R. J. Lamb

Reinforcing operants other than abstinence in drug abuse treatment: an effective alternative for reducing drug use.

This study examines the effectiveness of using vouchers to reinforce either the provision of urine samples testing negative for illicit drugs (UA group) or the completion of objective, individually defined, treatment-plan-related tasks (TP group). A third group was assigned to the clinics standard treatment (STD group). Participants were randomly assigned to groups after a 6-week baseline-stabilization period. Urine specimens were collected thrice weekly throughout the study. In the UA condition, participants earned

Cocaine use and HIV risk behavior in methadone maintenance patients

5 (U.S. dollars) in vouchers for each drug-free urine submitted. In the TP condition, participants earned up to

Self-injection of d,1-3,4-methylenedioxymethamphetamine (MDMA) in the baboon

15 in vouchers per week for demonstrating completion of treatment plan tasks assigned by their counselors. Contingencies were in effect for 12 weeks, after which all participants received the clinics standard treatment. Urinalysis results indicate that the TP intervention was significantly more effective in reducing illicit drug use than either the UA or STD interventions. These effects were maintained with a trend toward continuing improvement for the TP groups even after contingencies were discontinued.

Self-injection of barbiturates, benzodiazepines and other sedative-anxiolytics in baboons

This study examined sexual and drug use behavior in 247 methadone maintenance patients, to explore the association of cocaine use with human immunodeficiency virus (HIV) risk behavior. In univariate analyses, cocaine use was positively associated with any drug injection, number of injections, and sexual intercourse without condoms. These relationships remained significant after controlling for other drug use and demographic factors. Heroin use also contributed to injection-related risk. We conclude that cocaine use represents a continued source of risk for exposure to HIV in this population, and that more aggressive efforts are warranted to reduce illicit drug use, particularly of heroin and cocaine, in methadone patients.

Schedule of voucher delivery influences initiation of cocaine abstinence

MDMA (d,1-3,4-Methylenedioxymethamphetamine HCl; “ecstasy”) self-injection (0.1–3.2 mg/kg/injection) was examined in baboons under conditions in which baseline responding was maintained by intravenous injections of cocaine HCl (0.32 mg/kg/injection). Drug was available under a FR 160-response schedule of intravenous injection. Each drug injection was followed by a 3-h time out allowing a maximum of eight injections per day. MDMA or MDMA vehicle (saline) was substituted for cocaine for a period of 14 or more days followed by a return to the cocaine baseline. MDMA (0.32–3.2 mg/kg/inj) maintained more injections and higher responses rates than were maintained by saline. The maximal number of injections maintained by MDMA and the maximal response rate maintained by MDMA were less than those maintained under baseline conditions with cocaine. The highest dose of MDMA tested maintained a cyclic pattern of self-injection, i.e., days of high numbers of injections intermixed with days of low numbers of injections. At the highest dose of MDMA tested, concurrent food maintained behavior was suppressed to an extent that food intake was also decreased.

Relative abuse liability of triazolam: Experimental assessment in animals and humans

Self-injection of 12 sedative-anxiolytics was examined in baboons. Intravenous injections and initiation of a 3-h time-out were dependent upon completion of a fixed-ratio schedule requirement, permitting eight injections per day. Before testing each dose of drug, self-injection performance was established with cocaine. Subsequently, a test dose was substituted for cocaine. At some doses, all five of the benzodiazepines examined (alprazolam, bromazepam, chlordiazepoxide, lorazepam, triazolam) maintained rates (number of injections per day) of drug self-injection above vehicle control in each of the baboons tested. Maximum rates of benzodiazepine self-injection were generally submaximal. Of the benzodiazepines examined, triazolam maintained the highest rates of self-injection. Among the three barbiturates tested, methohexital generally maintained high rates of self-injection in contrast to hexobarbital and phenobarbital, which only maintained low rates. Of the four non-benzodiazepine non-barbiturate sedatives examined, both chloral hydrate and methyprylon occasionally maintained high rates of self-injection. Although there were differences within and across animals, baclofen maintained intermediate rates of self-injection. The novel anxiolytic buspirone maintained only low rates of self-injection that were not different from vehicle. This study further validates the self-injection methodology for assessing sedative-anxiolytic abuse liability and provides new information about drug elimination rate as a determinant of drug self-administration.Self-injection of 12 sedative-anxiolytics was examined in baboons. Intravenous injections and initiation of a 3-h time-out were dependent upon completion of a fixed-ratio schedule requirement, permitting eight injections per day. Before testing each dose of drug, self-injection performance was established with cocaine. Subsequently, a test dose was substituted for cocaine. At some doses, all five of the benzodiazepines examined (alprazolam, bromazepam, chlordiazepoxide, lorazepam, triazolam) maintained rates (number of injections per day) of drug self-injection above vehicle control in each of the baboons tested. Maximum rates of benzodiazepine self-injection were generally submaximal. Of the benzodiazepines examined, triazolam maintained the highest rates of self-injection. Among the three barbiturates tested, methohexital generally maintained high rates of self-injection in contrast to hexobarbital and phenobarbital, which only maintained low rates. Of the four non-benzodiazepine non-barbiturate sedatives examined, both chloral hydrate and methyprylon occasionally maintained high rates of self-injection. Although there were differences within and across animals, baclofen maintained intermediate rates of self-injection. The novel anxiolytic buspirone maintained only low rates of self-injection that were not different from vehicle. This study further validates the self-injection methodology for assessing sedative-anxiolytic abuse liability and provides new information about drug elimination rate as a determinant of drug self-administration.

