Comparisons of Δ9-Tetrahydrocannabinol and Anandamide on a Battery of Cognition-Related Behavior in Nonhuman Primates.
Brian D Kangas, Michael Z Leonard, Vidyanand G Shukla, Shakiru O Alapafuja, Spyros P Nikas, Alexandros Makriyannis, Jack Bergman
Journal of Pharmacology and Experimental Therapeutics January 29, 2016 DOI: 10.1124/jpet.115.228189 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Squirrel monkeys |
| Interventions | Δ9-tetrahydrocannabinol URB597 anandamide methanandamide rimonabant |
| Topics | Cannabis |
| Keywords | Animals Saimiri Benzamides Carbamates Piperidines Pyrazoles Arachidonic acids Endocannabinoids Behavior, animal Motivation Cognition Discrimination learning Memory, short-term Reversal learning Psychomotor performance Attention Dose-response relationship, drug Male Polyunsaturated alkamides Dronabinol Rimonabant |
| Key findings | Δ9-THC produced dose-related impairments of discrimination-based cognitive behavior, with potency varying across tasks (discriminative capability < learning < flexibility < short-term memory), and disrupted attention; anandamide and URB597 alone had no effects, and progressive ratio breakpoints were largely unaffected by all drugs. The authors suggest metabolically stable anandamide forms may have lesser adverse cognitive effects than Δ9-THC. |
Abstract
The primary psychoactive ingredient of marijuana, Δ(9)-tetrahydrocannabinol (Δ(9)-THC), has medicinal value but also produces unwanted deleterious effects on cognitive function, promoting the search for improved cannabinergic therapeutics. The present studies used a battery of touchscreen procedures in squirrel monkeys to compare the effects of different types of cannabinergic drugs on several measures of performance including learning (repeated acquisition), cognitive flexibility (discrimination reversal), short-term memory (delayed matching-to-sample), attention (psychomotor vigilance), and motivation (progressive ratio). Drugs studied included the cannabinoid agonist Δ(9)-THC, fatty acid amide hydrolase (FAAH) inhibitor cyclohexylcarbamic acid 3-carbamoylbiphenyl-3-yl ester (URB597), and endocannabinoid anandamide and its stable synthetic analog methanandamide [(R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide]. The effects of Δ(9)-THC and anandamide after treatment with the cannabinoid receptor type 1 inverse agonist/antagonist rimonabant [5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1Hpyrazole-3-carboxamide] and the FAAH inhibitor URB597, respectively, also were examined. The results showed the following: 1) Δ(9)-THC produced dose-related impairments of discrimination-based cognitive behavior with potency that varied across tasks (discriminative capability < learning < flexibility < short-term memory); 2) anandamide alone and URB597 alone were without effect on all endpoints; 3) anandamide following URB597 pretreatment and methanandamide had negligible effects on discriminative capability, learning, and reversal, but following large doses affected delayed matching-to-sample performance in some subjects; 4) all drugs, except anandamide and URB597, disrupted attention; and 5) progressive ratio breakpoints were generally unaffected by all drugs tested, suggesting little to no effect on motivation. Taken together, these data indicate that metabolically stable forms of anandamide may have lesser adverse effects on cognitive functions than Δ(9)-THC, possibly offering a therapeutic advantage in clinical settings.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 6
- A Multimodal Preclinical Assessment of MDMA in Female and Male Rats: Prohedonic, Cognition Disruptive, and Prosocial Effects. Psychedelic Medicine June 1, 2024
- Chronic Δ9-tetrahydrocannabinol exposure during adolescence is associated with persistent behavioural tolerance in adult nonhuman primates. British Journal of Pharmacology November 1, 2025
- Chronic Δ9-tetrahydrocannabinol exposure in adolescent nonhuman primates: persistent abnormalities in economic demand and brain functional connectivity. Neuropsychopharmacology February 1, 2025
- Effect of Cannabis on Memory Consolidation, Learning and Retrieval and Its Current Legal Status in India: A Review. Biomolecules January 12, 2023
- Chronic Δ9-THC in Rhesus Monkeys: Effects on Cognitive Performance and Dopamine D2/D3 Receptor Availability. Journal of Pharmacology and Experimental Therapeutics February 2018
and 1 more in the library
Cites 7
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- Δ⁹Tetrahydrocannabinol impairs visuo-spatial associative learning and spatial working memory in rhesus macaques. Journal of Psychopharmacology October 2012
- The fatty acid amide hydrolase inhibitor URB 597: interactions with anandamide in rhesus monkeys. British Journal of Pharmacology September 2011
- Effects of Endocannabinoid System Modulation on Cognitive and Emotional Behavior Frontiers in Behavioral Neuroscience July 22, 2011
- Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers Molecular Psychiatry July 12, 2011
and 2 more in the library