The acute effects of cannabinoids on memory in humans: a review
Cannabis is one of the most frequently used substances. Cannabis and its constituent cannabinoids are known to impair several aspects of cognitive function, with the most robust effects on short-term episodic and working memory in humans. A large body of the work in this area occurred in the 1970s before the discovery of cannabinoid receptors. Recent advances in the knowledge of cannabinoid receptors’ function have rekindled interest in examining effects of exogenous cannabinoids on memory and in understanding the mechanism of these effects.
The literature about the acute effects of cannabinoids on memory tasks in humans is reviewed. The limitations of the human literature including issues of dose, route of administration, small sample sizes, sample selection, effects of other drug use, tolerance and dependence to cannabinoids, and the timing and sensitivity of psychological tests are discussed. Finally, the human literature is discussed against the backdrop of preclinical findings.
Acute administration of Δ-9-THC transiently impairs immediate and delayed free recall of information presented after, but not before, drug administration in a dose- and delay-dependent manner. In particular, cannabinoids increase intrusion errors. These effects are more robust with the inhaled and intravenous route and correspond to peak drug levels.
This profile of effects suggests that cannabinoids impair all stages of memory including encoding, consolidation, and retrieval. Several mechanisms, including effects on long-term potentiation and long-term depression and the inhibition of neurotransmitter (GABA, glutamate, acetyl choline, dopamine) release, have been implicated in the amnestic effects of cannabinoids. Future research in humans is necessary to characterize the neuroanatomical and neurochemical basis of the memory impairing effects of cannabinoids, to dissect out their effects on the various stages of memory and to bridge the expanding gap between the humans and preclinical literature.
KeywordsCannabinoids Cannabis Marijuana Δ-9-THC Memory Learning Cognition
cannabinoid 1 receptor
- Aigner TG (1988) Delta-9-tetrahydrocannabinol impairs visual recognition memory but not discrimination learning in rhesus monkeys. Psychopharmacology (Berl) 95:507–511Google Scholar
- Atkinson R, Shiffrin RM (1968) Human memory: a proposed system and its control processes. New York Academic Press, New YorkGoogle Scholar
- Baddeley A (1999) Essentials of human memory. Psychology PressGoogle Scholar
- Budney AJ, Moore BA, Vandrey RG, Hughes JR (2003) The time course and significance of cannabis withdrawal. J Abnorm Psychology 112:393–402Google Scholar
- Chait LD, Perry JL (1994) Acute and residual effects of alcohol and marijuana, alone and in combination, on mood and performance. Psychopharmacology (Berl) 115:340–349Google Scholar
- Chait LD, Zacny JP (1992) Reinforcing and subjective effects of oral delta 9-THC and smoked marijuana in humans. Psychopharmacology 107:255–262Google Scholar
- 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 (Berl) 164:61–70Google Scholar
- Da Silva GE, Takahashi RN (2002) SR 141716A prevents delta 9-tetrahydrocannabinol-induced spatial learning deficit in a Morris-type water maze in mice. Prog neuropsychopharmacol Biol Psychiatry 26:321–325Google Scholar
- de Oliveira Alvares L, de Oliveira LF, Camboim C, Diehl F, Genro BP, Lanziotti VB, Quillfeldt JA (2005) Amnestic effect of intrahippocampal AM251, a CB1-selective blocker, in the inhibitory avoidance, but not in the open field habituation task, in rats. Neurobiol Learn Mem 83:119–124PubMedGoogle Scholar
- Hooker WD, Jones RT (1987) Increased susceptibility to memory intrusions and the Stroop interference effect during acute marijuana intoxication. Psychopharmacology (Berl) 91:20–24Google Scholar
- Ilan AB, Smith ME, Gevins A (2004) Effects of marijuana on neurophysiological signals of working and episodic memory. Psychopharmacology (Berl) 176:214–222Google Scholar
- Kanayama G, Rogowska J, Pope HG, Gruber SA, Yurgelun-Todd DA (2004) Spatial working memory in heavy cannabis users: a functional magnetic resonance imaging study. Psychopharmacology (Berl) 176:239–247Google Scholar
- Miller LL, Cornett TL, Brightwell DR, McFarland DJ, Drew WG, Wikler A (1977b) Marijuana: effects on storage and retrieval of prose material. Psychopharmacology (Berl) 51:311–316Google Scholar
- Miller LL, McFarland DJ, Cornett TL, Brightwell DR, Wikler A (1977d) Marijuana: effects on free recall and subjective organization of pictures and words. Psychopharmacology (Berl) 55:257–262Google Scholar
- Miller LL, Cornett T, Nallan G (1978) Marijuana: effect on nonverbal free recall as a function of field dependence. Psychopharmacology (Berl) 58:297–301Google Scholar
- Rodriguez de Fonseca F, Del Arco I, Bermudez-Silva FJ, Bilbao A, Cippitelli A, Navarro M (2005) The endocannabinoid system: physiology and pharmacology. Alcohol 40:2–14Google Scholar
- Tanda G, Goldberg SR (2003) Cannabinoids: reward, dependence, and underlying neurochemical mechanisms—a review of recent preclinical data. Psychopharmacology (Berl) 169:115–134Google Scholar
- Tulving E (1972) Episodic and semantic memory. Academic Press, New YorkGoogle Scholar
- Van Sickle MD, Duncan M, Kingsley PJ, Mouihate A, Urbani P, Mackie K, Stella N, Makriyannis A, Piomelli D, Davison JS, Marnett LJ, Di Marzo V, Pittman QJ, Patel KD, Sharkey KA (2005) Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 310:329–332PubMedGoogle Scholar
- Varvel SA, Anum EA, Lichtman AH (2005) Disruption of CB(1) receptor signaling impairs extinction of spatial memory in mice. Psychopharmacology (Berl) 179:863–872Google Scholar
- Witkin HA, Oltman PK (1967) Cognitive style. Int J Neurol 6:119–137Google Scholar