Cocaine self-administration appears to be mediated by dopamine uptake inhibition

This study examined whether voucher delivery arrangements affect treatment outcome. First, 90 cocaine-dependent adults were randomly assigned to behavioral counseling or counseling plus vouchers for cocaine-free urine samples. The value of each voucher was low at the beginning but increased as the patient progressed (Voucher Schedule 1). Voucher Schedule 1 produced no improvements relative to counseling only. Next, 23 patients received vouchers on either Voucher Schedule 1 or Voucher Schedule 2. Voucher Schedule 2 began with high voucher values, but requirements for earning vouchers increased as the patient progressed. Average durations of cocaine abstinence were 6.9 weeks on Voucher Schedule 2 versus 2.0 weeks on Voucher Schedule 1 (p = .02). This confirms that vouchers can assist in initiating abstinence and that voucher delivery arrangements are critical.

Self-administration in baboons and the discriminative stimulus effects in rats of bupropion, nomifensine, diclofensine and imipramine

The abuse liability of a drug is a positive, interactive function of the reinforcing and adverse effects of the drug. The relative abuse liability of the hypnotic benzodiazepine, triazolam, has been controversial. This paper reviews animal and human studies bearing on its relative abuse liability, including data on pharmacological profile, reinforcing effects, liking, speed of onset, discriminative stimulus effects, subjective effects, physiological dependence, rebound and early morning insomnia, drug produced anxiety, lethality in overdose, psychomotor impairment, interactions with ethanol, anterograde amnesia, impaired awareness of drug effect, and other psychiatric and behavioral disturbances. It is concluded that the abuse liability of triazolam is less than that of the intermediate duration barbiturates such as pentobarbital. Although there are considerable data indicating similarities of triazolam to other benzodiazepines, there is also substantial speculation among clinical investigators and some limited data suggesting that the abuse liability of triazolam is greater than that of a variety of other benzodiazepines, and virtually no credible data or speculation that it is less. Further research will be necessary to clarify definitively the abuse liability of triazolam relative to other benzodiazepines.

Natural classes of treatment response.

1. While cocaine binds to several known sites in the brain, the binding site or receptor associated with its reinforcing or addictive properties has not been identified as such. 2. The identification of the pharmacologically relevant receptor(s) requires that an association exist between the potency of a variety of cocaine of cocaine-related drugs in animal models of substance and their potency at a binding site in the brain. 3. Our experiments indicate that the potencies of cocaine-like drugs in animal studies of drug self-administration are correlated with their potencies in inhibiting 3H-mazindol binding to dopamine transporters in the rat striatum. Cocaine binding to several other presynaptic and postsynaptic binding sites does not appear to be associated with the reinforcing effects of the drug. 4. Thus, the cocaine receptor related to substance abuse appears to be the binding site associated with inhibition of dopamine uptake on the dopaminergic nerve terminals.

From telephone to office: intake attendance as a function of appointment delay.

The behavioral effects of the antidepressants nomifensine, diclofensine, bupropion, and imipramine were examined using a cocaine substitution drug self-administration procedure in baboons and a cocaine drug discrimination procedure in rats. Intravenous self-administration of the antidepressants was examined in baboons under conditions in which baseline responding was maintained by intravenous injections of cocaine HCl (0.32 mg/kg/injection). Drug was available under a fixed-ratio 80-response or 160-response schedule of intravenous injection. Each drug injection was followed by a 3-h time-out allowing a maximum of eight injections per day. The antidepressants or their vehicles were substituted for cocaine for a period of 15 days, followed by a return to the cocaine baseline. Nomifensine, diclofensine, and bupropion all maintained self-administration behavior at levels above those maintained by their respective vehicles. Some doses of nomifensine, diclofensine, and bupropion maintained levels of behavior similar to those maintained under baseline cocaine conditions. High doses of imipramine maintained levels of behavior above those maintained by its vehicle, but the amount of behavior maintained under these conditions was extremely small. In a second experiment rats were trained to discriminate 32 µmol/kg cocaine (IP 10 min presession) from no drug in a two-lever food reinforced drug discrimination procedure in which responding on one lever was reinforced following ten consecutive responses when the session was preceded by cocaine administration, while responding on the other lever was similarly reinforced in the absence of cocaine pretreatment. Cocaine, nomifensine, diclofensine, and bupropion all dose-dependently occasioned cocaine-appropriate responding. Imipramine did not occasion cocaine-appropriate responding over a range of behaviorally active doses.