Chronic Δ9-THC in Rhesus Monkeys: Effects on Cognitive Performance and Dopamine D2/D3 Receptor Availability.
William S John, Thomas J Martin, Kiran Kumar Solingapuram Sai, Susan H Nader, H Donald Gage, Akiva Mintz, Michael A Nader
Journal of Pharmacology and Experimental Therapeutics February 2018 DOI: 10.1124/jpet.117.244194 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 6 |
| Population | Adult male rhesus monkeys |
| Dose | 0.01-0.56 mg/kg, i.v. (acute); 1.0-2.0 mg/kg, s.c. (chronic) |
| Duration | 12 weeks of daily THC; residual effects assessed 22 hours after administration; abstinence follow-up up to 2 weeks |
| Measures | Cambridge Neuropsychological Test Automated Battery (CANTAB), fixed-ratio (FR) 10 schedule of food presentation, body temperature, positron emission tomography with [11C]-raclopride |
| Topics | Cannabis |
| Key findings | Acute THC impaired cognition in a task-specific manner and dose-dependently reduced food-maintained responding and body temperature. Chronic daily THC produced persistent residual impairment only in working memory, with differential tolerance to acute cognitive effects; working memory recovered within two weeks of abstinence. D2/D3 receptor availability did not differ from controls after four weeks of chronic THC. |
Abstract
Cannabis-related impairments to cognitive function may represent novel therapeutic targets for cannabis-use disorder, although the nature, persistence, and reversibility of such deficits remain unclear. Adult male rhesus monkeys (N = 6) responded in the morning on tasks designed to assess different cognitive domains using the Cambridge Neuropsychological Test Automated Battery (CANTAB) touchscreens followed by responding maintained under a fixed-ratio (FR) 10 schedule of food presentation in different operant chambers. First, the acute effects of Δ9-tetrahydrocannabinol (THC; 0.01-0.56 mg/kg, i.v.) on cognitive performance, FR responding, and body temperature were determined. Next, THC (1.0-2.0 mg/kg, s.c.) was administered daily after FR 10 sessions for 12 weeks, during which the residual effects of THC (i.e., 22 hours after administration) on cognition were examined and the acute effects of THC were redetermined. In a subgroup of monkeys, dopamine D2/D3 receptor availability was assessed after 4 weeks of chronic THC exposure and compared with drug-naive controls using positron emission tomography and [11C]-raclopride (N = 4/group). Acute THC pretreatments dose-dependently decreased FR responding and body temperature, and impairment to cognitive performance was task specific. During chronic treatment, THC produced persistent residual impairment only to working memory; tolerance differentially developed to acute cognitive impairments. There was recovery from residual cognitive impairments to working memory within 2 weeks of abstinence. Compared with controls, D2/D3 receptor availability was not altered during chronic THC treatment. In conclusion, THC-induced disruptions in cognition were task-specific, as was tolerance development, and not related to changes in D2/D3 receptor availability. Intervention strategies for cannabis-use disorder that enhance working memory performance may facilitate positive treatment outcomes.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 3
- Optogenetic brain‐stimulation reward: A new procedure to re‐evaluate the rewarding versus aversive effects of cannabinoids in dopamine transporter‐Cre mice Addiction Biology February 3, 2021
- The effects of naturalistic cannabis use on cognition and subjective experience in older adults with normal cognitive function Journal of Psychopharmacology November 3, 2025
- A systematic review of neuroimaging and acute cannabis exposure in age-of-risk for psychosis Translational Psychiatry April 13, 2021
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and 21 more in the library