, Volume 71, Issue 2, pp 201–202 | Cite as

An abstinence syndrome following chronic administration of delta-9-tetrahydrocannabinol in rhesus monkeys

  • Alice B. Fredericks
  • Neal L. Benowitz
Short Report


Chaired, chronically catheterized rhesus monkeys were administered IV delta-9-tetrahydrocannabinol (THC), 0.5 mg/kg every 6 h for 3 weeks. Following the first THC injection, the animals appeared heavy-lidded, immobile, and unresponsive to observation. Tolerance developed to these behaviors during the 3 weeks of THC administration, although the animals remained subdued compared to baseline. Following discontinuation of THC, animals showed an increase in gross movement, eye contact, and tooth baring of greater frequency and/or duration than observed before THC. This presumably represents a cannabis abstinence syndrome.

Key words

Chronic delta-9-tetrahydrocannabinol (THC) Cannabis Marijuana Tolerance Dependence Abstinence Behavior Rhesus monkey 


  1. Benowitz NL, Jones RT (1975) Cardiovascular effects of prolonged delta-9-tetrahydrocannabinol ingestion. Clin Pharmacol Ther 18:287–297Google Scholar
  2. Deneau GA, Kaymakcalan S (1971) Physiological and psychological dependence to synthetic delta-9-tetrahydrocannabinol (THC) in rhesus monkeys. Pharmacologis 13:246Google Scholar
  3. Feinberg I, Wender PH, Koresko RL, Gottlieb F, Piehuta TA (1969) Differential effects of chlorpromazine and phenobarbital on EEG sleep patterns. J Psychiatr Res 7:101–109Google Scholar
  4. Harris RT, Water W, McLendon D (1974) Evaluation of reinforcing capability of delta-9-tetrahydrocannabinol in rhesus monkeys. Psychopharmacologia 37:23–29Google Scholar
  5. Hökfelt B, Hedeland H, Dymling JF (1970) The influence of catapres on catecholamines, renin and aldosterone in man. In: Conolly ME (ed) Catapres in hypertension. Butterworth, LondonGoogle Scholar
  6. Jones RT, Benowitz NL (1976) The 30 day trip: Clinical studies of cannabis tolerance and dependence. In: Braude C, Szara S (eds) Pharmacology of marijuana. Raven Press, New York, p 627Google Scholar
  7. McMillan DE, Dewey WL, Harris LS (1971) Characteristics of tetrahydrocannabinol tolerance. Ann NY Acad Sci 91:83–99Google Scholar
  8. Oswald I, Evans TI, Lewis SA (1969) Addictive drugs cause suppression of paradoxical sleep with withdrawal rebounds. In: Steinberg H (ed) Scientific basis of drug dependence. T. and A. Churchill, London, p 243Google Scholar
  9. Stadnicki SW, Schaeppi U, Rosenkrantz H, Braude MD (1974) Crude marihuana extract: EEG and behavioral effects of chronic oral administration in rhesus monkeys. Psychopharmacologia 37:225–233Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • Alice B. Fredericks
    • 1
    • 2
  • Neal L. Benowitz
    • 1
    • 2
  1. 1.Primate Laboratory of the Division of clinical Pharmacology, Departments of Medicine and Psychiatry, School of MedicineUniversity of CaliforniaSan Francisco
  2. 2.Clinical Pharmacology Unit of the Medical ServiceSan Francisco General Hospital Medical CenterSan FranciscoUSA

Personalised recommendations