Skip to main content

Sub-chronic impact of cannabinoids in street cannabis on cognition, psychotic-like symptoms and psychological well-being

  • C. J. A. Morgan (a1), C. Gardener (a1), G. Schafer (a1), S. Swan (a1), C. Demarchi (a1), T. P. Freeman (a1), P. Warrington (a1), I. Rupasinghe (a1), A. Ramoutar (a1), N. Tan (a1), G. Wingham (a1), S. Lewis (a1) and H. V. Curran (a1)...

Cannabis varies considerably in levels of its two major constituent cannabinoids – (delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Recently, we found evidence that those who smoked cannabis containing detectable levels of CBD had fewer psychotic-like symptoms than those whose cannabis had no CBD. The present study aimed, first, to replicate those findings and, second, to determine whether protective effects of CBD may extend to other harms of cannabis, such as memory impairment and reduced psychological well-being.


A total of 120 current cannabis smokers, 66 daily users and 54 recreational users were classified into groups according to whether analysis of their hair revealed the presence or absence of CBD and high versus low levels of THC. All were assessed on measures of psychosis-like symptoms, memory (prose recall; source memory) and depression/anxiety.


Lower psychosis-like symptoms were found in those whose hair had CBD compared with those without. However, this was seen only in recreational users, who had higher levels of THC in their hair. Higher THC levels in hair were associated with increased depression and anxiety. Prose recall and source memory were poorer in daily users with high THC levels in hair while recognition memory was better in individuals with CBD present in hair.


CBD attenuates the psychotic-like effects of cannabis over time in recreational users. Higher THC negatively impacts on memory and psychological well-being. These findings raise concerns for the harms stemming from use of varieties such as ‘skunk’ (sensimillia), which lack any CBD but currently dominate the supply of cannabis in many countries.

