Table 1.

Evaluation of the reinforcing effects of cannabinoids with operant self-administration procedures in laboratory animals

Dose range Vehicle	Species	Procedure	Results	Reference
Delta-9-Tetrahydrocannabinol (Δ9-THC)
25-100 μg/kg/inj. PVP, Saline	Rhesus Monkeys	IVSA Substitution for phencyclidine Inhalation	Low rates of responding; No clear evidence that responding for THC could persist above vehicle control levels over repeated daily sessions	Pickens et al., 1973
100-400 μg/kg/inj. Tween-20, Saline	Rhesus Monkeys	IVSA Naïve subjects Substitution for cocaine	Negative results in naïve subjects 2 monkeys out of 6 acquired THC IVSA after physical dependence to THC had been established and 1 monkey following cocaine self-administration	1Deneau and Kaymakcalan, 1971; Kaymakcalan et al., 1973
25-300 μg/kg/inj. PVP, Saline	Rhesus Monkeys	IVSA Naïve subjects; Substitution for cocaine, cocaine-THC mixture; IVSA measured after exposure to programmed infusions of THC	Negative results	Harris et al., 1974
Cannabis resin suspension (contained 30-330 μg of THC/ml)	Rats	Oral SA	Negative results	2Leite and Carlini, 1974
Aqueous hashish suspension (contained 1.25-125 μg of THC/ml)	Rats	Oral SA	Negative results	3Corcoran and Amit, 1974
3-300 μg/kg/inj. EL-620, Ethanol, Saline	Rhesus Monkeys	IVSA Substitution for cocaine	Negative results	Carney et al., 1977
7.5-300 μg/kg/inj. Tween-20, Saline	Rats	IVSA Naïve subjects	Low incidence of lever-pressing; Maximal incidence of rats self-administering THC was only 40 % on the highest dose	Van Ree et al., 1978
6.25-50 μg/kg/inj. Tween-80, Saline	Rats	IVSA Naïve Subjects	IVSA in food-deprived rats when a pellet of food was automatically delivered at 1-min intervals; Behavior immediately disappeared when a diet restriction or the automatic food presentation was discontinued	Takahashi and Singer, 1979; 1980
17-100 μg/kg/inj. EL-620, Ethanol, Saline	Rhesus Monkeys	IVSA Substituted for phencyclidine	Negative results	Mansbach et al., 1994
2-8 μg/kg/inj. Tween-80, Ethanol, Saline	Squirrel Monkeys	IVSA Substituted for cocaine after saline extinction period	Persistent and reliable IVSA; Peak rates of responding at THC dose of 4 μg/kg/inj.	Tanda et al., 2000
1-16 μg/kg/inj. Tween-80, Ethanol, Saline	Squirrel Monkeys	IVSA Naïve Subjects	Persistent and reliable IVSA; Peak rates of responding at THC dose of 4 μg/kg/inj.	Justinova et al., 2003; 2004
WIN 55,512-2
10-500 μg/kg/inj. Cremophor, Saline	Mice	IVSA Naïve subjects	Positive results; Single IVSA session in restrained mice	Martellotta et al., 1998
100 μg/kg/inj. Cremophor, Saline	Mice	IVSA Naïve subjects	Positive results in wild-type mice (CB1+/+) Negative results in CB1 receptor knockout mice (CB1-/-)	Ledent et al., 1999
10-100 μg/kg/inj. Cremophor, Saline	Mice	IVSA Naïve subjects	Positive results; Single IVSA session in restrained mice	Navarro et al., 2001
6.25-50 μg/kg/inj. Tween-80, Saline	Rats	IVSA Naïve subjects	Positive results; Peak rates of responding at WIN 55,212-2 dose of 12.5 μg/kg/inj.; Freely moving rats; Diet-restriction necessary to demonstrate self-administration	Fattore et al., 2001; Spano et al., 2004
CP 55,940
0.3-3 μg/kg/inj. EL-620, Ethanol, Saline	Rhesus Monkeys	IVSA Substituted for phencyclidine	Negative results	Mansbach et al., 1994
0.1-1.6 μg/infusion ACP, Cremophor, Saline	Rats	ICVSA Naïve subjects	Positive results, Water-restricted rats; Concurrent delivery of water with each infusion	Braida et al., 2001
HU-210
5 μg/kg/inj. Cremophor, Saline	Mice	IVSA Naïve subjects	Positive results; One-session self-administration in restrained mice	Navarro et al., 2001
SR 141716 (Rimonabant)
1-100 μg/kg/inj. EL-620, Ethanol, Saline	Rhesus Monkeys	IVSA Substitution for cocaine	Negative results	Beardsley et al., 2002

IVSA - Intravenous Self-administration; ICVSA - Intracerebroventricular Self-administration; PVP - Polyvinylpyrollidone; EL-620 - Emulphor ; ACP - artificial cerebrospinal fluid

¹Deneau GA, Kaymakcalan S. Physiological and psychological dependence to synthetic Δ⁹-Tetrahydrocannabinol (THC) in rhesus monkeys. The Pharm acologist 1971;13:246;

²Leite JR , Carlini E A . Failure to obtain “cannabis-directed behavior” and abstinence syndrome in rats chronically treated with cannabis sativa extracts. Psychopharmacologia. 1974;36(2):133-45;

³Corcoran ME , Amit Z. Reluctance of rats to drink hashish suspensions: free-choice and forced consumption, and the effects of hypothalamic stimulation. Psychopharmacologia. 1974;35(2):129-47