Biphasic effects of THC in memory and cognition

Eur J Clin Invest. 2018 May;48(5):e12920. doi: 10.1111/eci.12920. Epub 2018 Apr 2.


A generally undesired effect of cannabis smoking is a reversible disruption of short-term memory induced by delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis. However, this paradigm has been recently challenged by a group of scientists who have shown that THC is also able to improve neurological function in old animals when chronically administered at low concentrations. Moreover, recent studies demonstrated that THC paradoxically promotes hippocampal neurogenesis, prevents neurodegenerative processes occurring in animal models of Alzheimer's disease, protects from inflammation-induced cognitive damage and restores memory and cognitive function in old mice. With the aim to reconcile these seemingly contradictory facts, this work will show that such paradox can be explained within the framework of hormesis, defined as a biphasic dose-response.

Keywords: Alzheimer's disease; biphasic dose response; cannabis; delta-9-tetrahydrocannabinol; hormesis; neuroprotection.

Publication types

  • Review

MeSH terms

  • Age Factors
  • Alzheimer Disease / prevention & control
  • Animals
  • Cognition / drug effects*
  • Cognition Disorders / chemically induced*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Dronabinol / adverse effects*
  • Hippocampus / metabolism
  • Humans
  • Marijuana Smoking / adverse effects
  • Marijuana Smoking / physiopathology
  • Memory Disorders / chemically induced*
  • Memory, Short-Term / drug effects*
  • Neurogenesis / drug effects
  • Nootropic Agents / pharmacology
  • Receptor, Cannabinoid, CB1 / metabolism


  • Nootropic Agents
  • Receptor, Cannabinoid, CB1
  • Dronabinol