Corresponding author
*Address for correspondence: Dr C. J. A. Morgan, Clinical Psychopharmacology Unit, University College London, Gower St, London WC1E 6BT, UK. (Email:
Hide All
Beck AT, Steer RA, Ball R, Ranieri W (1996). Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients. Journal of Personality Assessment 67, 588597.
Bergamaschi MM, Queiroz RH, Chagas MH, de Oliveira DC, De Martinis BS, Kapczinski F, Quevedo J, Roesler R, Schroder N, Nardi AE, Martin-Santos R, Hallak JE, Zuardi AW, Crippa JA (2011). Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology 36, 12191226.
Bhattacharyya S, Morrison PD, Fusar-Poli P, Martin-Santos R, Borgwardt S, Winton-Brown T, Nosarti C, O'Carroll CM, Seal M, Allen P, Mehta MA, Stone JM, Tunstall N, Giampietro V, Kapur S, Murray RM, Zuardi AW, Crippa JA, Atakan Z, McGuire PK (2010). Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology 35, 764774.
Curran HV, Brignell C, Fletcher S, Middleton P, Henry J (2002). Cognitive and subjective dose-response effects of acute oral Delta 9-tetrahydrocannabinol (THC) in infrequent cannabis users. Psychopharmacology (Berlin) 164, 6170.
D'Souza DC, Perry E, MacDougall L, Ammerman Y, Cooper T, Wu YT, 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.
Demirakca T, Sartorius A, Ende G, Meyer N, Welzel H, Skopp G, Mann K, Hermann D (2010). Diminished gray matter in the hippocampus of cannabis users: possible protective effects of cannabidiol. Drug and Alcohol Dependence 114, 242245.
Di Forti M, Morrison PD, Butt A, Murray RM (2007). Cannabis use and psychiatric and cogitive disorders: the chicken or the egg? Current Opinion in Psychiatry 20, 228234.
Di Forti M, Morgan C, Dazzan P, Pariante C, Mondelli V, Marques TR, Handley R, Luzi S, Russo M, Paparelli A, Butt A, Stilo SA, Wiffen B, Powell J, Murray RM (2009). High potency cannabis and the risk of psychosis. British Journal of Psychiatry 195, 488491.
Gonzalez R (2007). Acute and non-acute effects of cannabis on brain functioning and neuropsychological performance. Neuropsychology Review 17, 347361.
Guimares FS, Chiaretti TM, Graeff FG (1990). Antianxiety effects of cannabidiol in the elevated plus-maze. Psychopharmacology 100, 558559.
Hardwick S, King LA (2008). Home Office Cannabis Potency Study. Home Office Scientific Development Branch: St Albans.
Henquet C, Murray R, Linszen D, van Os J (2005). The environment and schizophrenia: the role of cannabis use. Schizophrenia Bulletin 31, 608612.
Hermann D, Sartorius A, Welzel H, Walter S, Skopp G, Ende G, Mann K (2007). Dorsolateral prefrontal cortex N-acetylaspartate/total creatine (NAA/tCr) loss in male recreational cannabis users. Biological Psychiatry 61, 12811289.
Karschner EL, Darwin WD, Goodwin RS, Wright S, Huestis MA (2011). Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration. Clinical Chemistry 57, 6675.
Koethe D, Giuffrida A, Schreiber D, Hellmich M, Schultze-Lutter F, Ruhrmann S, Klosterkotter J, Piomelli D, Leweke FM (2009). Anandamide elevation in cerebrospinal fluid in initial prodromal states of psychosis. British Journal of Psychiatry 194, 371372.
Krystal JH, Karper LP, Bennett A, D'Souza DC, Abi-Dargham A, Morrisey K, Charney DS (1998). Interactive effects of subanesthetic ketamine and subhypnotic lorazepam in humans. Psychopharmacology 135, 213299.
Leweke FM, Giuffrida A, Koethe D, Schreiber D, Nolden BM, Kranaster L, Neatby MA, Schneider M, Gerth CW, Hellmich M, Klosterkotter J, Piomelli D (2007). Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: impact of cannabis use. Schizophrenia Research 94, 2936.
Luscher B, Shen Q, Sahir N (2010). The GABAergic deficit hypothesis of major depressive disorder. Molecular Psychiatry 16, 383406.
Mason O, Morgan CJ, Dhiman SK, Patel A, Parti N, Patel A, Curran HV (2009). Acute cannabis use causes increased psychotomimetic experiences in individuals prone to psychosis. Psychological Medicine 39, 951956.
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 CJ, Freeman TP, Schafer GL, Curran HV (2010 a). Cannabidiol attenuates the appetitive effects of delta(9)-tetrahydrocannabinol in humans smoking their chosen cannabis. Neuropsychopharmacology 35, 18791885.
Morgan CJ, Schafer G, Freeman TP, Curran HV (2010 b). Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study. British Journal of Psychiatry 197, 285290.
Morgan CJ, Curran HV (2008). Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis. British Jounal of Psychiatry 192, 306307.
Overall JE, Gorham DR (1962). The Brief Psychiatric Rating Scale. Psychological Reports 10, 799812.
Pertwee RG (2008). The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. British Journal of Pharmacology 153, 199215.
Raine A (1991). The SPQ: a scale for the assessment of schizotypal personality based on DSM-III-R criteria. Schizophrenia Bulletin 17, 555564.
Ren Y, Whittard J, Higuera-Matas A, Morris CV, Hurd YL (2009). Cannabidiol, a nonpsychotropic component of cannabis, inhibits cue-induced heroin seeking and normalizes discrete mesolimbic neuronal disturbances. Journal of Neuroscience 29, 1476414769.
Scallet AC, Uemura E, Andrews A, Ali SF, McMillan DE, Paule MG, Brown RM, Slikker W Jr. (1987). Morphometric studies of the rat hippocampus following chronic delta-9-tetrahydrocannabinol (THC). Brain Research 436, 193198.
Solowij N, Michie PT, Fox AM (1991). Effects of long-term cannabis use on selective attention: an event-related potential study. Pharmacology Biochemistry and Behavior 40, 683688.
Spielberger C (1983). State-Trait Anxiety Inventory (Form Ys). Mind Garden: Palo Alto, California.
UNODC (2009). World Drug Report 2009. United Nations Publication. United Nations Office on Drugs and Crime: Wien.
Ventura MA, Green MF, Shaner A, Liberman RP (1993). Training and quality assurance with the brief psychiatric rating scale: ‘The drift buster’. International Journal of Methods in Psychiatric Research 3, 221224.
Wechsler D (2001). Wechsler Test of Adult Reading. Psychological Corportation: San Antonio, TX.
Wilding EL, Rugg MD (1996). An event-related potential study of recognition memory with and without retrieval of source. Brain 119, 889905.
Wilson B, Cockburn J, Baddeley A (1985). The Rivermead Behavioural Memory Test. Thames Valley Test Company: Bury St. Edmunds, UK.
Wolf SA, Bick-Sander A, Fabel K, Leal-Galicia P, Tauber S, Ramirez-Rodriguez G, Muller A, Melnik A, Waltinger TP, Ullrich O, Kempermann G (2010). Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis. Cell Communication and Signaling 8, 12.
Zuardi AW, Crippa JA, Hallak JE, Moreira FA, Guimaraes FS (2006). Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Brazilian Journal of Medical and Biological Research 39, 421429.
Zuardi AW, Crippa JA, Hallak JE, Pinto JP, Chagas MH, Rodrigues GG, Dursun SM, Tumas V (2009). Cannabidiol for the treatment of psychosis in Parkinson's disease. Journal of Psychopharmacology 23, 979983.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 30
Total number of PDF views: 196 *
Loading metrics...

Abstract views

Total abstract views: 1250 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 25th February 2018. This data will be updated every 24 hours.