettes. Pharmacology, Biochemistry and Behavior 66, 553558.
Koskinen, J, Lohonen, J, Koponen, H, Isohanni, M, Miettunen, J (2010). Rate of cannabis use disorders in clinical samples of patients with schizophrenia: a meta-analysis. Schizophrenia Bulletin 36, 11151130.
Kumari, V, Gray, JA, Mitterschiffthaler, MT, Das, M, Zachariah, E, Vythelingum, GN, Williams, SC, Simmons, A, Sharma, T (2003). Cognitive effects of nicotine in humans: an fMRI study. NeuroImage 19, 10021013.
Lawn, W, Freeman, TP, Pope, RA, Joye, A, Harvey, L, Hindocha, C, Mokrysz, C, Moss, A, Wall, MB, Bloomfield, MA (2016). Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis ‘amotivational'hypotheses. Psychopharmacology 233, 35373552.
Le Foll, B, Goldberg, SR (2004). Rimonabant, a CB1 antagonist, blocks nicotine-conditioned place preferences. Neuroreport 15, 21392143.
Levin, ED, Mcclernon, FJ, Rezvani, AH (2006). Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization. Psychopharmacology (Berl) 184, 523539.
Levin, ED, Simon, BB (1998). Nicotinic acetylcholine involvement in cognitive function in animals. Psychopharmacology 138, 217230.
Marteau, TM, Bekker, H (1992). The development of a six-item short-form of the state scale of the Spielberger State-Trait Anxiety Inventory (STAI). British Journal of Clinical Psychology 31, 301306.
Mason, OJ, Morgan, CJ, Stefanovic, A, Curran, HV (2008). The psychotomimetic states inventory (PSI): measuring psychotic-type experiences from ketamine and cannabis. Schizophrenia Research 103, 138142.
Mendelson, JH, Sholar, MB, Goletiani, N, Siegel, AJ, Mello, NK (2005). Effects of low- and high-nicotine cigarette smoking on mood states and the HPA axis in men. Neuropsychopharmacology 30, 17511763.
Mendelson, JH, Sholar, MB, Mutschler, NH, Jaszyna-Gasior, M, Goletiani, NV, Siegel, AJ, Mello, NK (2003). Effects of intravenous cocaine and cigarette smoking on luteinizing hormone, testosterone, and prolactin in men. Journal of Pharmacology and Experimental Therapeutics 307, 339348.
Mokrysz, C, Freeman, T, Korkki, S, Griffiths, K, Curran, H (2016). Are adolescents more vulnerable to the harmful effects of cannabis than adults; A placebo-controlled study in human males. Translational Psychiatry 6, e961.
Moore, TH, Zammit, S, Lingford-Hughes, A, Barnes, TR, Jones, PB, Burke, M, Lewis, G (2007). Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 370, 319328.
Morgan, CJA, Dodds, C, Furby, H, Pepper, F, Fam, J, Freeman, T, Hughes, E, Doeller, C, King, J, Stone, J, Howes, O (2014). Long-term heavy ketamine use is associated with spatial memory impairment and altered hippocampal activation. Frontiers in Psychiatry 5, 111.
Morrison, P, Zois, V, Mckeown, D, Lee, T, Holt, D, Powell, J, Kapur, S, Murray, R (2009). The acute effects of synthetic intravenous Δ 9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychological Medicine 39, 16071616.
Penetar, DM, Kouri, EM, Gross, MM, Mccarthy, EM, Rhee, CK, Peters, EN, Lukas, SE (2005). Transdermal nicotine alters some of marihuana's effects in male and female volunteers. Drug and Alcohol Dependence 79, 211223.
Picciotto, MR, Caldarone, BJ, King, SL, Zachariou, V (2000). Nicotinic receptors in the brain: links between molecular biology and behavior. Neuropsychopharmacology 22, 451465.
Rabin, RA, George, TP (2015). A review of co-morbid tobacco and cannabis use disorders: possible mechanisms to explain high rates of co-use. American Journal on Addictions 24, 105116.
Raine, A (1991). The SPQ: a scale for the assessment of schizotypal personality based on DSM-III-R criteria. Schizophrenia Bulletin 17, 555.
Ramaekers, JG, Kauert, G, Theunissen, EL, Toennes, SW, Moeller, ML (2009). Neurocognitive performance during acute THC intoxication in heavy and occasional cannabis users. Journal of Psychopharmacology 23, 266277.
Rowell, PP, Carr, LA, Garner, AC (1987). Stimulation of [3H] dopamine release by nicotine in rat nucleus accumbens. Journal of Neurochemistry 49, 14491454.
Schuster, RM, Crane, NA, Mermelstein, R, Gonzalez, R (2015). Tobacco may mask poorer episodic memory among young adult cannabis users. Neuropsychology 29, 759766.
Schuster, RM, Mermelstein, RJ, Hedeker, D (2016). Ecological momentary assessment of working memory under conditions of simultaneous Marijuana and tobacco use. Addiction 8, 14661476.
Shoaib, M (2008). The cannabinoid antagonist AM251 attenuates nicotine self-administration and nicotine-seeking behaviour in rats. Neuropharmacology 54, 438444.
Snodgrass, JG, Corwin, J (1988). Pragmatics of measuring recognition memory: applications to dementia and amnesia. Journal of Experimental Psychology: General 117, 3450.
Spielberger, CD, Gorsuch, RL, Lushene, RE, Vagg, PR (1970). State-trait anxiety inventory (STAI). BiB 2010, 180.
Stanislaw, H, Todorov, N (1999). Calculation of signal detection theory measures. Behavior Research Methods, Instruments, & Computers 31, 137149.
Valjent, E, Mitchell, JM, Besson, MJ, Caboche, J, Maldonado, R (2002). Behavioural and biochemical evidence for interactions between Δ9-tetrahydrocannabinol and nicotine. British Journal of Pharmacology 135, 564578.
Van Der Pol, P, Liebregts, N, Brunt, T, Van Amsterdam, J, De Graaf, R, Korf, DJ, Van Den Brink, W, Van Laar, M (2014). Cross-sectional and prospective relation of cannabis potency, dosing and smoking behaviour with cannabis dependence: an ecological study. Addiction 109, 11011109.
Van Gastel, WA, Maccabe, JH, Schubart, CD, Vreeker, A, Tempelaar, W, Kahn, RS, Boks, MPM (2013). Cigarette smoking and cannabis use are equally strongly associated with psychotic-like experiences: a cross-sectional study in 1929 young adults. Psychological Medicine 43, 23932401.
Wilson, BA, Cockburn, J, Baddeley, AD (1991). The Rivermead Behavioural Memory Test. Thames Valley Test Company: Suffolk.


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