Abstract
Rats were trained in a two-lever operant box in a drug discrimination procedure to respond differentially to the effects induced by 3 mg/kg of (-)Δ 9-tetrahydrocannabinol and the drug vehicle. Tests with (-)Δ 8-THC and the dimethyl-heptyl (DMH) homologue of (-)Δ 8-THC indicated that (-)Δ 8-THC-DMH was more potent but had a slower onset of action than (-)Δ 8-THC. Two ways of testing the onset and duration of action were compared. In one procedure (separate tests) the time course of the drug action was established by testing each time interval on separate days with a new injection each test day, whereas in the other procedure (repeated tests) all intervals were evaluated after a single injection. The results were similar for both procedures. The median time intervals for the decay of the (-)Δ 8-THC stimulus were 122 and 127 min for the separate and repeated tests procedures respectively. The median time intervals for the onset of action of the (-)Δ 9-THC effects of (-)Δ 8-THC were 65 and 62 min for the separate and repeated tests procedures respectively. The median time intervals for the decay of (-)Δ 8-THC-DMH (0.30 and 0.56 mg/kg) was between 8 and 24 h after injection. Furthermore, a stereoselective action is indicated, as (+)Δ 8-THC (5.6 and 10 mg/kg) did not substitute for (-)Δ 9-THC.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Balster RL, Ford RD (1978) The discriminative stimulus properties of cannabinoids: a review. In: Ho BT, Richards DW III, Chute DL (eds) Drug discrimination and state dependent learning. Academic, New York, pp 131–147
Barry H III, Kubena RK (1972) Discriminative stimulus characteristics of alcohol, marihuana and atropine. In: Singh JM, Miller L, Lal H (eds) Drug addiction: Experimental pharmacology. Futura, Mount Kisco, pp 3–16
Bueno OFA, Carlini EA, Finkelfarb E, Suzuki US (1976) 156-1, ethanol, and amphetamine as discriminative stimulus — generalization tests with other drugs. Psychopharmacologia 46:235–243
Edery H, Grunfeld Y, Ben-Zvi Z, Mechoulam R (1971) Structural requirements for cannabinoid activity. Ann NY Acad Sci 191:40–53
Edery H, Grunfeld Y, Porath G, Ben-Zvi Z, Shani A, Mechoulam R (1972) Structure-activity relationships in the tetrahydrocannabinol series. Arzneim-Forsch 22:1995–2003
Ferster CB, Skinner BF (1957) Schedules of reinforcement. Appleton-Century-Crofts, New York
Holtzman SG (1980) Phencyclidine-like discriminative effects of opioids in the rat. J Pharmacol Exp Ther 214:614–619
Järbe TUC, Henriksson BG (1974) Discriminative response control produced with hashish, tetrahydrocannabinols (Δ 8-THC and Δ 8-THC), and other drugs. Psychopharmacologia 40:1–16
Järbe TUC, Johansson JO, Henriksson BG (1975) 156-4 and pentobarbital as discriminative cues in the mongolian gerbil (Meriones unguiculatus). Pharmacol Biochem Behav 3:403–410
Järbe TUC, Johansson JO, Henriksson BG (1976) Characteristics of tetrahydrocannabinol (THC)-produced discrimination in rats. Psychopharmacology 48:181–187
Järbe TUC, Henriksson BG, Ohlin GC (1977) 157-1 as a discriminative cue in pigeons: effects of 157-2, CBD, and CBN. Arch Int Pharmacodyn 228:68–72
Järbe TUC, McMillan DE (1980) 157-3 as a discriminative stimulus in rats and pigeons: generalization to THC metabolites and SP-111. Psychopharmacology 71:281–289
Johansson J, Järbe TUC, Henriksson BG (1975) Acute and subchronic influences of tetrahydrocannabinols on water and food intake, body weight, and temperature in male rats. T-I-T J Life Sci 5:17–27
Jones G, Pertwee RG, Gill EW, Paton WDM, Nilsson IM, Widman M, Agurell S (1974) Relative pharmacological potency in mice of optical isomers of Δ 1-tetrahydrocannabinol. Biochem Pharmacol 23:439–446
Kettens-Van Den Bosch JJ, Salemink CA, Van Noordwijk J, Khan I (1980) Biological activity of the tetrahydrocannabinols. J Ethnopharmacol 2:197–231
Krimmer EC, Barry H III (1977) Discriminable stimuli produced by marihuana constituents. In: Lal H (ed) Discriminative stimulus properties of drugs. Plenum, New York, pp 121–135
Litchfield JT, Wilcoxon F (1949) A simplified method for evaluating dose-effect experiments. J Pharmacol Exp Ther 96:99–113
Mechoulam R, Braun P, Gaoni R (1972) Synthesis of Relative pharmacological potency in mice of optical isomers of Δ 1-THC related cannabinoids. J Am Chem Soc 94:6159–6165
Mechoulam R, Edery H (1973) Structure-activity relationships in the cannabinoid series. In: Mechoulam R (ed) Marijuana-chemistry, pharmacology, metabolism and clinical effects. Academic, London, pp 101–136
Mechoulam R, Lander N, Dikstein S, Carlini EA, Blumenthal M (1976) On the therapeutic possibilities of some cannabinoids. In: Cohen S, Stillman RA (eds) The therapeutic potential of marihuana. Plenum, New York, pp 35–45
Owen DB (1962) Handbook of statistical tables. Addison-Esley, Palo Alto, p 363
Revuelta AV, Cheney DL, Costa E, Lander N, Mechoulam R (1980) Reduction of hippocampal acetylcholine turnover in rats treated with (-)Δ 8-tetrahydrocannabinol and its 1′, 2′,-dimethyl-heptyl homolog. Brain Res 195:445–452
Shannon HE (1981) Evaluation of phencyclidine analogs on the basis of their discriminative stimulus properties in rats. J Pharmacol Exp Ther 216:543–551
Siegel S (1956) Nonparametric statistics. McGraw-Hill, New York, pp 75–83
Silverman PB, Ho BT (1980) Amphetamine discrimination: onset of the stimulus. Pharmacol Biochem Behav 12:303–304
Staddon JER (1975) Learning as adaptation. In: Estes WK (ed) Handbook of learning and cognitive processes. Vol 2. Conditioning and behavior theory. LEA Publishers. Hillsdale, pp 37–98
Weissman A (1978) Generalization of the discriminative stimulus properties of Δ 9-tetrahydrocannabinol to cannabinoids with therapeutic potential. In: Colpaert FC, Rosecrans JA (eds) Stimulus properties of drugs: Ten years of progress. Elsevier/North Holland, Amsterdam, pp 99–122
Wilson RS, May EL (1975) Analgesic properties of the tetrahydrocannabinols, their metabolites, and analogs. J Med Chem 18:700–703
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Järbe, T.U.C., Swedberg, M.D.B. & Mechoulam, R. A repeated tests procedure to assess onset and duration of the cue properties of (−)Δ 9-THC, (−)Δ 8-THC-DMH and (+)Δ 8-THC. Psychopharmacology 75, 152–157 (1981). https://doi.org/10.1007/BF00432178
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00432178