Interactions of delta9-tetrahydrocannabinol with d-amphetamine, cocaine, and nicotine in rats.

The acute, reciprocal dose-response interactions between delta9-tetrahydrocannabinol (delta9-THC; 2.5, 5.0 and 10.0 mg/kg; IG) and each of three stimulants - d-amphetamine (dA; 1, 2 and 4 mg/kg; IP), cocaine (COC; 10, 20 and 30 mg/kg; IP), and nicotine (NIC; 0.25, 0.5 and 1.0 mg/kg; IP) were studied for their effects on performance of a conditioned avoidance response (CAR), photocell activity, heart rate, body temperature, and rotarod performance. delta9-THC impaired CAR and rotarod performance, depressed photocell activity, and decreased heart rate and body temperature. None of the three stimulants influenced CAR performance, but dA and COC increased the number of intertrial responses, and this latter effect was partially antagonized by delta9-THC. dA and COC, but not NIC, stimulated photocell activity. delta9-THC completely blocked this effect of dA, whereas there was mutual antagonism between delta9-THC and COC on this measure and NIC markedly potentiated the depression caused by delta9-THC. dA and COC tended to offset the impairment of rotarod performance caused by delta9-THC, whereas NIC augmented it. The bradycardia and hypothermia caused by delta9-THC tended to be augmented by these stimulants, especially NIC. The interactions were also studied after subacute treatment for six days with delta9-THC and/or each of the three stimulants. There was evidence for tolerance to the effects of delta9-THC on all measures and this tolerance generally resulted in less interactive effects between delta9-THC and the stimulants. Little or no tolerance was seen for the effects of the three stimulants or their interaction with delta9-THC. The time course of radioactivity derived from 14C-delta9-THC and each of the radiolabelled stimulants was determined in plasma and brain. Only minor interactive effects were found and, in general, they could not account for the functional interactions.

Time-action and behavioral effects of amphetamine, ethanol, and acetylmethadol.

As time increased between drug administration and the start of experimental sessions, effects of drugs on food-maintained responding in rhesus monkeys increased to a maximum and then decreased. d-Amphetamine, ethanol, and alpha-l-acetylmethadol (LAAM) generally decreased high response rates in one component of a chain schedule, while very low response rates in another component were increased reliably only by ethanol. The time of peak LAAM and ethanol concentrations in blood or plasma corresponded with or overlapped the time of maximal behavioral effect, while the time of maximal behavioral effect with d-amphetamine occurred somewhat prior to the time of peak plasma-amphetamine concentration. With d-amphetamine and perhaps with ethanol, effects on operant responding were greater after 30-min pretreatment intervals than after six-hr pretreatment intervals despite higher plasma or blood concentrations at six hours than at 30 min.

Interactions between delta9-tetrahydrocannabinol and phencyclidine hydrochloride in rats.

delta9-Tetrahydrocannabinol (THC; 2.5, 5.0, 10.0 mg/kg, PO) impaired avoidance and rotarod performance, and caused bradycardia and hypothermia. Phencyclidine (PCP; 1.25, 2.5, 5.0 mg/kg, IP) impaired avoidance and rotarod performance and caused a marked increase in photocell activity. When combined, the depressant properties of each drug were enhanced and the stimulation of photocell activity cg/kg THC and its interactions with PCP followed subacute treatment for six days, whereas many of the effects of PCP were enhanced after subacute treatment with a dose of 2.5 mg/kg. Open-field behavior was affected by each drug alone and in combination in a similar way as photocell activity, but the depression caused by their interaction was greater; both drugs caused an increase in urination. Response rates on an FR-10 schedule of food reinforcement were decreased by 2.5 mg/kg PCP, but not by 5.0 mg/kg THC; the combination caused greater response suppression than either drug alone. The functional interactions between THC and PCP were not related to changes in the concentrations of 14C or 3H in plasma or brain derived from 14C-delta9-THC and 3H-PCP, respectively.

Teratologic evaluation of delta9-tetrahydrocannabinol in mice, including a review of the literature.

Pregnant CD1 mice received 5, 15, 50, 150 mg/kg/day of delta9-THC in sesame oil on days 6-15 of gestation orally by gavage and were killed about one day before expected delivery. Treatment had no effect on the maternal weight gain, prenatal mortality rate, fetal weight, and the frequency of gross external, internal, and skeletal abnormalities.